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+{"question_id": "65cfae831930410b13000015", "question": "What is the use of P85-Ab?", "answer": "P85-Ab is a promising novel biomarker for nasopharyngeal carcinoma screening.", "relevant_passage_ids": ["37646678"], "type": "summary", "snippets": [{"offsetInBeginSection": 342, "offsetInEndSection": 859, "text": "METHODS: We designed a peptide library representing highly ranked B-cell epitopes of EBV coding sequences to identify novel serologic biomarkers for nasopharyngeal carcinoma. After a retrospective case-control study, the performance of the novel biomarker anti-BNLF2b total antibody (P85-Ab) was validated through a large-scale prospective screening program and compared with that of the standard two-antibody-based screening method (EBV nuclear antigen 1 [EBNA1]-IgA and EBV-specific viral capsid antigen [VCA]-IgA).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37646678"}, {"offsetInBeginSection": 1715, "offsetInEndSection": 1938, "text": "CONCLUSIONS: Our results suggest that P85-Ab is a promising novel biomarker for nasopharyngeal carcinoma screening, with higher sensitivity, specificity, and positive predictive value than the standard two-antibody method. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37646678"}, {"offsetInBeginSection": 517, "offsetInEndSection": 1108, "text": "After a retrospective case-control study, the performance of the novel biomarker anti-BNLF2b total antibody (P85-Ab) was validated through a large-scale prospective screening program and compared with that of the standard two-antibody-based screening method (EBV nuclear antigen 1 [EBNA1]-IgA and EBV-specific viral capsid antigen [VCA]-IgA).RESULTS: P85-Ab was the most promising biomarker for nasopharyngeal carcinoma screening, with high sensitivity (94.4%; 95% confidence interval [CI], 86.4 to 97.8) and specificity (99.6%; 95% CI, 97.8 to 99.9) in the retrospective case-control study.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37646678"}, {"offsetInBeginSection": 1530, "offsetInEndSection": 1937, "text": "The combination of P85-Ab and the two-antibody method markedly increased the positive predictive value to 44.6% (95% CI, 33.8 to 55.9), with sensitivity of 70.2% (95% CI, 56.0 to 81.4).CONCLUSIONS: Our results suggest that P85-Ab is a promising novel biomarker for nasopharyngeal carcinoma screening, with higher sensitivity, specificity, and positive predictive value than the standard two-antibody method.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37646678"}]}
+{"question_id": "662fc44b187cba990d000015", "question": "What are the indicated prophylaxis treatments for acute cholinergic syndrome secondary to irinotecan?", "answer": "Lack of difference in the incidence of cholinergic syndrome observed in irinotecan-treated patients suggests atropinediphenoxylate and hyoscyamine may both be effective prophylactic option", "relevant_passage_ids": ["25839059", "30244364", "29705823", "30564875", "11956509", "17264330", "34248544", "14504920", "9726096", "30449850", "37885319", "11419562", "30042278", "29562843", "10570064"], "type": "list", "snippets": [{"offsetInBeginSection": 1548, "offsetInEndSection": 1738, "text": "Lack of difference in the incidence of cholinergic syndrome observed in irinotecan-treated patients suggests atropinediphenoxylate and hyoscyamine may both be effective prophylactic options.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25839059"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1064, "text": "BACKGROUND/AIM: Cholinergic syndrome frequently occurs within the first 24\u00a0h after irinotecan injection. We evaluated the prophylactic effect of scopolamine butylbromide on irinotecan-related cholinergic syndrome.PATIENTS AND METHODS: Fifty-nine patients who received irinotecan-based regimens at our outpatient chemotherapy clinic between April 2013 and May 2014 were enrolled. Patients who developed irinotecan-related cholinergic syndrome were prophylactically administered scopolamine butylbromide at the next scheduled treatment. Risk factors for irinotecan-related cholinergic syndrome were determined using logistic regression analysis.RESULTS: Irinotecan-related cholinergic syndrome occurred in 50.8% of patients. Scopolamine butylbromide administration significantly reduced the incidence to 3.4% (P\u2009<\u20090.01). The irinotecan dose (\u2265\u2009150\u00a0mg/m2) was the only risk factor associated with irinotecan-related cholinergic syndrome. The incidence of cholinergic syndrome in patients with this risk factor was 75%.CONCLUSION: Scopolamine butylbromide was effectiv", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30564875"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1469, "text": "Cholinergic syndrome is an acute adverse reaction associated with irinotecan. Development of cholinergic syndrome can be ameliorated or prevented by administering various anticholinergics, including atropine sulfate or scopolamine butylbromide. Although many of the side effects are transient and non-life-threatening, their onset is painful and can lower a patient's quality of life (QoL). This retrospective study was performed to identify predictive factors of the development of irinotecan-related cholinergic syndrome in order to develop future strategies for improving the QoL of patients undergoing chemotherapy. We enrolled 150 cancer patients who underwent chemotherapy, which included irinotecan, in our outpatient chemotherapy center between October 2014 and January 2017. For regression analysis, variables related to the development of irinotecan-related cholinergic syndrome were extracted from the patient's clinical records. The degree of cholinergic syndrome was classified as follows: grade 0\u2009=\u2009not developed; grade 1\u2009=\u2009developed but did not require anticholinergic drugs; and grade 2\u2009=\u2009developed and required anticholinergic drugs or stopping the chemotherapy due to cholinergic syndrome. Multivariate ordered logistic regression analysis was performed to identify predictive factors for the development of irinotecan-related cholinergic syndrome. Threshold measurements were determined using a receiver operating characteristic analysis (ROC) curve.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29705823"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1203, "text": "BACKGROUND: Cholinergic syndrome is an acute adverse event frequently observed in patients administered irinotecan, and can sometimes negatively affect their quality of life. In some manifestations of the syndrome such as bradycardia, careful monitoring of patients is advised. In this study, we retrospectively investigated the risk factors associated with irinotecan-induced cholinergic syndrome in Japanese patients with cancer.METHODS: Patients who received irinotecan-based chemotherapy between April 2014 and June 2018 were examined. Patient backgrounds and clinical data during the first cycle of an irinotecan-containing regimen, including cholinergic syndrome manifestation within 24\u00a0h after the start of treatment, were collected from medical records. Univariate and multivariate analyses were performed to assess the risk of irinotecan-induced cholinergic syndrome.RESULTS: Among 179 patients administered an irinotecan-containing regimen, 51 experienced cholinergic syndrome after the initiation of treatment. The most common symptom was sweating followed by diarrhea, abdominal pain, lacrimation, and nasal discharge. 42 patients developed symptoms of cholinergic syndrome during their firs", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30244364"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1787, "text": "Irinotecan hydrochloride (irinotecan) is a chemotherapeutic agent used in the treatment of solid tumors. In addition to severe neutropenia and delayed diarrhea, irinotecan causes cholinergic syndrome, characterized by abdominal pain and acute diarrhea. The latter symptoms are frequently observed during and after irinotecan treatment. Here, we have discussed the case of a patient who completely recovered from abdominal pain following the administration of loperamide hydrochloride (loperamide) at a dose of 2 mg, before infusing irinotecan. In contrast, anticholinergic drugs were not as effective in alleviating symptoms. A 28-year-old man with stage IV rectal cancer with peritoneal metastasis was prescribed with fluorouracil, irinotecan, and levofolinate calcium (FOLFIRI), in addition to cetuximab. Anticholinergic drugs, such as scopolamine butylbromide (scopolamine) or atropine sulfate (atropine), were administered to treat abdominal pain that was considered as irinotecan-induced cholinergic syndrome, but monotherapy was not effective. Thereafter, oral loperamide (2 mg) with atropine (0.25 mg) was prescribed before irinotecan infusion. Consequently, the patient did not experience any abdominal pain during and after irinotecan treatment. Loperamide is an opioid receptor agonist and decreases the activity of the myenteric plexus of the intestinal wall. It also inhibits the release of both acetylcholine and prostaglandins, resulting in decreased inhibition of peristaltic movement. We assumed that its mechanism solely or in combination contributed to symptom relief. We hypothesized that the synergistic anticholinergic interaction between loperamide and atropine resulted in marked suppression of irinotecan-induced cholinergic syndrome compared to loperamide alone.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34248544"}, {"offsetInBeginSection": 0, "offsetInEndSection": 827, "text": "We investigated the incidence of cholinergic symptoms related to irinotecan hydrochloride(CPT-11)and examined their association with clinical factors. The subjects were 61 patients with colorectal cancer for whom combination chemotherapy with CPT-11 was indicated between May 2008 and December 2014. The incidence of CPT-11-related cholinergic symptoms was investigated. Cholinergic symptoms were observed in 46 patients(75.4%), of whom 29(47.5%)showed Grade 2 or higher symptoms as follows: nasal discharge(47.5%), lacrimation(39.3%), nausea/vomiting(29.5%), and watery stool (26.2%). The results of the multivariate analysis showed that high-dose CPT-11 administration(150mg/m2)was a significant risk factor for the appearance of cholinergic symptoms and that PS 0 was a significant factor for reducing the onset of symptoms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30449850"}, {"offsetInBeginSection": 473, "offsetInEndSection": 1544, "text": "Cancer patients suffer from the cholinergic syndrome caused by irinotecan and other Top1 inhibitors. Irinotecan-treated patients have developed cholinergic syndrome due to acetylcholinesterase (AChE) enzyme inhibition. It appears that irinotecan or its metabolites directly interact with AChE and inhibit its role of converting acetylcholine to choline, leading to an accumulation of acetylcholine and subsequent symptoms of the cholinergic syndrome. The phytochemicals present in Phyllanthus emblica, commonly referred to as amla, have been studied to determine their therapeutic effects. As an alternative treatment for cancer, this study explores the potential of phytochemicals found in amla to target and inhibit the Top1 protein. Additionally, the study aims to identify a non-inhibitor for AChE. Molecular docking studies assessed phytochemical binding affinities to Top1 and AChE enzymes, and ADME analyses were performed to assess their drug-likeness properties. Subsequently, molecular dynamic simulation was employed to assess the stability of these compounds.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37885319"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1421, "text": "Irinotecan (Camptosar\u00a9, CPT-11), a topoisomerase I inhibitor, is a commonly used cytotoxic chemotherapeutic in the treatment of multiple malignancies, particularly of gastrointestinal origin. Dysarthria secondary to irinotecan has been described as a rare side effect in a few case reports with limited data to recommend appropriate management. We describe herein a large single institution experience of patients with gastrointestinal malignancies who experienced dysarthria while being treated with irinotecan-based chemotherapy regimens (FOLFIRINOX or FOLFIRI+/-bevacizumab). Eighteen patients developed neurological manifestations during irinotecan infusion with the majority ( n\u2009=\u200917) developing dysarthria. Patients also experienced other known side effects including cholinergic effects (abdominal bloating, diarrhea, facial flushing, diaphoresis, and rhinorrhea), nausea, fatigue, perioral paresthesia and musculoskeletal discomfort. The dysarthria occurred as early as with the first infusion of irinotecan ( n\u2009=\u20099), but several patients did not develop symptoms until subsequent infusions (range, 1-6). Dose alterations of irinotecan did not obviously impact the reccurrence or severity of dysarthria. Management strategies included close observation, atropine, slower irinotecan infusion rate, and reassurance. Dysarthria resolved without consequence in all patients within hours of completion of the infusion.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29562843"}, {"offsetInBeginSection": 0, "offsetInEndSection": 358, "text": "BACKGROUND: Cholinergic syndrome is a well established acute adverse reaction associated with irinotecan. Cholinergic side effects can be ameliorated or prevented with anticholinergic agents. To date, no formal studies have compared atropine-diphenoxylate and hyoscyamine as premedications for prophylaxis of the cholinergic syndrome with irinotecan infusion", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25839059"}, {"offsetInBeginSection": 191, "offsetInEndSection": 358, "text": " To date, no formal studies have compared atropine-diphenoxylate and hyoscyamine as premedications for prophylaxis of the cholinergic syndrome with irinotecan infusion", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25839059"}, {"offsetInBeginSection": 191, "offsetInEndSection": 496, "text": " To date, no formal studies have compared atropine-diphenoxylate and hyoscyamine as premedications for prophylaxis of the cholinergic syndrome with irinotecan infusion.OBJECTIVES: To compare the incidence of cholinergic syndrome with irinotecan using atropine-diphenoxylate or hyoscyamine as premedication", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25839059"}, {"offsetInBeginSection": 807, "offsetInEndSection": 1151, "text": "Anticholinergic drugs, such as scopolamine butylbromide (scopolamine) or atropine sulfate (atropine), were administered to treat abdominal pain that was considered as irinotecan-induced cholinergic syndrome, but monotherapy was not effective. Thereafter, oral loperamide (2 mg) with atropine (0.25 mg) was prescribed before irinotecan infusion.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34248544"}, {"offsetInBeginSection": 105, "offsetInEndSection": 358, "text": " Cholinergic side effects can be ameliorated or prevented with anticholinergic agents. To date, no formal studies have compared atropine-diphenoxylate and hyoscyamine as premedications for prophylaxis of the cholinergic syndrome with irinotecan infusion", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25839059"}, {"offsetInBeginSection": 807, "offsetInEndSection": 1049, "text": "Anticholinergic drugs, such as scopolamine butylbromide (scopolamine) or atropine sulfate (atropine), were administered to treat abdominal pain that was considered as irinotecan-induced cholinergic syndrome, but monotherapy was not effective.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34248544"}, {"offsetInBeginSection": 935, "offsetInEndSection": 1120, "text": "The incidence of cholinergic syndrome in patients with this risk factor was 75%.CONCLUSION: Scopolamine butylbromide was effective in preventing irinotecan-related cholinergic syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30564875"}, {"offsetInBeginSection": 192, "offsetInEndSection": 693, "text": "To date, no formal studies have compared atropine-diphenoxylate and hyoscyamine as premedications for prophylaxis of the cholinergic syndrome with irinotecan infusion.OBJECTIVES: To compare the incidence of cholinergic syndrome with irinotecan using atropine-diphenoxylate or hyoscyamine as premedication.METHODS: We conducted a retrospective, single-center, nonrandomized, cohort study of adult patients treated with atropine-diphenoxylate or hyoscyamine as premedication before receiving irinotecan.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25839059"}, {"offsetInBeginSection": 574, "offsetInEndSection": 691, "text": "Irinotecan-treated patients have developed cholinergic syndrome due to acetylcholinesterase (AChE) enzyme inhibition.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37885319"}, {"offsetInBeginSection": 328, "offsetInEndSection": 544, "text": "A cholinergic syndrome resulting from the inhibition of acetylcholinesterase activity by irinotecan is frequently seen within the first 24 hours after irinotecan administration but is easily controlled with atropine.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9726096"}, {"offsetInBeginSection": 78, "offsetInEndSection": 244, "text": "Development of cholinergic syndrome can be ameliorated or prevented by administering various anticholinergics, including atropine sulfate or scopolamine butylbromide.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29705823"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1484, "text": "BACKGROUND: Cholinergic syndrome is a well established acute adverse reaction associated with irinotecan. Cholinergic side effects can be ameliorated or prevented with anticholinergic agents. To date, no formal studies have compared atropine-diphenoxylate and hyoscyamine as premedications for prophylaxis of the cholinergic syndrome with irinotecan infusion.OBJECTIVES: To compare the incidence of cholinergic syndrome with irinotecan using atropine-diphenoxylate or hyoscyamine as premedication.METHODS: We conducted a retrospective, single-center, nonrandomized, cohort study of adult patients treated with atropine-diphenoxylate or hyoscyamine as premedication before receiving irinotecan. For all irinotecan infusions, intravenous atropine was administered for patients experiencing any cholinergic reaction.RESULTS: A total of 532 irinotecan cycles (354 cycles for atropine-diphenoxylate group; 178 cycles for hyoscyamine group) were analyzed in 80 patients. Overall incidence of cholinergic syndrome did not differ between atropine-diphenoxylate (8.2%) and hyoscyamine (9.0%) groups (P = .76). The incidence of cholinergic syndrome after the \u00a3rst cycle of irinotecan was similar between the 2 arms, atropine-diphenoxylate (14.6%) and hyoscyamine (10.7%), with P = .74. The most common cholinergic symptoms documented were abdominal pain or cramping, and diarrhea.LIMITATIONS: This study was subjected to vulnerabilities to bias and random error because of its observational ret", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25839059"}, {"offsetInBeginSection": 0, "offsetInEndSection": 863, "text": "BACKGROUND: The anticancer drug irinotecan induces cholinergic side effects that are currently ascribed to the blockade of acetylcholinesterase. This study investigated (1) the pattern of acetylcholinesterase activity in patients receiving treatment with irinotecan and (2) the relationship between acetylcholinesterase activity and plasma concentrations of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38), and SN-38 glucuronide (SN-38G).METHODS: Twenty-five patients with advanced colorectal cancer were treated with 250 mg/m(2) irinotecan administered by intravenous infusion for 60 minutes. Blood samples were collected before drug infusion and at 15 minutes and 45 minutes after the start of drug infusion. Blood acetylcholinesterase activity was determined by a colorimetric enzymatic assay, and irinotecan, SN-38, and SN-38G concentrations were determine", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11956509"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1520, "text": "Irinotecan (CPT-11) is an anticancer drug that occasionally produces acute cholinergic side effects. Preliminary findings suggest that these are mediated through the inhibition of acetylcholinesterase (AChE). In this study, the inhibition of various AChEs by CPT-11 was studied. The lactone form of CPT-11 resulted in apparent noncompetitive inhibition of electric eel and both human recombinant and erythrocyte AChE with K(i) values of 0.065, 0.19, and 0.29 microM, respectively. The carboxylate form of CPT-11 was approximately 10 times less potent. Apparent noncompetitive inhibition of AChE may arise through several mechanisms, and those relevant to CPT-11 were identified from key experimental findings. First, the inhibition by CPT-11 was found to be instantly reversible in dilution studies. Second, incubation of the enzyme with CPT-11 before the introduction of neostigmine protected the enzyme from inactivation. Third, regeneration of the active enzyme after preincubation with neostigmine was totally suppressed by the addition of 2 microM CPT-11, indicating that CPT-11 is a potent inhibitor of decarbamoylation and, by inference, deacylation. Additional experiments with tacrine revealed functional differences between these two inhibitors. Also, preliminary molecular modeling of the interaction between AChE and CPT-11 indicated that the latter does not bind at the same site as tacrine. Displacement studies with the peripheral site-specific ligand, propidium, confirmed that CPT-11 binds at this site.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10570064"}, {"offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "Cholinergic syndrome is an acute adverse reaction associated with irinotecan. Development of cholinergic syndrome can be ameliorated or prevented by administering various anticholinergics, including atropine sulfate or scopolamine butylbromide.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29705823"}, {"offsetInBeginSection": 105, "offsetInEndSection": 496, "text": " Cholinergic side effects can be ameliorated or prevented with anticholinergic agents. To date, no formal studies have compared atropine-diphenoxylate and hyoscyamine as premedications for prophylaxis of the cholinergic syndrome with irinotecan infusion.OBJECTIVES: To compare the incidence of cholinergic syndrome with irinotecan using atropine-diphenoxylate or hyoscyamine as premedication", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25839059"}, {"offsetInBeginSection": 987, "offsetInEndSection": 1308, "text": "The main adverse effects of these agents are myelosuppression, oral mucositis, diarrhoea, acute cholinergic syndrome, nausea and emesis, neurotoxicity, hand-foot syndrome and other cutaneous adverse effects, ocular toxicity, cardiotoxicity, small bowel toxicity, asthenia, elevated liver transaminase levels and alopecia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11419562"}, {"offsetInBeginSection": 410, "offsetInEndSection": 564, "text": "inute infusion every 3 weeks. Concomitant treatments included atropine for cholinergic symptoms, loperamide for diarrhea at the first liquid stool, and pr", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17264330"}]}
+{"question_id": "662cf81b187cba990d000001", "question": "What is the function of FAM134B (also called JK-1, RETREG1)?", "answer": "FAM134B (also called JK-1, RETREG1), a member of the family with sequence similarity 134, was originally discovered as an oncogene in esophageal squamous cell carcinoma. However, its most famous function is that of an ER-phagy-regulating receptor", "relevant_passage_ids": ["37813237", "37728036", "36056188", "31930741", "33199694", "30556279", "31147549", "32102874", "35477002", "33843059", "29226326", "37273064", "31996076", "30177506", "28617241", "33052704", "34338405", "30794892", "29964340", "26040720", "29233873", "35253652"], "type": "summary", "snippets": [{"offsetInBeginSection": 6, "offsetInEndSection": 119, "text": "FAM134B, the initial endoplasmic reticulum (ER)-phagy receptor identified, facilitates ER-phagy during ER stress.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37813237"}, {"offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "FAM134B-induced endoplasmic reticulum (ER)-phagy exacerbates cisplatin-insulted hair cell apoptosis \uff1aPossible relation to excessive ER stress.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37813237"}, {"offsetInBeginSection": 252, "offsetInEndSection": 417, "text": "We aim to investigate the molecular mechanism by which FAM134B inhibits autophagy of HCC cells by reducing the expression of ER stress-related degradation proteins. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37728036"}, {"offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Upregulation of FAM134B inhibits endoplasmic reticulum stress-related degradation protein expression and promotes hepatocellular carcinogenesis.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37728036"}, {"offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "O-GlcNAc transferase regulates intervertebral disc degeneration by targeting FAM134B-mediated ER-phagy.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36056188"}, {"offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "FAM134B oligomerization drives endoplasmic reticulum membrane scission for ER-phagy.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31930741"}, {"offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "FAM134B (also called JK-1, RETREG1), a member of the family with sequence similarity 134, was originally discovered as an oncogene in esophageal squamous cell carcinoma. However, its most famous function is that of an ER-phagy-regulating receptor.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33199694"}, {"offsetInBeginSection": 0, "offsetInEndSection": 496, "text": "FAM134B (also called JK-1, RETREG1), a member of the family with sequence similarity 134, was originally discovered as an oncogene in esophageal squamous cell carcinoma. However, its most famous function is that of an ER-phagy-regulating receptor. Over the decades, the powerful biological functions of FAM134B were gradually revealed. Overwhelming evidence indicates that its dysfunction is related to pathophysiological processes such as neuropathy, viral replication, inflammation, and cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33199694"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1435, "text": "FAM134B is an autophagy regulator of endoplasmic reticulum and acts as a cancer suppressor in colon cancer. However, the molecular signaling pathways by which FAM134B interacts within colon carcinogenesis is still unknown. Herein, this study aims to determine the interacting partners of FAM134B for the first time in colon cancer and to explore the precise location of FAM134B in cancer signalling pathways. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) followed by anti-FAM134B co-immune precipitation of FAM134B interacting complex was used to identify the potential interactors of FAM134B in colon cancer cells. Western blot and confocal microscopic analysis were used to validate the physical interactions of FAM134B with the interactors. Lentiviral shRNA mediated silencing of FAM134B was used to examine the modulation of FAM134B interactors in cells. We have identified 29 novel binding partners, including CAP1, RPS28, FTH1, KDELR2, MAP4, EB1, PSMD6, PPIB/CYPB etc. Subsequent immunoassays confirmed the direct physical interactions of FAM134B with CAP1, EB1, CYPB, and KDELR2 in colon cancer cells. Exogenous suppression of FAM134B has led to significant upregulation of EB1 as well as reduction of KDELR2 expression. It was noted that overexpression of EB1 promotes WNT/\u03b2-catenin signaling pathways via inactivating tumor suppressor APC followed by activating \u03b2-catenin in colorectal carcinogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29964340"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1781, "text": "BACKGROUND: Family with sequence similarity 134, member B (FAM134B), also known as Reticulophagy regulator 1 (RETREG1), is an ER-phagy receptor involved in ER homeostasis. Congenital mutations in the FAM134B gene have been reported to be associated with hereditary sensory and autonomic neuropathy type 2B (HSAN2B); however, the molecular differences between wild-type and HSAN2B-linked FAM134B are not fully understood.METHODS AND RESULTS: We prepared several human FAM134B constructs, such as the HSAN2B-linked mutant, and compared their features with those of wild-type FAM134B by transfecting these constructs into FAM134B-deficient Neuro2a cells. Although intrinsic FAM134B protein expression in wild-type Neuro2a cells was affected by the supply of amino acids in the culture medium, the expression of each HSAN2B-linked mutant FAM134B protein was hardly affected by serum and amino acid deprivation. On the other hand, the intracellular localization of GFP-tagged HSAN2B-linked mutants, except for P7Gfs133X, overlapped well with ER-localized SP-RFPKDEL and did not differ from that of GFP-tagged wild-type FAM134B. However, analysis of protein\u2012protein interactions using the NanoBiT reporter assay revealed the difference between wild-type and C-terminal truncated mutant FAM134B. Furthermore, this NanoBiT assay demonstrated that both wild-type and G216R FAM134B interacted with LC3/GABARAPL1 to the same extent, but the FAM134B construct with mutations near the LC3-interacting region (LIR) did not. Similar to the NanoBiT assay, the C-terminal-truncated FAM134B showed lower ER-phagy activities, as assessed by the cotransfection of GFP-tagged reporters.CONCLUSIONS: We showed that wild-type and HSAN2B-linked FAM134B have different molecular characteristics by transfec", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37273064"}, {"offsetInBeginSection": 232, "offsetInEndSection": 1377, "text": "Being one such receptor, FAM134B plays critical roles in cellular processes such as protein quality control and neuronal survival. FAM134B has also been associated with different cancers, although its exact role remains elusive. We report here that the FAM134B gene encodes not one but at least two different protein isoforms: the full-length and the NH2 terminally truncated forms. Their relative expression shows extreme variation, both within normal tissues and among cancer types. Expression of full-length FAM134B is restricted to the brain, testis, spleen, and prostate. In contrast, NH2 terminally truncated FAM134B is dominant in the heart, skeletal muscle, kidney, pancreas, and liver. We compared wild-type and knockout mice to study the role of the Fam134b gene in starvation. NH2 terminally truncated FAM134B-2 was induced in the liver, skeletal muscle, and heart but not in the pancreas and stomach following starvation. Upon starvation, Fam134b-/- mice differed from wild-type mice by less weight loss and less hyperaminoacidemic and hypocalcemic response but increased levels of serum albumin, total serum proteins, and \u03b1-amylase.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33052704"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1657, "text": "Fam134b (JK-1, RETREG1) was first identified as an oncogene in esophageal squamous cell carcinoma. However, the roles of FAM134B during tumorigenesis of hepatocellular carcinoma (HCC) and in epithelial-to-mesenchymal transition (EMT) were previously unclear. In this study, we investigated the function of FAM134B in HCC and the related tumorigenesis mechanisms, as well as how FAM134B induces EMT. We detected the expression of FAM134B in a normal hepatic cell line, HCC cell lines, fresh specimens, and a HCC tissue microarray. A retrospective study of 122 paired HCC tissue microarrays was used to analyze the correlation between FAM134B and clinical features. Gain- and loss-of-function experiments, rescue experiments, Akt pathway activator/inhibitors, nude mice xenograft models, and nude mice lung metastasis models were used to determine the underlying mechanisms of FAM134B in inducing tumorigenesis and EMT in\u00a0vitro and in\u00a0vivo. The expression level of FAM134B was highly elevated in HCC, as compared with that in normal liver tissues and normal hepatic cells. Overexpression of FAM134B was significantly associated with tumor size (P\u00a0=\u00a00.025), pathological vascular invasion (P\u00a0=\u00a00.026), differentiation grade (P\u00a0=\u00a00.023), cancer recurrence (P\u00a0=\u00a00.044), and portal vein tumor thrombus (P\u00a0=\u00a00.036) in HCC. Patients with high expression of FAM134B had shorter overall survival and disease-free survival than patients with non-high expression of FAM134B. Furthermore, knockdown of FAM134B with shRNAs inhibited cell growth and motility, as well as tumor formation and metastasis in nude mice, all of which were promoted by overexpression of FAM134B.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30556279"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1333, "text": "Family with sequence similarity 134, member B (FAM134B) is an autophagy regulator of endoplasmic reticulum first discovered to be involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC). The present study examined the functional behavior of FAM134B in cancer cells and the association of FAM134B expression with clinicopathologic factors in patients with ESCC. Expression at both the mRNA and protein levels was investigated using real-time polymerase chain reaction and immunohistochemistry. The results were correlated with the clinical and pathological features of the patients. In addition, in vitro functional assays were used to investigate the roles of FAM134B in ESCC cells in response to gene silencing with shRNA lentiviral particles. Overexpression of FAM134B mRNA and protein was present in 31.2% (n\u202f=\u202f29/93) and 36.6% (n\u202f=\u202f41/112), respectively, in tumors, whereas downregulation occurred in 39.8% (n\u202f=\u202f37/93) and 63.4% (n\u202f=\u202f71/112), respectively. Expression of FAM134B protein in ESCC correlated with histologic grade (P\u202f=\u202f.002) and pathologic stage (P\u202f=\u202f.012). In vitro suppression of FAM134B in ESCC induced significant reductions of cell proliferation and colony formation (P\u202f<\u202f.05). In addition, suppression of FAM134B caused reduction of wound healing, migration, and invasion capacities of ESCC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30794892"}, {"offsetInBeginSection": 127, "offsetInEndSection": 521, "text": "This review aimed to summarize various functions of FAM134B since our first discovery of the gene in 2001. The protein encoded by FAM134B is a reticulophagy receptor that regulates turnover of the endoplasmic reticulum (ER) by selective phagocytosis. Absence or non-functional expression of FAM134B protein impairs ER-turnover and thereby is involved in the pathogenesis of some human diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29226326"}, {"offsetInBeginSection": 234, "offsetInEndSection": 747, "text": "The protein encoded by FAM134B is a reticulophagy receptor that regulates turnover of the endoplasmic reticulum (ER) by selective phagocytosis. Absence or non-functional expression of FAM134B protein impairs ER-turnover and thereby is involved in the pathogenesis of some human diseases. FAM134B inhibition contributes to impair proteostasis in the ER due to the accumulation of misfolded or aggregated proteins, which in turn leads to compromised neuronal survival and progressive neuronal degenerative diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29226326"}, {"offsetInBeginSection": 234, "offsetInEndSection": 521, "text": "The protein encoded by FAM134B is a reticulophagy receptor that regulates turnover of the endoplasmic reticulum (ER) by selective phagocytosis. Absence or non-functional expression of FAM134B protein impairs ER-turnover and thereby is involved in the pathogenesis of some human diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29226326"}, {"offsetInBeginSection": 127, "offsetInEndSection": 377, "text": "This review aimed to summarize various functions of FAM134B since our first discovery of the gene in 2001. The protein encoded by FAM134B is a reticulophagy receptor that regulates turnover of the endoplasmic reticulum (ER) by selective phagocytosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29226326"}, {"offsetInBeginSection": 234, "offsetInEndSection": 377, "text": "The protein encoded by FAM134B is a reticulophagy receptor that regulates turnover of the endoplasmic reticulum (ER) by selective phagocytosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29226326"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "BACKGROUND: Family with sequence similarity 134, member B (FAM134B), also known as Reticulophagy regulator 1 (RETREG1), is an ER-phagy receptor involved in ER homeostasis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37273064"}, {"offsetInBeginSection": 514, "offsetInEndSection": 662, "text": "FAM134B (also known as RETREG1) and RTN3 are reticulon-type proteins that are able to remodel the ER network and ensure the basal membrane turnover.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30177506"}, {"offsetInBeginSection": 0, "offsetInEndSection": 690, "text": "FAM134B (also called JK-1, RETREG1), a member of the family with sequence similarity 134, was originally discovered as an oncogene in esophageal squamous cell carcinoma. However, its most famous function is that of an ER-phagy-regulating receptor. Over the decades, the powerful biological functions of FAM134B were gradually revealed. Overwhelming evidence indicates that its dysfunction is related to pathophysiological processes such as neuropathy, viral replication, inflammation, and cancer. This review describes the biological functions of FAM134B, focusing on its role in ER-phagy. In addition, we summarize the diseases in which it is involved and review the underlying mechanisms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33199694"}, {"offsetInBeginSection": 230, "offsetInEndSection": 362, "text": "FAM134B plays an important role in regulating selective ER-phagy, and is related to the occurrence and development of many diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35477002"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1196, "text": "Degradation of endoplasmic reticulum (ER) by selective autophagy (ER-phagy) is crucial for ER homeostasis. However, it remains unclear how ER scission is regulated for subsequent autophagosomal sequestration and lysosomal degradation. Here, we show that oligomerization of ER-phagy receptor FAM134B (also referred to as reticulophagy regulator 1 or RETREG1) through its reticulon-homology domain is required for membrane fragmentation in\u00a0vitro and ER-phagy in\u00a0vivo. Under ER-stress conditions, activated CAMK2B phosphorylates the reticulon-homology domain of FAM134B, which enhances FAM134B oligomerization and activity in membrane fragmentation to accommodate high demand for ER-phagy. Unexpectedly, FAM134B G216R, a variant derived from a type II hereditary sensory and autonomic neuropathy (HSAN) patient, exhibits gain-of-function defects, such as hyperactive self-association and membrane scission, which results in excessive ER-phagy and sensory neuron death. Therefore, this study reveals a mechanism of ER membrane fragmentation in ER-phagy, along with a signaling pathway in regulating ER turnover, and suggests a potential implication of excessive selective autophagy in human diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31930741"}, {"offsetInBeginSection": 388, "offsetInEndSection": 521, "text": "FAM134A, FAM134B/RETREG1, and FAM134C are essential for maintaining ER morphology in a LC3-interacting region (LIR)-dependent manner.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34338405"}, {"offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Fam134b (JK-1, RETREG1) was first identified as an oncogene in esophageal squamous cell carcinoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30556279"}, {"offsetInBeginSection": 0, "offsetInEndSection": 398, "text": "Fam134b (JK-1, RETREG1) was first identified as an oncogene in esophageal squamous cell carcinoma. However, the roles of FAM134B during tumorigenesis of hepatocellular carcinoma (HCC) and in epithelial-to-mesenchymal transition (EMT) were previously unclear. In this study, we investigated the function of FAM134B in HCC and the related tumorigenesis mechanisms, as well as how FAM134B induces EMT.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30556279"}, {"offsetInBeginSection": 229, "offsetInEndSection": 334, "text": "FAM134B, responsible for the turnover of ER sheets and SEC62 that regulates ER recovery following stress.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28617241"}, {"offsetInBeginSection": 1536, "offsetInEndSection": 1724, "text": "FAM134B inhibits HCC cell autophagy and promotes the progression of liver cancer by inhibiting the expression of ER stress-related degradation factors such as DERL2, EDEM1, SEL1L and HRD1.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37728036"}, {"offsetInBeginSection": 235, "offsetInEndSection": 1210, "text": "Accordingly, DENV and ZIKV restrict ER turnover by protease-mediated cleavage of reticulophagy regulator 1 (RETREG1), also known as FAM134B, an autophagy receptor responsible for targeted ER sheet degradation. Given that the induction of autophagy may play an important role in flavivirus replication, the antiviral role of RETREG1 suggests that specialized autophagic pathways may have differential effects on the flavivirus life cycle. We previously identified BPI fold-containing family B member 3 (BPIFB3) as a regulator of autophagy that negatively controls enterovirus replication. Here, we show that in contrast to enteroviruses, BPIFB3 functions as a positive regulator of DENV and ZIKV infection and that its RNA interference-mediated silencing inhibits the formation of viral replication organelles. Mechanistically, we show that depletion of BPIFB3 enhances RETREG1-dependent reticulophagy, leading to enhanced ER turnover and the suppression of viral replication.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32102874"}, {"offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "FAM134B is an autophagy regulator of endoplasmic reticulum and acts as a cancer suppressor in colon cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29964340"}, {"offsetInBeginSection": 0, "offsetInEndSection": 335, "text": "FAM134B (also called JK-1, RETREG1), a member of the family with sequence similarity 134, was originally discovered as an oncogene in esophageal squamous cell carcinoma. However, its most famous function is that of an ER-phagy-regulating receptor. Over the decades, the powerful biological functions of FAM134B were gradually revealed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33199694"}, {"offsetInBeginSection": 0, "offsetInEndSection": 739, "text": "The autophagy receptor for selective reticulophagy, RETREG1/FAM134B is essential for ER maintenance, and its dysfunction is associated with neuronal disorders, vascular dementia, or viral infections. The protein consists of the reticulon-homology domain (RHD) that is flanked at the N- and C-termini by an intrinsically disordered protein region (IDPR), where the C terminal IDPR carries the indispensable LC3-interacting region (LIR) motif for the interaction with LC3. The RHD of RETREG1 is presumed to play a role in membrane remodeling, but the absence of a known 3D structure of this domain so far prevented researchers from gaining mechanistic insights into how the RETREG1 RHD curves membranes, and thereby facilities reticulophagy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31996076"}, {"offsetInBeginSection": 235, "offsetInEndSection": 965, "text": "Here, we show that oligomerization of ER-phagy receptor FAM134B (also referred to as reticulophagy regulator 1 or RETREG1) through its reticulon-homology domain is required for membrane fragmentation in\u00a0vitro and ER-phagy in\u00a0vivo. Under ER-stress conditions, activated CAMK2B phosphorylates the reticulon-homology domain of FAM134B, which enhances FAM134B oligomerization and activity in membrane fragmentation to accommodate high demand for ER-phagy. Unexpectedly, FAM134B G216R, a variant derived from a type II hereditary sensory and autonomic neuropathy (HSAN) patient, exhibits gain-of-function defects, such as hyperactive self-association and membrane scission, which results in excessive ER-phagy and sensory neuron death.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31930741"}, {"offsetInBeginSection": 238, "offsetInEndSection": 442, "text": "Notably, emerging data are clarifying the molecular mechanisms of FAM134B function in organelle membrane morphogenesis and the regulation of signaling pathways, such as the Wnt and AKT signaling pathways.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33843059"}, {"offsetInBeginSection": 281, "offsetInEndSection": 679, "text": "Using molecular modeling and molecular dynamics (MD) simulations, we assemble a structural model for the RHD of FAM134B. Through MD simulations of FAM134B in flat and curved membranes, we relate the dynamic RHD structure with its two wedge-shaped transmembrane helical hairpins and two amphipathic helices to FAM134B functions in membrane-curvature induction and curvature-mediated protein sorting.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31147549"}, {"offsetInBeginSection": 1079, "offsetInEndSection": 1236, "text": "Therefore, selective ER-phagy via FAM134 proteins is indispensable for mammalian cell homeostasis and controls ER morphology and turnover in mice and humans.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26040720"}, {"offsetInBeginSection": 682, "offsetInEndSection": 901, "text": "We will focus on the recently discovered selective autophagy pathway for ER, ER-phagy, with particular emphasis on the structure and function of known mammalian ER-phagy receptors, namely FAM134B, SEC62, RTN3 and CCPG1.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29233873"}, {"offsetInBeginSection": 1086, "offsetInEndSection": 1210, "text": " During this process, the ER-phagy receptor FAM134B anchors and fragments ER, and then binds with LC3 to form autophagosomes", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35253652"}]}
+{"question_id": "661688cefdcbea915f000053", "question": "What cancers are associated with human papilloma virus?", "answer": "Human papillomavirus (HPV) infection is associated with several types of cancer, including:\n\n1. Cervical cancer (almost 100% of cases)\n2. Anal cancer (80-93% of cases) \n3. Oropharyngeal cancer, including the base of the tongue and tonsils (12-63% of cases)\n4. Vaginal cancer (40-64% of cases)\n5. Vulvar cancer (40-51% of cases)\n6. Penile cancer (36-40% of cases)\n\nHPV is considered a necessary cause of cervical cancer and is also strongly associated with a significant proportion of cancers at the other sites listed above.", "relevant_passage_ids": ["36868166", "36691362", "36730877"], "type": "list", "snippets": [{"offsetInBeginSection": 418, "offsetInEndSection": 545, "text": "HPVs in neck and head squamous cell carcinoma, esophageal cancer, cervical cancer, head and neck cancer, brain and lung tumours", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36868166"}, {"offsetInBeginSection": 550, "offsetInEndSection": 600, "text": "male cancers of the mouth, throat, anus, and penis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36691362"}, {"offsetInBeginSection": 27, "offsetInEndSection": 98, "text": "head and neck cancers (HNCs) with human papillomavirus (HPV) positivity", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36730877"}]}
+{"question_id": "662fdb1e187cba990d000019", "question": "What is the role of the transcription factor activator protein 2 (AP-2) alpha (TFAP2A) in tumor formation and metastasis?", "answer": "Members of the activator protein 2 (AP-2) transcription factor (TF) family (TFAP2) are known to play a role in both physiological processes and cancer development. Specifically, TFAP2A has been shown to be implicated in the formation and progression of various tumors. According to the pathways of the downstream targets, its regulatory effects on tumorigenesis can involve stemness and epithelial-mesenchymal-transition (EMT), interactions with the tumor microenvironment, and cell cycle and DNA damage repair. For example, TFAP2A can facilitate melanoma metastasis through transcriptional activation of genes within the E2F pathway and has also been linked to increased lymph node metastasis in basal-squamous bladder cancer.", "relevant_passage_ids": ["34210752", "37083077", "37291585", "36831334", "36410635", "33824285", "35117502", "19671168", "14744778", "17695722", "36707053", "11310795", "10721491", "20731046", "24335623", "9632718"], "type": "summary", "snippets": [{"offsetInBeginSection": 685, "offsetInEndSection": 1031, "text": "According to the pathways in which the downstream targets are involved in, the regulatory effects of TFAP2 on tumorigenesis are generally summarized as follows: stemness and EMT, interaction between TFAP2 and tumor microenvironment, cell cycle and DNA damage repair, ER- and ERBB2-related signaling pathway, ferroptosis and therapeutic response. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37291585"}, {"offsetInBeginSection": 401, "offsetInEndSection": 514, "text": "As a transcription factor, TFAP2 regulates the downstream targets directly by binding to their regulatory region.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37291585"}, {"offsetInBeginSection": 283, "offsetInEndSection": 428, "text": "Here we demonstrate that AP-2\u03b1 facilitates melanoma metastasis through transcriptional activation of genes within the E2F pathway including EZH2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34210752"}, {"offsetInBeginSection": 1153, "offsetInEndSection": 1388, "text": "These findings demonstrate that melanoma metastasis is driven by the AP-2\u03b1/EZH2 pathway and suggest that AP-2\u03b1 expression can be used as a biomarker to predict responsiveness to EZH2 inhibitors for the treatment of advanced melanomas. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34210752"}, {"offsetInBeginSection": 1402, "offsetInEndSection": 1603, "text": "AP-2\u03b1 drives melanoma metastasis by upregulating E2F pathway genes including EZH2 through inhibition of the NuRD repression complex, serving as a biomarker to predict responsiveness to EZH2 inhibitors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34210752"}, {"offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Transcription factor AP\u20112 alpha (TFAP2A) is a critical cell growth regulator that is overexpressed in various tumor tissues.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37083077"}, {"offsetInBeginSection": 399, "offsetInEndSection": 570, "text": "TFAP2A was highly expressed in cervical tumor tissues. TFAP2A was also found to be associated with a higher tumor stage, lymph node metastasis and a poor patient survival.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37083077"}, {"offsetInBeginSection": 933, "offsetInEndSection": 1133, "text": "Collectively, in the present study it was demonstrated that TFAP2A is a transcription factor of PD\u2011L1 and a prognostic factor with clinical value, identifying a positive feedback loop of TFAP2A/PD\u2011L1.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37083077"}, {"offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Members of the activator protein 2 (AP-2) transcription factor (TF) family are known to play a role in both physiological processes and cancer development. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36831334"}, {"offsetInBeginSection": 12, "offsetInEndSection": 121, "text": "Overexpression of TFAP2A has been linked to increased lymph node metastasis in basal-squamous bladder cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36410635"}, {"offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "The transcription factor family activator protein 2 (TFAP2) is vital for regulating both embryonic and oncogenic development.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37291585"}, {"offsetInBeginSection": 685, "offsetInEndSection": 1030, "text": "According to the pathways in which the downstream targets are involved in, the regulatory effects of TFAP2 on tumorigenesis are generally summarized as follows: stemness and EMT, interaction between TFAP2 and tumor microenvironment, cell cycle and DNA damage repair, ER- and ERBB2-related signaling pathway, ferroptosis and therapeutic response.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37291585"}, {"offsetInBeginSection": 488, "offsetInEndSection": 706, "text": "Researches reveal that the modulation of AP-2 in tumorigenesis may be dual, either inhibitory or promoting, which depends on the specific tissues,stages of cancer progression and difference between five family members.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20731046"}, {"offsetInBeginSection": 1475, "offsetInEndSection": 1707, "text": "Since AP-2 also regulates other genes that are involved in the progression of human melanoma such as c-KIT, E-cadherin, MMP-2, and p21(WAF-1), we propose that loss of AP-2 is a crucial event in the development of malignant melanoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9632718"}]}
+{"question_id": "66300f53187cba990d00001d", "question": "Which vaccines are safe to be administered for all pregnancies?", "answer": "Vaccines safe to be administered to all pregnancies are inactivated vaccines, such as tetanus toxoid (TT; tetanus, diphtheria, acellular pertussis (Tdap) and Flu vaccines.", "relevant_passage_ids": ["33773923"], "type": "list", "snippets": [{"offsetInBeginSection": 362, "offsetInEndSection": 508, "text": " Vaccines safe to be administered to all pregnant ladies are tetanus toxoid (TT; tetanus, diphtheria, acellular pertussis (Tdap) and Flu vaccines.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33773923"}, {"offsetInBeginSection": 322, "offsetInEndSection": 361, "text": "Inactivated vaccines are generally safe", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33773923"}]}
+{"question_id": "65d36e761930410b13000044", "question": "What is the use of lebrikizumab?", "answer": "Lebrikizumab scan be used for moderate-to-severe atopic dermatitis.", "relevant_passage_ids": ["36630140", "36948491", "37401345", "36994947", "37266844"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Efficacy and Safety of Lebrikizumab in Combination With Topical Corticosteroids in Adolescents and Adults With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial (ADhere).", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36630140"}, {"offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "Importance: Lebrikizumab (LEB), a high-affinity monoclonal antibody targeting interleukin (IL)-13, demonstrated efficacy and safety in patients with moderate-to-severe atopic dermatitis (AD) during 16 weeks of monotherapy in a phase 2b trial, and two 52-week phase 3 trials.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36630140"}, {"offsetInBeginSection": 2555, "offsetInEndSection": 2810, "text": "Conclusions and Relevance: In this randomized phase 3 clinical trial, LEB+TCS was associated with improved outcomes in adolescents and adults with moderate-to-severe AD compared with TCS alone, and safety was consistent with previously reported AD trials.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36630140"}, {"offsetInBeginSection": 0, "offsetInEndSection": 477, "text": "The U.S. Food and Drug Administration approval of dupilumab for moderate-to-severe atopic dermatitis shifted the paradigm from use of broad, systemic immunosuppressants to a safer, targeted treatment and led to the emergence of newer interleukin (IL)-4/IL-13 directed biologics and small molecule therapies, namely Janus kinase (JAK) inhibitors (JAKi). Tralokinumab and emerging (not yet approved) lebrikizumab, which both target IL-13, are alternative biologics to dupilumab. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36948491"}, {"offsetInBeginSection": 133, "offsetInEndSection": 200, "text": " This review characterizes lebrikizumab as AD treatment in adults. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37401345"}, {"offsetInBeginSection": 770, "offsetInEndSection": 871, "text": "Results from clinical trials suggest that lebrikizumab may be a viable alternative for AD management.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37401345"}, {"offsetInBeginSection": 1768, "offsetInEndSection": 2009, "text": "CONCLUSIONS: After a 16-week induction period with lebrikizumab Q2W, lebrikizumab Q2W and Q4W maintained similar improvement of the signs and symptoms of moderate-to-severe AD, with a safety profile consistent with previously published data.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36994947"}, {"offsetInBeginSection": 0, "offsetInEndSection": 355, "text": "BACKGROUND: Lebrikizumab is a novel, high-affinity monoclonal antibody that selectively binds to interleukin (IL)-13.OBJECTIVES: To evaluate the efficacy and safety of lebrikizumab monotherapy in adolescent and adult patients with moderate-to-severe atopic dermatitis (AD) over 52 weeks of treatment in ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36994947"}, {"offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Lebrikizumab for the Treatment of Moderate-to-Severe Atopic Dermatitis.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37266844"}, {"offsetInBeginSection": 1243, "offsetInEndSection": 1356, "text": "Lebrikizumab seems to be a promising emerging targeted biological agent for patients with moderate-to-severe AD. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37266844"}]}
+{"question_id": "662fc981187cba990d000018", "question": "Is CT colonography a cost-effective test for colorectal cancer screening?", "answer": "CT colonography would cost more and result in more deaths overall compared with colonoscopy, the latter remained the dominant strategy. Cost-effectiveness of CTC screening is heterogeneous, due largely to between-study differences in comparators and parameter values. Future studies should: compare CTC with currently favored tests, especially fecal immunochemical tests; consider extra-colonic findings; and conduct comprehensive sensitivity analyses.", "relevant_passage_ids": ["29485322", "23006522", "16217110", "17156139", "10445561", "19188317", "19332851", "21361717", "20482825", "21813740", "20369905", "29702925", "19380558", "20664028", "28130651", "30647823", "18612821", "32938642", "22549102", "23182509", "32761199", "30659991", "29441568", "28988790", "35719832", "18413551", "18584178", "28681075", "29927637", "32933928", "35187245", "20003555", "12173353", "26350285", "36292015", "21444171", "26068773", "21141419", "20731011", "19261464", "27194458", "27542076", "38091064", "37510196", "37507217", "17112797", "11641151", "33014138", "19048626", "26993649", "20802341", "27196588", "20833348"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1636, "offsetInEndSection": 1776, "text": "Because of the higher participation rates, CT colonography screening for colorectal cancer is more cost-effective than colonoscopy screening", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29485322"}, {"offsetInBeginSection": 1667, "offsetInEndSection": 1995, "text": "Evidence on cost-effectiveness of CTC screening is heterogeneous, due largely to between-study differences in comparators and parameter values. Future studies should: compare CTC with currently favored tests, especially fecal immunochemical tests; consider extra-colonic findings; and conduct comprehensive sensitivity analyses.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23006522"}, {"offsetInBeginSection": 1343, "offsetInEndSection": 1510, "text": "CTC appeared cost-effective versus no screening and, in general, flexible sigmoidoscopy and fecal occult blood testing. Results were mixed comparing CTC to colonoscopy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23006522"}, {"offsetInBeginSection": 1230, "offsetInEndSection": 1733, "text": "CT colonography would cost more and result in more deaths overall compared with colonoscopy, the latter remained the dominant strategy. Our results were sensitive to CT colonography's test performance characteristics, the malignant risk of missed adenomas, the risk of perforation and related death, the procedural costs and differences in screening adherence.INTERPRETATION: At present, CT colonography cannot be recommended as a primary means of population-based colorectal cancer screening in Canada.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16217110"}, {"offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Colorectal Cancer: Cost-effectiveness of Colonoscopy versus CT Colonography Screening with Participation Rates and Costs.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29485322"}, {"offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Evaluation of the benefits, harms and cost-effectiveness of potential alternatives to iFOBT testing for colorectal cancer screening in Australia.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29441568"}, {"offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Recent diagnostic procedures for colorectal cancer screening: Are they cost-effective?", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28988790"}, {"offsetInBeginSection": 1003, "offsetInEndSection": 1624, "text": "Colonoscopy was more cost-effective in the screening strategies with one or two lifetime screenings, whereas CT colonography was more cost-effective in strategies with more lifetime screenings. CT colonography was the preferred test for willingness-to-pay-thresholds of \u20ac3200 per QALY gained and higher, which is lower than the Dutch willingness-to-pay threshold of \u20ac20 000. With equal participation, colonoscopy was the preferred test independent of willingness-to-pay thresholds. The findings were robust for most of the sensitivity analyses, except with regard to relative screening costs and subsequent participation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29485322"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1155, "text": "OBJECTIVE: Unit costs of screening CT colonography (CTC) can be useful for cost-effectiveness analyses and for health care decision-making. We evaluated the unit costs of CTC as a primary screening test for colorectal cancer in the setting of a randomized trial in Italy.METHODS: Data were collected within the randomized SAVE trial. Subjects were invited to screening CTC by mail and requested to have a pre-examination consultation. CTCs were performed with 64- and 128-slice CT scanners after reduced or full bowel preparation. Activity-based costing was used to determine unit costs per-process, per-participant to screening CTC, and per-subject with advanced neoplasia.RESULTS: Among 5242 subjects invited to undergo screening CTC, 1312 had pre-examination consultation and 1286 ultimately underwent CTC. Among 129 subjects with a positive CTC, 126 underwent assessment colonoscopy and 67 were ultimately diagnosed with advanced neoplasia (i.e., cancer or advanced adenoma). Cost per-participant of the entire screening CTC pathway was \u20ac196.80. Average cost per-participant for the screening invitation process was \u20ac17.04 and \u20ac9.45 for the pre-examin", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28681075"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1740, "text": "BACKGROUND: Computed tomography (CT) colonography's effectiveness, its associated patient advantages, and its potential role to increase colorectal cancer (CRC) screening rates have been demonstrated in previous research, but whether CT colonography has a cost advantage relative to optical colonoscopy for the commercially insured US population has not been assessed.OBJECTIVE: To compare the costs of CRC screening using CT colonography or optical colonoscopy for commercially insured people in the United States.METHODS: Using retrospective commercial healthcare claims data and peer-reviewed studies, we performed a simulated multiyear, matched-case comparison of the costs of CT and optical colonoscopies for CRC screening. We estimated commercial optical colonoscopy costs per screening based on the 2016 Truven Health MarketScan Commercial Database and ancillary services, such as bowel preparation, anesthesia, pathology, and complication costs. We developed 4 scenarios for CT colonography cost per screening using the ratio of commercial to Medicare fees, and calculated ancillary service and follow-up costs from payers' costs for these services when associated with optical colonoscopies. For comparison, we converted the costs per screening to the costs per screening year per person using real-world screening intervals that were obtained from peer-reviewed studies.RESULTS: In 2016, the average optical colonoscopy screening cost for commercial payers was $2033 (N = 406,068), or $340 per screening year per person. With our highest-cost CT colonography scenario, CT colonography costs 22% less, or $265 per screening year, than optical colonoscopy, mostly because of the advantages for patients of no anesthesia and the grea", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30647823"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1822, "text": "CT colonography for colorectal cancer screening has been proved to be effective and cost-saving. CT colonography uses minimally invasive evaluation of colorectum and has better patient acceptance, which appears to be a promising screening modality to improve low colorectal cancer screening rate. This study investigated the utilization patterns of CT colonography and factors associated with its use among U.S. adult population. This retrospective cross-sectional study analyzed the National Health Interview Survey 2015 and 2018. U.S. adults ages 45 or older without a history of colorectal cancer were included. Survey design-adjusted Wald F tests were used to compare the utilization of CT colonography during the study period. Multivariable logistic regression was used to identify the predictors of CT colonography among individual socioeconomic and health-related characteristics. The study sample included 34,768 individuals representing 129,430,319 U.S. adult population ages 45 or older. The overall utilization of CT colonography increased from 0.79% in 2015 to 1.33% in 2018 (P < 0.001). 54.5% study participants reported being up-to-date on recommended colorectal cancer screening; of those, 1.8% used CT colonography. Compared with individuals ages 65+, those ages 45-49 years were 2.08 times (OR, 2.08, 95% confidence interval, 1.01-4.35) more likely to use CT colonography. Socioeconomically disadvantaged characteristics (e.g., racial/ethnic minority, low income, publicly funded insurance) were associated with a greater likelihood of CT colonography. This study demonstrated an increasing trend in utilization of CT colonography for colorectal cancer screening in U.S. adults. Younger individuals, racial/ethnic minorities, or those with lower income appear to have a higher CT colonography utilization.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32938642"}, {"offsetInBeginSection": 0, "offsetInEndSection": 973, "text": "OBJECTIVE: Surveillance following colorectal cancer (CRC) resection uses optical colonoscopy (OC) to detect intraluminal disease and CT to detect extracolonic recurrence. CT colonography (CTC) might be an efficient use of resources in this situation because it allows for intraluminal and extraluminal evaluations with one test.DESIGN: We developed a simulation model to compare lifetime costs and benefits for a cohort of patients with resected CRC. Standard of care involved annual CT for 3 years and OC for years 1, 4 and every 5 years thereafter. For the CTC-based strategy, we replace CT+OC at year 1 with CTC. Patients with lesions greater than 6\u2009mm detected by CTC underwent OC. Detection of an adenoma 10\u2009mm or larger was followed by OC at 1\u2009year, then every 3 years thereafter. Test characteristics and costs for CTC were derived from a clinical study. Medicare costs were used for cancer care costs as well as alternative test costs. We discounted costs and effec", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32933928"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1567, "text": "Purpose. As part of a clinical trial comparing the utility of computed tomographic colonography (CTC) and optical colonoscopy (OC) for post colorectal cancer resection surveillance, we explored the diagnostic yield and costs of a strategy of CTC followed by OC if a polyp is observed (abbreviated CTC_S), versus OC 1 year following curative bowel resection, using the detection of actionable polyps on OC as the criterion. Methods. Using data from 231 patients who underwent same-day CTC followed by OC, we created a decision tree that outlined the choices and outcomes at 1-year clinical follow-up. Colorectal polyp prevalence, sensitivity, and specificity of CTC were compared with five exemplary studies and meta-analyses. Detection criteria were derived for \u22656 mm or \u226510 mm polyps. OC was the gold standard. Costs were gleaned from cataloging components of the cases at the principal investigator's institution. Analyses included marginal cost of the OC strategy to detect additional actionable polyps and number of polyps missed per 10,000 patients. Results. At our prevalence of 0.156 for \u22656 mm (0.043 \u226510 mm), CTC_S would miss 779 \u22656 mm actionable polyps per 10,000 patients (\u226510 mm: 173 per 10,000). Cost to detect an additional \u22656 mm polyp in this cohort is $5,700 (\u226510 mm: $28,000). Sensitivity analyses demonstrate that any improvement in performance characteristics would raise the cost of OC to detect more actionable polyps. Similar results were seen using Medicare costs, or when literature values were used for performance characteristics. Conclusion.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35187245"}, {"offsetInBeginSection": 1625, "offsetInEndSection": 1777, "text": "Conclusion Because of the higher participation rates, CT colonography screening for colorectal cancer is more cost-effective than colonoscopy screening.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29485322"}, {"offsetInBeginSection": 1625, "offsetInEndSection": 1934, "text": "Conclusion Because of the higher participation rates, CT colonography screening for colorectal cancer is more cost-effective than colonoscopy screening. The implementation of CT colonography screening requires previous satisfactory resolution to the question as to how best to deal with extracolonic findings.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29485322"}, {"offsetInBeginSection": 1625, "offsetInEndSection": 2007, "text": "Conclusion Because of the higher participation rates, CT colonography screening for colorectal cancer is more cost-effective than colonoscopy screening. The implementation of CT colonography screening requires previous satisfactory resolution to the question as to how best to deal with extracolonic findings. \u00a9 RSNA, 2018 Online supplemental material is available for this article.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29485322"}, {"offsetInBeginSection": 1485, "offsetInEndSection": 1934, "text": "The findings were robust for most of the sensitivity analyses, except with regard to relative screening costs and subsequent participation. Conclusion Because of the higher participation rates, CT colonography screening for colorectal cancer is more cost-effective than colonoscopy screening. The implementation of CT colonography screening requires previous satisfactory resolution to the question as to how best to deal with extracolonic findings.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29485322"}, {"offsetInBeginSection": 1153, "offsetInEndSection": 1530, "text": "SIONS: CT colonography is an effective screening test for colorectal neoplasia. However, it is more expensive and generally less effective than optical colonoscopy. CT colonography can be reasonably cost-effective when the diagnostic accuracy of CT colonography is high, as with primary 3-dimensional technology, and if costs are about 60% of those of optical colonoscopy. Over", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17156139"}, {"offsetInBeginSection": 1485, "offsetInEndSection": 1777, "text": "The findings were robust for most of the sensitivity analyses, except with regard to relative screening costs and subsequent participation. Conclusion Because of the higher participation rates, CT colonography screening for colorectal cancer is more cost-effective than colonoscopy screening.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29485322"}, {"offsetInBeginSection": 1153, "offsetInEndSection": 1322, "text": "SIONS: CT colonography is an effective screening test for colorectal neoplasia. However, it is more expensive and generally less effective than optical colonoscopy. CT c", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17156139"}, {"offsetInBeginSection": 93, "offsetInEndSection": 484, "text": "CT colonography is an accurate technique for the detection of colorectal cancer and its precursors in symptomatic patients and for screening. Radiation exposure in CT colonography is limited and is no major drawback for the use of CT colonography for screening. Aspects important to screening with CT colonography have not been studied yet, such as participation rate and cost effectiveness.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20003555"}, {"offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "In the Netherlands, the introduction of screening for colorectal cancer is being considered. CT colonography is an accurate technique for the detection of colorectal cancer and its precursors in symptomatic patients and for screening.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20003555"}, {"offsetInBeginSection": 553, "offsetInEndSection": 752, "text": "However, CT colonography can be a cost-effective complement to traditional colonoscopy if it is reasonably priced and if appropriate cut-off levels (>6 mm polyp) are used to increase its sensitivity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18612821"}, {"offsetInBeginSection": 1023, "offsetInEndSection": 1232, "text": "However, optical colonoscopy is a dominant strategy if the sensitivity of CT colonography for 1 cm adenomas is 83% or lower.CONCLUSIONS: CT colonography is an effective screening test for colorectal neoplasia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17156139"}, {"offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "BACKGROUND: We examined the cost-effectiveness of 2- and 3-dimensional computerized tomography (CT) colonography as a screening test for colorectal neoplasia.METHODS: We created a Markov model of the natural history of colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17156139"}, {"offsetInBeginSection": 351, "offsetInEndSection": 552, "text": "CT colonography cannot be a stand-alone technique for colorectal cancer screening because, unlike conventional colonoscopy, it does not possess a therapeutic option or a definite diagnostic capability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18612821"}, {"offsetInBeginSection": 1500, "offsetInEndSection": 1811, "text": "The ICER of 5-year CTC and 10-year CTC versus optical colonoscopy was $23,234 and $2,144 per life-year gained, respectively.CONCLUSION: Because of its ability to simultaneously screen for both CRC and AAA, CTC is a highly cost-effective and clinically efficacious screening strategy for the Medicare population.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19380558"}, {"offsetInBeginSection": 1271, "offsetInEndSection": 1729, "text": "For the two screening procedures to become similarly cost-effective, CT colonoscopy needs to be associated with an initial compliance rate 15-20% better or procedural costs 54% less than colonoscopy.CONCLUSIONS: To become cost-effective and be able to compete with colonoscopy in screening for colorectal cancer, CT or MR colonography would need be offered at a very low price or result in compliance rates much better than those associated with colonoscopy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10445561"}, {"offsetInBeginSection": 158, "offsetInEndSection": 861, "text": "The current UK CRC screening programme is faecal occult blood testing (FOBT), despite evidence from modelling studies to suggest that more cost-effective technologies exist.OBJECTIVE: To assess the cost effectiveness of CT colonography (CTC) for colorectal cancer screening from the perspective of the UK NHS.METHODS: A state-transition Markov model was constructed to estimate lifetime costs and health outcomes of a cohort of individuals screened at age 60-69 years using four different CRC screening technologies: FOBT, flexible sigmoidoscopy, optical colonoscopy and CTC.RESULTS: CTC screening offered every 10 years was cost saving compared with the current UK programme of biennial FOBT screening.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20369905"}, {"offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "PURPOSE: To estimate the cost-effectiveness of computed tomographic (CT) colonography for colorectal cancer (CRC) screening in average-risk asymptomatic subjects in the United States aged ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21813740"}, {"offsetInBeginSection": 1118, "offsetInEndSection": 1306, "text": ", assuming a 3% discount rate.RESULTS: CT colonography at 5- and 10-year screening intervals was more costly and less effective than FOBT plus flexible sigmoidoscopy in all three models in", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21813740"}, {"offsetInBeginSection": 1521, "offsetInEndSection": 1661, "text": " ratio: $26,300 per life-year gained). CT colonography at 5- and 10-year screening intervals and colonoscopy were net beneficial compared wi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21813740"}, {"offsetInBeginSection": 1846, "offsetInEndSection": 2030, "text": "s to pay $50,000 per life-year gained.CONCLUSION: All three models predict CT colonography to be more costly and less effective than non-CT colonographic screening but net beneficial c", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21813740"}, {"offsetInBeginSection": 1339, "offsetInEndSection": 1570, "text": "Resolving these issues will imply new cost-effectiveness analyses for LC screening with chest low dose CT and for CRC screening with CT colonography and, especially, for the double LC and CRC screening with a single-appointment CT.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36292015"}, {"offsetInBeginSection": 997, "offsetInEndSection": 1524, "text": "tandard deviations.RESULTS: For a given adherence rate, CTC screening was always the most effective but not the most cost-effective. FOBT was the least effective but most cost-effective strategy. OC was of intermediate efficacy and the least cost-effective strategy. Without screening, treatment of 123 CRC per 10,000 individuals would cost \u20ac3,444,000. For 60% adherence, the respective costs of preventing and treating, respectively 49 and 74 FOBT-detected, 73 and 50 CTC-detected and 63 and 60 OC-detected CRC would be \u20ac2,810", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21444171"}, {"offsetInBeginSection": 853, "offsetInEndSection": 1406, "text": "s is also included.RESULTS: When compared with no screening, all CRC screening strategies evaluated in this review were cost effective. There was disagreement as to which screening strategy was the most cost effective. However, sigmoidoscopy combined with fecal blood testing always dominated either strategy alone. Studies comparing colonoscopy with fecal blood testing, sigmoidoscopy, or both had mixed results.CONCLUSIONS: Compared with no screening, all CRC screening strategies are more cost effective. Study results disagree as to which screening ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26068773"}, {"offsetInBeginSection": 114, "offsetInEndSection": 266, "text": "Delays in colonoscopy following a positive fecal immunochemical test increase the likelihood of advanced adenomas and colorectal cancer (CRC) occurrence", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37510196"}, {"offsetInBeginSection": 150, "offsetInEndSection": 307, "text": "Patients with one or two small polyps (6-9\u2009mm) at screening CT colonography (CTC) are offered CTC surveillance at 3 years but may elect immediate colonoscopy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37507217"}, {"offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "BACKGROUND: We examined the cost-effectiveness of 2- and 3-dimensional computerized tomography (CT) colonography as a screening test for colorecta", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17156139"}, {"offsetInBeginSection": 1444, "offsetInEndSection": 1690, "text": "54% less than colonoscopy.CONCLUSIONS: To become cost-effective and be able to compete with colonoscopy in screening for colorectal cancer, CT or MR colonography would need be offered at a very low price or result in compliance rates much better ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10445561"}, {"offsetInBeginSection": 218, "offsetInEndSection": 438, "text": "The aim of this review is to summarise the available cost-effectiveness evidence for colonoscopy versus CT-colonography screening, and to pay special attention to assumptions regarding test characteristics and adherence.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19261464"}, {"offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "OBJECTIVE: Unit costs of screening CT colonography (CTC) can be useful for cost-effectiveness analyses and for health care decis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28681075"}, {"offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "OBJECTIVE: CT colonography (CTC) is a recommended test for colorectal cancer (CRC) screening according to the updated 2008 American Cancer Society ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19380558"}, {"offsetInBeginSection": 148, "offsetInEndSection": 331, "text": " invasive. We aimed to assess the potential of CT colonography (CTC) and MR colonography (MRC) in terms of (cost-effectiveness) using the Adenoma and Serrated pathway to Colorectal CA", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27194458"}, {"offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Simulation modeling is extensively applied to CT colonography (CTC) to define its long-term efficacy and cost-effectiveness for colorectal cancer (CRC) screening.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23182509"}, {"offsetInBeginSection": 1171, "offsetInEndSection": 1539, "text": "However, in the probabilistic sensitivity analysis, CTC dominated FOBT in only 5.9% of simulations and was cost effective at a threshold of pound30,000 per QALY gained in 48% of simulations.CONCLUSIONS: CTC has the potential to provide a cost-effective option for CRC screening in the UK NHS and may be cost saving compared with the current programme of biennial FOBT.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20369905"}, {"offsetInBeginSection": 1318, "offsetInEndSection": 1525, "text": "CT colonography can be reasonably cost-effective when the diagnostic accuracy of CT colonography is high, as with primary 3-dimensional technology, and if costs are about 60% of those of optical colonoscopy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17156139"}, {"offsetInBeginSection": 0, "offsetInEndSection": 752, "text": "CT colonography or virtual colonoscopy is a fairly new modality that has the potential to play a significant role in screening for colon cancer. CT colonography is an attractive option for two specific reasons. First, it is non-invasive and, second, it obviates the need for sedation. It thus overcomes the two major drawbacks of optical colonoscopy. CT colonography cannot be a stand-alone technique for colorectal cancer screening because, unlike conventional colonoscopy, it does not possess a therapeutic option or a definite diagnostic capability. However, CT colonography can be a cost-effective complement to traditional colonoscopy if it is reasonably priced and if appropriate cut-off levels (>6 mm polyp) are used to increase its sensitivity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18612821"}, {"offsetInBeginSection": 269, "offsetInEndSection": 425, "text": " screening.AIM: To compare the efficacy and cost-effectiveness of CTC screening in a simulated Italian population with those of colonoscopy and flexible sig", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17112797"}, {"offsetInBeginSection": 1008, "offsetInEndSection": 1129, "text": "copy, FS and CTC, respectively. FS appeared to be less cost-effective than CTC, whilst colonoscopy appeared to be an expe", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17112797"}, {"offsetInBeginSection": 809, "offsetInEndSection": 953, "text": " polyps are found.RESULTS: Under baseline conditions, screening by CT colonography costs $24,586 per life-year saved, compared with $20,930 spen", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10445561"}, {"offsetInBeginSection": 1244, "offsetInEndSection": 1443, "text": "ography both rise to 100%. For the two screening procedures to become similarly cost-effective, CT colonoscopy needs to be associated with an initial compliance rate 15-20% better or procedural costs", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10445561"}, {"offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Virtual colonoscopy (CT colonography) promises to become a primary method for colorectal cancer screening and return radiologists to a major role in colon cancer prevention.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11641151"}, {"offsetInBeginSection": 174, "offsetInEndSection": 380, "text": "Results from major centers in the United States show accuracy to be comparable to conventional colonoscopy for detection of polyps of significant size--that is, greater than 10 mm--with few false-positives.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11641151"}, {"offsetInBeginSection": 926, "offsetInEndSection": 1396, "text": "with each strategy.RESULTS: Compared with no screening, FIT was associated with a 14.0 quality-adjusted life year (QALY) increase of \u20ac50,520 per 1000 individuals, giving an incremental cost-effectiveness ratio (ICER) of \u20ac3600/QALY. Only stool DNA and blood-based testing were associated with a QALY increase compared with FIT, with stool DNA weakly dominated by blood-based testing, and the latter associated with an ICER of \u20ac154,600/QALY compared with FIT. All other st", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33014138"}, {"offsetInBeginSection": 368, "offsetInEndSection": 953, "text": "evaluated.METHODS: The cost-effectiveness of two screening strategies using CT colonography or conventional colonoscopy was compared by computer models based on a Markov process. We supposed that a hypothetical population of 100,000 subjects aged 50 yr undergoes a screening procedure every 10 yr. Suspicious findings of CT colonography are worked-up by colonoscopy. After polypectomy, colonoscopy is repeated every 3 yr until no adenomatous polyps are found.RESULTS: Under baseline conditions, screening by CT colonography costs $24,586 per life-year saved, compared with $20,930 spen", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10445561"}, {"offsetInBeginSection": 306, "offsetInEndSection": 1201, "text": "The potential role is the use of CTC as a first-line screening method together with Fecal Occult Blood Test, sigmoidoscopy and colonoscopy. However, despite the fact that CTC has been officially endorsed for CRC screening of average-risk individuals by different scientific societies including the American Cancer Society, the American College of Radiology, and the US Multisociety Task Force on Colorectal Cancer, other entities, such as the US Preventive Services Task Force, have considered the evidence insufficient to justify its use as a mass screening method. Medicare has also recently denied reimbursement for CTC as a screening test. Nevertheless, multiple advantages exist for using CTC as a CRC screening test: high accuracy, full evaluation of the colon in virtually all patients, non-invasiveness, safety, patient comfort, detection of extracolonic findings and cost-effectiveness.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20731011"}, {"offsetInBeginSection": 759, "offsetInEndSection": 1175, "text": "yielded the Wessling et al study.CONCLUSION: CTC can achieve high accuracy, but only under specific conditions using multi-detector CT scanners, primary 3D data interpretation, well-prepared patients, collimation of < or = 1.25 mm, and data interpretation by an experienced radiologist. Cost-effectiveness and compliance in the general population, as well as radiation exposure and follow-up requirements with colono", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21141419"}, {"offsetInBeginSection": 331, "offsetInEndSection": 663, "text": "tire colon. The success of screening depends on the participation rate. We designed a randomized trial to compare the uptake, yield and costs of direct colonoscopy population screening, using either a telephone consultation or a consultation at the outpatient clinic, versus CT colonography first, with colonoscopy in CT colonograph", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20482825"}, {"offsetInBeginSection": 537, "offsetInEndSection": 916, "text": "The incremental cost-effectiveness ratios of colonoscopy and CT-colonography versus no screening remained under 20,000 euro and 30,000 euro per life year gained, respectively. Although, both screening modalities were cost-effective according to most international thresholds, in most of the economic evaluations colonoscopy seemed more cost-effective than colonography screening.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19261464"}, {"offsetInBeginSection": 1193, "offsetInEndSection": 1458, "text": "similar for CTC and optical colonoscopy. All three strategies were highly cost-effective compared with no screening, with an incremental cost-effectiveness ratio (ICER) of $6,088, $1,251, and $1,104 per life-year gained for 5-year CTC, 10-year CTC, and 10-year opti", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19380558"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1443, "text": "OBJECTIVE: Computed tomography (CT) or magnetic resonance (MR) colonography is a new technique that uses data generated from CT or MR imaging to create two- and three-dimensional scans of the colon. It has been advocated to become the new primary technique of screening for colorectal cancer. The economic feasibility of such recommendation, however, has not yet been evaluated.METHODS: The cost-effectiveness of two screening strategies using CT colonography or conventional colonoscopy was compared by computer models based on a Markov process. We supposed that a hypothetical population of 100,000 subjects aged 50 yr undergoes a screening procedure every 10 yr. Suspicious findings of CT colonography are worked-up by colonoscopy. After polypectomy, colonoscopy is repeated every 3 yr until no adenomatous polyps are found.RESULTS: Under baseline conditions, screening by CT colonography costs $24,586 per life-year saved, compared with $20,930 spent on colonoscopy screening. The incremental cost-effectiveness ratios comparing CT colonography to no screening and colonoscopy to CT colonography were $11,484 and $10,408, respectively. Screening by colonoscopy remains more cost-effective even if the sensitivity and specificity of CT colonography both rise to 100%. For the two screening procedures to become similarly cost-effective, CT colonoscopy needs to be associated with an initial compliance rate 15-20% better or procedural costs", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10445561"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1119, "text": "BACKGROUND: We examined the cost-effectiveness of 2- and 3-dimensional computerized tomography (CT) colonography as a screening test for colorectal neoplasia.METHODS: We created a Markov model of the natural history of colorectal cancer. Effectiveness of screening was based upon the diagnostic accuracy of tests in detecting polyps and cancer.RESULTS: CT colonography every 5 or 10 yr was effective and cost-effective relative to no screening. Optical colonoscopy dominates 2-dimensional CT colonography done every 5 or 10 yr. Optical colonoscopy is weakly dominant over 3-dimensional CT colonography done every 10 yr. 3-D CT colonography done every 5 yr is more effective than optical colonoscopy every 10 yr, but costs an incremental 156,000 dollars per life-year gained. Sensitivity analyses show that test costs, accuracy, and adherence are critical determinants of incremental cost-effectiveness. 3-D CT colonography every 5 yr is a dominant strategy if optical colonoscopy costs 1.6 times more than CT colonography. However, optical colonoscopy is a dominant strategy if the sensitivity of CT colonography for 1 ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17156139"}, {"offsetInBeginSection": 0, "offsetInEndSection": 712, "text": "Colorectal cancer screening is an effective public health strategy for decreasing colorectal cancer mortality. Since many screening modalities exist, it needs to be determined what the most cost-effective strategy is. The aim of this review is to summarise the available cost-effectiveness evidence for colonoscopy versus CT-colonography screening, and to pay special attention to assumptions regarding test characteristics and adherence. A literature search resulted in twelve economic evaluations that could be included in the review. The incremental cost-effectiveness ratios of colonoscopy and CT-colonography versus no screening remained under 20,000 euro and 30,000 euro per life year gained, respectively.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19261464"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1192, "text": "OBJECTIVE: CT colonography (CTC) is a recommended test for colorectal cancer (CRC) screening according to the updated 2008 American Cancer Society guidelines. CTC can also accurately detect abdominal aortic aneurysm (AAA). This collaborative gastroenterology-radiology project evaluated the cost-effectiveness and clinical efficacy of CTC in the Medicare population.MATERIALS AND METHODS: A computerized Markov model simulated the development of CRC and AAA in a hypothetical cohort of 100,000 U.S. adults > or = 65 years old. Screening with CTC at 5- and 10-year intervals using a 6-mm size threshold for polypectomy was compared with primary optical colonoscopy screening every 10 years and with no screening. Base case costs for CTC and optical colonoscopy were $674 and $795, respectively. The costs of the imaging workup for extracolonic findings at CTC were also included.RESULTS: CTC resulted in 7,786 and 7,027 life-years gained at 5- and 10-year intervals, respectively, compared with 6,032 life-years gained with 10-year optical colonoscopy. The increase in overall efficacy with CTC was primarily due to prevention of AAA rupture because CRC prevention and CRC detection rates were", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19380558"}, {"offsetInBeginSection": 0, "offsetInEndSection": 908, "text": "BACKGROUND: Computerized tomographic (CT) colonography is a potential alternative to colonoscopy for colorectal cancer screening. Its main advantage, a better safety profile, may be offset by its limitations: lower sensitivity, need for colonoscopy in cases where results are positive, and expense.METHODS: We performed an economic evaluation, using decision analysis, to compare CT colonography with colonoscopy for colorectal cancer screening in patients over 50 years of age. Three-year outcomes included number of colonoscopies, perforations and adenomas removed; deaths from perforation and from colorectal cancer from missed adenomas; and direct health care costs. The expected prevalence of adenomas, test performance characteristics of CT colonography and colonoscopy, and probability of colonoscopy complications and cancer from missed adenomas were derived from the literature. Costs were determine", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16217110"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1186, "text": "OBJECTIVE: Imaging may be promising for colorectal cancer (CRC) screening, since it has test characteristics comparable with colonoscopy but is less invasive. We aimed to assess the potential of CT colonography (CTC) and MR colonography (MRC) in terms of (cost-effectiveness) using the Adenoma and Serrated pathway to Colorectal CAncer model.METHODS: We compared several CTC and MRC strategies with 5- or 10-yearly screening intervals with no screening, 10-yearly colonoscopy screening and biennial faecal immunochemical test (FIT) screening. We assumed trial-based participation rates in the base-case analyses and varied the rates in sensitivity analyses. Incremental lifetime costs and health effects were estimated from a healthcare perspective.RESULTS: The health gain of CTC and MRC was similar and ranged from 0.031 to 0.048 life-year gained compared with no screening, for 2-5 screening rounds. Lifetime costs per person for MRC strategies were \u20ac60-110 higher than those for CTC strategies with an equal number of screening rounds. All imaging-based strategies were cost-effective compared with no screening. FIT screening was the dominant screening strategy, leading to most LY", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27194458"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1314, "text": "OBJECTIVES: The European Code Against Cancer recommends individuals aged \u2265 50 should participate in colorectal cancer screening. CT-colonography (CTC) is one of several screening tests available. We systematically reviewed evidence on, and identified key factors influencing, cost-effectiveness of CTC screening.METHODS: PubMed, Medline, and the Cochrane library were searched for cost-effectiveness or cost-utility analyses of CTC-based screening, published in English, January 1999 to July 2010. Data was abstracted on setting, model type and horizon, screening scenario(s), comparator(s), participants, uptake, CTC performance and cost, effectiveness, ICERs, and whether extra-colonic findings and medical complications were considered.RESULTS: Sixteen studies were identified from the United States (n = 11), Canada (n = 2), and France, Italy, and the United Kingdom (1 each). Markov state-transition (n = 14) or microsimulation (n = 2) models were used. Eleven considered direct medical costs only; five included indirect costs. Fourteen compared CTC with no screening; fourteen compared CTC with colonoscopy-based screening; fewer compared CTC with sigmoidoscopy (8) or fecal tests (4). Outcomes assessed were life-years gained/saved (13), QALYs (2), or both (1). Three considered extra-colonic findings; sev", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23006522"}, {"offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "Simulation modeling is extensively applied to CT colonography (CTC) to define its long-term efficacy and cost-effectiveness for colorectal cancer (CRC) screening. CTC is effective in reducing CRC incidence and mortality (40%-77% and 58%-84%, respectively). Several factors may explain this variability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23182509"}, {"offsetInBeginSection": 1741, "offsetInEndSection": 1998, "text": "ly reduced use of pathology services.CONCLUSIONS: The use of CT colonography for CRC testing offers effective screening, patient-centered advantages, and lower costs compared with optical colonoscopy, and may be particularly appealing to the currently unscr", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30647823"}, {"offsetInBeginSection": 746, "offsetInEndSection": 1027, "text": "Newer technologies for colorectal cancer screening, including computed tomographic colonography (CTC), faecal DNA test, and Pillcam Colon are less invasive and accurate, however, they are not cost-effective, as their cost was higher than all other established screening strategies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28988790"}, {"offsetInBeginSection": 9, "offsetInEndSection": 422, "text": "As part of a clinical trial comparing the utility of computed tomographic colonography (CTC) and optical colonoscopy (OC) for post colorectal cancer resection surveillance, we explored the diagnostic yield and costs of a strategy of CTC followed by OC if a polyp is observed (abbreviated CTC_S), versus OC 1 year following curative bowel resection, using the detection of actionable polyps on OC as the criterion.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35187245"}, {"offsetInBeginSection": 160, "offsetInEndSection": 317, "text": "ecurrence. CT colonography (CTC) might be an efficient use of resources in this situation because it allows for intraluminal and extraluminal evaluations wit", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32933928"}, {"offsetInBeginSection": 1242, "offsetInEndSection": 1393, "text": "In comparison to other CRC screening techniques, CTC offers a safe and accurate option that is particularly useful when colonoscopy is contraindicated.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29927637"}, {"offsetInBeginSection": 0, "offsetInEndSection": 343, "text": "BACKGROUND: We examined the cost-effectiveness of 2- and 3-dimensional computerized tomography (CT) colonography as a screening test for colorectal neoplasia.METHODS: We created a Markov model of the natural history of colorectal cancer. Effectiveness of screening was based upon the diagnostic accuracy of tests in detecting polyps and cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17156139"}, {"offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "BACKGROUND: We examined the cost-effectiveness of 2- and 3-dimensional computerized tomography (CT) colonography as a screening test for colorectal neoplasia.METHODS: We created a Markov model of the natural history of colorectal cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17156139"}, {"offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "BACKGROUND: We examined the cost-effectiveness of 2- and 3-dimensional computerized tomography (CT) colonography as a screening test for colorectal neoplasia", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17156139"}, {"offsetInBeginSection": 1378, "offsetInEndSection": 1777, "text": "With equal participation, colonoscopy was the preferred test independent of willingness-to-pay thresholds. The findings were robust for most of the sensitivity analyses, except with regard to relative screening costs and subsequent participation. Conclusion Because of the higher participation rates, CT colonography screening for colorectal cancer is more cost-effective than colonoscopy screening.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29485322"}, {"offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "BACKGROUND: Computerized tomographic (CT) colonography is a potential alternative to colonoscopy for colorectal cancer screening. Its main advantage, a better safety profile, may be offset by its limitations: lower sensitivity, need for colonoscopy in cases where results are positive, and expense", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16217110"}, {"offsetInBeginSection": 977, "offsetInEndSection": 1289, "text": "For CTC to gain similar life-years as colonoscopy screening every 10 years, it should be offered every 5 years with referral of polyps >or=6 mm. For this strategy to be as cost-effective as colonoscopy screening, the costs must not exceed $285 or 43% of colonoscopy costs (range in sensitivity analysis: 39-47%).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19048626"}, {"offsetInBeginSection": 444, "offsetInEndSection": 682, "text": "CTC needs to achieve a higher attendance rate or cost less than colonoscopy to be cost-effective relative to colonoscopy. Fortunately, both conditions appear to be achievable if CTC becomes a widely utilized and reimbursed screening tool.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23182509"}, {"offsetInBeginSection": 713, "offsetInEndSection": 916, "text": "Although, both screening modalities were cost-effective according to most international thresholds, in most of the economic evaluations colonoscopy seemed more cost-effective than colonography screening.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19261464"}, {"offsetInBeginSection": 537, "offsetInEndSection": 712, "text": "The incremental cost-effectiveness ratios of colonoscopy and CT-colonography versus no screening remained under 20,000 euro and 30,000 euro per life year gained, respectively.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19261464"}, {"offsetInBeginSection": 325, "offsetInEndSection": 416, "text": " polyps and cancer.RESULTS: CT colonography every 5 or 10 yr was effective and cost-effecti", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17156139"}, {"offsetInBeginSection": 1584, "offsetInEndSection": 1759, "text": ",144 per life-year gained, respectively.CONCLUSION: Because of its ability to simultaneously screen for both CRC and AAA, CTC is a highly cost-effective and clinically efficac", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19380558"}, {"offsetInBeginSection": 303, "offsetInEndSection": 443, "text": "CTC is cost-effective compared with no screening, indicating that it represents an attractive test noncompliance with the available options.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23182509"}, {"offsetInBeginSection": 1036, "offsetInEndSection": 1323, "text": "anges in underlying parameter values. CTC remained cost effective under a range of assumptions in the univariate sensitivity analysis. However, in the probabilistic sensitivity analysis, CTC dominated FOBT in only 5.9% of simulations and was cost effective at a threshold of pound30,000 ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20369905"}, {"offsetInBeginSection": 2209, "offsetInEndSection": 2476, "text": "eimbursed at $488 per scan.CONCLUSIONS: CTC could be a cost-effective option for colorectal cancer screening among Medicare enrollees if the reimbursement rate per scan is substantially less than that for colonoscopy or if a large proportion of otherwise unscreened p", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20664028"}, {"offsetInBeginSection": 1464, "offsetInEndSection": 1678, "text": "terms of costs and effects.CONCLUSION: CTC and MRC have potential for CRC screening, compared with no screening and compared with three rounds of 10-yearly colonoscopy screening. When taking FIT screening as the re", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27194458"}, {"offsetInBeginSection": 1745, "offsetInEndSection": 1907, "text": "ective compared with no screening.CONCLUSIONS: In an updated review, we found that common CRC screening strategies and computed tomographic colonography continued", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30659991"}]}
+{"question_id": "662cf888187cba990d000002", "question": "is Cryoglobulinemic vasculitis (CV), also known as mixed cryoglobulinemic syndrome (MCS), a systemic vasculitis that affects large blood vessels.", "answer": "Cryoglobulinemic vasculitis (CV), also known as mixed cryoglobulinemic syndrome (MCS), is a systemic vasculitis that affects small blood vessels.", "relevant_passage_ids": ["37698547", "33292799", "36169798", "25547031", "19918044", "33793154", "37916482", "31988822", "35258723", "21173736", "16344620", "37901234", "14740431", "37100623", "29433114", "16079934", "28509128", "25552807"], "type": "yesno", "snippets": [{"offsetInBeginSection": 12, "offsetInEndSection": 159, "text": ": Cryoglobulinemic vasculitis (CV), also known as mixed cryoglobulinemic syndrome (MCS), is a systemic vasculitis that affects small blood vessels.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37698547"}, {"offsetInBeginSection": 11, "offsetInEndSection": 286, "text": " The mixed cryoglobulinemia (MC) syndrome is a systemic inflammatory syndrome that causes small-to-medium vessel vasculitis due to cryoglobulin-containing immune complexes most commonly caused by chronic hepatitis C virus (HCV), and rarely by chronic hepatitis B virus (HBV).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33292799"}, {"offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Cryoglobulinemic vasculitis (CV) or mixed cryoglobulinemic syndrome (MCS) is a systemic small-vessel vasculitis characterized by the proliferation of B-cell clones producing pathogenic immune complexes, called cryoglobulins.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36169798"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1104, "text": "INTRODUCTION: Cryoglobulinemic vasculitis (CV), also known as mixed cryoglobulinemic syndrome (MCS), is a systemic vasculitis that affects small blood vessels. It exhibits a wide range of clinical manifestations, making its treatment a continuing challenge for physicians.AREAS COVERED: We conducted a comprehensive review to evaluate the current status of diagnosis, management, and treatment of mixed cryoglobulinemia (MC). The accurate clinical and serological evaluation plays a vital role in diagnosing MC, identifying potential comorbidities, and monitoring its main manifestations and complications. Treatment strategies should be individualized based on the underlying etiopathogenesis, the severity of organ involvement, and the associated underlying disease. At present, the two mainstays of CV treatment are direct antiviral agents (for HCV-related CV) and B-cell-targeted therapy.EXPERT OPINION: MC remains one of the few autoimmune diseases where the etiology is known, at least for the majority of patients. Its pathogenetic mechanism offers a unique opportunity to investigate the interpla", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37698547"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1098, "text": "Cryoglobulinemic vasculitis (CV) or mixed cryoglobulinemic syndrome (MCS) is a systemic small-vessel vasculitis characterized by the proliferation of B-cell clones producing pathogenic immune complexes, called cryoglobulins. It is often secondary to hepatitis C virus (HCV), autoimmune diseases, and hematological malignancies. CV usually has a mild benign clinical course, but severe organ damage and life-threatening manifestations can occur. Recently, evidence in favor of rituximab (RTX), an anti-CD 20 monoclonal antibody, is emerging in CV: nevertheless, questions upon the safety of this therapeutic approach, especially in HCV patients, are still being issued and universally accepted recommendations that can help physicians in MCS treatment are lacking. A Consensus Committee provided a prioritized list of research questions to perform a systematic literature review (SLR). A search was made in Medline, Embase, and Cochrane library, updated to August 2021. Of 1227 article abstracts evaluated, 27 studies were included in the SLR, of which one SLR, 4 RCTs, and 22 observational studies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36169798"}, {"offsetInBeginSection": 0, "offsetInEndSection": 647, "text": "Cryoglobulinemic vasculitis (CV) is a systemic inflammatory syndrome involving small- to medium-sized vessels. Almost half of hepatitis C-infected patients have detectable cryoglobulins levels, but only very few develop clinical manifestations. In this case report, we bring forth a diagnostic challenge of CV. A\u00a052-year-old man with untreated hepatitis C (high viral load), diabetes mellitus, hypertension, and chronic kidney disease 4 (CKD) with solitary left kidney\u00a0presented with one month of bilateral hand pain that started in\u00a0his right hand, progressed to involve the left with numbness more on the palmer aspects and lateral three fingers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31988822"}, {"offsetInBeginSection": 0, "offsetInEndSection": 666, "text": "Cryoglobulinemic vasculitis (CV) is a\u00a0rare immune complex disease of small vessels (capillaries, venules or arterioles) with detection of cryoglobulins (CG). These are serum proteins that precipitate at temperatures below the normal body temperature. The laboratory diagnostics are logistically challenging because the temperature of the blood sample must be maintained continuously at 37\u202f\u00b0C until arrival in the laboratory to prevent early precipitation of the proteins with adsorption to corpuscular blood components. Cryoglobulins can be divided into three classes (types\u00a0I-III), with each class associated with specific underlying diseases and symptom complexes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35258723"}, {"offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "INTRODUCTION: Cryoglobulinemic vasculitis (CV), also known as mixed cryoglobulinemic syndrome (MCS), is a systemic vasculitis that affects small blood vessels. It exhibits a wide range of clinical manifestations, making its treatment a continuing challenge for physicians", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37698547"}, {"offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "INTRODUCTION: Cryoglobulinemic vasculitis (CV), also known as mixed cryoglobulinemic syndrome (MCS), is a systemic vasculitis that affects small blood vessels", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37698547"}, {"offsetInBeginSection": 0, "offsetInEndSection": 424, "text": "INTRODUCTION: Cryoglobulinemic vasculitis (CV), also known as mixed cryoglobulinemic syndrome (MCS), is a systemic vasculitis that affects small blood vessels. It exhibits a wide range of clinical manifestations, making its treatment a continuing challenge for physicians.AREAS COVERED: We conducted a comprehensive review to evaluate the current status of diagnosis, management, and treatment of mixed cryoglobulinemia (MC)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37698547"}, {"offsetInBeginSection": 0, "offsetInEndSection": 368, "text": "PURPOSE OF REVIEW: Cryoglobulinemic vasculitis is an immune-complex-mediated systemic vasculitis involving small-medium-sized vessels. A causative role of hepatitis C virus in over 80% patients has been definitively established, with heterogeneous geographical distribution. This review focuses on recent etiopathogenetic, clinico-diagnostic, and therapeutical studies", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16344620"}, {"offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "INTRODUCTION: Cryoglobulinemic vasculitis (CV), also known as mixed cryoglobulinemic syndrome (MCS), is a systemic vasculitis that affects small blood vessels.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37698547"}, {"offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "BACKGROUND: The mixed cryoglobulinemia (MC) syndrome is a systemic inflammatory syndrome that causes small-to-medium vessel vasculitis due to cryoglobulin-containing immune complexes most commonly caused by chronic hepatitis C virus (HCV), and rarely by chronic hepatitis B virus (HBV).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33292799"}, {"offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "OBJECTIVE: Mixed cryoglobulinemia (MC) is a systemic vasculitis of small and medium-size vessels, often associated with the hepatitis C virus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19918044"}, {"offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Cryoglobulinemic vasculitis is an immune complex-mediated vasculitis predominantly affecting small vessels.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16079934"}, {"offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Cryoglobulinemic vasculitis (CV) is a systemic inflammatory syndrome involving small- to medium-sized vessels.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31988822"}, {"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Cryoglobulinemic vasculitis (CV) is an immune-complex-mediated systemic vasculitis involving small-medium sized vessels.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14740431"}, {"offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "OBJECTIVE: Cryoglobulinemic vasculitis (CV) involving small- and medium-sized vessels is very frequently associated with hepatitis C virus and may be responsible for multiple organ involvement and skin u", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25547031"}, {"offsetInBeginSection": 415, "offsetInEndSection": 549, "text": "Cryoglobulinemic vasculitis is an immune complex-mediated systemic disorder involving mostly small, but sometimes also larger vessels.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21173736"}, {"offsetInBeginSection": 19, "offsetInEndSection": 264, "text": "Cryoglobulinemic vasculitis (CV) is an immune complex mediated small vessel vasculitis characterized by the presence of cryoglobulins in serum, often associated with hepatitis C infection, systemic autoimmune diseases or hematological conditions", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37916482"}, {"offsetInBeginSection": 14, "offsetInEndSection": 133, "text": "Cryoglobulinemic vasculitis is a type of small vessel vasculitis diseases that can cause dysfunction in multiple organs", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37901234"}, {"offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "PURPOSE OF REVIEW: Cryoglobulinemic vasculitis (CV) is an immune complex mediated small vessel vasculitis characterized by the presence of cryoglobulins in serum, often associated with hepatitis C infection, systemic autoimmune diseases or hemato", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37916482"}, {"offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "BACKGROUND: The mixed cryoglobulinemia (MC) syndrome is a systemic inflammatory syndrome that causes small-to-medium vessel vasculitis due to cryoglobulin-containing immune complexes most commonly caused by chronic hepatitis C virus (HCV), and rarely by chronic hepatitis B ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33292799"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "OBJECTIVE: Mixed cryoglobulinemia (MC) is a systemic vasculitis of small and medium-size vessels, often associated with the hepatit", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19918044"}, {"offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "Mixed cryoglobulinemic syndrome, which is a systemic vasculitis characterized by the immune complex deposition in small- and medium-sized arteries and most often due to chronic hepatitis C virus (HCV) infection, sometimes clinically manifests as refractory glomerulonephritis or nephritic syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28509128"}, {"offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "Cryoglobulinemic vasculitis (CV) is an immune-complex-mediated systemic vasculitis involving small-medium sized vessels. A causative role of hepatitis C virus (HCV) in over 4/5 patients has been definitely established on the basis of epidemiological, pathological, and laboratory studies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14740431"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1013, "text": "INTRODUCTION: Mixed cryoglobulinemia (MC) is a B-cell lymphoproliferative disorder largely attributable to Hepatitis C virus (HCV) infection. MC clinical manifestations are determined by systemic vasculitis of low/medium sized vessels (mixed cryoglobulinemia syndrome or cryoglobulinemic vasculitis [CV]) caused by the deposition of cryoglobulins in blood vessels.EVIDENCE ACQUISITION: A systematic review was performed via the Medline and Scopus databases to evaluate studies concerning CV treatment with new direct antiviral agents (DAAs) and their effect on the syndrome.EVIDENCE SYNTHESIS: The introduction of interferon-free protocols has led to more evident positive effects than those observed in the treatment of hepatitis C. In fact, IFN-free, DAA-based therapy minimized side effects permitting the treatment of previously contraindicated patients and led to a particularly high SVR rate and to a clinical/immunological response in the majority of patients, even if at different levels in different pati", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33793154"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1043, "text": "OBJECTIVE: Mixed cryoglobulinemia (MC) is a systemic vasculitis of small and medium-size vessels, often associated with the hepatitis C virus. Research has shown an emerging role for chemokines and type 1 cytokines in the pathophysiology of this vasculitis. Interleukin 1 (IL-1) plays a role in initiating the cascade of immunoinflammatory responses, and levels of the interferon-gamma (IFN-gamma) inducible chemokine CXCL10 have been shown to be significantly associated with the presence of active vasculitis in patients with MC. We evaluated serum levels of IL-1beta, IFN-gamma, and CXCL10 in a series of patients with hepatitis C-related MC (MC+HCV), and correlated these measurements with clinical disease features.METHODS: Serum IL-1beta, IFN-gamma, and CXCL10 were assayed in 54 patients with MC+HCV, in 54 sex- and age-matched patients with type C chronic hepatitis without cryoglobulinemia (HCV+), and in 54 controls.RESULTS: MC+HCV patients showed significantly higher mean IL-1beta and CXCL10 serum levels than controls (p < 0.01) o", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19918044"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1342, "text": "Mixed cryoglobulinemic syndrome, which is a systemic vasculitis characterized by the immune complex deposition in small- and medium-sized arteries and most often due to chronic hepatitis C virus (HCV) infection, sometimes clinically manifests as refractory glomerulonephritis or nephritic syndrome. Patients with mixed cryoglobulinemic nephropathy who have a rapidly progressive glomerulonephritis should receive immunosuppressive therapy. After disease stabilization, patients should receive concurrent therapy for the underlying HCV infection. The standard therapy of a chronic HCV infection is IFN monotherapy or IFN combined with ribavirin; however, after the introduction of direct-acting antivirals (DAAs), the standard therapy for patients with HCV genotype 1 has dramatically changed. We report a case of HCV-associated cryoglobulinemic membranoproliferative glomerulonephritis (MPGN) successfully treated by daclatasvir and asunaprevir, which are IFN-free DAAs for HCV, in combination with angiotensin II receptor blocker without immunosuppressive therapy. The patient developed severe nephrotic syndrome with progressive kidney dysfunction. Blood examination revealed a high copy number of HCV-RNA (6.4 log IU/mL, type 1), cryoglobulinemia, paraproteinemia of IgM-\u03ba, and hypocomplementemia. Histological analysis showed MPGN type 1.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28509128"}, {"offsetInBeginSection": 842, "offsetInEndSection": 894, "text": "CV is a rare immune complex small-vessel vasculitis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37100623"}, {"offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "PURPOSE OF REVIEW: Cryoglobulinemic vasculitis is an immune-complex-mediated systemic vasculitis involving small-medium-sized vessels", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16344620"}, {"offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Cryoglobulinemic vasculitis is a small vessel vasculitis that has been associated with chronic infections and autoimmune, lymphoproliferative, and neoplastic disorders.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25552807"}, {"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Introduction: Cryoglobulinemic vasculitis is a type of small vessel vasculitis diseases that can cause dysfunction in mu", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37901234"}, {"offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "PURPOSE OF REVIEW: Cryoglobulinemic vasculitis (CV) is an immune complex mediated small vessel vasculitis characterized by the presence of cry", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37916482"}]}
+{"question_id": "66155e7dfdcbea915f00004c", "question": "Consequences for the newborn of infection by Zika virus during pregnancy.", "answer": "In the newborn, infection by Zika virus during pregnancy might cause: microcephalia, pyramidal and extrapyramidal symptoms, hypertonia, cerebral palsy, epilepsy, subcortical calcifications, ocular alterations, congenital contractures, neuronal death in utero.", "relevant_passage_ids": ["37458166", "37482558", "37042942", "36867568"], "type": "list", "snippets": [{"offsetInBeginSection": 25, "offsetInEndSection": 39, "text": "microcephalic ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37458166"}, {"offsetInBeginSection": 206, "offsetInEndSection": 252, "text": "reduction in neuron numbers and neuronal death", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37458166"}, {"offsetInBeginSection": 351, "offsetInEndSection": 378, "text": "decrease in neuronal number", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37458166"}, {"offsetInBeginSection": 473, "offsetInEndSection": 486, "text": "microcephaly ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37482558"}, {"offsetInBeginSection": 81, "offsetInEndSection": 142, "text": "cerebral palsy (CP) associated with congenital Zika infection", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37042942"}, {"offsetInBeginSection": 795, "offsetInEndSection": 809, "text": "cerebral palsy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37042942"}, {"offsetInBeginSection": 888, "offsetInEndSection": 896, "text": "Epilepsy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37042942"}, {"offsetInBeginSection": 403, "offsetInEndSection": 415, "text": "microcephaly", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36867568"}, {"offsetInBeginSection": 417, "offsetInEndSection": 443, "text": "subcortical calcifications", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36867568"}, {"offsetInBeginSection": 465, "offsetInEndSection": 488, "text": "congenital contractures", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36867568"}, {"offsetInBeginSection": 490, "offsetInEndSection": 506, "text": "early hypertonia", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36867568"}, {"offsetInBeginSection": 445, "offsetInEndSection": 463, "text": "ocular alterations", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36867568"}, {"offsetInBeginSection": 512, "offsetInEndSection": 556, "text": "pyramidal as well as extrapyramidal symptoms", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36867568"}]}
+{"question_id": "66302090187cba990d00002a", "question": "Which are the key transcription factors known to drive glioma progression and therapy resistance?", "answer": "Gliomas portray a large and heterogeneous group of CNS tumors, encompassing a wide range of low- to high-grade tumors, as defined by histological and molecular characteristics. The identification of signature mutations and other molecular abnormalities has largely impacted tumor classification, diagnosis, and therapy. Transcription factors (TFs) are master regulators of gene expression programs, which ultimately shape cell fate and homeostasis. A variety of TFs have been detected to be aberrantly expressed in brain tumors, being highly implicated in critical pathological aspects and progression of gliomas. Some examples of oncogenic (GLI-1/2/3, E2F1-8, STAT3, and HIF-1/2) and tumor suppressor (NFI-A/B, TBXT, MYT1, and MYT1L) TFs that are deregulated in gliomas and are subsequently associated with tumor development, progression, and migratory potential, have already been described.", "relevant_passage_ids": ["35409080", "28414309", "37821870", "37087499", "32064771", "31678994", "37349788", "35563134", "32680567", "16389942", "33720698", "27002148", "10392639", "32703494", "31614149", "30216501", "26534766", "23645448"], "type": "list", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 882, "text": "Gliomas portray a large and heterogeneous group of CNS tumors, encompassing a wide range of low- to high-grade tumors, as defined by histological and molecular characteristics. The identification of signature mutations and other molecular abnormalities has largely impacted tumor classification, diagnosis, and therapy. Transcription factors (TFs) are master regulators of gene expression programs, which ultimately shape cell fate and homeostasis. A variety of TFs have been detected to be aberrantly expressed in brain tumors, being highly implicated in critical pathological aspects and progression of gliomas. Herein, we describe a selection of oncogenic (GLI-1/2/3, E2F1-8, STAT3, and HIF-1/2) and tumor suppressor (NFI-A/B, TBXT, MYT1, and MYT1L) TFs that are deregulated in gliomas and are subsequently associated with tumor development, progression, and migratory potential.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35409080"}, {"offsetInBeginSection": 541, "offsetInEndSection": 650, "text": "FOXM1 and FOXOs have been recognized as crucial transcription factors in tumor cells, including glioma cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37821870"}, {"offsetInBeginSection": 921, "offsetInEndSection": 1092, "text": "We conclude that p52-induced ETS1 overexpression in glioma cells remodels the genome-wide regulatory network of p52 and ETS1 to transcriptionally drive cancer progression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37087499"}, {"offsetInBeginSection": 614, "offsetInEndSection": 882, "text": "Herein, we describe a selection of oncogenic (GLI-1/2/3, E2F1-8, STAT3, and HIF-1/2) and tumor suppressor (NFI-A/B, TBXT, MYT1, and MYT1L) TFs that are deregulated in gliomas and are subsequently associated with tumor development, progression, and migratory potential.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35409080"}, {"offsetInBeginSection": 352, "offsetInEndSection": 750, "text": "The transcription factor EGR1 (early growth response 1), a member of a zinc finger transcription factor family, has been described as tumor suppressor in gliomas when ectopically overexpressed. Although EGR1 expression in human glioblastomas has been associated with patient survival, its precise location in tumor territories as well as its contribution to glioblastoma progression remain elusive.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27002148"}, {"offsetInBeginSection": 90, "offsetInEndSection": 510, "text": "Chronic inflammation is a key driver of glioma progression as it promotes aberrant activation of inflammatory pathways such as NF-\u03baB signalling, which drives cancer cell invasion and angiogenesis. NF-\u03baB factors typically dimerise with its own family members, but emerging evidence of their promiscuous interactions with other oncogenic factors has been reported to promote transcription of new target genes and function.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37087499"}, {"offsetInBeginSection": 314, "offsetInEndSection": 813, "text": "The forkhead box (FOX) transcription factors comprise a collection of proteins that play various roles in numerous complex molecular cascades and have been discovered to be differentially expressed in distinct glioma subtypes. FOXM1 and FOXOs have been recognized as crucial transcription factors in tumor cells, including glioma cells. Accumulating data indicates that FOXM1 acts as an oncogene in various types of cancers, and a significant part of studies has investigated its function in glioma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37821870"}, {"offsetInBeginSection": 541, "offsetInEndSection": 952, "text": "FOXM1 and FOXOs have been recognized as crucial transcription factors in tumor cells, including glioma cells. Accumulating data indicates that FOXM1 acts as an oncogene in various types of cancers, and a significant part of studies has investigated its function in glioma. Although recent studies considered FOXO subgroups as tumor suppressors, there are pieces of evidence that they may have an oncogenic role.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37821870"}]}
+{"question_id": "662e29f9187cba990d00000a", "question": "What are the genotypes of Japanese Encephalitis Virus (JEV)?", "answer": "Japanese Encephalitis Virus (JEV) has 5 genotypes: G1, G2, G3, G4 and G5.", "relevant_passage_ids": ["36450570"], "type": "list", "snippets": [{"offsetInBeginSection": 28, "offsetInEndSection": 45, "text": "Genotypes 1 and 3", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36450570"}, {"offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Japanese encephalitis virus (JEV) is a mosquito-borne virus belonging to the JEV serocomplex within the genus Flavivirus, family Flaviviridae. It has 5 genotypes, G1-G5, based on the envelope (E) protein nucleotide sequence.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36450570"}]}
+{"question_id": "65d373151930410b13000048", "question": "What medication were tested in the TRICOTEL trial?", "answer": "TRICOTEL was a multicentre, open-label, single-arm, phase 2 study that tested atezolizumab, vemurafenib, and cobimetinib in patients with melanoma with CNS metastases.", "relevant_passage_ids": ["37459873", "35940183"], "type": "list", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Atezolizumab, vemurafenib, and cobimetinib in patients with melanoma with CNS metastases (TRICOTEL): a multicentre, open-label, single-arm, phase 2 study.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37459873"}, {"offsetInBeginSection": 349, "offsetInEndSection": 1296, "text": "METHODS: TRICOTEL was a multicentre, open-label, single-arm, phase 2 study done in two cohorts: a BRAFV600 wild-type cohort and a BRAFV600 mutation-positive cohort, recruited at 21 hospitals and oncology centres in Brazil, France, Germany, Hungary, Italy, Spain, and Switzerland. Eligible patients were aged 18 years or older with previously untreated metastatic melanoma, brain metastases of 5 mm or larger in at least one dimension, and an Eastern Cooperative Oncology Group performance status of 2 or less. Patients in the BRAFV600 wild-type cohort received intravenous atezolizumab (840 mg, days 1 and 15 of each 28-day cycle) plus oral cobimetinib (60 mg once daily, days 1-21). Patients in the BRAFV600 mutation-positive cohort received intravenous atezolizumab (840 mg, days 1 and 15 of each 28-day cycle) plus oral vemurafenib (720 mg twice daily) plus oral cobimetinib (60 mg once daily, days 1-21); atezolizumab was withheld in cycle 1. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37459873"}, {"offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Atezolizumab, vemurafenib, and cobimetinib in patients with melanoma with CNS metastases (TRICOTEL): a multicentre, open-label, single-arm, phase 2 study.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35940183"}, {"offsetInBeginSection": 193, "offsetInEndSection": 2870, "text": "metastases. We aimed to evaluate atezolizumab in combination with cobimetinib or vemurafenib plus cobimetinib in patients with melanoma with CNS metastases.METHODS: TRICOTEL was a multicentre, open-label, single-arm, phase 2 study done in two cohorts: a BRAFV600 wild-type cohort and a BRAFV600 mutation-positive cohort, recruited at 21 hospitals and oncology centres in Brazil, France, Germany, Hungary, Italy, Spain, and Switzerland. Eligible patients were aged 18 years or older with previously untreated metastatic melanoma, CNS metastases of 5 mm or larger in at least one dimension, and an Eastern Cooperative Oncology Group performance status of 2 or less. Patients in the BRAFV600 wild-type cohort received intravenous atezolizumab (840 mg, days 1 and 15 of each 28-day cycle) plus oral cobimetinib (60 mg once daily, days 1-21). Patients in the BRAFV600 mutation-positive cohort received intravenous atezolizumab (840 mg, days 1 and 15 of each 28-day cycle) plus oral vemurafenib (720 mg twice daily) plus oral cobimetinib (60 mg once daily, days 1-21); atezolizumab was withheld in cycle 1. Treatment was continued until progression, toxicity, or death. The primary outcome was intracranial objective response rate confirmed by assessments at least 4 weeks apart, as assessed by independent review committee (IRC) using modified Response Evaluation Criteria in Solid Tumours version 1.1. Because of early closure of the BRAFV600 wild-type cohort, the primary endpoint of intracranial objective response rate by IRC assessment was not done in this cohort; intracranial objective response rate by investigator assessment was reported instead. Efficacy and safety were analysed in all patients who received at least one dose of study medication. This trial is closed to enrolment and is registered with ClinicalTrials.gov, NCT03625141.FINDINGS: Between Dec 13, 2018, and Dec 7, 2020, 65 patients were enrolled in the BRAFV600 mutation-positive cohort; the BRAFV600 wild-type cohort was closed early after enrolment of 15 patients. Median follow-up was 9\u00b77 months (IQR 6\u00b73-15\u00b70) for the BRAFV600 mutation-positive cohort and 6\u00b72 months (3\u00b75-23\u00b70) for the BRAFV600 wild-type cohort. Intracranial objective response rate was 42% (95% CI 29-54) by IRC assessment in the BRAFV600 mutation-positive cohort and 27% (95% CI 8-55) by investigator assessment in the BRAFV600 wild-type cohort. Treatment-related grade 3 or worse adverse events occurred in 41 (68%) of 60 patients who received atezolizumab plus vemurafenib plus cobimetinib in the BRAFV600 mutation-positive cohort, the most common of which were lipase increased (15 [25%] of 60 patients) and blood creatine phospho", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35940183"}, {"offsetInBeginSection": 193, "offsetInEndSection": 3340, "text": "metastases. We aimed to evaluate atezolizumab in combination with cobimetinib or vemurafenib plus cobimetinib in patients with melanoma with CNS metastases.METHODS: TRICOTEL was a multicentre, open-label, single-arm, phase 2 study done in two cohorts: a BRAFV600 wild-type cohort and a BRAFV600 mutation-positive cohort, recruited at 21 hospitals and oncology centres in Brazil, France, Germany, Hungary, Italy, Spain, and Switzerland. Eligible patients were aged 18 years or older with previously untreated metastatic melanoma, brain metastases of 5 mm or larger in at least one dimension, and an Eastern Cooperative Oncology Group performance status of 2 or less. Patients in the BRAFV600 wild-type cohort received intravenous atezolizumab (840 mg, days 1 and 15 of each 28-day cycle) plus oral cobimetinib (60 mg once daily, days 1-21). Patients in the BRAFV600 mutation-positive cohort received intravenous atezolizumab (840 mg, days 1 and 15 of each 28-day cycle) plus oral vemurafenib (720 mg twice daily) plus oral cobimetinib (60 mg once daily, days 1-21); atezolizumab was withheld in cycle 1. Treatment was continued until progression, toxicity, or death. The primary outcome was intracranial objective response rate confirmed by assessments at least 4 weeks apart, as assessed by independent review committee (IRC) using modified Response Evaluation Criteria in Solid Tumours version 1.1. Because of early closure of the BRAFV600 wild-type cohort, the primary endpoint of intracranial objective response rate by IRC assessment was not done in this cohort; intracranial objective response rate by investigator assessment was reported instead. Efficacy and safety were analysed in all patients who received at least one dose of study medication. This trial is closed to enrolment and is registered with ClinicalTrials.gov, NCT03625141.FINDINGS: Between Dec 13, 2018, and Dec 7, 2020, 65 patients were enrolled in the BRAFV600 mutation-positive cohort; the BRAFV600 wild-type cohort was closed early after enrolment of 15 patients. Median follow-up was 9\u00b77 months (IQR 6\u00b73-15\u00b70) for the BRAFV600 mutation-positive cohort and 6\u00b72 months (3\u00b75-23\u00b70) for the BRAFV600 wild-type cohort. Intracranial objective response rate was 42% (95% CI 29-54) by IRC assessment in the BRAFV600 mutation-positive cohort and 27% (95% CI 8-55) by investigator assessment in the BRAFV600 wild-type cohort. Treatment-related grade 3 or worse adverse events occurred in 41 (68%) of 60 patients who received atezolizumab plus vemurafenib plus cobimetinib in the BRAFV600 mutation-positive cohort, the most common of which were lipase increased (15 [25%] of 60 patients) and blood creatine phosphokinase increased (11 [18%]). Eight (53%) of 15 patients treated with atezolizumab plus cobimetinib in the BRAFV600 wild-type cohort had treatment-related grade 3 or worse adverse events, most commonly anaemia (two [13%]) and dermatitis acneiform (two [13%]). Treatment-related serious adverse events occurred in 14 (23%) of 60 patients who received triplet therapy in the BRAFV600 mutation-positive cohort and two (13%) of 15 in the BRAFV600 wild-type cohort. No treat", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37459873"}]}
+{"question_id": "66214ff0b9f8b89d7e000006", "question": "What are the most frequent side effects of regorafenib?", "answer": "The most common grade 3-4 adverse reactions with the drug are hand foot skin reactions (HFSR), diarrhea, hypertension,  fatigue and laboratory abnormalities", "relevant_passage_ids": ["35716310", "26327919", "24980770", "24675266", "29914591", "23560833", "30323618", "33411256", "31663730", "27398042", "24821824", "38050698", "27617607", "30313066", "35635652", "30606885", "29212191", "36217043", "31106665", "26034039", "23700287", "37142953", "23610528", "22568966", "22421192", "25998375", "31365177", "22959186", "29175677", "31195212", "24623990"], "type": "list", "snippets": [{"offsetInBeginSection": 1266, "offsetInEndSection": 1438, "text": "The most frequent grade 3 or 4 side effects were laboratory abnormalities (62%). PFS was 2.6\u00a0months (range 0.8-8.2\u00a0months), and the OS was 6.2\u00a0months (range 0.9-24\u00a0months).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35716310"}, {"offsetInBeginSection": 837, "offsetInEndSection": 967, "text": "The most common grade 3-4 adverse reactions with the drug are hand foot skin reactions (HFSR), diarrhea, hypertension and fatigue.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26327919"}, {"offsetInBeginSection": 604, "offsetInEndSection": 743, "text": "Common treatment-related adverse events were diarrhoea, decreased appetite, increase in serum creatinine, malaise, nausea and eye disorders", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38050698"}, {"offsetInBeginSection": 214, "offsetInEndSection": 1534, "text": "lignancies. However, the adverse events (AEs) associated with regorafenib have not been systematically investigated. Hence, we performed a meta-analysis to identify AEs associated with regorafenib in patients with advanced solid tumors.METHODS: The databases of PubMed, MEDLINE, and Embase and abstracts presented in American Society of Clinical Oncology annual meetings were searched for relevant publications from January 2004 to September 2017. Eligible studies were limited to prospective randomized controlled trials (RCTs) that evaluate the use of regorafenib in patients with advanced solid tumors. Incidence, relative risk (RR), and 95% CIs were calculated using a random or fixed effects model on the basis of the heterogeneity of the included studies.RESULTS: A total of 2,065 patients from six RCTs were included, and 1,340 of them received regorafenib and 725 received a placebo. Sixteen all-grade AEs and 15 high-grade AEs were investigated for their association with regorafenib. Results showed that hand-foot skin reaction (HFSR; 54%), diarrhea (33%), fatigue (32%), hypertension (31%), oral mucositis (28%), and anorexia (23%) were the most frequent clinical AEs. The most common high-grade (grade, \u22653) AEs were HFSR (16%), hypertension (13%), fatigue (6%), increased aspartate aminotransferase (AST; 6%)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30323618"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1547, "text": "Regorafenib, a multikinase inhibitor, is effective in treating metastatic colorectal cancer (mCRC). Hypertension is a frequently occurring adverse effect caused by regorafenib regardless of previous treatment with vascular endothelial growth factor (VEGF) inhibitors in almost all patients. We identified the risk factors associated with regorafenib-induced severe hypertension. Patients with mCRC (n\u2009=\u2009100) who received regorafenib were evaluated retrospectively. The primary endpoint was the evaluation of the risk factors for grade\u2009\u2265\u20093 hypertension. The association between pre-existing hypertension at baseline and grade\u2009\u2265\u20093 hypertension symptoms was also assessed. Patients with pre-existing hypertension at baseline accounted for 55% of the total patients. The starting doses of regorafenib were 160\u00a0mg (49.0% of patients), 120\u00a0mg (29.0%), and 80\u00a0mg (22.0%). The incidence of grade\u2009\u2265\u20093 hypertension was 30.0%. The median time to grade\u2009\u2265\u20093 symptom development was 7\u00a0days (range:\u00a01-56\u00a0days). Additional antihypertensive treatment was administered to 83.6% of patients who developed hypertension. Logistic regression analyses revealed that baseline pre-existing hypertension complications and previous anti-VEGF treatment for\u2009\u2265\u2009700\u00a0days were independent risk factors for grade\u2009\u2265\u20093 hypertension development. Further analyses revealed that pre-existing hypertension before anti-VEGF treatment (primary hypertension) was significantly related to the symptom development (adjusted odds ratio, 8.74; 95% confidence interval, 2.86-26.72; P\u2009=\u20090.0001).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36217043"}, {"offsetInBeginSection": 136, "offsetInEndSection": 1843, "text": "lid tumors.METHODS: Eligible studies from MEDLINE, Google Scholar, Cochrane Library, Clinical key, EBSCO publishing and Ovid, which had reported cardiovascular adverse events potentially caused by regorafenib were absorbed. Data of clinical characteristics and cardiovascular events including hypertension, hemorrhage, thrombosis, and heart failure were extracted from selected literatures for the final analysis. Pooled analysis of cardiovascular adverse events was developed by relative risks (RRs) and corresponding 95% confidence intervals (CIs) with software STATA 13.0 and RevMan 5.3.RESULTS: Thirty studies including 3813 patients were fit into analysis. The incidences of cardiovascular events of all-grade were: hypertension, 36.8% (95% CI, 29.8%-43.8%), hemorrhage, 8.6% (95% CI, 3.2%-14%), thrombosis, 1.4% (95% CI, 0.1%-2.8%), and heart failure, 2.9% (95% CI, 0.3%-5.6%). The incidences of cardiovascular events of high-grade were: hypertension, 9.9% (95% CI, 7.4%-12.4%), hemorrhage, 1.2% (95% CI, 0.3%-2.2%), thrombosis, 1.6% (95% CI, 0.2%-3.4%), and heart failure, 2.9% (95% CI, 0.3%-5.6%). The RRs and their 95% CIs of all-grade cardiovascular events among patients treated with regorafenib were: hypertension, 4.10 (95% CI, 3.07-5.46; P\u200a<\u200a.00001), hemorrhage, 2.71 (95% CI, 1.45-5.08; P\u200a=\u200a.002), thrombosis, 1.27 (95% CI, 0.49-3.27; P\u200a=\u200a.62), and heart failure, 0.79 (95% CI, 0.16-3.94; P\u200a=\u200a.77). The RRs and their 95% CIs of high-grade cardiovascular events among patients treated with regorafenib were: hypertension, 5.82 (95% CI, 3.46-9.78; P\u200a<\u200a.00001), hemorrhage, 0.90 (95% CI, 0.50-1.61; P\u200a=\u200a.72), thrombosis, 1.28 (95% CI, 0.48-3.41; P\u200a=\u200a.62), and heart failure, 1.15 (95% CI, 0.23-5", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30313066"}, {"offsetInBeginSection": 339, "offsetInEndSection": 2137, "text": "fe setting.MATERIALS AND METHODS: Patients with mCRC were prospectively registered and initially received \u2264160 mg oral regorafenib daily, at the investigator's discretion, for weeks 1-3 of each 4-week cycle. The study's primary aim was to assess safety, particularly unexpected clinically significant adverse drug reactions (ADRs). A Cox's proportional hazards model was used to evaluate the association between OS, hand-foot skin reaction (HFSR), and baseline characteristics.RESULTS: We evaluated 1,227 of 1,301 patients (enrolled from March 2013 to May 2015). ADRs occurred in 89.3% of patients (mostly within the first 4 weeks) and were a major reason for discontinuing treatment. The most frequent ADRs were HFSR, liver injury, and hypertension. The cumulative incidence of HFSR and liver injury was higher in patients who initially received 160 mg than in those who received \u2264120 mg. The incidence of hypertension and fatigue was similar between groups. Median OS was 6.9 months (95% confidential interval, 6.4-7.4). OS was associated with early onset of HFSR and good performance status (PS) but not with the initial dose.CONCLUSION: The outcomes of this study were consistent with those of clinical trials. There were no new safety concerns. Regorafenib treatment would not be recommended for patients with higher PS.IMPLICATIONS FOR PRACTICE: Previous clinical trials demonstrated regorafenib improved overall survival in patients with metastatic colorectal cancer who progress after standard chemotherapies. Because the eligibility criteria of the trials were restricted compared with a real-world setting, the data from the trials may not fully represent the profiles of regorafenib in clinical practice. This large-scale observational study showed that the safety and effectiveness of r", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30606885"}, {"offsetInBeginSection": 302, "offsetInEndSection": 570, "text": " Adverse events include asthenia, hypertension, diarrhea, and hand-foot skin reaction (HFSR), with the latter representing one of the most clinically significant untoward events. The incidence and risk of HFSR with regorafenib have not been systematically investigated", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23700287"}, {"offsetInBeginSection": 302, "offsetInEndSection": 707, "text": " Adverse events include asthenia, hypertension, diarrhea, and hand-foot skin reaction (HFSR), with the latter representing one of the most clinically significant untoward events. The incidence and risk of HFSR with regorafenib have not been systematically investigated.METHODS: We conducted a meta-analysis to ascertain the incidence and risk of developing HFSR in cancer patients treated with regorafenib", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23700287"}, {"offsetInBeginSection": 778, "offsetInEndSection": 943, "text": "The most frequent adverse events of grade 3 or higher related to regorafenib were hand-foot skin reaction, fatigue, diarrhea, hypertension, and rash or desquamation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23610528"}, {"offsetInBeginSection": 839, "offsetInEndSection": 1150, "text": "The most common adverse events of regorafenib include dermatologic and mucosal toxicities (especially hand-foot skin reaction, rash, and oral mucositis), constitutional symptoms (e.g., fatigue, nausea, and weight loss), vascular effects (especially hypertension), and gastrointestinal symptoms (e.g., diarrhea).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24821824"}, {"offsetInBeginSection": 539, "offsetInEndSection": 698, "text": "Common side effects include asthenia/tiredness, loss of appetite, hand-foot skin syndrome, diarrhea, mucositis, weight loss, infections, hypertension and rash.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23560833"}, {"offsetInBeginSection": 685, "offsetInEndSection": 795, "text": "53 days (range 7-280 days). The most common treatment-related toxicities included hand-foot skin reaction, fat", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22568966"}, {"offsetInBeginSection": 1202, "offsetInEndSection": 1330, "text": "n days off in repeating 28-day cycles. The most common drug-related grade 3 or 4 AEs were dermatologic AEs (hand-foot skin react", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22421192"}, {"offsetInBeginSection": 174, "offsetInEndSection": 268, "text": "Diarrhea is one of the most frequently observed adverse reactions associated with regorafenib.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31663730"}, {"offsetInBeginSection": 244, "offsetInEndSection": 362, "text": "The most common drug-related adverse events with regorafenib are hypertension, hand-foot skin reactions, and diarrhea.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24980770"}, {"offsetInBeginSection": 0, "offsetInEndSection": 671, "text": "Patients with metastatic colorectal cancer (mCRC) frequently experience treatment-related adverse events (AEs), which may lead to nonadherence or discontinuation from their treatment regimen. In the phase 3 CORRECT study, the addition of regorafenib to best supportive care (BSC) significantly increased overall survival and progression-free survival compared with placebo plus BSC in patients with mCRC who had progressed on all approved standard care therapies. Although regorafenib showed an acceptable safety profile, patients experienced treatment-related AEs such as hand-foot skin reaction, hypertension, oral mucositis, diarrhea, fatigue, and liver abnormalities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24675266"}, {"offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "BACKGROUND: Regorafenib, a multikinase inhibitor, causes a high frequency of hand-foot skin react", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37142953"}, {"offsetInBeginSection": 1608, "offsetInEndSection": 1891, "text": "erse events occurred in 86% of patients. The most frequent adverse events of any grade were fatigue (35%), diarrhea (20%), and hand-foot skin reaction (20%). Grade 3 or 4 treatment-related adverse events occurred in 10 patients (35%). Three patients (10%) were admitted to hospital d", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27398042"}, {"offsetInBeginSection": 1020, "offsetInEndSection": 1196, "text": " The most commonly reported drug-related adverse events among patients receiving regorafenib in the GRID trial were hand-foot skin reaction, hypertension, diarrhoea and fatigue", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25998375"}, {"offsetInBeginSection": 813, "offsetInEndSection": 983, "text": "During regorafenib (6.3\u00a0months), all patients had at least one adverse event (AE), the most common grade 3/4 AEs were fatigue (n\u00a0=\u00a07) and dermatological reaction (n\u00a0=\u00a05).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31365177"}, {"offsetInBeginSection": 1521, "offsetInEndSection": 1880, "text": "all of which were partial responses. Drug-related adverse events occurred in 48 patients (98%) and drug-related serious adverse events in 17 (35%). Grade 3 drug-related adverse events were common, most frequently hand and foot skin reaction (16 patients, 33%), diarrhoea (five patients, 10%), renal failure (five patients, 10%), fatigue (four patients, 8%), a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22959186"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1381, "text": "Regorafenib is a multikinase inhibitor for the treatment of metastatic colorectal cancer. Regorafenib-induced hand-foot skin reaction (HFSR) is a common side effect during treatment. The reported frequency of HFSR was 80% (grade 3: 28%) in the Japanese subpopulation in the CORRECT trial; however, more detailed data regarding HFSR in terms of onset and sites of susceptibility are unclear. Additionally, the risk factors for regorafenib-induced severe HFSR are unknown. The aim of this study was to compare HFSR between the hands and feet and identify preexisting risk factors for severe HFSR in Japanese patients receiving regorafenib. We retrospectively examined the onset and severity of HFSR on the hands and feet of patients with metastatic colorectal cancer treated with regorafenib from May 2013 to October 2015 in the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. In addition, we examined the possible association between preexisting clinical factors and severe HFSR. Our results showed that no significant difference in the incidence of HFSR of any grade was observed between the hands (71%) and feet (74%) (p\u2009=\u20090.63). The incidence of grade 3 HFSR was more frequent on the feet (33%) than on the hands (8%) (p\u2009<\u20090.01). The onset of grade 3 HFSR was earlier on the feet than on the hands (p\u2009<\u20090.001). No preexisting risk factor was identified.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29914591"}, {"offsetInBeginSection": 800, "offsetInEndSection": 1011, "text": "The incidences of regorafenib associated all-grade and high-grade hematologic toxicities were: thrombocytopenia, 22% and 3%; anemia, 20% and 3%; neutropenia, 10% and 2%, and leucopenia, 13% and 2%, respectively.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29212191"}, {"offsetInBeginSection": 100, "offsetInEndSection": 290, "text": "Hypertension is a frequently occurring adverse effect caused by regorafenib regardless of previous treatment with vascular endothelial growth factor (VEGF) inhibitors in almost all patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36217043"}, {"offsetInBeginSection": 113, "offsetInEndSection": 249, "text": "r patients. However, various toxicities, such as hand-foot skin reaction (HFSR), fatigue, and liver dysfunction have limited the use of ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35635652"}, {"offsetInBeginSection": 1286, "offsetInEndSection": 1474, "text": "nt at the time of analysis. The most reported grade 3 and above side effects included rash (41.9%), fatigue (39.6 %), hypertension (25.6%), mucositis (21.9%), hand-foot syndrome (2.3%), an", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33411256"}, {"offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Regorafenib is a second-generation multikinase inhibitor that is approved for the treatment of metastatic colon cancer and advanced gastrointestinal stromal tumors. Hand-foot skin reaction, alopecia, and oral mucositis are well-established side effects of this medication.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27617607"}, {"offsetInBeginSection": 165, "offsetInEndSection": 419, "text": "Hand-foot skin reaction, alopecia, and oral mucositis are well-established side effects of this medication. Herein, we discuss a 60-year-old woman who developed a lobular and septal granulomatous panniculitis after six months of therapy with regorafenib.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27617607"}, {"offsetInBeginSection": 165, "offsetInEndSection": 591, "text": "Hand-foot skin reaction, alopecia, and oral mucositis are well-established side effects of this medication. Herein, we discuss a 60-year-old woman who developed a lobular and septal granulomatous panniculitis after six months of therapy with regorafenib. Biopsy demonstrated focal lobular and septal granulomatous inflammation admixed with septal fibrosis and lobular lymphohistiocytic infiltrate associated with fat necrosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27617607"}, {"offsetInBeginSection": 165, "offsetInEndSection": 272, "text": "Hand-foot skin reaction, alopecia, and oral mucositis are well-established side effects of this medication.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27617607"}, {"offsetInBeginSection": 0, "offsetInEndSection": 37, "text": "Regorafenib- associated panniculitis.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27617607"}, {"offsetInBeginSection": 1180, "offsetInEndSection": 1365, "text": "sociation with regorafenib. Results showed that hand-foot skin reaction (HFSR; 54%), diarrhea (33%), fatigue (32%), hypertension (31%), oral mucositis (28%), and anorexia (23%) were the", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30323618"}, {"offsetInBeginSection": 1366, "offsetInEndSection": 1533, "text": "most frequent clinical AEs. The most common high-grade (grade, \u22653) AEs were HFSR (16%), hypertension (13%), fatigue (6%), increased aspartate aminotransferase (AST; 6%", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30323618"}, {"offsetInBeginSection": 1120, "offsetInEndSection": 1248, "text": "supported these results. The most frequently reported adverse events were hand-foot-skin reaction (25%-86%), hypertension (11%-4", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29175677"}, {"offsetInBeginSection": 471, "offsetInEndSection": 646, "text": "Fatigue, diarrhoea, hand-foot skin reaction, nausea, vomiting, decreased appetite, hypertension and weight loss are among the most common AEs experienced with these four TKIs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31195212"}, {"offsetInBeginSection": 1079, "offsetInEndSection": 1382, "text": "In this review, we highlight regorafenib's mechanism of action, present key efficacy data from the CORRECT trial, and discuss how to proactively manage common adverse events (eg, hand-foot skin reaction, hypertension, oral mucositis, diarrhea, and fatigue) experienced by patients receiving regorafenib.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24623990"}]}
+{"question_id": "662cf8db187cba990d000003", "question": "Is Periostin a novel biomarker of TH2-driven asthma?", "answer": "Serum periostin associates with type-2 inflammation in asthmatic airways, but also reflects whole body periostin levels originating from multiple sources.", "relevant_passage_ids": ["36763690", "36753209", "37260069", "25037608", "28398635", "27751727", "29342461", "24247042", "27054127", "25838094", "35278445", "34796003", "24759559", "29879994", "37794472", "30342583", "33203095", "28942959", "30964557", "29648484", "30574168", "33228831", "24748808", "25479456", "22857879", "24300416"], "type": "yesno", "snippets": [{"offsetInBeginSection": 11, "offsetInEndSection": 167, "text": " Serum periostin associates with type-2 inflammation in asthmatic airways, but also reflects whole body periostin levels originating from multiple sources. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36763690"}, {"offsetInBeginSection": 1, "offsetInEndSection": 81, "text": " novel assay for improved detection of sputum periostin in patients with asthma.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36763690"}, {"offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Periostin as an important biomarker of inflammatory phenotype T2 in Brazilian asthma patients.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36753209"}, {"offsetInBeginSection": 11, "offsetInEndSection": 193, "text": "The aim of this study was to assess the laboratory performance of periostin associated with a panel of biomarkers to identify the inflammatory phenotype of Brazilian asthma patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36753209"}, {"offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Relationship of Serum Periostin With Asthma Control in Children: Single Center Experience", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37260069"}, {"offsetInBeginSection": 11, "offsetInEndSection": 102, "text": "To determine the association between serum periostin levels and asthma control in children.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37260069"}, {"offsetInBeginSection": 956, "offsetInEndSection": 1072, "text": "Asthmatic children have a high serum periostin level, and its higher levels are associated with poor asthma control.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37260069"}, {"offsetInBeginSection": 1290, "offsetInEndSection": 1372, "text": "Periostin proved to be an important biomarker for the identification of T2 asthma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36753209"}, {"offsetInBeginSection": 1615, "offsetInEndSection": 1810, "text": "n. Sputum periostin is worth considering as a phenotype-specific biomarker in asthma as its proximity to the airways may eliminate some of the confounding factors known to affect serum periostin.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36763690"}, {"offsetInBeginSection": 1481, "offsetInEndSection": 1614, "text": ". Using this assay, sputum periostin was detectable and associated with more disease-relevant parameters in asthma than serum periost", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36763690"}, {"offsetInBeginSection": 1109, "offsetInEndSection": 1311, "text": "This study combines a panel of non-T2 inflammatory markers (low periostin, low blood-eosinophils, and low FeNO), to determine if this group of patients can maintain asthma control during ICS withdrawal.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37794472"}, {"offsetInBeginSection": 736, "offsetInEndSection": 1251, "text": "d an AUC greater than 65%. Periostin (OR: 12,550; 95% CI: 2,498-63,063) and IL-6 (OR: 7,249; 95% CI: 1,737-30,262) revealed to be suitable asthma inflammation biomarkers. Blood eosinophils, FeNO, total IgE, IL-6, TNF, and IFN-g showed correlations with clinical severity characteristics in asthmatic patients. Periostin showed higher values in T2 asthma (p = 0.006) and TNF in non-T2 asthma (p = 0.029).CONCLUSION: The panel of biomarkers proposed for the identification of the inflammatory phenotype of asthmatic p", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36753209"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1768, "text": "BACKGROUND: Serum thymus and activation-regulated chemokine (TARC) and periostin are reliable biomarkers in eosinophilicasthma.OBJECTIVE: This study was carried out to determine the use of periostin and TARC as biomarkers in asthma and to comparethe superiority of one over the other, especially in asthma with an eosinophilic phenotype.METHODS: The study was conducted with 87 patients with asthma and 42 healthy control subjects. Patients with asthma were also divided into eosinophilic and non-eosinophilic phenotypes. A pulmonary function test was performed in all the participants,and serum and induced sputum TARC, periostin concentrations, eosinophils, and total immunoglobulin E valueswere examined.RESULTS: TARC and periostin levels were significantly higher in the asthma group than in the control group (p < 0.001). The serum TARC level in the eosinophilic group was significantly higher than in the non-eosinophilic and control groups(p < 0.001). The induced sputum TARC level was significantly higher in the non-eosinophilic group than in the control group(p < 0.001). The TARC and periostin levels of the patients were evaluated by using receiver operator characteristic analysis.The cutoff value for TARC was determined to be 1415.39 ng/L; likewise, the cutoff value for periostin was 107.60 ng/L. Thepresent study detected that serum levels of TARC correlated to serum levels of periostin (r = 0.54; p = 0.032). Furthermore,when evaluating correlations between serum and sputum levels, there was a correlation detected between TARC and periostinin serum, whereas this correlation was stronger in sputum: r = 0.66, p = 0.020; and r = 0.62, p = 0.028, respectively.CONCLUSION: Serum and sputum TARC and periostin may contribute for monitoring the improve", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33228831"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1609, "text": "OBJECTIVE: Periostin, a matricellular protein, is produced from airway epithelial cells and lung fibroblasts by IL-13. It has been suggested that periostin is involved in allergic inflammation and fibrosis. However, the usefulness of serum periostin measurement in the assessment of airway inflammation and remodeling and management of asthmatic patients is still debated. We aimed to determine whether serum periostin levels reflect eosinophilic airway inflammation and airway remodeling in asthma.METHODS: We examined the relationship of serum periostin levels with clinical features, biomarkers for eosinophilic airway inflammation, fraction of exhaled nitric oxide (FeNO) levels and blood eosinophil counts, and pulmonary functions in 235 well-controlled asthmatic patients on inhaled corticosteroids (ICS) treatment.RESULTS: Serum periostin levels were positively correlated with blood eosinophil counts (%) and age (r = 0.36 and 0.23, respectively), and were negatively correlated with body weight and FEV1/FVC (%) (r = -0.24 and - 0.23, respectively) in well-controlled asthmatic patients on ICS treatment (daily dose of 453\u00a0\u00b5g equivalent to fluticasone propionate). Blood eosinophil counts and serum periostin levels were similarly associated with increased FeNO levels (\u226540 ppb) in the asthmatics. Serum periostin levels were better associated with fixed airflow limitation (FEV1/FVC ratio <70%) than FeNO levels, blood eosinophil counts or total IgE levels in the asthmatics. Multivariate analysis showed that fixed airflow limitation was significantly associated with high serum periostin levels (\u2265", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29648484"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1206, "text": "Periostin and thymic stromal lymphopoietin (TSLP) are newly described markers of obstructive airway diseases and the mechanism by which both markers participate in immune response remains poorly understood. The aim of our study was to determine periostin and TSLP concentration in serum and induced sputum (IS) in patients with atopic asthma, chronic obstructive pulmonary disease (COPD), and controls, as well as to evaluate the potential link between periostin, TSLP, and Th2 immune response. Serum and IS levels of periostin, TSLP, IL-4, and IL-13 were determined in 12 atopic asthmatics, 16 COPD sufferers, and 10 controls. We noticed a significantly higher IS periostin and TSLP concentration at protein and mRNA level in asthmatics compared to the two other groups; additionally, periostin and TSLP were correlated positively with IS eosinophil count. A strong positive correlation between IS periostin and TSLP protein levels (r = 0.96) as well as mRNA expression level (r = 0.95) was found in patients with asthma. The results of our study show that periostin and TSLP are associated with eosinophilic airway inflammation and seem to be important drivers of atopic asthma but not COPD pathobiology.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33203095"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1728, "text": "BACKGROUND: Periostin has been shown to be a marker of Type 2 airway inflammation, associated with airway eosinophilia. It has a potential role in identifying asthmatics who may be responsive to treatment with monoclonal antibody therapy directed against Type 2 cytokines, such as interleukin (IL)-13, IL-4 receptor subunit-\u03b1 and immunoglobulin E. The clinical utility of periostin measurements depends on better understanding of factors that may affect serum periostin levels, such as race. We aimed to identify the ranges of serum periostin in Chinese adults both with and without asthma, and compare them with those previously identified in Caucasian adults.METHODS: A two-centred cross-sectional study, recruiting 188 Chinese adults, aged 18 to 75\u00a0years. 120 participants had no history of asthma or chronic obstructive pulmonary disease. 68 participants had a doctor's diagnosis of asthma and were on current treatment. Univariate comparisons of periostin by dichotomous variables were made using t-tests with logarithmic transformation as the distribution of periostin was skewed.RESULTS: In the Chinese non-asthma group, periostin levels were sex-, but not age-dependent, with females having higher periostin levels. The individual predicted (90% CI) reference range for periostin in females was 61.1\u00a0ng/ml (41.6 to 89.8) ng/ml and in males was 53.2\u00a0ng/ml (36.1 to 78.3) ng/ml. There was no difference in median serum periostin levels between Chinese non-asthmatics and Chinese asthmatics, 57.0 versus 56.8\u00a0ng/ml, difference (95% CI) 0.1 (-\u20094.2 to 4.2) ng/ml, P\u2009=\u20090.94. The median serum periostin levels were higher in Chinese non-asthmatics than Caucasian non-asthmatics, 57.0 versus 49.7\u00a0ng/ml, difference (95% CI) 8.2 ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30574168"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1976, "text": "The involvement of periostin in Th2-dependent allergic inflammation has been documented. However, the significance of periostin as a biomarker of local allergic inflammation in the nasal mucosa (NM) of patients with atopic bronchial asthma (BA) and allergic rhinitis (AR) is yet to be determined. The aim of the study was to determine the presence of periostin and evaluate its role as a non-invasive marker of allergic inflammation in the nasal secretions of children with atopic BA and AR.MATERIALS AND METHODS: In 43 patients aged 4-17 years with atopic BA and AR, the NM was examined using nasal video-endoscopy and (if indicated) computed tomography; the amount of periostin in the nasal secretion was determined by the enzyme immunoassay.RESULTS: Exacerbation of AR was accompanied by a statistically significant increase in the level of periostin in the nasal secretion: up to 0.84 [0.06; 48.79] ng/mg, whereas in remission, that was 0.13 [0.00; 0.36] ng/mg; p=0.04. This value increased progressively as the severity of AR increased from 0.16 [0.00; 0.36] ng/mg in the mild course to 0.20 [0.00; 9.03] ng/mg in AR of moderate severity, and to 10.70 [0.56; 769.20] ng/mg in most severe cases; p=0.048. Hypertrophy or polyposis of the nasal and/or paranasal mucosa was detected in 34.9% (15/43) of the examined patients. The concentration of periostin in the nasal secretion was lower in children without NM hypertrophy: 0.18 [0.001; 4.30] ng/mg vs 0.78 [0.13; 162.10] ng/mg in patients with NM hypertrophy; the differences were close to statistically significant: p=0.051. The level of nasal periostin depended on the clinical form of hypertrophy in the sinonasal mucosa, reaching 0.17 [0.00; 0.32] ng/mg in children with polyposis hyperplasia of NM and 21.6 [10.70; 1516.80] ng/mg - with hypertrophy of the NM in the medial surface of the concha; p=0.02.CONCLUSION: Exacerbation and increased severity of AR in patients with atopic BA are accompanied by an increased l", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34796003"}, {"offsetInBeginSection": 284, "offsetInEndSection": 1844, "text": "The serum level of periostin, an extracellular matrix protein activated by Th2 cytokines, is recognized as a biomarker for Th2-mediated eosinophilic asthma and contributes to enhanced airway inflammation and remodeling. However, the role of periostin in arsenic-related asthma is unknown. Therefore, this study was designed to explore the associations of serum periostin levels with arsenic exposure and the features of asthma in 442 individuals in Bangladesh who participated in our previous study. Exposure levels of the participants were determined by measuring the arsenic concentrations in drinking water, hair, and nails through inductively coupled plasma mass spectroscopy. Periostin levels in serum were assessed by immunoassay. In this study, we found that serum periostin levels of the participants were increased with increasing exposure to arsenic. Notably, even the participants with 10.1-50\u00a0\u03bcg/L arsenic in drinking water had significantly higher levels of periostin than participants with <10\u00a0\u03bcg/L of water arsenic. Elevated serum periostin levels were positively associated with serum levels of Th2 mediators, such as interleukin (IL)-4, IL-5, IL-13, and eotaxin. Each log increase in periostin levels was associated with approximately eight- and three-fold increases in the odds ratios (ORs) for reversible airway obstruction (RAO) and asthma symptoms, respectively. Additionally, causal mediation analyses revealed that arsenic exposure metrics had both direct and indirect (periostin-mediated) effects on the risk of RAO and asthma symptoms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35278445"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1063, "text": "Periostin, an extracellular matrix protein belonging to the fasciclin family, has been shown to play a critical role in the process of remodeling during tissue/organ development or repair. Periostin functions as a matricellular protein in cell activation by binding to their receptors on cell surface, thereby exerting its biological activities. After we found that periostin is a downstream molecule of interleukin (IL)-4 and IL-13, signature cytokines of type 2 immune responses, we showed that periostin is a component of subepithelial fibrosis in bronchial asthma, the first formal proof that periostin is involved in allergic inflammation. Subsequently, a great deal of evidence has accumulated demonstrating the significance of periostin in allergic inflammation. It is of note that in skin tissues, periostin is critical for amplification and persistence of allergic inflammation by communicating between fibroblasts and keratinocytes. Furthermore, periostin has been applied to development of novel diagnostics or therapeutic agents for allergic diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28942959"}, {"offsetInBeginSection": 0, "offsetInEndSection": 578, "text": "Periostin and dipeptidyl peptidase-4 (DPP-4) are proteins induced by type 2 cytokines interleukin (IL)-4 and IL-13 and show increased expression in asthma and diseases with type 2 inflammation, including atopic dermatitis and chronic rhinosinusitis. Both proteins can also be induced by other stimuli, such as profibrotic factors, which may confound their specificity as biomarkers of IL-13 pathway activation and type 2-driven disease. DPP-4 is important in glucose metabolism; therefore, serum concentrations may be confounded by the presence of concomitant metabolic disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30342583"}, {"offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "Periostin, a novel biomarker of TH2-driven asthma.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247042"}, {"offsetInBeginSection": 244, "offsetInEndSection": 373, "text": " This review focuses on the emerging data surrounding the use of one such biomarker for T helper 2 (TH2)-driven asthma: periostin", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247042"}, {"offsetInBeginSection": 244, "offsetInEndSection": 531, "text": " This review focuses on the emerging data surrounding the use of one such biomarker for T helper 2 (TH2)-driven asthma: periostin.RECENT FINDINGS: Periostin is an extracellular matrix protein that is induced by interleukin (IL)-4 and IL-13 in airway epithelial cells and lung fibroblasts", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247042"}, {"offsetInBeginSection": 91, "offsetInEndSection": 531, "text": " Biomarkers are currently being investigated to better characterize the disease phenotypes and to identify the responders to specific targeted therapies. This review focuses on the emerging data surrounding the use of one such biomarker for T helper 2 (TH2)-driven asthma: periostin.RECENT FINDINGS: Periostin is an extracellular matrix protein that is induced by interleukin (IL)-4 and IL-13 in airway epithelial cells and lung fibroblasts", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247042"}, {"offsetInBeginSection": 93, "offsetInEndSection": 388, "text": " The molecular phenotypes in asthma are Th2 high and Th2 low. Serum periostin is a biomarker which aid in understanding Th2 high eosinophilic asthma.AIM: The present study aimed to identify whether or not serum periostin is a systemic biomarker for eosinophilic airway inflammation in asthmatics", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27054127"}, {"offsetInBeginSection": 244, "offsetInEndSection": 662, "text": " This review focuses on the emerging data surrounding the use of one such biomarker for T helper 2 (TH2)-driven asthma: periostin.RECENT FINDINGS: Periostin is an extracellular matrix protein that is induced by interleukin (IL)-4 and IL-13 in airway epithelial cells and lung fibroblasts. It has proven to be an important biomarker of TH2-associated airway inflammation and a potential predictor of airway eosinophilia", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247042"}, {"offsetInBeginSection": 116, "offsetInEndSection": 269, "text": "Since periostin is associated with Th2 driven inflammation and inhaled corticosteroid (ICS)-response in asthma, it could function as a biomarker in COPD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29879994"}, {"offsetInBeginSection": 91, "offsetInEndSection": 373, "text": " Biomarkers are currently being investigated to better characterize the disease phenotypes and to identify the responders to specific targeted therapies. This review focuses on the emerging data surrounding the use of one such biomarker for T helper 2 (TH2)-driven asthma: periostin", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247042"}, {"offsetInBeginSection": 93, "offsetInEndSection": 241, "text": " The molecular phenotypes in asthma are Th2 high and Th2 low. Serum periostin is a biomarker which aid in understanding Th2 high eosinophilic asthma", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27054127"}, {"offsetInBeginSection": 245, "offsetInEndSection": 532, "text": "This review focuses on the emerging data surrounding the use of one such biomarker for T helper 2 (TH2)-driven asthma: periostin.RECENT FINDINGS: Periostin is an extracellular matrix protein that is induced by interleukin (IL)-4 and IL-13 in airway epithelial cells and lung fibroblasts.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247042"}, {"offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "BACKGROUND: Periostin is being investigated as a potential biomarker for T-helper-2 (Th2)-driven asthma or eosinophilic inflammation and may help to identify patients more likely to benefit from interleukin-13-targeted treatments.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27751727"}, {"offsetInBeginSection": 0, "offsetInEndSection": 594, "text": "BACKGROUND: Recent studies recommend periostin as a systemic biomarker of eosinophilic airway inflammation to predict responses to novel treatments that targets eosinophilic TH2-driven inflammation in asthmatic patients.OBJECTIVE: To investigate the clinical implications of serum periostin levels in patients with aspirin-exacerbated respiratory disease (AERD) based on its overlapping TH2-mediated pathogenesis with the eosinophilic asthma.METHODS: Serum periostin levels were measured by human periostin enzyme-linked immunosorbent assay (ELISA) in serum samples from 277 adults with asthma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25037608"}, {"offsetInBeginSection": 1303, "offsetInEndSection": 1616, "text": "Serum periostin had a sensitivity and specificity of 97.18% and 86.67% with a diagnostic accuracy of 94.06%.CONCLUSION: Serum periostin appears to be a more sensitive tool for detection of airflow limitation in asthmatic patients with a Th2 high eosinophilic phenotype when compared to AEC and sputum eosinophils.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27054127"}, {"offsetInBeginSection": 155, "offsetInEndSection": 472, "text": "Serum periostin is a biomarker which aid in understanding Th2 high eosinophilic asthma.AIM: The present study aimed to identify whether or not serum periostin is a systemic biomarker for eosinophilic airway inflammation in asthmatics.MATERIALS AND METHODS: The study was designed as a prospective, case control study.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27054127"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "BACKGROUND: Periostin has been suggested as a novel, phenotype-specific biomarker for asthma driven by type 2 inflammation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28398635"}, {"offsetInBeginSection": 356, "offsetInEndSection": 954, "text": "asthma: periostin.RECENT FINDINGS: Periostin is an extracellular matrix protein that is induced by interleukin (IL)-4 and IL-13 in airway epithelial cells and lung fibroblasts. It has proven to be an important biomarker of TH2-associated airway inflammation and a potential predictor of airway eosinophilia. It has also been shown to predict response to treatment with inhaled corticosteroids in patients with these characteristics. Furthermore, recent asthma clinical trials have established that serum periostin may have value in predicting the response to targeted therapy with biologic agents s", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247042"}, {"offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "BACKGROUND: Recent studies recommend periostin as a systemic biomarker of eosinophilic airway inflammation to predict responses to novel treatments that targets eosinophilic TH2-driven inflammation in asthmat", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25037608"}, {"offsetInBeginSection": 274, "offsetInEndSection": 508, "text": "Induced sputum cell count is the gold standard for identifying eosinophilic inflammation in asthma although several noninvasive biomarkers, including fractional exhaled nitric oxide and periostin, are emerging as potential surrogates.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24748808"}, {"offsetInBeginSection": 1307, "offsetInEndSection": 1807, "text": "A\u00a0logistic regression model, including sex, age, body mass index, IgE levels, blood eosinophil numbers, Feno levels, and serum periostin levels, in 59 patients with severe asthma showed that, of these indices, the serum periostin level was the single best predictor of airway eosinophilia (P\u00a0= .007).CONCLUSION: Periostin is a systemic biomarker of airway eosinophilia in asthmatic patients and has potential utility in\u00a0patient selection for emerging asthma therapeutics targeting\u00a0T(H)2 inflammation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22857879"}, {"offsetInBeginSection": 1450, "offsetInEndSection": 1792, "text": "In contrast, neither atopic status, control status of asthma, nor quality of life were related with the \"high-periostin\" phenotype.CONCLUSION: Elevated periostin concentrations in serum were correlated with a specific phenotype of eosinophilic asthma, late-onset and often complicated by obstructive pulmonary dysfunction and nasal disorders.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25838094"}, {"offsetInBeginSection": 116, "offsetInEndSection": 268, "text": "Since periostin is associated with Th2 driven inflammation and inhaled corticosteroid (ICS)-response in asthma, it could function as a biomarker in COPD", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29879994"}, {"offsetInBeginSection": 169, "offsetInEndSection": 305, "text": "Periostin, a biomarker that reflects Th2-driven inflammatory diseases such as asthma, may play an important role in the asthmatic airway", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29342461"}, {"offsetInBeginSection": 12, "offsetInEndSection": 229, "text": "Periostin is being investigated as a potential biomarker for T-helper-2 (Th2)-driven asthma or eosinophilic inflammation and may help to identify patients more likely to benefit from interleukin-13-targeted treatments", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27751727"}, {"offsetInBeginSection": 12, "offsetInEndSection": 220, "text": "Recent studies recommend periostin as a systemic biomarker of eosinophilic airway inflammation to predict responses to novel treatments that targets eosinophilic TH2-driven inflammation in asthmatic patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25037608"}, {"offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "BACKGROUND: Periostin is being investigated as a potential biomarker for T-helper-2 (Th2)-driven asthma or eosinophilic inflammation and may help to identify patients more likely to benefit from interleukin-13-targeted", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27751727"}, {"offsetInBeginSection": 284, "offsetInEndSection": 503, "text": "The serum level of periostin, an extracellular matrix protein activated by Th2 cytokines, is recognized as a biomarker for Th2-mediated eosinophilic asthma and contributes to enhanced airway inflammation and remodeling.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35278445"}, {"offsetInBeginSection": 356, "offsetInEndSection": 628, "text": "asthma: periostin.RECENT FINDINGS: Periostin is an extracellular matrix protein that is induced by interleukin (IL)-4 and IL-13 in airway epithelial cells and lung fibroblasts. It has proven to be an important biomarker of TH2-associated airway inflammation and a potentia", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247042"}, {"offsetInBeginSection": 750, "offsetInEndSection": 932, "text": "nse or adjustment and FeNO levels. Serum periostin is a strong serum biomarker for eosinophilic airway inflammation and an indicator of Th2-targeted therapy (such as lebrikizumab or ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24300416"}, {"offsetInBeginSection": 597, "offsetInEndSection": 853, "text": "serum periostin measurements by describing observations made in a KiHAC multicenter cohort with periostin used as a marker of pulmonary function decline and refractory Th2/eosinophilic inflammation in patients with asthma receiving long-term ICS treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24759559"}, {"offsetInBeginSection": 0, "offsetInEndSection": 753, "text": "PURPOSE OF REVIEW: Asthma is a heterogeneous disease with multiple, overlapping phenotypes. Biomarkers are currently being investigated to better characterize the disease phenotypes and to identify the responders to specific targeted therapies. This review focuses on the emerging data surrounding the use of one such biomarker for T helper 2 (TH2)-driven asthma: periostin.RECENT FINDINGS: Periostin is an extracellular matrix protein that is induced by interleukin (IL)-4 and IL-13 in airway epithelial cells and lung fibroblasts. It has proven to be an important biomarker of TH2-associated airway inflammation and a potential predictor of airway eosinophilia. It has also been shown to predict response to treatment with inhaled corticosteroids in p", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247042"}, {"offsetInBeginSection": 66, "offsetInEndSection": 839, "text": "phenotypes. Periostin, a molecule inducible with interleukin (IL)-4 or IL-13 in bronchial epithelial cells, is a biomarker of \"TH2-high\" asthma. The objective of this study is to examine whether the serum periostin concentrations are correlated with the severity, specific phenotype(s), or comorbidity of asthma.METHODS: Serum concentrations of periostin were measured in 190 Japanese asthmatic patients and 11 healthy controls. The protocol was registered under UMIN 000002980 in the clinical trial registry.RESULTS: The serum concentrations of periostin were significantly higher (P\u00a0=\u00a00.014) in asthmatics [70.0 (54.0-93.5)\u00a0ng/ml] than in healthy subjects [57.0 (39.0-63.0)\u00a0ng/ml], though we found no correlation between serum periostin concentrations and treatment steps", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25838094"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1642, "text": "BACKGROUND: Periostin has been suggested as a novel, phenotype-specific biomarker for asthma driven by type 2 inflammation. However, large studies examining relationships between circulating periostin and patient characteristics are lacking and the suitability of periostin as a biomarker in asthma remains unclear.AIM: To examine circulating periostin in healthy controls and subjects with asthma from the general population with different severity and treatment profiles, both with and without chronic rhinosinusitis (CRS), in relation to other biomarkers and clinical characteristics.METHODS: Serum periostin was examined by ELISA in 1100 subjects aged 17-76 from the Swedish Global Allergy and Asthma European Network (GA(2)LEN) study, which included 463 asthmatics with/without chronic rhinosinusitis (CRS), 98 individuals with CRS only, and 206 healthy controls. Clinical tests included measurement of lung function, Fraction of exhaled NO (FeNO), IgE, urinary eosinophil-derived neurotoxin (U-EDN), and serum eosinophil cationic protein (S-ECP), as well as completion of questionnaires regarding respiratory symptoms, medication, and quality of life.RESULTS: Although median periostin values showed no differences when comparing disease groups with healthy controls, multiple regression analyses revealed that periostin was positively associated with higher FeNO, U-EDN, and total IgE. In patients with asthma, an inverse relationship with lung function was also observed. Current smoking was associated with decreased periostin levels, whereas increased age and lower body mass index (BMI) related to higher periostin levels in subjec", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28398635"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1177, "text": "BACKGROUND: Periostin is being investigated as a potential biomarker for T-helper-2 (Th2)-driven asthma or eosinophilic inflammation and may help to identify patients more likely to benefit from interleukin-13-targeted treatments. We report the development and analytic performance of the investigational use only ARCHITECT Periostin Immunoassay, a new automated assay developed to detect serum periostin concentrations.METHODS: We assessed assay performance in terms of precision, sensitivity, linearity, interference from classical immunoassay interferents and representatives of common asthma medications, specimen handling, and isoform reactivity. The assay was also used to assess the biological variability of serum periostin concentrations in samples from healthy volunteers and from subjects with uncontrolled asthma (the intended use population).RESULTS: The percentage CVs for 5-day total precision, assessed using two instruments, was <6% across 2 controls and one serum-based panel. Limit of quantitation was 4ng/mL (dilution adjusted concentration), suiting the needs for this application. Dilution analysis yielded linear results and no endogenous sample or drug ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27751727"}, {"offsetInBeginSection": 0, "offsetInEndSection": 904, "text": "BACKGROUND: Recent studies recommend periostin as a systemic biomarker of eosinophilic airway inflammation to predict responses to novel treatments that targets eosinophilic TH2-driven inflammation in asthmatic patients.OBJECTIVE: To investigate the clinical implications of serum periostin levels in patients with aspirin-exacerbated respiratory disease (AERD) based on its overlapping TH2-mediated pathogenesis with the eosinophilic asthma.METHODS: Serum periostin levels were measured by human periostin enzyme-linked immunosorbent assay (ELISA) in serum samples from 277 adults with asthma. Serum periostin levels were compared between patients with AERD and aspirin tolerant asthma (ATA) with other asthma phenotypes, such as severe or nonsevere asthma and eosinophilic or noneosinophilic asthma. The association of serum periostin levels with clinical parameters (including disease severity and com", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25037608"}, {"offsetInBeginSection": 80, "offsetInEndSection": 1363, "text": "es of asthma. The molecular phenotypes in asthma are Th2 high and Th2 low. Serum periostin is a biomarker which aid in understanding Th2 high eosinophilic asthma.AIM: The present study aimed to identify whether or not serum periostin is a systemic biomarker for eosinophilic airway inflammation in asthmatics.MATERIALS AND METHODS: The study was designed as a prospective, case control study. Patients who presented with consistent symptoms of asthma and confirmed by spirometry with reversibility were the cases. The controls were healthy subjects who had no history of lung disease with normal lung function. The sputum and blood samples were collected from both the groups. Sputum eosinophils, Absolute Eosinophil Counts (AEC) and serum periostin levels were compared between the groups.RESULTS: The study comprised of 101 participants in which 30 were controls and 71 were cases. In the study group, mean post FEV1 was 64.45. There was a positive correlation of sputum eosinophils with severity of obstruction. The ROC curve analysis showed the cut-off value of 24.556 for serum periostin with the p-value of <0.001. As the severity of obstruction increased, the serum periostin levels were also found to be increased. Serum periostin had a sensitivity and specificity of 97.18% ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27054127"}, {"offsetInBeginSection": 116, "offsetInEndSection": 1046, "text": "Since periostin is associated with Th2 driven inflammation and inhaled corticosteroid (ICS)-response in asthma, it could function as a biomarker in COPD. The aim of this study was to analyze if serum periostin is elevated in COPD compared to healthy controls, if it is affected by smoking status, if it is linked to inflammatory cell counts in blood, sputum and endobronchial biopsies, and if periostin can predict ICS-response in COPD patients.Serum periostin levels were measured using Elecsys Periostin immunoassay. Correlations between periostin and inflammatory cell count in blood, sputum and endobronchial biopsies were analyzed. Additionally, the correlation between serum periostin levels and treatment responsiveness after 6 and 30\u00a0months was assessed using i.e. \u0394FEV1% predicted, \u0394CCQ score and \u0394RV/TLC ratio. Forty-five COPD smokers, 25 COPD past-smokers, 22 healthy smokers and 23 healthy never-smokers were included.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29879994"}, {"offsetInBeginSection": 157, "offsetInEndSection": 1634, "text": "rtant role. Periostin, a biomarker that reflects Th2-driven inflammatory diseases such as asthma, may play an important role in the asthmatic airway. Although periostin is mainly produced in airway epithelial cells and fibroblasts after interleukin (IL)-13 stimulation, whether BSM cells produce periostin remains unclear. Therefore, we investigated periostin production in BSM cells and the mechanisms involved.METHODS: Human BSM cells were cultured, and the effect of IL-13 stimulation on periostin production was evaluated using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). We evaluated the phosphorylation of signal transducer and activator of transcription factor 6 (STAT6), extracellular signal-regulated kinase (ERK)1/2, and Akt after IL-13 stimulation. Furthermore, using ELISA, we evaluated the influence of several phosphorylation inhibitors on periostin production.RESULTS: Periostin mRNA expression increased in a dose- and time-dependent manner after IL-13 stimulation; periostin production was induced 24 and 48 h after stimulation. IL-13 stimulation induced the phosphorylation of STAT6, ERK1/2, and Akt. IL-13-induced periostin production was attenuated by inhibiting STAT6 phosphorylation and strongly suppressed by inhibiting mitogen-activated protein kinase kinase 1/2 phosphorylation or phosphatidylinositol 3-kinase (PI3K) phosphorylation.CONCLUSIONS: BSM cells produced periostin after IL-13 stimulation, via the J", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29342461"}, {"offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "BACKGROUND: Periostin has been shown to be a marker of Type 2 airway inflammation, associated with airway e", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30574168"}, {"offsetInBeginSection": 266, "offsetInEndSection": 533, "text": "Since periostin is induced mainly by IL-4 and IL-13, signature type 2 cytokines, and it is highly expressed in the subepithelial regions of many chronic allergic diseases, periostin has emerged as a novel biomarker reflecting type 2 inflammation in allergic diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30964557"}, {"offsetInBeginSection": 1064, "offsetInEndSection": 1257, "text": "Serum periostin can reflect local production of periostin in inflamed lesions induced by Th2-type immune responses and also can predict the efficacy of Th2 antagonists against bronchial asthma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28942959"}, {"offsetInBeginSection": 154, "offsetInEndSection": 241, "text": " Serum periostin is a biomarker which aid in understanding Th2 high eosinophilic asthma", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27054127"}, {"offsetInBeginSection": 154, "offsetInEndSection": 471, "text": " Serum periostin is a biomarker which aid in understanding Th2 high eosinophilic asthma.AIM: The present study aimed to identify whether or not serum periostin is a systemic biomarker for eosinophilic airway inflammation in asthmatics.MATERIALS AND METHODS: The study was designed as a prospective, case control study", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27054127"}, {"offsetInBeginSection": 154, "offsetInEndSection": 388, "text": " Serum periostin is a biomarker which aid in understanding Th2 high eosinophilic asthma.AIM: The present study aimed to identify whether or not serum periostin is a systemic biomarker for eosinophilic airway inflammation in asthmatics", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27054127"}, {"offsetInBeginSection": 654, "offsetInEndSection": 944, "text": "Promising biomarkers are sputum eosinophils, serum periostin and exhaled nitric oxide. Periostin could differentiate between Th2-high and Th2-low asthma (Th2-high patients are more responsive to glucocorticoids) and the less-defined asthma types which often present a therapeutic challenge.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25479456"}]}
+{"question_id": "66168a89fdcbea915f000054", "question": "Burkitt lymphoma and Epstein-Barr virus.", "answer": "Burkitt lymphoma (BL) is a highly aggressive B-cell non-Hodgkin lymphoma, often associated with Epstein-Barr virus (EBV) infection. The three main clinical variants of BL are endemic, sporadic, and immunodeficiency-associated. The endemic variant is most common in equatorial Africa, where malaria is prevalent, and nearly all cases are EBV-positive. The sporadic variant is more common in North America and Europe, with a male-to-female ratio of 3:1 and approximately 20-30% of cases are EBV-positive. The immunodeficiency-associated variant is often seen in HIV-infected individuals and post-transplant patients, with a male-to-female ratio of 1:1 and a high prevalence of EBV infection (25-40%).\n\nThe primary oncogenic event in BL is the dysregulation of the c-myc gene by one of three chromosomal translocations, which place the myc gene under the control of an immunoglobulin gene enhancer. This translocation is found in 90% of BL cases. Additional mutations, such as TP53, ARF, USP7, and SIN3A mutations, are necessary for lymphoma development.\n\nEBV infection contributes to BL pathogenesis by promoting cellular growth through modification of normal signaling pathways and limiting apoptosis in cells with c-myc translocations. Malaria infection can further contribute to the development of endemic BL by causing genomic instability and promoting B-cell proliferation.\n\nDiagnosis of BL involves the detection of clonal rearrangements of immunoglobulin heavy chain genes and characteristic histopathological features. Treatment typically includes chemotherapy regimens, such as GMALL-B-ALL/NHL2002, modified Magrath, COPADM, hyper-CVAD, and CALGB 8811, which can be associated with rituximab. Prognosis is generally better for children, with a 90% overall cure rate in developed countries. However, outcomes are worse for adults, especially in cases of failed initial treatment or return of the disease.\n\nIn summary, EBV infection is a key factor in the pathogenesis of BL, particularly in the endemic variant, and malaria infection can further contribute to its development. The primary oncogenic event is the dysregulation of the c-myc gene, and additional mutations are necessary for lymphoma development. Diagnosis is based on the detection of clonal rearrangements of immunoglobulin heavy chain genes and characteristic histopathological features, and treatment typically includes chemotherapy regimens.", "relevant_passage_ids": ["37046794", "19165855", "19874382"], "type": "summary", "snippets": [{"offsetInBeginSection": 199, "offsetInEndSection": 458, "text": "Diseases linked to this virus include hematologic malignancies such as diffuse large B-cell lymphoma, Hodgkin lymphoma, Burkitt lymphoma, primary CNS lymphoma, and NK/T-cell lymphoma, epithelial malignancies such as nasopharyngeal carcinoma and gastric cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37046794"}, {"offsetInBeginSection": 557, "offsetInEndSection": 597, "text": "not all BL cases are associated with EBV", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19165855"}, {"offsetInBeginSection": 599, "offsetInEndSection": 841, "text": "about 95% of the cases in Central Africa, 40 to 50% of the cases in HIV-infected individuals and 10 to 20% of the sporadic cases harbour the viral information and express at least one viral antigen (EBNA1) and a number of non-coding viral RNA", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19165855"}, {"offsetInBeginSection": 1066, "offsetInEndSection": 1230, "text": "Although epidemiological evidence clearly points to a role of the virus in the African cases, the role of EBV in the pathogenesis of BL has remained largely elusive", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19165855"}, {"offsetInBeginSection": 676, "offsetInEndSection": 1001, "text": "the precise role of EBV in the carcinogenic process is currently poorly understood, the presence of the virus in all tumour cells provides opportunities for the development of novel therapeutic and diagnostic approaches. The study of EBV and its role in carcinomas continues to provide insights into the carcinogenic process ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19874382"}]}
+{"question_id": "663020de187cba990d00002c", "question": "What tumor suppressor genes are commonly affected by glioblastoma mutations or deletions?", "answer": "The etiology of glioblastoma multiforme (GBM), the most serious form of brain cancer, remains obscure, although it has been proposed that cancer risk is a function of random polymerase errors that occur during stem cell division and the resulting mutations in oncogenes and tumor suppressor genes. In particular, the most commonly affected tumor suppressor genes in GBM are p53, PTEN, p16/CDKN2, and RB, leading to activation of the PI3K/Akt and Ras/MAPK pathways, which provide targets for therapy.", "relevant_passage_ids": ["18726148", "8548755", "10079373", "30899826", "9426052", "9007876", "9690672", "10949938", "11083071", "9217972", "18381405", "33828082", "28464039", "30898893", "11549271", "28401302", "12580545", "29769617", "36031351", "30542515", "35203456", "17151929", "11051241", "9484844", "31151164", "10416987", "12175345", "14519639", "9591629", "9393744", "7887443", "9619835", "10433932", "23311918", "11563632", "21397855", "11964046", "11303623", "10653004", "15924253", "10328589", "22736234", "28856550", "19086579", "9622068", "12875726", "11941579", "30200436", "23798791", "18974105", "17456751", "10541865", "12005388"], "type": "list", "snippets": [{"offsetInBeginSection": 139, "offsetInEndSection": 287, "text": "Malignant gliomas commonly overexpress the oncogenes EGFR and PDGFR and contain mutations and deletions of the tumor suppressor genes PTEN and TP53.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18726148"}, {"offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "p16 is involved in a cell cycle regulatory cascade that includes cyclin-dependent kinase 4 (cdk4), cyclin D1, and pRb (retinoblastoma). Alterations of each of these components have been described in primary human glioblastoma multiforme (GBM) or in GBM cell lines.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8548755"}, {"offsetInBeginSection": 355, "offsetInEndSection": 475, "text": "we studied the relationship between abnormalities of CDKN2/p16 and RB, the two commonly involved tumor suppressor genes,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8548755"}, {"offsetInBeginSection": 1649, "offsetInEndSection": 1807, "text": "The findings also provide corroborative evidence that CDKN2/p16 and RB are the critical glioma tumor suppressor genes on chromosomes 9p and 13q, respectively.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8548755"}, {"offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "The genetic alterations frequently involved in glial malignancies are in the tumor suppressor genes, Rb and p53. An altered Rb expression or p53 overexpression is thought to indicate defective tumor suppression and subsequently more aggressive tumors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10079373"}, {"offsetInBeginSection": 0, "offsetInEndSection": 532, "text": "The etiology of glioblastoma multiforme (GBM), the most serious form of brain cancer, remains obscure, although it has been proposed that cancer risk is a function of random polymerase errors that occur during stem cell division and the resulting mutations in oncogenes and tumor suppressor genes. Analysis of the 8 genes (PTEN, TP53, EGFR, PIK3R1, PIK3CA, NF1, RB1, IDH1) that are mutated in at least 5% of GBM tumors indicates a non-random mutation pattern that reflects a significant role for hydrolytic deamination at CpG sites.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30899826"}, {"offsetInBeginSection": 288, "offsetInEndSection": 406, "text": "Some of these alterations lead to activation of the P13K/Akt and Ras/MAPK pathways, which provide targets for therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18726148"}, {"offsetInBeginSection": 0, "offsetInEndSection": 521, "text": "Gliomas are the most frequent primary tumors of central nervous system and represent a heterogeneous group of tumors that originates from the glial cells. TP53, PTEN, and CDKN2A are important tumor suppressor genes that encode proteins involved in sustaining cellular homeostasis by different signaling pathways. Though genetic alterations in these genes play a significant role in tumorigenesis, few studies are available regarding the incidence and relation of concomitant TP53, PTEN, and CDKN2A alterations in gliomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31151164"}, {"offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Frequent co-alterations of TP53, p16/CDKN2A, p14ARF, PTEN tumor suppressor genes in human glioma cell lines.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10416987"}, {"offsetInBeginSection": 303, "offsetInEndSection": 849, "text": "Mutations/deletions were found at the following frequencies: TP53 (76.5%), p14ARF (64.7%), p16 (64.7%), PTEN (73.5%). Thus, there was a high incidence of alterations in the cellular pathways involving the p53 transcription factor (94.1%), the retinoblastoma protein (64.7%) and the PTEN phosphatase (73.5%) and 91% of cell lines carried mutations in two or more pathways. This provides the first clear genetic evidence that these tumor suppressors participate in biological pathways which are functioning separately/independently in glioma cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10416987"}, {"offsetInBeginSection": 1255, "offsetInEndSection": 1384, "text": "These findings confirm that PTEN is one of the chromosome 10 tumor suppressor genes involved in the development of glioblastomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9619835"}, {"offsetInBeginSection": 129, "offsetInEndSection": 300, "text": "The PTEN (phosphatase, tensin homologue, deleted on chromosome TEN; MIM # 601728) tumor suppressor gene has an essential biological role in the formation of glioblastomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17151929"}, {"offsetInBeginSection": 180, "offsetInEndSection": 303, "text": "The tumor suppressor gene PTEN (MMAC1) on chromosome 10q23 is mutated in approximately 30% of glioblastomas (WHO Grade IV).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9690672"}, {"offsetInBeginSection": 862, "offsetInEndSection": 1017, "text": "The data suggest that a number of tumor suppressor genes on chromosome 10, in addition to PTEN/MMAC1, may be associated with astrocytic glioma development.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9591629"}, {"offsetInBeginSection": 375, "offsetInEndSection": 496, "text": "Here, we describe deletion of the p18(INK4c) cdk inhibitor as a novel genetic alteration driving the pathogenesis of GBM.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18381405"}, {"offsetInBeginSection": 559, "offsetInEndSection": 668, "text": "By using comparative multiplex PCR, homozygous deletions of the CDKN2/p16 gene were detected in 24 GBMs (57%)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8548755"}, {"offsetInBeginSection": 229, "offsetInEndSection": 370, "text": "Mutational inactivation of PTEN has been reported in various malignancies, including endometrial cancers, ovarian cancers, and glioblastomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11964046"}, {"offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "PTEN/MMAC1 (phosphatase and tensin homolog/mutated in multiple advanced cancers 1) is a tumor suppressor gene, the inactivation of which is an important step in the progression of gliomas to end-stage glioblastoma multiforme.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11303623"}, {"offsetInBeginSection": 439, "offsetInEndSection": 631, "text": "Loss of heterozygosity (LOH) on chromosome 10 (LOH#10) is the most frequent genetic alteration in glioblastomas; the involvement of tumor suppressor genes, other than PTEN, has been suggested.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10653004"}, {"offsetInBeginSection": 100, "offsetInEndSection": 236, "text": "Loss of heterozygosity of chromosome 10 and mutations in the tumor suppressor gene PTEN on 10q are molecular hallmarks of glioblastomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15924253"}, {"offsetInBeginSection": 582, "offsetInEndSection": 740, "text": "PTEN mutations were detected in 20/142 glioblastomas, 1/7 giant cell glioblastomas, 1/2 gliosarcomas, 1/30 pilocytic astrocytomas and 2/22 oligodendrogliomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9619835"}, {"offsetInBeginSection": 144, "offsetInEndSection": 357, "text": "We recently reported that PTEN (MMAC1) on 10q23.3 is mutated in approximately 30% of primary (de novo) glioblastomas but rarely in secondary glioblastomas that progressed from low-grade or anaplastic astrocytomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10433932"}, {"offsetInBeginSection": 1532, "offsetInEndSection": 1648, "text": "These data indicate that the vast majority of GBMs probably have inactivation of the p16-cdk4/cyclin D1-pRb pathway.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8548755"}]}
+{"question_id": "6630211d187cba990d00002d", "question": "Is there an association between specific genotypes and the risk of ASD for Duchenne Muscular Dystrophy?", "answer": "No, further research is needed regarding the association of DMD genotypes and ASD.", "relevant_passage_ids": ["36565132"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1585, "offsetInEndSection": 1665, "text": " Further research is needed regarding Dp140 and Dp71, especially in DMD for ASD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36565132"}, {"offsetInBeginSection": 1211, "offsetInEndSection": 1346, "text": "However, there was no association of genotype with ASD, only a trend was observed for Dp71+ vs. Dp71-, with a PR of 0.61 (0.35, 1.06). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36565132"}]}
+{"question_id": "65d144b81930410b13000041", "question": "Coffee Bean Sign is characteristic to which disease?", "answer": "Coffee Bean Sign is characteristic to volvulus.", "relevant_passage_ids": ["35773776", "36779459", "37761402", "36263824", "36168370", "35859918", "33088563", "18322966", "28626382", "20028915"], "type": "factoid", "snippets": [{"offsetInBeginSection": 1020, "offsetInEndSection": 1669, "text": ". In addition, X-ray signs including disproportionate sigmoid dilatation, distended inverted 'U' in sigmoid, coffee bean sign, opposed wall sign, direction of apex of sigmoid loop, liver overlap sign, northern exposure sign and proximal colonic dilatation and CT features including whirl sign, 'X' marks the spot sign, split wall sign and number of transition points were reported for each case. The clinical management and outcomes including morbidity, mortality, endoscopic decompression and need for surgery were also evaluated. The subtype of volvulus was correlated with the above X-ray signs, CT features and clinical management and outcomes. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35773776"}, {"offsetInBeginSection": 396, "offsetInEndSection": 441, "text": "Coffee bean sign was seen in abdominal x-ray.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36779459"}, {"offsetInBeginSection": 0, "offsetInEndSection": 746, "text": "Sigmoid volvulus (SV) occurs rarely in children. After encountering two cases of recurrent SV, we reviewed the literature to define the recurrence risk, identify outcome predictors and to give treatment recommendations. We found 256 cases reported in children (mean age 10.2 years, gender ratio (m:f) 2.3:1). Associations exist with Hirschsprung disease (HD) in 10%, neurodevelopmental disorders in 10.9% and chronic constipation in 10.2%. Common symptoms and clinical signs were abdominal pain (85%), distension (85%), tenderness (54%) and vomiting (59%). Signs of peritonitis were present in 14% and indicated a gangrenous sigmoid (X2 = 45.33; p < 0.001). A total of 183 had abdominal radiographs, and 65% showed a positive 'coffee-bean-sign'. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37761402"}, {"offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Coffee bean sign, steel pan sign, and whirl sign in sigmoid volvulus.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36263824"}, {"offsetInBeginSection": 55, "offsetInEndSection": 249, "text": "A plain radiograph showed the coffee bean sign, suggesting sigmoid volvulus (SV). The CT scans disclosed the steel pan sign, the whirl sign, and the beak-shaped transition point, confirming SV. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36263824"}, {"offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Teaching Point: The coffee bean sign, the whirl sign, and the bird's beak sign are the key findings on abdominal CT of cecal volvulus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35859918"}, {"offsetInBeginSection": 55, "offsetInEndSection": 135, "text": "A plain radiograph showed the coffee bean sign, suggesting sigmoid volvulus (SV)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36263824"}, {"offsetInBeginSection": 55, "offsetInEndSection": 307, "text": "A plain radiograph showed the coffee bean sign, suggesting sigmoid volvulus (SV). The CT scans disclosed the steel pan sign, the whirl sign, and the beak-shaped transition point, confirming SV. He improved with colonoscopic decompression and detorsion.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36263824"}, {"offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "The presence of the coffee bean sign is pathognomonic of sigmoid volvulus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33088563"}, {"offsetInBeginSection": 585, "offsetInEndSection": 941, "text": "CT findings suggesting bowel compromise were compared with pathologic and endoscopic findings.RESULTS: The most sensitive scanogram findings were absence of rectal gas (19 of 21 cases, 90%) and an inverted-U-shaped distended sigmoid (18 of 21 cases, 86%) followed by the coffee bean sign and disproportionate sigmoid enlargement (both 16 of 21 cases, 76%).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20028915"}, {"offsetInBeginSection": 836, "offsetInEndSection": 1055, "text": "Preterm labor, specific prenatal sonographic findings (for example, the coffee bean sign) and bluish discoloration of the abdominal wall could suggest intrauterine midgut volvulus requiring prompt surgical intervention.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18322966"}, {"offsetInBeginSection": 503, "offsetInEndSection": 589, "text": "A plain abdominal X-ray demonstrated a coffee bean sign indicating a sigmoid volvulus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28626382"}, {"offsetInBeginSection": 55, "offsetInEndSection": 136, "text": "A plain radiograph showed the coffee bean sign, suggesting sigmoid volvulus (SV).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36263824"}, {"offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "A Symptomatic Coffee Bean: Acute Sigmoid Volvulus.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28626382"}, {"offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "A 66-year-old man presented with abdominal distension. A plain radiograph showed the coffee bean sign, suggesting sigmoid volvulus (SV).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36263824"}, {"offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "A 66-year-old man presented with abdominal distension. A plain radiograph showed the coffee bean sign, suggesting sigmoid volvulus (SV). The CT scans disclosed the steel pan sign, the whirl sign, and the beak-shaped transition point, confirming SV.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36263824"}, {"offsetInBeginSection": 55, "offsetInEndSection": 248, "text": "A plain radiograph showed the coffee bean sign, suggesting sigmoid volvulus (SV). The CT scans disclosed the steel pan sign, the whirl sign, and the beak-shaped transition point, confirming SV.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36263824"}, {"offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Intrauterine midgut volvulus without malrotation: diagnosis from the 'coffee bean sign'.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18322966"}]}
+{"question_id": "662fc351187cba990d000014", "question": "What role does epiregulin and amphiregulin play in the use of EGFR inhibitors for colorectal cancer?", "answer": "High tumor levels of the EGFR ligands amphiregulin (AREG) and epiregulin (EREG) are associated with anti-EGFR agent response in metastatic colorectal cancer (mCRC).  AREG and EREC are biomarkers of response to EGFR inhibitors.", "relevant_passage_ids": ["17664471", "33888518", "23885463", "23959273", "30252132", "26867820", "33775193", "19663767", "32943459", "27344184", "19738126", "37363997", "27422777", "27570430", "27272216", "32533590", "34884633", "37594733", "25053989", "31519572", "34893673", "22409860", "20631481"], "type": "summary", "snippets": [{"offsetInBeginSection": 1471, "offsetInEndSection": 1660, "text": " Patients with tumors that have high gene expression levels of epiregulin and amphiregulin and patients with wild-type K-ras are more likely to have disease control on cetuximab treatment. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17664471"}, {"offsetInBeginSection": 9, "offsetInEndSection": 176, "text": "High tumor mRNA levels of the EGFR ligands amphiregulin (AREG) and epiregulin (EREG) are associated with anti-EGFR agent response in metastatic colorectal cancer (mCRC", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33888518"}, {"offsetInBeginSection": 9, "offsetInEndSection": 305, "text": "The antiepidermal growth factor receptor (EGFR) antibody cetuximab shows activity in multiple epithelial tumor types; however, responses are seen in only a subset of patients. This study was conducted to identify markers that are associated with disease control in patients treated with cetuximab", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17664471"}, {"offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "Amphiregulin Expression Is a Predictive Biomarker for ", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32943459"}, {"offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Expression of the epidermal growth factor ligands amphiregulin (AREG) and epiregulin (EREG) is positively correlated with a response to EGFR-targeted therapies in colorectal cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30252132"}, {"offsetInBeginSection": 380, "offsetInEndSection": 547, "text": "First, upstream molecules, including epiregulin (EREG) and amphiregulin (AREG), might play different roles according to their abnormal levels in tumor tissue and serum", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27422777"}, {"offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Prognostic and predictive biomarkers in metastatic colorectal cancer anti-EGFR therapy.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27570430"}, {"offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Epidermal growth factor receptor (EGFR) and its ligands amphiregulin (AREG) and epiregulin (EREG) play a central role in the development of colorectal cancer, but the prognostic values of AREG and EREG are controversial", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27344184"}, {"offsetInBeginSection": 12, "offsetInEndSection": 263, "text": "High EREG and AREG expression, and left-sided primary tumours are associated with superior efficacy of anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer (CRC), but a unifying explanation of these findings is lacking.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27272216"}, {"offsetInBeginSection": 0, "offsetInEndSection": 390, "text": "Overexpression of the EGFR ligands amphiregulin (AREG)/epiregulin (EREG) may be a surrogate of EGFR dependency regardless of sidedness in metastatic colorectal cancer. High AREG/EREG may be coupled with negative hyper-selection (i.e., lack of genomic drivers of primary resistance beyond RAS and BRAF) to identify patients with right-sided tumors and potential sensitivity to EGFR blockade.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37594733"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1003, "text": "Expression of the epidermal growth factor ligands amphiregulin (AREG) and epiregulin (EREG) is positively correlated with a response to EGFR-targeted therapies in colorectal cancer. Gene-body methylation sites, which show a strong inverse correlation with AREG and EREG gene expression, were identified in cell lines using targeted 454 FLX-bisulfite sequencing and SIRPH analyses for AREG/EREG promoters and intragenic CpGs. Upon treatment of colorectal cancer cells with 5-aza-2'-desoxycytidine, methylation decreases at specific intragenic CpGs accompanied by upregulation of AREG and EREG gene expression. The same AREG gene-body methylation was also found in human colorectal cancer samples and is independent of KRAS and NRAS mutations. Methylation is specifically decreased in the tumor epithelial compartment as compared to stromal tissue and normal epithelium. Investigation of a promoter/enhancer function of the AREG exon 2 region revealed a potential promoter function in reverse orientation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30252132"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1477, "text": "PURPOSE: Amphiregulin (AREG) and epiregulin (EREG) are ligands of EGFR. Predictive information for anti-EGFR treatment in metastatic colorectal cancer (mCRC) was observed, but data for other agents is limited.EXPERIMENTAL DESIGN: Ligand mRNA expression; RAS, BRAF, PIK3CA mutations; and EGFR expression were assessed by qRT-PCR, pyrosequencing, and IHC, respectively, in mCRC tumor tissue of patients participating in the randomized controlled trials FIRE-1, CIOX, and FIRE-3. Normalized mRNA expression was dichotomized using median and third quartile. Overall (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier method including univariate and multivariate Cox regression analyses. Penalized spline regression analysis tested interaction of mRNA expression and outcome.RESULTS: Of 688 patients with available material, high AREG expression was detected in 343 (>median) and 172 (>3rd quartile) patients. High AREG expression was associated with significantly higher OS [26.2 vs. 21.5 months, HR = 0.80; 95% confidence interval (CI), 0.68-0.94; P = 0.007], PFS (10.0 vs. 8.1 months, HR = 0.74; 95% CI, 0.63-0.86; P = 0.001), and objective response rate (63.1% vs. 51.6%, P = 0.004) compared to low expression at both threshold values. This effect remained significant in multivariate Cox regression analysis (OS: P = 0.01, PFS: P = 0.002). High AREG mRNA expression interacted significantly with the efficacy of cetuximab compared with bevacizumab (OS: P =", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32943459"}, {"offsetInBeginSection": 0, "offsetInEndSection": 662, "text": "For patients with metastatic colorectal cancer (mCRC), epidermal growth factor receptor (EGFR) inhibitors are limited to patients with RAS wild-type tumours. Not all patients will benefit from treatment and better predictive biomarkers are needed. Here we investigated the prognostic and predictive impact of the EGFR ligands amphiregulin (AREG) and epiregulin (EREG). Expression levels were assessed by immunohistochemistry on 99 KRAS wild-type tumours. AREG and EREG positivity was seen in 49% and 50% of cases, respectively. No difference in expression was observed by primary tumour side. There was no significant difference in OS by AREG or EREG expression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33775193"}, {"offsetInBeginSection": 0, "offsetInEndSection": 992, "text": "BACKGROUND/AIM: Amphiregulin (AREG) and epiregulin (EREG) mRNA expression levels are predictors of response to anti-EGFR antibody therapy. Left-sided colon cancer is more sensitive to anti-EGFR antibodies than right-sided, although the mechanism is unclear. The aim of this study was to determine the relationship between AREG, EREG mRNA expression levels and tumor location as well as the efficacy of anti-EGFR antibody agents.MATERIALS AND METHODS: Real-time PCR was used to assess AREG and EREG mRNA expression in metastatic colorectal cancer (CRC) samples from 153 patients.RESULTS: Among KRASwt samples, high AREG expression (AREGHigh) was significantly more common in left-sided tumors than in right-sided. Among patients who received anti-EGFR antibody, response rates were significantly higher in AREGHigh than in AREGLow In the left-sided tumor group, overall survival was significantly longer in patients with high EREG levels than with low levels, whereas the right-sided tumor gro", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31519572"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1243, "text": "Amphiregulin (AREG) is an epidermal growth factor receptor (EGFR) ligand. The aim of this study was to investigate the effects of baseline plasma AREG levels in KRAS, NRAS, and BRAF wild-type metastatic colorectal cancer (CRC) on treatment outcome with palliative first-line cetuximab\u2009+\u2009FOLFIRI chemotherapy. Chemotherapy outcomes were analyzed based on baseline plasma AREG levels. The clinical findings were further validated using an in vitro model of CRC. Among 35 patients, the progression-free survival (PFS) was significantly inferior in patients with high AREG than in those with low AREG levels: 10.9 vs. 24.2\u00a0months, respectively (p\u2009=\u20090.008). However, after failure of first-line chemotherapy, AREG levels were associated with neither PFS (4.8 vs. 11.6\u00a0months; p\u2009=\u20090.215) nor overall survival (8.4 vs. 13.3\u00a0months; p\u2009=\u20090.975). In SNU-C4 and Caco-2 cells which were relatively sensitive to cetuximab among the seven CRC cell lines tested, AREG significantly decreased the anti-proliferative effect of cetuximab (p\u2009<\u20090.05) via AKT and ERK activation. However, after acquiring cetuximab resistance with gradual exposure for more than 6\u00a0months, AREG neither increased colony formation nor activated AKT and ERK after cetuximab treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34893673"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1596, "text": "PURPOSE: High tumor production of the EGFR ligands, amphiregulin (AREG) and epiregulin (EREG), predicted benefit from anti-EGFR therapy for metastatic colorectal cancer (mCRC) in a retrospective analysis of clinical trial data. Here, AREG/EREG IHC was analyzed in a cohort of patients who received anti-EGFR therapy as part of routine care, including key clinical contexts not investigated in the previous analysis.EXPERIMENTAL DESIGN: Patients who received panitumumab or cetuximab \u00b1 chemotherapy for treatment of RAS wild-type mCRC at eight UK cancer centers were eligible. Archival formalin-fixed paraffin-embedded tumor tissue was analyzed for AREG and EREG IHC in six regional laboratories using previously developed artificial intelligence technologies. Primary endpoints were progression-free survival (PFS) and overall survival (OS).RESULTS: A total of 494 of 541 patients (91.3%) had adequate tissue for analysis. A total of 45 were excluded after central extended RAS testing, leaving 449 patients in the primary analysis population. After adjustment for additional prognostic factors, high AREG/EREG expression (n = 360; 80.2%) was associated with significantly prolonged PFS [median: 8.5 vs. 4.4 months; HR, 0.73; 95% confidence interval (CI), 0.56-0.95; P = 0.02] and OS [median: 16.4 vs. 8.9 months; HR, 0.66 95% CI, 0.50-0.86; P = 0.002]. The significant OS benefit was maintained among patients with right primary tumor location (PTL), those receiving cetuximab or panitumumab, those with an oxaliplatin- or irinotecan-based chemotherapy backbone, and those with tumor tissue obta", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37363997"}, {"offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Epidermal growth factor receptor (EGFR) and its ligands amphiregulin (AREG) and epiregulin (EREG) play a central role in the development of colorectal cancer, but the prognostic values of AREG and EREG are controversial.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27344184"}, {"offsetInBeginSection": 0, "offsetInEndSection": 401, "text": "Epidermal growth factor receptor (EGFR) and its ligands amphiregulin (AREG) and epiregulin (EREG) play a central role in the development of colorectal cancer, but the prognostic values of AREG and EREG are controversial. We conducted a meta-analysis of studies that investigated AREG and/or EREG mRNA levels in primary tumors to determine their prognostic value in metastatic colorectal cancer (mCRC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27344184"}, {"offsetInBeginSection": 0, "offsetInEndSection": 439, "text": "Epidermal growth factor receptor (EGFR) and its ligands amphiregulin (AREG) and epiregulin (EREG) play a central role in the development of colorectal cancer, but the prognostic values of AREG and EREG are controversial. We conducted a meta-analysis of studies that investigated AREG and/or EREG mRNA levels in primary tumors to determine their prognostic value in metastatic colorectal cancer (mCRC). In addition, RAS status was assessed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27344184"}, {"offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Expression of the epidermal growth factor ligands amphiregulin (AREG) and epiregulin (EREG) is positively correlated with a response to EGFR-targeted therapies in colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30252132"}, {"offsetInBeginSection": 0, "offsetInEndSection": 410, "text": "In the epidermal growth factor receptor (EGFR) pathway, polymorphisms in EGFR and its ligand EGF have been studied as biomarkers for anti-EGFR treatment. However, the potential pharmacogenetic role of other EGFR ligands such as amphiregulin (AREG) and epiregulin (EREG) has not been elucidated. We studied 74 KRAS and BRAF wild-type metastatic colorectal cancer patients treated with anti-EGFR plus irinotecan.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23959273"}, {"offsetInBeginSection": 0, "offsetInEndSection": 424, "text": "Expression of the epidermal growth factor ligands amphiregulin (AREG) and epiregulin (EREG) is positively correlated with a response to EGFR-targeted therapies in colorectal cancer. Gene-body methylation sites, which show a strong inverse correlation with AREG and EREG gene expression, were identified in cell lines using targeted 454 FLX-bisulfite sequencing and SIRPH analyses for AREG/EREG promoters and intragenic CpGs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30252132"}, {"offsetInBeginSection": 0, "offsetInEndSection": 608, "text": "Expression of the epidermal growth factor ligands amphiregulin (AREG) and epiregulin (EREG) is positively correlated with a response to EGFR-targeted therapies in colorectal cancer. Gene-body methylation sites, which show a strong inverse correlation with AREG and EREG gene expression, were identified in cell lines using targeted 454 FLX-bisulfite sequencing and SIRPH analyses for AREG/EREG promoters and intragenic CpGs. Upon treatment of colorectal cancer cells with 5-aza-2'-desoxycytidine, methylation decreases at specific intragenic CpGs accompanied by upregulation of AREG and EREG gene expression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30252132"}, {"offsetInBeginSection": 154, "offsetInEndSection": 410, "text": "However, the potential pharmacogenetic role of other EGFR ligands such as amphiregulin (AREG) and epiregulin (EREG) has not been elucidated. We studied 74 KRAS and BRAF wild-type metastatic colorectal cancer patients treated with anti-EGFR plus irinotecan.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23959273"}, {"offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "In the epidermal growth factor receptor (EGFR) pathway, polymorphisms in EGFR and its ligand EGF have been studied as biomarkers for anti-EGFR treatment. However, the potential pharmacogenetic role of other EGFR ligands such as amphiregulin (AREG) and epiregulin (EREG) has not been elucidated.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23959273"}, {"offsetInBeginSection": 609, "offsetInEndSection": 741, "text": "The same AREG gene-body methylation was also found in human colorectal cancer samples and is independent of KRAS and NRAS mutations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30252132"}, {"offsetInBeginSection": 943, "offsetInEndSection": 1085, "text": "In addition, high mRNA levels of the EGFR-ligands Epiregulin and Amphiregulin have been associated with increased responsiveness to cetuximab.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19663767"}, {"offsetInBeginSection": 1004, "offsetInEndSection": 1291, "text": "Retrospective comparison of the predictive power of AREG gene-body methylation versus AREG gene expression using samples from colorectal cancer patients treated with anti-EGFR inhibitors with complete clinical follow-up revealed that AREG expression is superior to AREG gene methylation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30252132"}, {"offsetInBeginSection": 176, "offsetInEndSection": 982, "text": "RNA expression of EGFR ligands epiregulin (EREG) and amphiregulin (AREG) may correlate with EGFR-targeted therapy efficacy in aCRC, so may represent a much-needed additional predictive marker for these drugs.OBJECTIVE: To examine a novel ligand model in a randomized clinical trial of panitumumab, irinotecan, and ciclosporin in colorectal cancer (PICCOLO) with with the a priori hypothesis that high tumor expression of either AREG or EREG would predict panitumumab therapy benefit in RAS-wt patients; and low expression, lack of efficacy.DESIGN, SETTING, AND PARTICIPANTS: Prospectively planned retrospective biomarker study from the PICCOLO trial, which tested the addition of panitumumab to irinotecan therapy in patients with KRAS wt aCRC who experienced failure with prior fluoropyrimidine treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26867820"}, {"offsetInBeginSection": 0, "offsetInEndSection": 480, "text": "PURPOSE: To study the power of the epidermal growth factor receptor (EGFR) epiregulin (EREG) and amphiregulin (AREG) ligands' expression in primary tumors to predict the outcome in patients with chemorefractory metastatic colorectal cancer (cmCRC) treated with the combination of cetuximab and irinotecan.PATIENTS AND METHODS: Gene expression measurements and KRAS mutation analysis were performed on archival formalin-fixed paraffin-embedded primary tumors of 220 cmCRC patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19738126"}, {"offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "PURPOSE: Amphiregulin (AREG) and epiregulin (EREG) are ligands of EGFR. Predictive information for ant", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32943459"}, {"offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "BACKGROUND: Amphiregulin (AREG) and Epiregulin (EREG), ligands of EGFR, are reported to be predictive biomarkers of colorectal cancer patients treated with Cetuximab, an anti-EG", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22409860"}, {"offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "For patients with metastatic colorectal cancer (mCRC), epidermal growth factor receptor (EGFR) inhibitors are limited to patients with RAS wild-type tumours.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33775193"}, {"offsetInBeginSection": 893, "offsetInEndSection": 1075, "text": "Our findings support that intergenic polymorphisms in the AREG gene region might help to identify colorectal cancer patients that will benefit from irinotecan plus anti-EGFR therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23959273"}, {"offsetInBeginSection": 597, "offsetInEndSection": 745, "text": "By contrast, the resistance of anti-EGFR therapy in CRC was driven by low EREG expression, aberrant genetic mutation and signal pathway alterations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34884633"}, {"offsetInBeginSection": 889, "offsetInEndSection": 1012, "text": "In RAS wild-type (WT) patients who received anti-EGFR therapy, high AREG and EREG expression was associated with longer OS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27344184"}, {"offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "BACKGROUND/AIM: Amphiregulin (AREG) and epiregulin (EREG) mRNA expression levels are predictors of response to anti-EGFR a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31519572"}, {"offsetInBeginSection": 552, "offsetInEndSection": 731, "text": "samples from 153 patients.RESULTS: Among KRASwt samples, high AREG expression (AREGHigh) was significantly more common in left-sided tumors than in right-sided. Among patients who", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31519572"}, {"offsetInBeginSection": 0, "offsetInEndSection": 888, "text": "Epidermal growth factor receptor (EGFR) and its ligands amphiregulin (AREG) and epiregulin (EREG) play a central role in the development of colorectal cancer, but the prognostic values of AREG and EREG are controversial. We conducted a meta-analysis of studies that investigated AREG and/or EREG mRNA levels in primary tumors to determine their prognostic value in metastatic colorectal cancer (mCRC). In addition, RAS status was assessed. Relevant articles were identified by searching the EMBASE, PubMed, and Cochrane Library databases. Hazard ratios (HR) with 95% confidence intervals (CIs) were calculated using a random-effects model. Nine studies involving 2167 patients were included in this meta-analysis. High AREG expression was associated with longer overall survival (OS) and progression-free survival (PFS). High EREG expression was also associated with prolonged OS and PFS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27344184"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1527, "text": "BACKGROUND: Amphiregulin (AREG) and Epiregulin (EREG), ligands of EGFR, are reported to be predictive biomarkers of colorectal cancer patients treated with Cetuximab, an anti-EGFR antibody. The purpose of this study is to determine the correlation of AREG and EREG expression between primary colorectal cancer and corresponding liver metastases.METHODS: One hundred twenty colorectal cancer patients with liver metastases (100 with synchronous metastases, 20 with metachronous) were evaluated. No patients had ever received anti-EGFR antibody agents. AREG and EREG mRNA expression from both the primary tumor and liver metastases were measured using real-time RT-PCR. KRAS codon 12, 13 mutation status was analyzed by direct sequencing.RESULTS: Modest, but significant, correlations were observed between primary tumor and corresponding liver metastases in both AREG mRNA expression (Rs = 0.54, p < 0.0001) and EREG mRNA expression (Rs = 0.58, p < 0.0001). AREG and EREG mRNA expression was strongly correlated in both the primary tumor (Rs = 0.81, p < 0.0001) and the liver metastases (Rs = 0.87, p < 0.0001). No significant survival difference was observed between low and high AREG or EREG patients when all 120 patients were analyzed. However, when divided by KRAS status, KRAS wild-type patients with low EREG mRNA levels in the primary site showed significantly better overall survival rates than those with high levels (p = 0.018). In multivariate analysis, low EREG expression was significantly associated with better o", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22409860"}, {"offsetInBeginSection": 0, "offsetInEndSection": 972, "text": "Anti-epidermal growth factor receptor (EGFR) therapy has established efficacy in metastatic colorectal cancer, but a significant number of patients do not respond to such treatment. Recently, various biomarkers were reported to be useful in predicting resistance to anti-EGFR. All the potential biomarkers predicting resistance to anti-EGFR are reviewed herein from five aspects. First, upstream molecules, including epiregulin (EREG) and amphiregulin (AREG), might play different roles according to their abnormal levels in tumor tissue and serum. Second, the EGFR amplification and distinct polymorphisms may have roles in identifying patients for initial anti-EGFR mAbs therapy, while rare EGFR mutations have limited predictive values. Third, among the downstream molecularly related factors, rat sarcoma viral oncogene (Ras) has been identified as a successful predictor, while B-Raf proto-oncogene (BRAF) is considered as a prognostic factor rather than a predictor.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27422777"}, {"offsetInBeginSection": 0, "offsetInEndSection": 990, "text": "BACKGROUND: Amphiregulin (AREG) and epiregulin (EREG) have been found to play pivotal roles in several malignancies. However, the correlation between their expression and clinicopathological factors in colorectal carcinoma (CRC) is yet to be further investigated. To clarify the clinical significance of AREG and EREG expression in CRC, we detected serum and tissue levels of AREG and EREG.PATIENTS AND METHODS: We detected serum AREG and EREG levels by ELISA, and tissue levels by immunohistochemical test in 73 patients with CRC. The correlation between each independent clinicopathological characteristic and AREG and EREG levels was examined.RESULTS: There was significant correlation between serum AREG level and vascular invasion. There was no correlation between EREG serum level and any clinicopathological characteristics. Among the 73 primary lesions, 51 were AREG-positive, and 48 were EREG-positive. AREG-positive status was significantly correlated with depth of tumor invasion", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20631481"}, {"offsetInBeginSection": 154, "offsetInEndSection": 892, "text": "However, the potential pharmacogenetic role of other EGFR ligands such as amphiregulin (AREG) and epiregulin (EREG) has not been elucidated. We studied 74 KRAS and BRAF wild-type metastatic colorectal cancer patients treated with anti-EGFR plus irinotecan. Twenty-two genetic variants in EGFR, EGF, AREG and EREG genes were selected using HapMap database and literature resources. Three tagging single-nucleotide polymorphisms in the AREG gene region (rs11942466 C>A, rs13104811 A>G, and rs9996584 C>T) predicted disease control in the multivariate analyses. AREG rs11942466 C>A and rs9996584 C>T were also associated with overall survival (OS). The functional polymorphism, EGFR rs712829 G>T, was associated with progression-free and OS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23959273"}, {"offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Overexpression of the EGFR ligands amphiregulin (AREG)/epiregulin (EREG) may be a surrogate of EGFR dependency regardless of sidedness in metastatic colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37594733"}, {"offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Amphiregulin (AREG) is an epidermal growth factor receptor (EGFR) ligand. The aim of this study was to investigate the effects of baseline plasma AREG levels in KRAS, ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34893673"}, {"offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "PURPOSE: High tumor production of the EGFR ligands, amphiregulin (AREG) and epiregulin (EREG), predicted benefit from anti-EGFR therapy for metastatic colorectal cancer (mCRC) in a retrospective analysis of clinical tr", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37363997"}, {"offsetInBeginSection": 503, "offsetInEndSection": 865, "text": " The proteins Amphiregulin and Epiregulin belong to the Epidermal growth factors family (EGF, that act through the EGFR. Over-expression of these proteins has been seen in a variety of malignancies and non-malignant pathologies. These proteins can be detected in samples from colorectal malignancies and inflammatory bowel disease by immunohistochemical staining", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23885463"}, {"offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "PURPOSE: High tumor mRNA levels of the EGFR ligands amphiregulin (AREG) and epiregulin (EREG) are associated with anti-EGFR agent response in metastatic colorectal cance", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33888518"}, {"offsetInBeginSection": 696, "offsetInEndSection": 921, "text": "A from pretreatment biopsies.RESULTS: Gene expression profiles showed that patients with tumors that express high levels of the EGFR ligands epiregulin and amphiregulin are more likely to have disease control with cetuximab (", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17664471"}, {"offsetInBeginSection": 961, "offsetInEndSection": 1310, "text": "treated in a similar setting.RESULTS: In KRAS wild type (WT) patients, there was a significant association between log-transformed ligand expression and response for EREG (odds ratio for objective response, 1.90; 95% CI, 1.27 to 2.83; P = .0005; concordance index [c-index], 0.681) and for AREG (odds ratio for objective response, 1.862; 95% CI, 1.2", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19738126"}, {"offsetInBeginSection": 882, "offsetInEndSection": 1085, "text": "New data seem to support the role of BRAF mutational status. In addition, high mRNA levels of the EGFR-ligands Epiregulin and Amphiregulin have been associated with increased responsiveness to cetuximab.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19663767"}, {"offsetInBeginSection": 693, "offsetInEndSection": 911, "text": "Gene ontology data showed the upregulation of genes related to EGFR signaling, and we identified that FGFR4 overexpression secretes EGFR ligands such as amphiregulin (AREG) with consequent activation of EGFR and ErbB3.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32533590"}, {"offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Epigenetic regulation of Amphiregulin and Epiregulin in colorectal cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30252132"}, {"offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "BACKGROUND/AIM: Amphiregulin (AREG) and epiregulin (EREG) mRNA expression levels are predictors of response to anti-EGFR antibody therapy. Left-sided colon cancer is more sensitive to anti-EGFR antibodies than right-sided, although the mechanism is unclear", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31519572"}]}
+{"question_id": "662cfc88187cba990d000008", "question": "What process does tRNA nucleotidyl transferase 1 (TRNT1)  catalyze?", "answer": "Addition of the trinucleotide cytosine/cytosine/adenine (CCA) to the 3' end of transfer RNAs (tRNAs) is essential for translation and is catalyzed by the enzyme TRNT1 (tRNA nucleotidyl transferase),", "relevant_passage_ids": ["36121781", "37239403", "25652405", "28390992", "30758723", "27370603", "32471101", "37215601", "32181284", "36646204", "30959222", "36409584", "21059936", "37334830", "29454993", "30917604", "29884622", "884105", "17204286", "26172425", "9510330", "15304219", "21071662", "15265870", "17949481"], "type": "factoid", "snippets": [{"offsetInBeginSection": 162, "offsetInEndSection": 231, "text": "TRNT1 gene encodes a CCA-adding tRNA nucleotidyl transferase enzyme. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36121781"}, {"offsetInBeginSection": 290, "offsetInEndSection": 438, "text": "tRNA Nucleotidyl Transferase 1 (TRNT1), the nuclear gene encoding the CCA-adding enzyme essential for modifying both nuclear and mitochondrial tRNAs", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37239403"}, {"offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Addition of the trinucleotide cytosine/cytosine/adenine (CCA) to the 3' end of transfer RNAs (tRNAs) is essential for translation and is catalyzed by the enzyme TRNT1 (tRNA nucleotidyl transferase), which functions in both the cytoplasm and mitochondria. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25652405"}, {"offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "tRNA nucleotidyl transferase 1 (TRNT1) is an essential enzyme catalyzing the addition of terminal cytosine-cytosine-adenosine (CCA) trinucleotides to all mature tRNAs, which is necessary for aminoacylation", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32471101"}, {"offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "Mutation in the gene encoding tRNA nucleotidyl transferase, CCA-adding 1 (TRNT1), an enzyme essential for the synthesis of the 3'-terminal CCA sequence in tRNA molecules, results in a disorder that features sideroblastic anemia, B-cell immunodeficiency, periodic fever, and developmental delay", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30758723"}, {"offsetInBeginSection": 178, "offsetInEndSection": 317, "text": "We recently identified novel hypomorphic mutations in the tRNA Nucleotidyl Transferase, CCA-Adding 1 (TRNT1) gene that cause early-onset RP", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28390992"}, {"offsetInBeginSection": 12, "offsetInEndSection": 220, "text": "TRNT1 (CCA-adding transfer RNA nucleotidyl transferase) enzyme deficiency is a new metabolic disease caused by defective post-transcriptional modification of mitochondrial and cytosolic transfer RNAs (tRNAs).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27370603"}, {"offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "Addition of the trinucleotide cytosine/cytosine/adenine (CCA) to the 3' end of transfer RNAs (tRNAs) is essential for translation and is catalyzed by the enzyme TRNT1 (tRNA nucleotidyl transferase), which functions in both the cytoplasm and mitochondria", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25652405"}, {"offsetInBeginSection": 0, "offsetInEndSection": 740, "text": "tRNA nucleotidyl transferase 1 (TRNT1) is an essential enzyme catalyzing the addition of terminal cytosine-cytosine-adenosine (CCA) trinucleotides to all mature tRNAs, which is necessary for aminoacylation. It was recently discovered that partial loss-of-function mutations in TRNT1 are associated with various, seemingly unrelated human diseases including sideroblastic anemia with B-cell immunodeficiency, periodic fevers and developmental delay (SIFD), retinitis pigmentosa with erythrocyte microcytosis, and progressive B-cell immunodeficiency. In addition, even within the same disease, the severity and range of the symptoms vary greatly, suggesting a broad, pleiotropic impact of imparting TRNT1 function on diverse cellular systems.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32471101"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1508, "text": "Tpt1 catalyzes the transfer of an internal 2'-monophosphate moiety (2'-PO4) from a \"branched\" 2'-PO4 RNA splice junction to NAD+ to form a \"clean\" 2'-OH, 3'-5' phosphodiester junction, ADP-ribose 1\u2033-2\u2033 cyclic phosphate, and nicotinamide. First discovered as an essential component of the Saccharomyces cerevisiae tRNA splicing machinery, Tpt1 is widely distributed in nature, including in taxa that have no yeast-like RNA splicing system. Here we characterize the RslTpt1 protein from the bacterium Runella slithyformis, in which Tpt1 is encoded within a putative RNA repair gene cluster. We find that (i) expression of RslTpt1 in yeast complements a lethal tpt1\u0394 knockout, and (ii) purified recombinant RslTpt1 is a bona fide NAD+-dependent 2'-phosphotransferase capable of completely removing an internal 2'-phosphate from synthetic RNAs. The in vivo activity of RslTpt1 is abolished by alanine substitutions for conserved amino acids Arg16, His17, Arg64, and Arg119. The R64A, R119A, and H17A mutants accumulate high levels of a 2'-phospho-ADP-ribosylated RNA reaction intermediate (2'-P-ADPR, evanescent in the wild-type RslTpt1 reaction), which is converted slowly to a 2'-OH RNA product. The R16A mutant is 300-fold slower than wild-type RslTpt1 in forming the 2'-P-ADPR intermediate. Whereas wild-type RsTpt1 rapidly converts the isolated 2'-P-ADPR intermediate to 2'-OH product in the absence of NAD+, the H17A, R119A, R64A, and R16A mutant are slower by factors of 3, 33, 210, and 710, respectively.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29884622"}, {"offsetInBeginSection": 142, "offsetInEndSection": 881, "text": "tRNA 2'-phosphotransferase 1 (TRPT1/TPT1/KptA) possesses ADP-ribosyltransferase (ART) activity\u00a0and is able to ADP-ribosylate nucleic acids. However, the underlying molecular mechanism remains elusive. Here, we determined crystal structures of TRPT1s in complex with NAD+ from Homo sapiens, Mus musculus and Saccharomyces cerevisiae. Our results revealed that the eukaryotic TRPT1s adopt common mechanisms for both NAD+ and nucleic acid substrate binding. The conserved SGR motif induces a significant conformational change in the donor loop upon NAD+ binding to facilitate the catalytic reaction of ART. Moreover, the nucleic acid-binding residue redundancy provides structural flexibility to accommodate different nucleic acid substrates.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37334830"}, {"offsetInBeginSection": 0, "offsetInEndSection": 363, "text": "The tRNAHis guanylyltransferase (Thg1) superfamily includes enzymes that are found in all three domains of life that all share the common ability to catalyze the 3' to 5' synthesis of nucleic acids. This catalytic activity, which is the reverse of all other known DNA and RNA polymerases, makes this enzyme family a subject of biological and mechanistic interest.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30917604"}, {"offsetInBeginSection": 0, "offsetInEndSection": 528, "text": "Mutations in the human TRNT1 gene encoding tRNA nucleotidyltransferase (tRNA-NT), an essential enzyme responsible for addition of the CCA (cytidine-cytidine-adenosine) sequence to the 3'-termini of tRNAs, have been linked to disease phenotypes including congenital sideroblastic anemia with B-cell immunodeficiency, periodic fevers and developmental delay (SIFD) or retinitis pigmentosa with erythrocyte microcytosis. The effects of these disease-linked mutations on the structure and function of tRNA-NT have not been explored.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29454993"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1095, "text": "In tRNA maturation, CCA-addition by tRNA nucleotidyltransferase is a unique and highly accurate reaction. While the mechanism of nucleotide selection and polymerization is well understood, it remains a mystery why bacterial and eukaryotic enzymes exhibit an unexpected and surprisingly low tRNA substrate affinity while they efficiently catalyze the CCA-addition. To get insights into the evolution of this high-fidelity RNA synthesis, the reconstruction and characterization of ancestral enzymes is a versatile tool. Here, we investigate a reconstructed candidate of a 2 billion years old CCA-adding enzyme from Gammaproteobacteria and compare it to the corresponding modern enzyme of Escherichia coli. We show that the ancestral candidate catalyzes an error-free CCA-addition, but has a much higher tRNA affinity compared with the extant enzyme. The consequence of this increased substrate binding is an enhanced reverse reaction, where the enzyme removes the CCA end from the mature tRNA. As a result, the ancestral candidate exhibits a lower catalytic efficiency in vitro as well as in vivo.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36409584"}, {"offsetInBeginSection": 0, "offsetInEndSection": 725, "text": "The I326T mutation in the TRNT1 gene encoding human tRNA nucleotidyltransferase (tRNA-NT) is linked to a relatively mild form of SIFD. Previous work indicated that the I326T variant was unable to incorporate AMP into tRNAs in vitro, however, expression of the mutant allele from a strong heterologous promoter supported in vivo CCA addition to both cytosolic and mitochondrial tRNAs in a yeast strain lacking tRNA-NT. To address this discrepancy, we determined the biochemical and biophysical characteristics of the I326T variant enzyme and the related variant, I326A. Our in vitro analysis revealed that the I326T substitution decreases the thermal stability of the enzyme and causes a ten-fold reduction in enzyme activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30959222"}, {"offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "tRNA nucleotidyl transferase 1 (TRNT1) is an essential enzyme catalyzing the addition of terminal cytosine-cytosine-adenosine (CCA) trinucleotides to all mature tRNAs, which is necessary for aminoacylation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32471101"}, {"offsetInBeginSection": 0, "offsetInEndSection": 356, "text": "Addition of the trinucleotide cytosine/cytosine/adenine (CCA) to the 3' end of transfer RNAs (tRNAs) is essential for translation and is catalyzed by the enzyme TRNT1 (tRNA nucleotidyl transferase), which functions in both the cytoplasm and mitochondria. Exome sequencing revealed TRNT1 mutations in two unrelated subjects with different clinical features.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25652405"}, {"offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "Addition of the trinucleotide cytosine/cytosine/adenine (CCA) to the 3' end of transfer RNAs (tRNAs) is essential for translation and is catalyzed by the enzyme TRNT1 (tRNA nucleotidyl transferase), which functions in both the cytoplasm and mitochondria.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25652405"}, {"offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "The maturation of tRNA and its quality control is crucial for aminoacylation and protein synthesis. The CCA enzyme, also known as tRNA nucleotidyltransferase, catalyzes the addition or repair of CCA at the 3'-terminus of tRNAs to facilitate aminoacylation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36646204"}, {"offsetInBeginSection": 100, "offsetInEndSection": 402, "text": "The CCA enzyme, also known as tRNA nucleotidyltransferase, catalyzes the addition or repair of CCA at the 3'-terminus of tRNAs to facilitate aminoacylation. Structural studies of CCA enzyme in complex with ATP and CTP suggested that adding CCA at the 3'-terminus of tRNAs is a sequential process [1-4].", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36646204"}, {"offsetInBeginSection": 100, "offsetInEndSection": 256, "text": "The CCA enzyme, also known as tRNA nucleotidyltransferase, catalyzes the addition or repair of CCA at the 3'-terminus of tRNAs to facilitate aminoacylation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36646204"}, {"offsetInBeginSection": 100, "offsetInEndSection": 568, "text": "The CCA enzyme, also known as tRNA nucleotidyltransferase, catalyzes the addition or repair of CCA at the 3'-terminus of tRNAs to facilitate aminoacylation. Structural studies of CCA enzyme in complex with ATP and CTP suggested that adding CCA at the 3'-terminus of tRNAs is a sequential process [1-4]. However, there are many inconsistent results of CCA addition from the biochemical studies, which raise the ambiguity about the CCA enzyme specificity in\u00a0vitro [5-7].", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36646204"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "The TRNT1 gene encodes tRNA nucleotidyltransferase 1, which catalyzes the addition of cytosine-cytosine-adenosine (CCA) to the ends of cytoplasmic and mitochondrial tRNAs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37215601"}, {"offsetInBeginSection": 1581, "offsetInEndSection": 1908, "text": "These data suggest that the clinical phenotypes associated with TRNT1 mutations are largely due to impaired mitochondrial translation, resulting from defective CCA addition to mitochondrial tRNA(Ser(AGY)), and that the severity of this biochemical phenotype determines the severity and tissue distribution of clinical features.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25652405"}, {"offsetInBeginSection": 207, "offsetInEndSection": 404, "text": "The tRNA(His) guanylyltransferase (Thg1) is a member of a unique enzyme family whose members catalyze an unprecedented reaction in biology: 3'-5' addition of nucleotides to nucleic acid substrates.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21059936"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1223, "text": "The I326T mutation in the TRNT1 gene encoding human tRNA nucleotidyltransferase (tRNA-NT) is linked to a relatively mild form of SIFD. Previous work indicated that the I326T variant was unable to incorporate AMP into tRNAs in vitro, however, expression of the mutant allele from a strong heterologous promoter supported in vivo CCA addition to both cytosolic and mitochondrial tRNAs in a yeast strain lacking tRNA-NT. To address this discrepancy, we determined the biochemical and biophysical characteristics of the I326T variant enzyme and the related variant, I326A. Our in vitro analysis revealed that the I326T substitution decreases the thermal stability of the enzyme and causes a ten-fold reduction in enzyme activity. We propose that the structural changes in the I326T variant that lead to these altered parameters result from a rearrangement of helices within the body domain of the protein which can be probed by the inability of the monomeric enzyme to form a covalent dimer in vitro mediated by C373. In addition, we confirm that the effects of the I326T or I326A substitutions are relatively mild in vivo by demonstrating that the mutant alleles support both mitochondrial and cytosolic CCA-addition in yeast.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30959222"}, {"offsetInBeginSection": 0, "offsetInEndSection": 331, "text": "Mutations in the gene encoding transfer RNA (tRNA) nucleotidyltransferase, CCA-adding 1 (TRNT1), an enzyme essential for the synthesis of the 3'-terminal CCA sequence in tRNA molecules, are associated with a rare syndrome of congenital sideroblastic anemia, B cell immunodeficiency, periodic fevers, and developmental delay (SIFD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32181284"}, {"offsetInBeginSection": 0, "offsetInEndSection": 417, "text": "Mutations in the human TRNT1 gene encoding tRNA nucleotidyltransferase (tRNA-NT), an essential enzyme responsible for addition of the CCA (cytidine-cytidine-adenosine) sequence to the 3'-termini of tRNAs, have been linked to disease phenotypes including congenital sideroblastic anemia with B-cell immunodeficiency, periodic fevers and developmental delay (SIFD) or retinitis pigmentosa with erythrocyte microcytosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29454993"}, {"offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Mutation in the gene encoding tRNA nucleotidyl transferase, CCA-adding 1 (TRNT1), an enzyme essential for the synthesis of the 3'-terminal CCA sequence in tRNA molecules, results in a disorder that features sideroblastic anemia, B-cell immunodeficiency, periodic fever, and developmental delay.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30758723"}, {"offsetInBeginSection": 43, "offsetInEndSection": 203, "text": "tRNA nucleotidyltransferase (tRNA-NT), an essential enzyme responsible for addition of the CCA (cytidine-cytidine-adenosine) sequence to the 3'-termini of tRNAs", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29454993"}, {"offsetInBeginSection": 0, "offsetInEndSection": 799, "text": "The TRNT1 gene encodes tRNA nucleotidyltransferase 1, which catalyzes the addition of cytosine-cytosine-adenosine (CCA) to the ends of cytoplasmic and mitochondrial tRNAs. The most common clinical phenotype associated with TRNT1 is autosomal recessive sideroblastic anemia with B-cell immunodeficiency, periodic fever, and developmental delay (SIFD). Muscle involvement has rarely been reported in TRNT1-related disorders. Here we report a Chinese patient with incomplete SIFD and hyperCKemia, and explored the skeletal muscle pathological changes. The patient was a 3-year-old boy with sensorineural hearing loss, sideroblastic anemia, and developmental delay since infancy. At the age of 11 months, significantly increased levels of creatine kinase were noted, accompanied by mild muscle weakness.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37215601"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1891, "text": "BACKGROUND: TRNT1 (CCA-adding transfer RNA nucleotidyl transferase) enzyme deficiency is a new metabolic disease caused by defective post-transcriptional modification of mitochondrial and cytosolic transfer RNAs (tRNAs).RESULTS: We investigated four patients from two families with infantile-onset cyclical, aseptic febrile episodes with vomiting and diarrhoea, global electrolyte imbalance during these episodes, sideroblastic anaemia, B lymphocyte immunodeficiency, retinitis pigmentosa, hepatosplenomegaly, exocrine pancreatic insufficiency and renal tubulopathy. Other clinical features found in children include sensorineural deafness, cerebellar atrophy, brittle hair, partial villous atrophy and nephrocalcinosis. Whole exome sequencing and bioinformatic filtering were utilised to identify recessive compound heterozygous TRNT1 mutations (missense mutation c.668T>C, p.Ile223Thr and a novel splice mutation c.342+5G>T) segregating with disease in the first family. The second family was found to have a homozygous TRNT1 mutation (c.569G>T), p.Arg190Ile, (previously published). We found normal mitochondrial translation products using passage matched controls and functional perturbation of 3' CCA addition to mitochondrial tRNAs (tRNA(Cys), tRNA(LeuUUR) and tRNA(His)) in fibroblasts from two patients, demonstrating a pathomechanism affecting the CCA addition to mt-tRNAs. Acute management of these patients included transfusion for anaemia, fluid and electrolyte replacement and immunoglobulin therapy. We also describe three-year follow-up findings after treatment by bone marrow transplantation in one patient, with resolution of fever and reversal of the abnormal metabolic profile.CONCLUSIONS: Our report highlights that TRNT1 mutations cause a spectrum of disease ranging from a childhood-onset complex disease with manifestations in most organs to an adult-onset isolated re", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27370603"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1580, "text": "Addition of the trinucleotide cytosine/cytosine/adenine (CCA) to the 3' end of transfer RNAs (tRNAs) is essential for translation and is catalyzed by the enzyme TRNT1 (tRNA nucleotidyl transferase), which functions in both the cytoplasm and mitochondria. Exome sequencing revealed TRNT1 mutations in two unrelated subjects with different clinical features. The first presented with acute lactic acidosis at 3 weeks of age and developed severe developmental delay, hypotonia, microcephaly, seizures, progressive cortical atrophy, neurosensorial deafness, sideroblastic anemia and renal Fanconi syndrome, dying at 21 months. The second presented at 3.5 years with gait ataxia, dysarthria, gross motor regression, hypotonia, ptosis and ophthalmoplegia and had abnormal signals in brainstem and dentate nucleus. In subject 1, muscle biopsy showed combined oxidative phosphorylation (OXPHOS) defects, but there was no OXPHOS deficiency in fibroblasts from either subject, despite a 10-fold-reduction in TRNT1 protein levels in fibroblasts of the first subject. Furthermore, in normal controls, TRNT1 protein levels are 10-fold lower in muscle than in fibroblasts. High resolution northern blots of subject fibroblast RNA suggested incomplete CCA addition to the non-canonical mitochondrial tRNA(Ser(AGY)), but no obvious qualitative differences in other mitochondrial or cytoplasmic tRNAs. Complete knockdown of TRNT1 in patient fibroblasts rendered mitochondrial tRNA(Ser(AGY)) undetectable, and markedly reduced mitochondrial translation, except polypeptides lacking Ser(AGY) codons.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25652405"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1241, "text": "Mutation in the gene encoding tRNA nucleotidyl transferase, CCA-adding 1 (TRNT1), an enzyme essential for the synthesis of the 3'-terminal CCA sequence in tRNA molecules, results in a disorder that features sideroblastic anemia, B-cell immunodeficiency, periodic fever, and developmental delay. Mutations in TRNT1 are also linked to phenotypes including retinitis pigmentosa, cataracts, and cardiomyopathy. To date, it has remained unclear how defective TRNT1 is linked to B-cell deficiency. Here we report the case of a 12-year-old boy without sideroblastic anemia who harbors novel compound heterozygous mutations in TRNT1. Immunophenotypic analysis revealed severely decreased levels of B cells and follicular helper T cells. In the bone marrow, B-cell maturation stopped at the CD19+CD10+CD20+/- pre-B-cell stage. Severe combined immunodeficiency mice transplanted with bone marrow hematopoietic stem cells from the patient showed largely normal B-cell engraftment and differentiation in the bone marrow and periphery at 24\u00a0weeks post-transplantation, comparable to those in mouse transplanted with healthy hematopoietic stem cells. Biochemical analysis revealed augmented endoplasmic reticulum (ER) stress response in activated T cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30758723"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1366, "text": "Mutations in the gene encoding transfer RNA (tRNA) nucleotidyltransferase, CCA-adding 1 (TRNT1), an enzyme essential for the synthesis of the 3'-terminal CCA sequence in tRNA molecules, are associated with a rare syndrome of congenital sideroblastic anemia, B cell immunodeficiency, periodic fevers, and developmental delay (SIFD). Clinical manifestations and immunological phenotypes were assessed in a Chinese patient with novel compound heterozygous mutations in TRNT1. The patient required multiple hospitalizations starting at the age of 2\u00a0years for recurrent fevers without an infective cause. During the febrile episode, the patient was found to have microcytic hypochromic anemia, B cell lymphopenia, and hypogammaglobulinemia. Targeted gene sequencing identified novel compound heterozygous mutations in the TRNT1 gene (c.525delT, p.Leu176X; c.938T>C, p.Leu313Ser). Immunophenotyping revealed increased CD8+ T cells, CD4+ terminally differentiated effector memory helper T lymphocytes (CD4 TEMRA), and CD4+ effector memory lymphocytes (CD4 EM). Analysis of CD4+ T subsets identified decreased T follicular helper cells (Tfh) with a biased phenotype to Th2-like cells. The patient also showed a lower percentage of switched memory B (smB) cells. Additionally, defects in the cytotoxicity of the patient's NK and \u03b3\u03b4T cells were shown by CD107alpha expression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32181284"}, {"offsetInBeginSection": 0, "offsetInEndSection": 296, "text": "The enzyme tRNA nucleotidyl transferase (EC 2.7.7.25) has been highly purified from whole adult houseflies. A molecular weight of 30 000 has been determined. The enzyme requires Mg2+ and tRNA deprived of the 3' terminal sequence CCA for activity in the incorporation of AMP and CMP onto the tRNA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/884105"}, {"offsetInBeginSection": 0, "offsetInEndSection": 622, "text": "Addition of the trinucleotide cytosine/cytosine/adenine (CCA) to the 3' end of transfer RNAs (tRNAs) is essential for translation and is catalyzed by the enzyme TRNT1 (tRNA nucleotidyl transferase), which functions in both the cytoplasm and mitochondria. Exome sequencing revealed TRNT1 mutations in two unrelated subjects with different clinical features. The first presented with acute lactic acidosis at 3 weeks of age and developed severe developmental delay, hypotonia, microcephaly, seizures, progressive cortical atrophy, neurosensorial deafness, sideroblastic anemia and renal Fanconi syndrome, dying at 21 months.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25652405"}, {"offsetInBeginSection": 0, "offsetInEndSection": 406, "text": "Mutation in the gene encoding tRNA nucleotidyl transferase, CCA-adding 1 (TRNT1), an enzyme essential for the synthesis of the 3'-terminal CCA sequence in tRNA molecules, results in a disorder that features sideroblastic anemia, B-cell immunodeficiency, periodic fever, and developmental delay. Mutations in TRNT1 are also linked to phenotypes including retinitis pigmentosa, cataracts, and cardiomyopathy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30758723"}, {"offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "BACKGROUND: TRNT1 (CCA-adding transfer RNA nucleotidyl transferase) enzyme deficiency is a new metabolic disease caused by defective post-transcriptional modification of mitochondrial and cytosolic transfer RNAs (tRNAs)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27370603"}, {"offsetInBeginSection": 0, "offsetInEndSection": 491, "text": "Mutation in the gene encoding tRNA nucleotidyl transferase, CCA-adding 1 (TRNT1), an enzyme essential for the synthesis of the 3'-terminal CCA sequence in tRNA molecules, results in a disorder that features sideroblastic anemia, B-cell immunodeficiency, periodic fever, and developmental delay. Mutations in TRNT1 are also linked to phenotypes including retinitis pigmentosa, cataracts, and cardiomyopathy. To date, it has remained unclear how defective TRNT1 is linked to B-cell deficiency.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30758723"}, {"offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "The human CCA-adding enzyme (tRNA nucleotidyltransferase) is an essential enzyme that catalyzes the addition of the CCA terminus to the 3' end of tRNA precursors, a reaction which is a fundamental prerequisite for mature tRNAs to become aminoacylated and to participate in protein biosynthesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17204286"}, {"offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "tRNA nucleotidyltransferase adds the invariant CCA-terminus to the tRNA 3'-end, a central step in tRNA maturation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26172425"}, {"offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "The CCA-adding enzyme [ATP(CTP):tRNA nucleotidyltransferase] catalyzes the addition and regeneration of the 3'-terminal CCA sequence of tRNAs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9510330"}, {"offsetInBeginSection": 142, "offsetInEndSection": 219, "text": "tRNA nucleotidyltransferase catalyzes the addition of CCA to 3' ends of tRNAs", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15304219"}, {"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "CCA-adding enzymes [ATP(CTP):tRNA nucleotidyltransferases] add CCA onto the 3' end of transfer RNA (tRNA) precursors without using a nucleic acid template.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21071662"}, {"offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "The CCA-adding enzyme ATP(CTP):tRNA nucleotidyltransferase builds and repairs the 3'-terminal CCA sequence of tRNA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15265870"}, {"offsetInBeginSection": 384, "offsetInEndSection": 493, "text": "family, the tRNA nucleotidyltransferase that synthesizes the 3'-terminal sequence C-C-A to all tRNAs (CCA-add", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17949481"}, {"offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "In tRNA maturation, CCA-addition by tRNA nucleotidyltransferase is a unique and highly accurate reaction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36409584"}, {"offsetInBeginSection": 115, "offsetInEndSection": 245, "text": "This CCA-adding enzyme is a specialized RNA polymerase that synthesizes the CCA sequence at high fidelity in all kingdoms of life.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26172425"}]}
+{"question_id": "6614f810fdcbea915f000043", "question": "What are the causes for heart and lung transplantation in children?", "answer": "End-stage cardiopulmonary failure.", "relevant_passage_ids": ["34991964", "33849770", "32067330"], "type": "list", "snippets": [{"offsetInBeginSection": 98, "offsetInEndSection": 131, "text": "end-stage cardiopulmonary failure", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34991964"}, {"offsetInBeginSection": 373, "offsetInEndSection": 389, "text": "single-ventricle", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34991964"}, {"offsetInBeginSection": 402, "offsetInEndSection": 421, "text": "tetralogy of Fallot", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34991964"}, {"offsetInBeginSection": 422, "offsetInEndSection": 462, "text": "major aortopulmonary collateral arteries", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34991964"}, {"offsetInBeginSection": 468, "offsetInEndSection": 496, "text": "prior Potts shunt palliation", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34991964"}, {"offsetInBeginSection": 9, "offsetInEndSection": 40, "text": "Pulmonary arterial hypertension", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33849770"}, {"offsetInBeginSection": 657, "offsetInEndSection": 687, "text": "primary pulmonary hypertension", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32067330"}, {"offsetInBeginSection": 698, "offsetInEndSection": 758, "text": "congenital heart disease(CHD) without Eisenmenger's syndrome", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32067330"}, {"offsetInBeginSection": 774, "offsetInEndSection": 785, "text": "CHD with ES", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32067330"}]}
+{"question_id": "662edc6f187cba990d00000c", "question": "Can enhancer-promoter interactions form independently of genomic distance?", "answer": "Topologically Associating Domains (TADs) have been suggested to facilitate and constrain enhancer-promoter interactions. A significant proportion of enhancer-promoter interactions are established across TAD boundaries in Drosophila embryos, but developmental genes are strikingly enriched in intra- but not inter-TAD interactions. Furthermore, contrary to intra-TAD interactions, the formation of inter-TAD enhancer-promoter interactions is not solely driven by genomic distance, with distal interactions sometimes favored over proximal ones. This suggests that other general mechanisms must exist to establish and maintain specific enhancer-promoter interactions across large distances", "relevant_passage_ids": ["38084924", "35418676", "37858706", "37511131", "35691341", "11742093", "24600469", "37451823", "35168174", "30395328", "31829768", "27799341", "11190466", "36824960", "23045397", "27932455", "36769179", "36717694"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Enhancer-promoter interactions can form independently of genomic distance and be functional across TAD boundaries", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38084924"}, {"offsetInBeginSection": 0, "offsetInEndSection": 453, "text": "Topologically Associating Domains (TADs) have been suggested to facilitate and constrain enhancer-promoter interactions. However, the role of TAD boundaries in effectively restricting these interactions remains unclear. Here, we show that a significant proportion of enhancer-promoter interactions are established across TAD boundaries in Drosophila embryos, but that developmental genes are strikingly enriched in intra- but not inter-TAD interactions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38084924"}, {"offsetInBeginSection": 827, "offsetInEndSection": 1196, "text": "Furthermore, contrary to intra-TAD interactions, the formation of inter-TAD enhancer-promoter interactions is not solely driven by genomic distance, with distal interactions sometimes favored over proximal ones. These observations suggest that other general mechanisms must exist to establish and maintain specific enhancer-promoter interactions across large distances.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38084924"}, {"offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Enhancer-promoter interactions can form independently of genomic distance and be functional across TAD boundaries.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38084924"}, {"offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Enhancers activate their cognate promoters over huge distances but how enhancer/promoter interactions become established is not completely understood", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37858706"}, {"offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "In higher eukaryotes, distance enhancer-promoter interactions are organized by topologically associated domains, tethering elements, and chromatin insulators/boundaries", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37511131"}, {"offsetInBeginSection": 595, "offsetInEndSection": 832, "text": "We show that active regulatory elements, independent of cohesin and polycomb, interact with each other across distances of tens of megabases in vertebrate and invertebrate genomes and that interactions correlate and change with activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37451823"}, {"offsetInBeginSection": 407, "offsetInEndSection": 610, "text": "TADs are also functional blocks of chromosomes as enhancers and their cognate promoters are normally located in the same TAD, even if their genomic distance from each other can be as large as a megabase.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30395328"}, {"offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Topologically Associating Domains (TADs) have been suggested to facilitate and constrain enhancer-promoter interactions. However, the role of TAD boundaries in effectively restricting these interactions remains unclear.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38084924"}]}
+{"question_id": "66300d3e187cba990d00001b", "question": "What is the prevalence of intellectual developmental disorders in Becker Muscular Dystrophy?", "answer": "The global prevalence of intellectual developmental disorder (IDD) is 8% in Becker muscular dystrophy.", "relevant_passage_ids": ["36440509"], "type": "factoid", "snippets": [{"offsetInBeginSection": 1369, "offsetInEndSection": 1471, "text": "The global prevalence of intellectual developmental disorder (IDD) was 8% in Becker muscular dystrophy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36440509"}, {"offsetInBeginSection": 655, "offsetInEndSection": 727, "text": "dies were included. The prevalence of IDD in BMD was 8.0% (95% confidenc", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36440509"}]}
+{"question_id": "65cfdf1c1930410b13000028", "question": "Mutation of which gene was implicated in Disabling pansclerotic morphea?", "answer": "Gain-of-function variants in STAT4 was implicated in Disabling pansclerotic morphea.", "relevant_passage_ids": ["37256972"], "type": "factoid", "snippets": [{"offsetInBeginSection": 1531, "offsetInEndSection": 1622, "text": "CONCLUSIONS: Gain-of-function variants in STAT4 caused DPM in the families that we studied.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37256972"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1095, "text": "BACKGROUND: Disabling pansclerotic morphea (DPM) is a rare systemic inflammatory disorder, characterized by poor wound healing, fibrosis, cytopenias, hypogammaglobulinemia, and squamous-cell carcinoma. The cause is unknown, and mortality is high.METHODS: We evaluated four patients from three unrelated families with an autosomal dominant pattern of inheritance of DPM. Genomic sequencing independently identified three heterozygous variants in a specific region of the gene that encodes signal transducer and activator of transcription 4 (STAT4). Primary skin fibroblast and cell-line assays were used to define the functional nature of the genetic defect. We also assayed gene expression using single-cell RNA sequencing of peripheral-blood mononuclear cells to identify inflammatory pathways that may be affected in DPM and that may respond to therapy.RESULTS: Genome sequencing revealed three novel heterozygous missense gain-of-function variants in STAT4. In vitro, primary skin fibroblasts showed enhanced interleukin-6 secretion, with impaired wound healing, contraction of the collagen m", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37256972"}, {"offsetInBeginSection": 1370, "offsetInEndSection": 1622, "text": "Single-cell RNA sequencing revealed expression patterns consistent with an immunodysregulatory phenotype that were appropriately modified through JAK inhibition.CONCLUSIONS: Gain-of-function variants in STAT4 caused DPM in the families that we studied.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37256972"}, {"offsetInBeginSection": 658, "offsetInEndSection": 960, "text": "We also assayed gene expression using single-cell RNA sequencing of peripheral-blood mononuclear cells to identify inflammatory pathways that may be affected in DPM and that may respond to therapy.RESULTS: Genome sequencing revealed three novel heterozygous missense gain-of-function variants in STAT4.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37256972"}]}
+{"question_id": "662fc122187cba990d000012", "question": "Does physical exercise reduce the risk of recurrence from colorectal cancer?", "answer": "Physical Activity performed before or after cancer diagnosis is related to reduced mortality risk among colorectal cancer survivors.  Physical Activity levels at diagnostis of metastatic colorecal cancer are associated with longer Overall survival.", "relevant_passage_ids": ["35205748", "30964753", "16822844", "20008694", "32533468", "32476493", "31139306", "36369926", "30866859", "30332430", "38081360", "37739688", "37651160", "37621241", "36878665", "36672434", "33344583", "35882678", "32972439", "21113761", "28987237", "15859955", "34638290"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1527, "offsetInEndSection": 1636, "text": " The present study provides evidence that higher PA levels at diagnosis of mCRC are associated with longer OS", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35205748"}, {"offsetInBeginSection": 165, "offsetInEndSection": 316, "text": "Exercise has emerged as fundamental therapeutic medicine in the management of cancer, associated with a lower risk of recurrence and increased survival", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38081360"}, {"offsetInBeginSection": 19, "offsetInEndSection": 163, "text": "Changes in body composition may affect colorectal cancer (CRC) patient's risk of cancer recurrence, secondary cancer, and other chronic diseases", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37739688"}, {"offsetInBeginSection": 1464, "offsetInEndSection": 1630, "text": "Higher postoperative physical activity is associated with improved overall survival after tumor recurrence in patients initially diagnosed with stage III colon cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37651160"}, {"offsetInBeginSection": 611, "offsetInEndSection": 806, "text": "There are some reports, although the evidence is not conclusive, that weight loss and lifestyle changes such as dietary modification and physical activity can reduce the risk of colorectal cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37621241"}, {"offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Association between physical activity and the time course of cancer recurrence in stage III colon cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36878665"}, {"offsetInBeginSection": 260, "offsetInEndSection": 430, "text": "This review focuses on epidemiology, the relationship between obesity and the risk associated with the development and recurrence of cancer and the management of obesity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36672434"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1157, "text": "In recent years, because of improved cancer screening, detection and treatment modalities, a rapid increase in the population of colorectal and other cancer survivors has been observed. The increasing population has justified the requirement of preventive strategies such as lifestyle modifications with regard to obesity, physical activity, diet and smoking. Physical activity may prevent approximately 15% of the colon cancers. Furthermore, several observational studies have demonstrated the efficacy and dose-dependent and anti-cancer effects of exercise on decreasing the mortality and risk of recurrence before and after the colorectal cancer (CRC) diagnosis. However, the required exercise dose, type and intensity are yet unclear. The results of randomised prospective studies are expected to determine the optimal amount, type and intensity of exercise and formulate the most appropriate exercise plan and guidelines, according to the requirements and comorbidities of the patients. In addition, recent studies have focused on the molecular and genetic mechanisms underlying the effect of physical activity on disease outcomes and recurrence rates.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31139306"}, {"offsetInBeginSection": 236, "offsetInEndSection": 1098, "text": "urvival.METHODS: An up-to-date systematic review was performed on the available literature between 2000 and 2021 on PubMed, EMBASE, Medline, and Cochrane Library databases. All studies reporting on the impact of exercise and colorectal cancer outcomes in patients treated for non-metastatic colorectal cancer were analysed. The main outcome measures were the overall survival (OS), cancer specific survival (CSS) and disease free survival (DFS).RESULTS: A total of 13 prospective observational studies were included, accounting for 19,135 patients. Compared to negligible physical activity, overall survival (OS) was significantly increased for both moderate and highest activity group (HR 0.82, 95% CI: 0.74-0.90, p\u2009<\u20090.001 and HR 0.64, 0.56-0.72, p\u2009<\u20090.001 respectively). This was also reflected in cancer specific survival (CSS) analysis, but not disease-free", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35882678"}, {"offsetInBeginSection": 285, "offsetInEndSection": 451, "text": "The effect of dose-dependent physical activity on mortality and recurrence rates of colorectal carcinoma has been unequivocally demonstrated in observational studies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33344583"}, {"offsetInBeginSection": 360, "offsetInEndSection": 738, "text": "Physical activity may prevent approximately 15% of the colon cancers. Furthermore, several observational studies have demonstrated the efficacy and dose-dependent and anti-cancer effects of exercise on decreasing the mortality and risk of recurrence before and after the colorectal cancer (CRC) diagnosis. However, the required exercise dose, type and intensity are yet unclear.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31139306"}, {"offsetInBeginSection": 360, "offsetInEndSection": 665, "text": "Physical activity may prevent approximately 15% of the colon cancers. Furthermore, several observational studies have demonstrated the efficacy and dose-dependent and anti-cancer effects of exercise on decreasing the mortality and risk of recurrence before and after the colorectal cancer (CRC) diagnosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31139306"}, {"offsetInBeginSection": 186, "offsetInEndSection": 665, "text": "The increasing population has justified the requirement of preventive strategies such as lifestyle modifications with regard to obesity, physical activity, diet and smoking. Physical activity may prevent approximately 15% of the colon cancers. Furthermore, several observational studies have demonstrated the efficacy and dose-dependent and anti-cancer effects of exercise on decreasing the mortality and risk of recurrence before and after the colorectal cancer (CRC) diagnosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31139306"}, {"offsetInBeginSection": 430, "offsetInEndSection": 665, "text": "Furthermore, several observational studies have demonstrated the efficacy and dose-dependent and anti-cancer effects of exercise on decreasing the mortality and risk of recurrence before and after the colorectal cancer (CRC) diagnosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31139306"}, {"offsetInBeginSection": 1299, "offsetInEndSection": 1757, "text": "Women who increased their activity (when comparing prediagnosis to postdiagnosis values) had a hazard ratio of 0.48 (95% CI, 0.24 to 0.97) for colorectal cancer deaths and a hazard ratio of 0.51 (95% CI, 0.30 to 0.85) for any-cause death, compared with those with no change in activity.CONCLUSION: Recreational physical activity after the diagnosis of stages I to III colorectal cancer may reduce the risk of colorectal cancer-specific and overall mortality.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16822844"}, {"offsetInBeginSection": 0, "offsetInEndSection": 443, "text": "PURPOSE: Physically active individuals have a lower risk of developing colorectal cancer but the influence of exercise on cancer survival is unknown.PATIENTS AND METHODS: By a prospective, observational study of 573 women with stage I to III colorectal cancer, we studied colorectal cancer-specific and overall mortality according to predefined physical activity categories before and after diagnosis and by change in activity after diagnosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16822844"}, {"offsetInBeginSection": 74, "offsetInEndSection": 168, "text": "ted States. Physical activity is associated with lower risk of colorectal cancer recurrence an", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30866859"}, {"offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "BACKGROUND: Physical activity may be associated with reduced risk of colore", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15859955"}, {"offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "BACKGROUND AND AIMS: Elevated circulating insulin is associated with increased risk of recurrence and cancer mortality in early-stage col", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28987237"}, {"offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "OBJECTIVE: We determined if postoperative physical activity prevents or delays cancer recurrence in patients with stage III colon cancer.METHODS: This cohort study nested within a randomised trial enrolled 1696 patients with surgically resected stage III colon cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36878665"}, {"offsetInBeginSection": 714, "offsetInEndSection": 823, "text": "Accumulated evidence suggests that physical activity is associated with a 25% reduction in colon cancer risk.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21113761"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1342, "text": "BACKGROUND: Although physically active individuals have a lower risk of developing colorectal cancer, few studies have examined whether exercise benefits colorectal cancer survivors.METHODS: Derived from the Health Professionals Follow-up Study, we studied colorectal cancer-specific and overall mortality in a cohort of 668 men with a history of stage I to stage III colorectal cancer according to predefined physical activity categories after diagnosis. To minimize bias by occult recurrences, we excluded men who died within 6 months of their postdiagnosis physical activity assessment.RESULTS: In a cohort of men with colorectal cancer and no apparent metastases at diagnosis, 50.4% exercised at least 18 metabolic equivalent task (MET) hours per week. Increased physical activity was significantly associated with improved colorectal cancer-specific mortality (P = .002 for trend) and overall mortality (P < .001 for trend). Men who engaged in more than 27 MET hours per week of physical activity had an adjusted hazard ratio for colorectal cancer-specific mortality of 0.47 (95% confidence interval, 0.24-0.92) compared with men who engaged in 3 or less MET hours per week of physical activity. The apparent benefit of physical activity was seen regardless of age, disease stage, body mass index, diagnosis year, tumor location, and pre", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20008694"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1547, "text": "PURPOSE: Physically active individuals have a lower risk of developing colorectal cancer but the influence of exercise on cancer survival is unknown.PATIENTS AND METHODS: By a prospective, observational study of 573 women with stage I to III colorectal cancer, we studied colorectal cancer-specific and overall mortality according to predefined physical activity categories before and after diagnosis and by change in activity after diagnosis. To minimize bias by occult recurrences, we excluded women who died within 6 months of their postdiagnosis physical activity assessment.RESULTS: Increasing levels of exercise after diagnosis of nonmetastatic colorectal cancer reduced cancer-specific mortality (P for trend = .008) and overall mortality (P for trend = .003). Compared with women who engaged in less than 3 metabolic equivalent task [MET] -hours per week of physical activity, those engaging in at least 18 MET-hours per week had an adjusted hazard ratio for colorectal cancer-specific mortality of 0.39 (95% CI, 0.18 to 0.82) and an adjusted hazard ratio for overall mortality of 0.43 (95% CI, 0.25 to 0.74). These results remained unchanged even after excluding women who died within 12 and 24 months of activity assessment. Prediagnosis physical activity was not predictive of mortality. Women who increased their activity (when comparing prediagnosis to postdiagnosis values) had a hazard ratio of 0.48 (95% CI, 0.24 to 0.97) for colorectal cancer deaths and a hazard ratio of 0.51 (95% CI, 0.30 to 0.85) for any-cause death, compared ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16822844"}, {"offsetInBeginSection": 74, "offsetInEndSection": 1596, "text": "ted States. Physical activity is associated with lower risk of colorectal cancer recurrence and mortality. Interventions are needed to increase physical activity in colorectal cancer survivors.METHODS: We conducted a 2-arm non-blinded pilot randomized controlled trial at the University of California, San Francisco among 42 individuals who had completed curative-intent treatment for colorectal cancer to determine the feasibility and acceptability of a 12-week (84\u2009days) physical activity intervention using a Fitbit Flex\u2122 and daily text messages. Participants were randomized 1:1 to receive the intervention with print educational materials or print educational materials alone. We explored the impact of the intervention versus usual care on physical activity using ActiGraph GT3X+ accelerometers pre-/post-intervention.RESULTS: We screened 406 individuals and randomized 42 to intervention (n\u00a0=\u200921) or control (n\u00a0=\u200921) groups. During the 12-week study, the intervention arm wore their Fitbits a median of 74\u2009days [88% of days in study period, interquartile range: 23-83\u2009days] and responded to a median of 34 (out of 46) text messages that asked for a reply (interquartile range: 13-38 text messages). Among the 16 intervention participants who completed the feedback survey, the majority (88%) reported that the intervention motivated them to exercise and that they were satisfied with their experience. No statistically significant difference in change in moderate-to-vigorous physical activity was found from baseli", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30866859"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1026, "text": "Physical activity is associated with reduced risks of colorectal cancer (CRC) incidence, recurrence and mortality. While these findings are consistent, the mechanism/s underlying this association remain unclear. Growing evidence supports the many ways in which differing characteristics of the gut microbiota can be tumourigenic or protective against CRC. CRC is characterised by significant dysbiosis including reduced short chain fatty acid-producing bacteria. Recent findings suggest that exercise can modify the gut microbiota, and these changes are inverse to the changes seen with CRC; however, this exercise-microbiota interaction is currently understudied in CRC. This review summarises parallel areas of research that are rapidly developing: The exercise-gut microbiota research and cancer-gut microbiota research and highlights the salient similarities. Preliminary evidence suggests that these areas are linked, with exercise mediating changes that promote the antitumorigenic characteristics of the gut microbiota.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36369926"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1617, "text": "BACKGROUND AND AIMS: Elevated circulating insulin is associated with increased risk of recurrence and cancer mortality in early-stage colorectal cancer (CRC). We conducted a randomized controlled trial to determine the effect of a 12-week home-based exercise program on fasting insulin, adipocytokines, and physical function in CRC survivors.METHODS: One hundred and twenty-three stage II-III CRC patients were randomly assigned to either a home-based exercise (n=62) or standard care control group (n=61) for 12weeks. Home-based exercise consisted of aerobic and resistance training, with a goal of obtaining \u226518 metabolic equivalent task (MET)-h/wk. Participants in the exercise group were instructed to participate in >18MET-h/wk. of aerobic and resistance exercise while the participants in the control group were asked to maintain their usual daily activity. The primary outcome was fasting insulin levels. Secondary outcomes were adiponectin, TNF-\u03b1 levels and 6min walk distance from baseline to post-intervention.RESULTS: After the 12-weeks, moderate-vigorous physical activity participation increased from 9.1\u00b114.7MET-h/wk. to 26.6\u00b121.7MET-h/wk. in the exercise group, with no change in the control group (p<0.01 for group and time interaction). Circulating insulin level decreased by 1\u03bcU/ml (6.0\u00b13.9 vs. 5.0\u00b13.5, p=0.009) in the exercise group with no change in the control group (p=0.022 for group and time interaction). A similar trend was observed in TNF-\u03b1 (p=0.030 for group and time interaction). Six minute walk distance increased by 25.2m in the exercise group with no change in the control group (p=0", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28987237"}, {"offsetInBeginSection": 550, "offsetInEndSection": 729, "text": "physical activity assessment.RESULTS: Increasing levels of exercise after diagnosis of nonmetastatic colorectal cancer reduced cancer-specific mortality (P for trend = .008) and o", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16822844"}]}
+{"question_id": "662a4b08b9f8b89d7e00000b", "question": "Oxysterol is produced by the oxidation of what waxy, fat-like substance made in the liver?", "answer": "Oxysterols are derived from either enzymatic or non-enzymatic oxidation of cholesterol.", "relevant_passage_ids": ["38036882", "38036880", "38036890", "38036887", "7657597", "26795945", "26461414", "20870006", "34920079", "31586653", "31301352", "29421651", "31009661", "32175830", "32335907", "34378892", "22884520", "32574926", "11111082", "33631213", "36316327", "36672175", "29993272", "24970128", "17346171", "22044627", "19035881", "12323083", "11239823", "23773414", "22026270", "38036877", "2268710", "19248802", "25255963", "17573819", "35154132", "24333430"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Oxysterols derive from either enzymatic or non-enzymatic oxidation of cholesterol. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38036887"}, {"offsetInBeginSection": 420, "offsetInEndSection": 567, "text": "Oxidized LDLs are enriched in oxidized products of cholesterol called oxysterols formed either by autoxidation, enzymatically, or by both mechanism", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38036882"}, {"offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "Oxysterols or cholesterol oxidation products a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38036880"}, {"offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Oxysterols, resulting from the oxidation of cholesterol, are formed either by autoxidation, enzymatically, or by both processes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38036890"}, {"offsetInBeginSection": 0, "offsetInEndSection": 696, "text": "Oxysterols are oxidized derivatives of cholesterol that are formed enzymatically or via reactive oxygen species or both. Cholesterol or oxysterols ingested as food are absorbed and packed into lipoproteins that are taken up by hepatic cells. Within hepatic cells, excess cholesterol is metabolised to form bile acids. The endoplasmic reticulum acts as the main organelle in the bile acid synthesis pathway. Metabolised sterols originating from this pathway are distributed within other organelles and in the cell membrane. The alterations to membrane oxysterol:sterol ratio affects the integrity of the cell membrane. The presence of oxysterols changes membrane fluidity and receptor orientation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31301352"}, {"offsetInBeginSection": 139, "offsetInEndSection": 573, "text": "Oxidation of cholesterol leads to the formation of a large number of oxidized products, generally known as oxysterols. They are intermediates in the biosynthesis of bile acids, steroid hormones, and 1,25- dihydroxyvitamin D3. Although oxysterols are considered as metabolic intermediates, there is a growing body of evidence that many of them are bioactive, and their absence or excess may be part of the cause of a disease phenotype.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32175830"}, {"offsetInBeginSection": 0, "offsetInEndSection": 504, "text": "Cholesterol is a precursor molecule for vitamin D, bile acids, and steroid hormones. Its oxidized forms, called oxysterols are by-products for synthesis, but also regulate cholesterol\u00e2s metabolism through different cell receptors. Cholesterol and oxysterols are important cell membrane components. Oxysterols show more biological activity than cholesterol itself, due to their pleiotropic cell effects. Oxysterol, contrary to cholesterol can cross the blood-brain barier and influence the nervous system.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34378892"}, {"offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Oxysterols are oxidised derivatives of cholesterol or its precursors post lanosterol. They are intermediates in the biosynthesis of bile acids, steroid hormones and 1,25-dihydroxyvitamin D3.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29421651"}, {"offsetInBeginSection": 0, "offsetInEndSection": 542, "text": "Oxysterols are oxygenated forms of cholesterol generated via autooxidation by free radicals and ROS, or formed enzymically by a variety of enzymes such as those involved in the synthesis of bile acids. Although found at very low concentrations in vivo, these metabolites play key roles in health and disease, particularly in development and regulating immune cell responses, by binding to effector proteins such as LXR\u03b1, ROR\u03b3 and Insig and directly or indirectly regulating transcriptional programmes that affect cell metabolism and function.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32335907"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1079, "text": "Cholestane-3\u03b2,5\u03b1,6\u03b2-triol (3\u03b2,5\u03b1,6\u03b2-triol) is formed from cholestan-5,6-epoxide (5,6-EC) in a reaction catalysed by cholesterol epoxide hydrolase, following formation of 5,6-EC through free radical oxidation of cholesterol. 7-Oxocholesterol (7-OC) and 7\u03b2-hydroxycholesterol (7\u03b2-HC) can also be formed by free radical oxidation of cholesterol. Here we investigate how 3\u03b2,5\u03b1,6\u03b2-triol, 7-OC and 7\u03b2-HC are metabolised to bile acids. We show, by monitoring oxysterol metabolites in plasma samples rich in 3\u03b2,5\u03b1,6\u03b2-triol, 7-OC and 7\u03b2-HC, that these three oxysterols fall into novel branches of the acidic pathway of bile acid biosynthesis becoming (25R)26-hydroxylated then carboxylated, 24-hydroxylated and side-chain shortened to give the final products 3\u03b2,5\u03b1,6\u03b2-trihydroxycholanoic, 3\u03b2-hydroxy-7-oxochol-5-enoic and 3\u03b2,7\u03b2-dihydroxychol-5-enoic acids, respectively. The intermediates in these pathways may be causative of some phenotypical features of, and/or have diagnostic value for, the lysosomal storage diseases, Niemann Pick types C and B and lysosomal acid lipase deficiency.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31009661"}, {"offsetInBeginSection": 0, "offsetInEndSection": 371, "text": "Oxysterols are bioactive lipids derived from cholesterol that are linked to inflammatory processes. Because obesity and metabolic syndrome are characterized by inflammation and altered cholesterol metabolism, we sought to investigate the variations of oxysterol levels and their metabolic pathways induced by obesity in the liver, hypothalamus, adipose tissue and plasma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26795945"}, {"offsetInBeginSection": 0, "offsetInEndSection": 454, "text": "Oxysterols are bioactive lipids derived from cholesterol that are linked to inflammatory processes. Because obesity and metabolic syndrome are characterized by inflammation and altered cholesterol metabolism, we sought to investigate the variations of oxysterol levels and their metabolic pathways induced by obesity in the liver, hypothalamus, adipose tissue and plasma. To this end, we used diet-induced and genetic (ob/ob and db/db) models of obesity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26795945"}, {"offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Oxysterols are bioactive lipids derived from cholesterol that are linked to inflammatory processes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26795945"}, {"offsetInBeginSection": 257, "offsetInEndSection": 612, "text": "LXRs are thought to be activated predominantly by oxysterols generated enzymatically from cholesterol in different cell organelles. Defects resulting in slowed release of cholesterol from late endosomes and lysosomes or reduction in sterol-27-hydroxylase activity lead to specific blocks in oxysterol production and impaired LXR-dependent gene activation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22884520"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Oxysterols, derived from cholesterol oxidation, are formed either by autoxidation, via enzymes, or by both processes [...].", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36672175"}, {"offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Oxysterols are a family of over 25 cholesterol metabolites naturally produced by enzymatic or radical oxidation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34920079"}, {"offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Oxysterols are oxidized derivatives of cholesterol that play regulatory roles in lipid biosynthesis and homeostasis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33631213"}, {"offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Cholesterol oxidation products, also named oxysterols, can be formed either by cholesterol auto-oxidation, enzymatically or both.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29993272"}, {"offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Oxysterols (oxidized derivatives of cholesterol and phytosterols) can be generated in the human organism through different oxidation processes, some requiring enzymes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20870006"}, {"offsetInBeginSection": 465, "offsetInEndSection": 512, "text": "Oxysterols, oxidized derivatives of cholesterol", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26461414"}, {"offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Oxysterols are oxidized 27-carbon cholesterol derivatives or by-products of cholesterol biosynthesis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24970128"}, {"offsetInBeginSection": 350, "offsetInEndSection": 619, "text": "Bile acids and oxysterols, formed from cholesterol, act as ligands to nuclear receptors regulating the expression of important genes in cholesterol homeostasis. Thus, the bioactivation of cholesterol into bile acids is crucial for regulation of cholesterol homeostasis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17346171"}, {"offsetInBeginSection": 465, "offsetInEndSection": 570, "text": "Oxysterols, oxidized derivatives of cholesterol were reported as activating ligands of Liver X Receptors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26461414"}, {"offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Cholesterol oxidation products (oxysterols) have been implicated in atherogenesis due to their presence in atherosclerotic tissue and their potent effects in vitro.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11239823"}, {"offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Oxysterols (oxidised cholesterol) may play a role in the pathogenesis of CVD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23773414"}, {"offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "INTRODUCTION: Products of oxidizing cholesterol-called oxysterols, are having different physicochemical properties and various from not-modified sterols, biolog", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22026270"}, {"offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Oxysterols, herein defined as derivatives of cholesterol with a hydroxyl group on the side chain, play several roles in lipid metabolism.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11111082"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1345, "text": "Cholesterol oxidation products (oxysterols) have been detected in many different tissues, often at concentrations 10(3) to 10(4) times lower than cholesterol. This constitutes a considerable risk of quantitation errors, since even a minor oxidation of cholesterol during sample processing would yield a substantial increase of oxysterol levels. It has therefore been suggested that some of the oxysterols do not occur in vivo and their detection in tissues merely are artifacts produced in vitro. In the present work, an 18O2 inhalation technique was developed in order to clarify which oxysterols are produced in vivo. Rats were exposed for 3 h to an atmosphere with a composition similar to normal air, except that it contained 18O2 instead of 16O2. Control rats were kept in 16O2-containing atmosphere throughout the experiment. The 18O enrichment of oxysterols in plasma and liver was determined by gas/liquid chromatography-mass spectrometry and mass isotopomer distribution analysis. In vivo formation of oxysterols, indicated by enrichment in 18O, was established for cholest-5-ene-3 beta, 7 alpha-diol, cholest-5-ene-3 beta, 7 beta-diol, 7-oxocholesterol, cholest-5-ene-3 beta,24-diol, cholest-5-ene-3 beta,25-diol, and cholest-5-ene-3 beta,27-diol. Additionally, it seems likely that cholest-5-ene-3 beta, 4 beta-diol is formed in vivo.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7657597"}, {"offsetInBeginSection": 0, "offsetInEndSection": 387, "text": "Cholesterol is a key molecule for synaptic transmission, and both central and peripheral synapses are cholesterol rich. During intense neuronal activity, a substantial portion of synaptic cholesterol can be oxidized by either enzymatic or non-enzymatic pathways to form oxysterols, which in turn modulate the activities of neurotransmitter receptors (e.g., NMDA and adrenergic receptors)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38036877"}, {"offsetInBeginSection": 0, "offsetInEndSection": 494, "text": "Oxysterols are oxygenated derivatives of cholesterol that contain an additional hydroxy, epoxide, or ketone group in the sterol nucleus and/or a hydroxyl group in the side chain of the cholesterol molecule. 27-Hydroxycholesterol (27HC) is a side-chain oxysterol that is oxygenated at the 27th carbon atom of cholesterol. The oxysterol (27HC) is produced via oxidation by sterol 27-hydroxylase (CYP27A1) and metabolized via oxysterol 7a-hydroxylase (CYP7B1) for bile acid synthesis in the liver.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36316327"}, {"offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "The effect of individual oxysterols--products of auto-oxidation of cholesterol on bile acid synthesis by cultivated rabbit hepatocytes was studied.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2268710"}, {"offsetInBeginSection": 0, "offsetInEndSection": 427, "text": "Oxysterols (oxidized derivatives of cholesterol and phytosterols) can be generated in the human organism through different oxidation processes, some requiring enzymes. Furthermore, oxysterols are also present in food due to lipid oxidation reactions caused by heating treatments, contact with oxygen, exposure to sunlight, etc., and they could be absorbed from the diet, at different rates depending on their side chain length.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20870006"}, {"offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Oxysterols are cholesterol oxidation products that are generated by enzymatic reactions through cytochrome P450 family enzymes or by non-enzymatic reactions involving reactive oxygen and nitrogen species.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22044627"}, {"offsetInBeginSection": 465, "offsetInEndSection": 1535, "text": "Oxysterols, oxidized derivatives of cholesterol were reported as activating ligands of Liver X Receptors. Interestingly, serum levels of agonist oxysterols such as 25-HC and 27-HC are significantly increased in NAFLD patients. By contrast, 22-s- HC is considered an antagonist ligand of LXR\u03b1. 22-s-Hc down-regulated expression of the FAS gene through an LXRE located in the promoter and abolished the effect of the synthetic LXR\u03b1 agonist. In addition it has been reported that 22-s-HC attenuated hepatic steatogenesis in a mouse model of high-fat-induced fatty liver. Very recently, it has been demonstrated that the inhibition of LXR\u03b1 by 22-s-HC dramatically represses steatosis and HIF-1 mediated activation of MCP-1 in ethanol-induced fatty liver injury in hepatocytes as well as in Kupferr cells. Our data demonstrated that High fat diet (HF) caused liver steatosis while an atherogenic diet (ATH) diet induced hepatocellular ballooning, but only the Ath+HF diet resulted in steatohepatitis with associated mitochondrial dysfunction and impaired mitochondriogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26461414"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1161, "text": "INTRODUCTION: Products of oxidizing cholesterol-called oxysterols, are having different physicochemical properties and various from not-modified sterols, biological activity. Amongst characteristic effects of these connections are: stopping the activity of HMG-CoA reductase, antiproliferative action, apoptosis induction, changes in the structure and functioning of the cell membrane and influence on remodeling of the immunological system. Mechanisms of oxysterols influence on the cellular level include a broad spectrum of complicated biological activities and they haven't been examined to the end yet.MATERIAL AND METHODS: In order to experiment execution the rat livers have been collected and the microscope sections have been made by standard technics, staining by haematoxylin and eosin (H&E). In each preparation 222 hepatic cells surrounding 10 central veins have been analysed and 222 hepatic cells occuring around 10 triads. The total surface ofcell, nucleus and cytoplasm have been taken for analysis.RESULTS: In all researched cases the analysed parameters have been reduced in area liver traid and central vein. Decreasing of area value of cell", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22026270"}, {"offsetInBeginSection": 0, "offsetInEndSection": 379, "text": "Oxysterols, herein defined as derivatives of cholesterol with a hydroxyl group on the side chain, play several roles in lipid metabolism. Members of this class regulate the expression of genes that participate in both sterol and fat metabolism, serve as substrates for the synthesis of bile acids, and are intermediates in the transfer of sterols from the periphery to the liver.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11111082"}, {"offsetInBeginSection": 0, "offsetInEndSection": 831, "text": "Cholesterol oxidation products (oxysterols) have been detected in many different tissues, often at concentrations 10(3) to 10(4) times lower than cholesterol. This constitutes a considerable risk of quantitation errors, since even a minor oxidation of cholesterol during sample processing would yield a substantial increase of oxysterol levels. It has therefore been suggested that some of the oxysterols do not occur in vivo and their detection in tissues merely are artifacts produced in vitro. In the present work, an 18O2 inhalation technique was developed in order to clarify which oxysterols are produced in vivo. Rats were exposed for 3 h to an atmosphere with a composition similar to normal air, except that it contained 18O2 instead of 16O2. Control rats were kept in 16O2-containing atmosphere throughout the experiment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7657597"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1443, "text": "Cholesterol oxidation products (oxysterols) have been implicated in atherogenesis due to their presence in atherosclerotic tissue and their potent effects in vitro. One of the major oxysterols currently of interest is 7-ketocholesterol (7K) and it has been suggested that the diet is an important source of this oxysterol. This investigation tested the hypothesis that 7K, delivered in a physiologically relevant vehicle, chylomicron remnant-like emulsion (CMR), would be metabolised and excreted by mice in a similar manner and to a similar extent as previously observed in rats when delivered in a chemically modified lipoprotein, acetylated low-density lipoprotein (acLDL). Indeed, the metabolism of 14C-7K delivered in CMR mirrored that of acLDL and was much more rapid than (3)H-cholesterol delivered simultaneously. The 7K-derived (14)C was cleared from the liver, appeared in the intestine and was excreted in the faeces. A substantial proportion of the 7K-derived (14)C in the intestine and faeces was aqueous-soluble, indicating metabolism to polar products, presumably bile acids. Moreover, while cholesterol-derived (3)H increased in the aorta, (14)C appeared transiently and there was no observable accumulation within 24 h. The data confirm our previous findings of rapid hepatic metabolism of 7K when delivered in acLDL and demonstrate that 7K delivered in a vehicle of dietary significance is similarly metabolised and excreted.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11239823"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1091, "text": "Oxysterols (oxidised cholesterol) may play a role in the pathogenesis of CVD. Similar to cholesterol, plant sterols are susceptible to oxidation. However, less is known about the potential atherogenicity of oxidised plant sterols (oxyphytosterols). In the present study, the atherogenicity of a mixture of oxyphytosterols was examined by feeding female LDL receptor-deficient (LDLR+/\u00a0-) mice for 35 weeks a control diet (atherogenic high-fat diet; n 9), an oxysterol diet (control diet+0\u00b7025\u00a0% (w/w) oxysterols; n 12) or an oxyphytosterol diet (control diet+0\u00b7025\u00a0% (w/w) oxyphytosterols; n 12). In the LDLR+/\u00a0- mice, serum levels of cholesterol, lipoprotein profiles, cholesterol exposure and inflammatory markers at the end of the experiment were comparable between the three diet groups. Nevertheless, the proportion of severe atherosclerotic lesions was significantly higher after oxysterol (41\u00a0%; P=\u00a00\u00b7004) and oxyphytosterol (34\u00a0%; P=\u00a00\u00b7011) diet consumption than after control diet consumption (26\u00a0%). Oxyphytosterol levels in the lesions were the highest in the oxyphytosterol group.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23773414"}, {"offsetInBeginSection": 0, "offsetInEndSection": 587, "text": "The research literature on atherosclerosis includes findings investigating the atherosclerotic effect of oxysterols, which are the oxidation products of cholesterol; and the literature on oxysterols refers to mechanisms by which oxysterols cause phospholipid packing defects in cell membranes. This review synthesizes these two bodies of research findings to describe how oxysterols cause phospholipid packing defects within the membranes of vascular endothelial cells, potentially increasing cell permeability of low-density lipoprotein cholesterol which may lead to atheroma formation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31586653"}, {"offsetInBeginSection": 0, "offsetInEndSection": 418, "text": "There are conflicting reports regarding the effect of dietary cholesterol-oxidation products (oxysterols) on the development of atherosclerosis in experimental animals. To address this issue, apolipoprotein (Apo) E-deficient mice were fed a purified diet (AIN-93) or the same purified diet containing 0.2 g cholesterol or 0.2 g oxysterols/kg. The dietary oxysterols had no significant effect on the serum lipid levels.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12323083"}, {"offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Oxysterols are oxygenated forms of cholesterol generated via autooxidation by free radicals and ROS, or formed enzymically by a variety of enzymes such as those involved in the synthesis of bile acids.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32335907"}, {"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Oxysterols are oxidized derivatives of cholesterol that are formed enzymatically or via reactive oxygen species or both.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31301352"}, {"offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Oxysterols are oxidised derivatives of cholesterol or its precursors post lanosterol.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29421651"}, {"offsetInBeginSection": 139, "offsetInEndSection": 257, "text": "Oxidation of cholesterol leads to the formation of a large number of oxidized products, generally known as oxysterols.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32175830"}, {"offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Oxysterols are critical regulators of inflammation and cholesterol metabolism in cells. They are oxidation products of cholesterol and may be differentially metabolised in subcellular compartments and in biological fluids.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32574926"}, {"offsetInBeginSection": 0, "offsetInEndSection": 428, "text": "Oxysterols are critical regulators of inflammation and cholesterol metabolism in cells. They are oxidation products of cholesterol and may be differentially metabolised in subcellular compartments and in biological fluids. New analytical methods are needed to improve our understanding of oxysterol trafficking and the molecular interplay between the cellular compartments required to maintain cholesterol/oxysterol homeostasis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32574926"}, {"offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Oxysterols are oxidized derivatives of cholesterol or by-products of cholesterol biosynthesis with multiple functions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19248802"}, {"offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Oxysterols are oxidized 27-carbon cholesterol derivatives or by-products of cholesterol biosynthesis, with a spectrum of biologic activities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24970128"}, {"offsetInBeginSection": 307, "offsetInEndSection": 531, "text": " cholesterol. Oxysterols are products of cholesterol oxidation that accumulate in conditions associated with increased cellular levels of reactive oxygen species, such as hypoxia and oxidative stress, activating LXR and inhi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25255963"}, {"offsetInBeginSection": 112, "offsetInEndSection": 302, "text": "Oxysterols and other cholesterol oxidation products are effective ligands of liver X activated receptor (LXR) nuclear receptors, major regulators of genes subserving cholesterol homeostasis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17573819"}, {"offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Oxysterols are oxygenated derivatives of cholesterol that contain an additional hydroxy, epoxide, or ketone group in the sterol nucleus and/or a hydroxyl group in the side chain of the cholesterol molecule.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36316327"}, {"offsetInBeginSection": 249, "offsetInEndSection": 368, "text": "Oxysterols are oxidized forms of cholesterol that regulate cellular cholesterol and alter immune responses to bacteria.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35154132"}, {"offsetInBeginSection": 443, "offsetInEndSection": 816, "text": "Oxysterols are formed in amounts proportional to cholesterol content in the cell and therefore LXR operate as cholesterol sensors which protect from cholesterol overload by inhibiting intestinal cholesterol absorption, stimulating cholesterol efflux from cells to high-density lipoproteins (HDL), its transport to the liver, conversion to bile acids, and biliary excretion.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19035881"}, {"offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Cholesterol oxidation products (oxysterols) have been detected in many different tissues, often at concentrations 10(3) to 10(4) times lower than cholesterol.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7657597"}, {"offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Liver X receptors LXR\u03b1 (NR1H3) and LXR\u03b2 (NR1H2) are transcription factors belonging to the nuclear receptor superfamily, activated by specific oxysterols, oxidized derivatives of cholestero", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24333430"}]}
+{"question_id": "65f84c78c4010b4d78000049", "question": "Is bowel transplantation commonly performed in patients with severe gastrointestinal disease?", "answer": "No. Bowel transplantation is extremely rarely performed.", "relevant_passage_ids": ["36755514", "37417206", "37495293", "8632926", "29528830", "10389331", "31711586", "31668184", "37097770", "28784223", "29336578", "15751317", "23420959", "9078200", "28130374", "25606643"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1047, "offsetInEndSection": 1107, "text": "5%) were potentially suitable for intestinal transplantation", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36755514"}, {"offsetInBeginSection": 792, "offsetInEndSection": 1055, "text": "patient underwent sequential intestine-liver transplantation at 8\u2009years of age due to end-stage liver disease (ESLD) and short bowel syndrome caused by massive bowel resection for internal hernia after partial external biliary diversion (PEBD) at 21\u2009months of age", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37417206"}, {"offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Intestinal transplantation and multivisceral transplantation are technically challenging and complex procedures mainly performed on patients with irreversible and non-medically manageable end-stage intestinal failure", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37495293"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1248, "text": "Small intestinal transplantation is performed for patients with intestinal failure who failed other surgical and medical treatment. It carries notable risks, including, but not limited to, acute and chronic cellular rejection and graft malfunction. Late severe acute intestinal allograft rejection is associated with increased risk of morbidity and mortality and, in the majority of cases, ends with total enterectomy. It usually results from subtherapeutic immunosuppression or nonadherence to medical treatment. We present the case of a 20-year-old patient who underwent isolated small bowel transplant for total intestinal Hirschsprung disease at age 7. Due to medication nonadherence, she developed severe late-onset acute cellular rejection manifested by high, bloody ostomy output and weight loss. Ileoscopy showed complete loss of normal intestinal anatomic landmarks and ulcerated mucosa. Graft biopsies showed ulceration and granulation tissue with severe architectural distortion consistent with severe intestinal graft rejection. She initially received intravenous corticosteroids and increased tacrolimus dose without significant improvement. Her immunosuppression was escalated to include infliximab and finally antithymocyte globulin.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31711586"}, {"offsetInBeginSection": 0, "offsetInEndSection": 599, "text": "Intestinal transplantation and multivisceral transplantation are technically challenging and complex procedures mainly performed on patients with irreversible and non-medically manageable end-stage intestinal failure. Increasingly, other organs besides small intestines are included in the allograft for which the terms \"composite intestinal transplantation\" and \"multivisceral transplantation\" are used. Commonly, complex vascular reconstructions are used for these procedures. Knowledge of surgical anatomy hence is essential for accurate interpretation of postoperative imaging in these patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37495293"}, {"offsetInBeginSection": 0, "offsetInEndSection": 862, "text": "Intestinal transplantation has evolved from its experimental origins in the mid-20th century to its status today as an established treatment option for patients with end-stage intestinal failure who cannot be sustained with total parenteral nutrition. The most common source of intestinal failure in both adults and children is short-bowel syndrome, but a host of other disease processes can lead to this common end-point. The development of intestinal transplantation has presented multiple hurdles for the transplant community, including technical challenges, immunologic pitfalls, and infectious complications. Despite these hurdles, the success rate has climbed over the past decades owing to achievements that include improved surgical techniques, new immunosuppressive regimens, and more effective strategies for posttransplant surveillance and management.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29528830"}, {"offsetInBeginSection": 0, "offsetInEndSection": 350, "text": "\"The intestinal transplantation is reserved for patients with life-threatening complications of permanent intestinal failure or underlying gastrointestinal disease. The choice of the allograft for a particular patient depends on several factors and the presence of concurrent organ failure, and availability of the donor organs, and specialized care.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31668184"}, {"offsetInBeginSection": 0, "offsetInEndSection": 566, "text": "The diagnosis of irreversible intestinal failure confers significant morbidity, mortality, and decreased quality of life. Patients with irreversible intestinal failure may be treated with intestinal transplantation. Intestinal transplantation may include intestine only, liver-intestine, or other visceral elements. Intestinal transplantation candidates present with systemic manifestations of intestinal failure requiring multidisciplinary evaluation at an intestinal transplantation center. Central access may be difficult in intestinal transplantation candidates.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28784223"}, {"offsetInBeginSection": 0, "offsetInEndSection": 945, "text": "PURPOSE OF REVIEW: The role of intestinal transplant has expanded in recent years and is no longer only considered for patients with no other options remaining. 5\u200ayear survival in high-volume centres is over 80% for certain graft types. The aim of this review is to update the audience on the current state of intestinal transplant, with a focus on recent medical and surgical advances.RECENT FINDINGS: There has been a greater understanding of the interplay and balance of host and graft immune responses, which may facilitate individualized immunosuppression. Some centres are now performing 'no-stoma' transplants, with preliminary data showing no adverse effects from this strategy and other surgical advances have lessened the physiological insult of the transplant operation. Earlier referrals are encouraged by transplant centres, such that vascular access or liver disease has not progressed too much to increase the technical and physio", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37097770"}, {"offsetInBeginSection": 151, "offsetInEndSection": 1735, "text": "Intestinal transplantation is now possible and in some conditions, constitutes the logical treatment option. Since 1985, more than 300 small-bowel grafts have been performed, involving the isolated small bowel with or without the colon (45%), the liver + small bowel (40%) or several organs (15%). 2/3 of recipients were under 20 years of age, and indications were short-bowel syndrome (64%), severe intractable diarrhea (13%), abdominal cancer (13%), or chronic intestinal pseudo-obstruction syndrome (8%). 51% of patients survived > 2 years after the graft. Patient and graft survival depends on the type of immunosuppression, i.e. Cyclosporine or FK 506. The results must be interpreted carefully as they represent the first experience in numerous centers using different immuno-suppressive protocols, without any randomization. The results from the largest of these centers more closely reflect the current situation and may exceed a 70% 2-year survival rate. Functional grafts lead to gastrointestinal autonomy (weaning of PN) while maintaining satisfactory nutritional status and normal growth in childhood. Intestinal transplantation is theoretically indicated for all patients permanently or persistently dependent on PN. However, as PN is generally well tolerated, even for long periods, each indication for transplantation must be carefully weighed up in terms of the iatrogenic risk and quality of life. When PN has reached its limits, especially those associated with vascular, infectious, hepatic or metabolic complications, intestinal transplantation must be undertaken.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10389331"}, {"offsetInBeginSection": 139, "offsetInEndSection": 1239, "text": "al Center.PATIENTS: During the past 4 years, 16 intestinal transplants have been performed in infants and children. Thirteen have been combined liver and bowel transplants, and the reminder were isolated intestinal transplants. Nearly half of the patients were younger than 1 year of age at the time of surgery, and the vast majority were younger than 5 years of age. All but one had short bowel syndrome.RESULTS: The 1-year actuarial patient and graft survival rates for recipients of liver and small bowel transplants were 76% and 61%, respectively. Eight of 13 patients who received liver and small bowel transplants remain alive at the time of this writing, with a mean length of follow-up of 263 (range, 7 to 1223) days. Six patients are currently free of total parenteral nutrition. All three patients receiving isolated intestinal transplants are alive and free of parenteral nutrition. The mean length of follow-up is 384 (range, 330 to 450) days. Major complications have included severe infections and rejection. Lymphoproliferative disease, graft-versus-host disease, and chylous ascites h", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8632926"}, {"offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Intestinal transplantation and multivisceral transplantation are technically challenging and complex procedures mainly performed on patients with irreversible and non-medically manageable end-stage intestinal failure.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37495293"}, {"offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "\"The intestinal transplantation is reserved for patients with life-threatening complications of permanent intestinal failure or underlying gastrointestinal disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31668184"}, {"offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "Intestinal transplantation represents a suitable treatment for patients with intestinal failure who then develop life-threatening complications of total parenteral nutrition and for some patients with complex abdominal disorders not suitable for conventional treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29336578"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Small intestinal transplantation is performed for patients with intestinal failure who failed other surgical and medical treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31711586"}, {"offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "Intestinal transplantation has evolved from its experimental origins in the mid-20th century to its status today as an established treatment option for patients with end-stage intestinal failure who cannot be sustained with total parenteral nutrition.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29528830"}, {"offsetInBeginSection": 842, "offsetInEndSection": 1004, "text": "Current guidelines restrict intestinal transplantation to patients who have had significant complications from PN including liver failure and repeated infections.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28130374"}, {"offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Intestinal transplantation is indicated for patients with intractable intestinal failure, especially when life-threatening complications of parenteral nutrition (PN) occur.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25606643"}, {"offsetInBeginSection": 1036, "offsetInEndSection": 1332, "text": "Although most of the long-term survivors are TPN-independent and have a good quality of life, the risk of the procedure and long-term adverse effects ofimmunosuppressive medication limits small bowel, or liver/small bowel transplantation only to patients with severe complications of TPN therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15751317"}, {"offsetInBeginSection": 535, "offsetInEndSection": 836, "text": "Intestinal transplantation is now a mature therapy with formal indications, especially in case of failure of Home Parenteral Nutrition (mainly Home Parenteral Nutrition-associated severe liver disease), where combined Liver-intestine transplantation is indicated before end-stage liver failure occurs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23420959"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "BACKGROUND: Intestinal transplantation is used in patients with short-bowel syndrome after repeated resections for Crohn's disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9078200"}]}
+{"question_id": "6630154c187cba990d000021", "question": "Which chromosome is most commonly affected by loss of heterozygosity in glioblastoma?", "answer": "Glioblastomas develop de novo (primary glioblastomas) or through progression from low-grade or anaplastic astrocytoma (secondary glioblastomas). There is increasing evidence that these glioblastoma subtypes develop through different genetic pathways. Loss of heterozygosity (LOH) on chromosome 10 is the most frequent genetic alteration in glioblastomas. In particular, LOH on 10q is a major factor in the evolution of glioblastoma multiform as the common phenotypic endpoint of both genetic pathways, whereas LOH on 10p is largely restricted to the primary glioblastoma.", "relevant_passage_ids": ["10653004", "1975510", "15924253", "8370584", "9690672", "28960585", "2544511", "19430887", "21483128", "10433932", "10850866", "1975968", "34970477", "1415476", "9393744", "17691218", "8098856", "1320666", "1384665", "10604735", "7687872", "9285695", "1357919", "8641967", "8651304", "1346255", "7621407", "10560660", "9591629", "9885980", "9499454"], "type": "factoid", "snippets": [{"offsetInBeginSection": 439, "offsetInEndSection": 551, "text": "Loss of heterozygosity (LOH) on chromosome 10 (LOH#10) is the most frequent genetic alteration in glioblastomas;", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10653004"}, {"offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "Glioblastomas develop de novo (primary glioblastomas) or through progression from low-grade or anaplastic astrocytoma (secondary glioblastomas). There is increasing evidence that these glioblastoma subtypes develop through different genetic pathways.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10653004"}, {"offsetInBeginSection": 1090, "offsetInEndSection": 1353, "text": "These results are in accordance with the view that LOH on 10q is a major factor in the evolution of glioblastoma multiform as the common phenotypic end point of both genetic pathways, whereas LOH on 10p is largely restricted to the primary (de novo) glioblastoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10653004"}, {"offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Loss of heterozygosity (LOH) on chromosome 10 frequently occurs in gliomas", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34970477"}, {"offsetInBeginSection": 439, "offsetInEndSection": 631, "text": "Loss of heterozygosity (LOH) on chromosome 10 (LOH#10) is the most frequent genetic alteration in glioblastomas; the involvement of tumor suppressor genes, other than PTEN, has been suggested.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10653004"}, {"offsetInBeginSection": 86, "offsetInEndSection": 253, "text": "Loss of heterozygosity (LOH) at markers of the long arm of chromosome 10 is the most common genetic alteration in glioblastoma, being detectable in up to 80% of cases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28960585"}, {"offsetInBeginSection": 342, "offsetInEndSection": 519, "text": "The most common genetic alteration detected involved allele losses of chromosome 10 loci; these losses were observed in all glioblastomas and in three of the anaplastic gliomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8370584"}, {"offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Loss of heterozygosity on chromosome 10 (LOH#10) is the most frequent genetic alteration in glioblastomas and occurs in more than 80% of cases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10433932"}, {"offsetInBeginSection": 831, "offsetInEndSection": 970, "text": "The majority (88%) of primary glioblastomas with LOH#10 showed LOH at all informative markers, suggesting loss of the entire chromosome 10.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10653004"}, {"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Loss of heterozygosity (LOH) for chromosome 10 is the most frequent genetic abnormality observed in high-grade gliomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10604735"}, {"offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Loss of heterozygosity (LOH) on chromosome 10 frequently occurs in gliomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34970477"}, {"offsetInBeginSection": 100, "offsetInEndSection": 236, "text": "Loss of heterozygosity of chromosome 10 and mutations in the tumor suppressor gene PTEN on 10q are molecular hallmarks of glioblastomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15924253"}, {"offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Loss of heterozygosity (LOH) from chromosome 10 is a hallmark of glioblastoma, the most malignant (grade IV) form of glioma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9393744"}, {"offsetInBeginSection": 263, "offsetInEndSection": 535, "text": "Primary glioblastomas are characterized by EGFR amplification/overexpression, PTEN mutation, homozygous p16 deletion, and loss of heterozygosity (LOH) on entire chromosome 10, whereas secondary glioblastomas frequently contain p53 mutations and show LOH on chromosome 10q.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10850866"}, {"offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Loss of heterozygosity (LOH) on chromosome 10 is the most frequent genetic alteration associated with the evolution of malignant astrocytic tumors and it may involve several loci.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9690672"}, {"offsetInBeginSection": 439, "offsetInEndSection": 550, "text": "Loss of heterozygosity (LOH) on chromosome 10 (LOH#10) is the most frequent genetic alteration in glioblastomas", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10653004"}, {"offsetInBeginSection": 0, "offsetInEndSection": 317, "text": "The loss of genetic material on chromosome 10q is frequent in different tumors and particularly in malignant gliomas. We analyzed 90 of these tumors and found loss of heterozygosity (LOH) in >90% of the informative loci in glioblastoma multiforme (GBM). Initial studies restricted the common LOH region to 10q24-qter.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8651304"}, {"offsetInBeginSection": 1267, "offsetInEndSection": 1394, "text": "LOH on chromosome 10 was found in 61% of glioblastomas, in 23% of anaplastic astrocytomas, but in 0% of low-grade astrocytomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1346255"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "The genetic abnormality most frequently identified in glioblastomas is loss of alleles on chromosome 10.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10560660"}, {"offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Deletions of chromosome 10 are the most frequent genetic abnormality in glioblastomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9591629"}, {"offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "Glioblastoma is the most frequent and aggressive brain tumor in the adult population. Loss of heterozygosity (LOH) at markers of the long arm of chromosome 10 is the most common genetic alteration in glioblastoma, being detectable in up to 80% of cases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28960585"}, {"offsetInBeginSection": 75, "offsetInEndSection": 258, "text": "Allelic deletions encompassing all or part of chromosome 10q occur frequently in GBMs, indicating that loss of one or more tumor suppressor genes on 10q plays a role in GBM formation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9499454"}, {"offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Cytogenetic and restriction fragment length polymorphism (RFLP) studies have shown that loss of one entire copy of chromosome 10 is a common genetic event in glioblastoma multiforme, the most malignant glial brain tumor in humans.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7687872"}, {"offsetInBeginSection": 1070, "offsetInEndSection": 1286, "text": "A high-resolution restriction fragment length polymorphism study of chromosome 10 loci in these patients showed that loss of broad regions of chromosome 10 was a common event, particularly in glioblastoma multiforme.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1975510"}]}
+{"question_id": "663023f3187cba990d000030", "question": "What is KineDMD?", "answer": "KineDMD is an ethomic biomarker, which is derived from daily-life behavioral data and whose value progresses with age in an S-shaped sigmoid curve form. It was derived from digital readouts of daily-life movement behavior and can predict disease progression in patients with muscular dystrophy and can potentially track the response to therapy.", "relevant_passage_ids": ["36658421"], "type": "summary", "snippets": [{"offsetInBeginSection": 950, "offsetInEndSection": 1367, "text": "we constructed a behavioral biomarker, termed the KineDMD ethomic biomarker, which is derived from daily-life behavioral data and whose value progresses with age in an S-shaped sigmoid curve form. The biomarker developed in this study, derived from digital readouts of daily-life movement behavior, can predict disease progression in patients with muscular dystrophy and can potentially track the response to therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36658421"}]}
+{"question_id": "65d12a181930410b1300002f", "question": "Can fluoroquinolones be used for patient with myasthenia gravis?", "answer": "No. Fluoroquinolones can worsen and therefore should not be used for patient with myasthenia gravis.", "relevant_passage_ids": ["36373673", "33719062", "32922263", "24029473", "21879778", "19232642", "7481384", "9521283"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1037, "offsetInEndSection": 1286, "text": "Medications that activate the immune system, such as immune checkpoint inhibitors, may cause new onset of disease, while those with actions on the neuromuscular junction, such as macrolides and fluoroquinolones, can cause acute worsening of disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36373673"}, {"offsetInBeginSection": 1601, "offsetInEndSection": 1712, "text": "Key classes of medications to use with caution include macrolides, fluoroquinolones, \u03b2-blockers, and magnesium.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36373673"}, {"offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "INTRODUCTION/AIMS: Anecdotal case reports have suggested a potential association of fluoroquinolones and macrolides with myasthenia gravis (MG) exacerbation, prompting warnings against the use of these drugs in this population.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33719062"}, {"offsetInBeginSection": 1609, "offsetInEndSection": 1896, "text": "DISCUSSION: Fluoroquinolone and macrolide antibiotics are prescribed frequently to patients with MG. While statistical imprecision precludes a definitive conclusion, elevated ORs for fluoroquinolones raise the possibility of an underpowered association that merits further investigation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33719062"}, {"offsetInBeginSection": 477, "offsetInEndSection": 886, "text": "Some clinical observations are substantiated by experimental data, indicating that presynaptic, postsynaptic or more complex pathomechanisms at the NMJ may be involved, depending on the individual compound. Most robust data exist for the risks associated with some antibiotics (e.g., aminoglycosides, ketolides, fluoroquinolones) and cardiovascular medications (e.g., class Ia antiarrhythmics, beta blockers).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32922263"}, {"offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "[Fluoroquinolone associated myasthenia gravis exacerbation: clinical analysis of 9 cases].", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24029473"}, {"offsetInBeginSection": 875, "offsetInEndSection": 995, "text": "CONCLUSION: Fluoroquinolone exposure may result in myasthenia gravis exacerbations in patients with underlying diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24029473"}, {"offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Fluoroquinolone-associated myasthenia gravis exacerbation: evaluation of postmarketing reports from the US FDA adverse event reporting system and a literature review.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21879778"}, {"offsetInBeginSection": 101, "offsetInEndSection": 224, "text": "In animal and in vitro models of experimentally-induced myasthenia gravis, fluoroquinolones exhibit neuromuscular blockade.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21879778"}, {"offsetInBeginSection": 2166, "offsetInEndSection": 2369, "text": "Healthcare professionals should be aware of this serious drug-disease association and carefully weigh the benefit-risks of fluoroquinolones when treating infections in non-ventilated myasthenic patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21879778"}, {"offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Fluoroquinolones has been rarely associated with exacerbation of myasthenia gravis (MG). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19232642"}, {"offsetInBeginSection": 198, "offsetInEndSection": 321, "text": "Fluoroquinolones of any generation may interfere with neuromuscular transmission and should be avoided in patients with MG.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19232642"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1574, "text": "INTRODUCTION/AIMS: Anecdotal case reports have suggested a potential association of fluoroquinolones and macrolides with myasthenia gravis (MG) exacerbation, prompting warnings against the use of these drugs in this population. However, large-scale and reliable population-based data that demonstrate this association are lacking. This study aims to examine the association between outpatient treatment with fluoroquinolones or macrolides and MG-related hospitalization.METHODS: A retrospective cohort study consisting of adult MG patients was conducted using a large de-identified healthcare claims database. Antibiotic prescription claims were identified, and MG-related hospitalizations were assessed at 15, 30, and 90\u2009days after the date of prescription. We used mixed effects survival regression with log-logistic distribution and independent covariance matrix to estimate odds ratios (ORs) of hospitalization for each potentially exacerbating antibiotic using beta-lactam as the reference and adjusting for covariates.RESULTS: Among 1556 MG patients receiving 894 fluoroquinolone prescriptions, 729 macrolide prescriptions, and 1608 beta-lactam prescriptions during the study period, there was no difference in 15, 30, or 90-day odds of MG-related hospitalization between fluoroquinolone or macrolide users compared to prescribed beta-lactams. However, estimates were higher for fluoroquinolones than macrolides, even after covariate adjustment (adjusted OR [aOR] 4.60, 95% confidence interval [CI] 0.55-38.57 for fluoroquinolones and OR 0.56, 95% CI 0.32-0.97 for mac", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33719062"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1484, "text": "PURPOSE: Myasthenia gravis (MG) is not commonly covered in pharmacy school curricula. However, many medications that have been reported to cause exacerbations of MG are among the top 200 most prescribed drugs. The purpose of this therapeutic update is to provide pharmacists with a general understanding of the pathophysiology and treatment of MG and describe common medications with the potential to cause new onset or acute worsening of this disease.SUMMARY: MG is an autoimmune disorder in which patients develop autoantibodies to a component of the neuromuscular junction, most frequently the acetylcholine receptor, resulting in impairment of skeletal muscle contraction. Although MG is not highly prevalent, there are up to 60,000 individuals with MG in the US, making it a disease that many pharmacists will likely encounter at least once in their career. Immunosuppressant medications and acetylcholinesterase inhibitors are the mainstays of treatment, although there is limited evidence as to which agents are most efficacious. Medications that activate the immune system, such as immune checkpoint inhibitors, may cause new onset of disease, while those with actions on the neuromuscular junction, such as macrolides and fluoroquinolones, can cause acute worsening of disease.CONCLUSION: MG, although not frequently covered in pharmacy school curricula, is a disease state for which it is not uncommon for pharmacists to provide care. Treatment tends to be patient specific,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36373673"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1063, "text": "Myasthenic syndromes are typically characterized by muscle weakness and increased fatigability due to an impaired transmission at the neuromuscular junction (NMJ). Most cases are caused by acquired autoimmune conditions such as myasthenia gravis (MG), typically with antibodies against the acetylcholine receptor (AChR). Different drugs are among the major factors that may complicate pre-existing autoimmune myasthenic conditions by further impairing transmission at the NMJ. Some clinical observations are substantiated by experimental data, indicating that presynaptic, postsynaptic or more complex pathomechanisms at the NMJ may be involved, depending on the individual compound. Most robust data exist for the risks associated with some antibiotics (e.g., aminoglycosides, ketolides, fluoroquinolones) and cardiovascular medications (e.g., class Ia antiarrhythmics, beta blockers). Apart from primarily autoimmune-mediated disorders of the NMJ, de novo myasthenic manifestations may also be triggered by medical treatments that induce an autoimmune reaction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32922263"}, {"offsetInBeginSection": 536, "offsetInEndSection": 783, "text": "The report of exacerbation of myasthenia gravis with other antibiotic belonging to the group of fluoroquinolones (ciprofloxacin, norfloxacin and ofloxacin) prompt us to recommend caution with the use of all fluoroquinolones in myasthenic patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7481384"}, {"offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "Fluoroquinolones has been rarely associated with exacerbation of myasthenia gravis (MG). We present a case of MG following a treatment with prulifloxacin, a new broad-spectrum oral fluoroquinolone. Fluoroquinolones of any generation may interfere with neuromuscular transmission and should be avoided in patients with MG.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19232642"}, {"offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Fluoroquinolones has been rarely associated with exacerbation of myasthenia gravis (MG).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19232642"}, {"offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Fluoroquinolones has been rarely associated with exacerbation of myasthenia gravis (MG). We present a case of MG following a treatment with prulifloxacin, a new broad-spectrum oral fluoroquinolone.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19232642"}, {"offsetInBeginSection": 2024, "offsetInEndSection": 2172, "text": "ONS: Fluoroquinolone exposure may result in potentially life-threatening myasthenia gravis exacerbations in patients with underlying disease. Health", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21879778"}, {"offsetInBeginSection": 432, "offsetInEndSection": 783, "text": "No additional factors which might have contributed to the exacerbation of myasthenia gravis were found. The report of exacerbation of myasthenia gravis with other antibiotic belonging to the group of fluoroquinolones (ciprofloxacin, norfloxacin and ofloxacin) prompt us to recommend caution with the use of all fluoroquinolones in myasthenic patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7481384"}, {"offsetInBeginSection": 773, "offsetInEndSection": 995, "text": "All patients improved upon the withdrawal of fluoroquinolone in conjunctions with other interventions.CONCLUSION: Fluoroquinolone exposure may result in myasthenia gravis exacerbations in patients with underlying diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24029473"}, {"offsetInBeginSection": 54, "offsetInEndSection": 180, "text": "Several case reports describe the exacerbation of muscle weakness in myasthenia gravis patients treated with fluoroquinolones.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9521283"}, {"offsetInBeginSection": 1979, "offsetInEndSection": 2115, "text": "after fluoroquinolone reintroduction.CONCLUSIONS: Fluoroquinolone exposure may result in potentially life-threatening myasthenia gravis ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21879778"}]}
+{"question_id": "66099eb9fdcbea915f000026", "question": "Are BRAF V600E mutation associated to worse prognosis in colorectal cancer patients?", "answer": "BRAF V600E mutation in microsatellite-stable colon cancer is associated with a significantly poorer survival", "relevant_passage_ids": ["21285991", "16024606", "29799910", "23650027", "32571791", "27672042", "25973534", "20162668", "30792536", "33330032", "25367198", "20501503", "20635392", "25862899", "37639010", "25636897", "24798160", "24859797", "32253230", "31840683", "36819812", "30463788", "29434925", "37760573", "30598662", "32095377", "24585723", "26376292", "26460303", "22228154", "27914130", "24833563", "28972961", "36130926", "34896698", "37369457", "36912150", "27034263", "19908233", "22899730", "34168268", "35567913", "37409251", "23549875", "35461290"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1335, "offsetInEndSection": 1440, "text": " Presence of mutated BRAF is one of the most powerful prognostic factors for advanced and recurrent CRC. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21285991"}, {"offsetInBeginSection": 888, "offsetInEndSection": 1179, "text": "The median overall survival (OS) for BRAF mutation-positive and KRAS 13 mutation-positive patients was 11.0 and 27.7 months, respectively, which was significantly worse than that for patients with wild-type (wt) KRAS and BRAF (40.6 months) (BRAF; HR=4.25, P<0.001, KRAS13; HR=2.03, P=0.024).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21285991"}, {"offsetInBeginSection": 1269, "offsetInEndSection": 1508, "text": "We conclude that the BRAF V600E mutation in microsatellite-stable colon cancer is associated with a significantly poorer survival in stages 2 to 4 colon cancer but has no effect on the excellent prognosis of microsatellite-unstable tumors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16024606"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1297, "text": "Background: BRAF V600E mutation is associated with poor prognosis of colorectal cancer (CRC) patients, but the comparison of clinic-pathologic features between V600E and non-V600E mutation was not well-known in CRC patients. The aim of this study is to evaluate the clinical and pathological features, prognostic value of BRAF mutations in CRC. Methods: We conducted a retrospective study to characterize the clinical and pathological features and survival of patients with BRAF mutated CRC. Patients were classified according to BRAF status as BRAF V600E mutation and non-V600E mutations. Difference of characteristics and survival between the two groups was analyzed. Results: There was no significant difference in gender, family history, location of primary tumor, metastatic sites between patients with BRAF-V600E mutation and non-V600E mutations. Patients with V600E mutation were younger than those with non-V600E mutations (p = 0.002). Patients with BRAF V600E mutation showed a poorer outcome than those with non-V600E mutations (23.1 vs. 49.9 months, respectively, p = 0.0024). Lack of CDX2 expression was associated with worse prognosis (mOS: 9.4 m vs. not reached, respectively, p = 0.016). Status of V600E mutation did not affect the mPFS and ORR of first-line or second-line treatmen", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33330032"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1508, "text": "PURPOSE: BRAF V600E mutations portend poor prognosis in metastatic colorectal cancer (mCRC); however, the true prevalence and prognosis are unknown, as unwell patients may not undergo BRAF sequencing.EXPERIMENTAL DESIGN: We reviewed a population-based cohort of 1,898 patients with colorectal cancer that underwent reflexive IHC mismatch repair (MMR) and BRAF V600E testing. Outcomes among IHC-detected BRAF V600E mCRC (BRAF IHC) were compared with patients with next-generation sequencing (NGS)-identified BRAF V600E-mutated mCRC from two institutions (BRAF NGS) with patients spanning from 2004 to 2018.RESULTS: All-stage population prevalence of BRAF V600E was 12.5% (238/1,898) and did not differ between early and metastatic stages (P = 0.094). Prevalence among mCRC was 10.6% (61/575), of whom 51 (83.6%) were referred to oncology and 26 (42.6%) had NGS testing. BRAF IHC had worse median overall survival (mOS) than BRAF NGS [5.5 vs. 20.4 months; HR, 2.90; 95% confidence interval (CI), 1.89-4.45; P < 0.0001], which persisted in multivariate analysis (P < 0.0001). Across a combined NGS and IHC cohort, BRAF V600E tumors with deficient MMR showed worse mOS compared with MMR proficient tumors (8.9 vs. 17.2 months; HR, 1.46; 95% CI, 0.96-2.27; P = 0.043). In this combined cohort, first-line progression-free survival was 5.9 months, with minimal differences between regimens. Within the population-based cohort, attrition between treatment lines was high with only 60.7% receiving first-line chemoth", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32571791"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1205, "text": "BACKGROUND: Recent advances in next-generation sequencing have enabled the detection of BRAF V600E mutations as well as BRAF non-V600E mutations in a single assay. The present work aimed to describe the clinicopathological characteristics and clinical outcome of the BRAF non-V600E mutant-type in colorectal cancer (CRC).PATIENTS AND METHODS: CRC samples from 111 Stage IV patients were analyzed for somatic mutations using a 415-gene comprehensive genomic sequencing panel. Patients were classified according to BRAF status as wild-type, V600E mutant-type, or non-V600E mutant-type. Differences between clinicopathological characteristics and genetic alterations were analyzed among the three groups. Overall survival (OS) and the response to anti-EGFR therapy were also analyzed.RESULTS: Comprehensive genomic sequencing revealed that 98 patients (88%), 7 patients (6%), and 6 patients (6%) were wild-type, V600E mutant-type, and non-V600E mutant-type, respectively. Non-V600E mutant-type tumors were frequently left-sided (83%), while V600E mutant-type tumors were frequently right-sided (86%; P\u00a0=\u00a00.025). Non-V600E mutant-type showed better OS than V600E mutant-type (P\u00a0=\u00a00.038), with no significant d", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30463788"}, {"offsetInBeginSection": 93, "offsetInEndSection": 769, "text": "A particularly bad prognosis might be expected for colorectal tumors with the unique molecular subtype BRAF V600E mutation. With the development of precision therapy, the advent of molecularly targeted therapies and immune checkpoint inhibitors has improved the outcome of intermediate to advanced colorectal cancer. However, the duration of drug benefit is usually short, and overall survival and progression-free survival remain suboptimal. Therefore, investigators are exploring more rational, safe, and effective drug combination regimens through clinical trials to provide longer survival for patients with such genetic mutations with metastatic colorectal cancer (mCRC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37639010"}, {"offsetInBeginSection": 161, "offsetInEndSection": 684, "text": "Patient populations continue to face poor disease prognoses due to the challenges of early detection and the molecular subtypes driving their colorectal cancer. Consequently, many patients present with metastatic colorectal cancer, which often limits options and shifts treatment focus away from curative interventions. BRAFV600E mutations are present in approximately 10% of colorectal cancer tumors and are associated with uninhibited cell proliferation, reduced apoptosis, and resistance to standard therapeutic options.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32253230"}, {"offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Background: BRAF V600E mutation is associated with poor prognosis of colorectal cancer (CRC) patients, but the comparison of clinic-pathologic features between V600E and non-V600E mutation was not well-known in CRC patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33330032"}, {"offsetInBeginSection": 0, "offsetInEndSection": 344, "text": "Background: BRAF V600E mutation is associated with poor prognosis of colorectal cancer (CRC) patients, but the comparison of clinic-pathologic features between V600E and non-V600E mutation was not well-known in CRC patients. The aim of this study is to evaluate the clinical and pathological features, prognostic value of BRAF mutations in CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33330032"}, {"offsetInBeginSection": 0, "offsetInEndSection": 491, "text": "Background: BRAF V600E mutation is associated with poor prognosis of colorectal cancer (CRC) patients, but the comparison of clinic-pathologic features between V600E and non-V600E mutation was not well-known in CRC patients. The aim of this study is to evaluate the clinical and pathological features, prognostic value of BRAF mutations in CRC. Methods: We conducted a retrospective study to characterize the clinical and pathological features and survival of patients with BRAF mutated CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33330032"}, {"offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "PURPOSE: In colorectal cancer (CRC), the BRAF V600E mutation is an important biomarker for poor prognosis, while high microsatellite instability (MSI-H) indicates good prognosis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27672042"}, {"offsetInBeginSection": 472, "offsetInEndSection": 719, "text": "BRAF V600E also predicts poor prognosis in microsatellite stable colorectal cancers and may be a marker of resistance to anti-EGFR therapy in metastatic disease. Currently, only molecular methods are available for assessing BRAF mutational status.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23650027"}, {"offsetInBeginSection": 0, "offsetInEndSection": 356, "text": "PURPOSE: In colorectal cancer (CRC), the BRAF V600E mutation is an important biomarker for poor prognosis, while high microsatellite instability (MSI-H) indicates good prognosis. Using a commercial BRAF V600E-specific antibody, we investigated the BRAF V600E mutation according to immunohistochemistry (IHC) and the MSI status in Japanese patients with CRC", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27672042"}, {"offsetInBeginSection": 329, "offsetInEndSection": 719, "text": "BRAF V600E in MLH1 deficient tumors implicates somatic tumor-only methylation of the MLH1 promoter region instead of a germline MLH1 mutation. BRAF V600E also predicts poor prognosis in microsatellite stable colorectal cancers and may be a marker of resistance to anti-EGFR therapy in metastatic disease. Currently, only molecular methods are available for assessing BRAF mutational status.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23650027"}, {"offsetInBeginSection": 472, "offsetInEndSection": 633, "text": "BRAF V600E also predicts poor prognosis in microsatellite stable colorectal cancers and may be a marker of resistance to anti-EGFR therapy in metastatic disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23650027"}, {"offsetInBeginSection": 472, "offsetInEndSection": 770, "text": "BRAF V600E also predicts poor prognosis in microsatellite stable colorectal cancers and may be a marker of resistance to anti-EGFR therapy in metastatic disease. Currently, only molecular methods are available for assessing BRAF mutational status. An immunohistochemical approach is evaluated here.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23650027"}, {"offsetInBeginSection": 1300, "offsetInEndSection": 1388, "text": "Conclusion: BRAF V600E mutation defines a distinct subgroup of CRC with worse prognosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33330032"}, {"offsetInBeginSection": 1117, "offsetInEndSection": 1460, "text": "HER2 amplification was an independent prognostic factor for worse disease-free survival (DFS) (HR = 2.53, 95% CI: 1.21-5.30, P = 0.014).CONCLUSION: The prevalence of HER2 amplification and BRAF V600E mutation in stage I-III CRC patients in Chinese was 6% and 4%, respectively, and HER2 amplification appeared to be associated with a worse DFS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32095377"}, {"offsetInBeginSection": 727, "offsetInEndSection": 890, "text": "Patients with mCRC BRAF V600E mutated (BRAFm) are generally associated with poor response to chemotherapy and short progression-free survival and overall survival.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36819812"}, {"offsetInBeginSection": 944, "offsetInEndSection": 1087, "text": "Patients with BRAF V600E mutation showed a poorer outcome than those with non-V600E mutations (23.1 vs. 49.9 months, respectively, p = 0.0024).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33330032"}, {"offsetInBeginSection": 1057, "offsetInEndSection": 1216, "text": "MSI status (P\u00a0<\u00a00.0001). Consistent with other published series, patients with BRAF V600E mutation exhibited a significantly shorter overall survival (hazard r", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27672042"}, {"offsetInBeginSection": 1218, "offsetInEndSection": 1381, "text": "io\u00a0=\u00a01.500, P\u00a0=\u00a00.0432). In particular, the microsatellite stable/BRAF mutation group had inferior prognosis compared with the MSI-H/BRAF wild-type group (hazard r", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27672042"}, {"offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "The BRAF(V600E) mutation confers worse prognosis to metastatic colorectal cancer (mCRC) patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24798160"}, {"offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "The B-type Raf kinase (BRAF) V600E mutation is a well-established biomarker for poor prognosis in metastatic colorectal cancer (mCRC) and is a highly attractive drug target.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24859797"}, {"offsetInBeginSection": 1269, "offsetInEndSection": 1506, "text": "latin, or irinotecan based chemotherapy. BRAF V600E mutation was present in 14 of 47 patients (30%). BRAF V600E patients demonstrated significantly worse median OS; 10.1 versus 17.3 months, P = 0.03. In multivariate analyses, BRAF V600E ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24585723"}, {"offsetInBeginSection": 795, "offsetInEndSection": 1180, "text": "This survival period was similar to the median overall survival among patients with metastatic CRC and BRAF mutations who were treated with the FOLFIRI regimen with or without cetuximab.CONCLUSIONS: Thus, the BRAF VK600-601E mutation may lead to an aggressive clinical course in CRC patients suffering from rapid progression and potential resistance to multiple therapeutic modalities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25636897"}, {"offsetInBeginSection": 1229, "offsetInEndSection": 1467, "text": "KRAS mutation conferred a poorer disease-free survival (HR = 0.6, 95% CI 0.38-0.97).CONCLUSIONS: The V600E BRAF mutation confers a worse prognosis to stage II and stage III colon cancer patients independently of disease stage and therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20501503"}, {"offsetInBeginSection": 953, "offsetInEndSection": 1214, "text": "Patients with double wild-type cancers (dWT; i.e., BRAF and KRAS wild-type) had a highly favourable survival with 5-year CSS of 93% (95% CI 84-100%), while patients with cancers harbouring mutations in either BRAF or KRAS, had 5-year CSS of 76% (95% CI 67-85%).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26376292"}, {"offsetInBeginSection": 9, "offsetInEndSection": 191, "text": "D: Patients with BRAFV600E-mutated metastatic colorectal cancer (mCRC) have a poorer prognosis as well as resistance to anti-EGFR antibodies. However, it is unclear whether BRAF muta", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28972961"}, {"offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Background: BRAF V600E mutation is associated with poor prognosis of colorectal cancer (CRC) patients, but the comparison of clinic-pathologic features between V600E and non-V600E mutation was not well-known in CRC patient", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33330032"}, {"offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "The BRAF(V600E) mutation confers worse prognosis to metastatic colorectal cancer (mCRC) patients. In addition, t", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24798160"}, {"offsetInBeginSection": 93, "offsetInEndSection": 254, "text": "ar pathway. BRAF mutations occur at an early stage of colorectal cancer and their presence, 10-20% of colorectal cancer (CRC), is usually associated with inferio", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25862899"}, {"offsetInBeginSection": 932, "offsetInEndSection": 1128, "text": "from colon cancer patients. BRAF V600E was associated with advanced TNM (P\u2009<\u20090.001), more distant metastases (P\u2009=\u20090.025), and worse overall survival (OS, P\u2009<\u20090.001; multivariate HR\u2009=\u20094.2, P\u2009=\u20090.00", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25367198"}, {"offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "PURPOSE: BRAF V600E mutations portend poor prognosis in metastatic colorectal cancer (mCRC); however, the true prevalence and prognosis are unknown, as unwell patients may not undergo BRAF s", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32571791"}, {"offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "PURPOSE: In colorectal cancer (CRC), the BRAF V600E mutation is an important biomarker for poor prognosis, while high microsatellite instability (MSI-H) indicates good p", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27672042"}, {"offsetInBeginSection": 224, "offsetInEndSection": 416, "text": "ar-factor-KB. Since RAC1b has been associated with the BRAF(V600E) mutation, associated with poor prognosis in CRC, we evaluated the role of RAC1b expression as a predictor of chemotherapy eff", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24833563"}, {"offsetInBeginSection": 2010, "offsetInEndSection": 2288, "text": "The V600E BRAF mutation had a stronger association with OS and DFS than the KRAS mutations (\u03b2 for OS, 10.15 vs 2.94; \u03b2 for DFS, 7.14 vs 2.27).Conclusions and Relevance: The presence of the V600E BRAF mutation was associated with worse prognosis and increased risk of recurrence.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29799910"}, {"offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "BRAF V600E-mutant colorectal cancer (CRC) is a rare subtype of colorectal cancer with poor prognosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36130926"}, {"offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "BACKGROUND: The BRAF V600E mutation is reportedly associated with inferior survival among colon canc", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25636897"}, {"offsetInBeginSection": 167, "offsetInEndSection": 321, "text": "Patients with BRAF V600E mutations, which occur in \u223c10%-15% of patients with mCRC, have a poorer prognosis compared with those with wild-type BRAF tumours", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34896698"}, {"offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "BRAF V600E mutations are associated with 8-10% of metastatic colorectal cancers (mCRC) and carry a poor prognosis with limited therapeutic options.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31840683"}, {"offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "BACKGROUND/AIM: Mutant BRAF V600E colorectal cancer accounts for 5% of metastatic colorectal cancers, and it has a poor response to systemic chemotherapy and a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37369457"}, {"offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "BACKGROUND: BRAF mutation occurs in 5%-10% of metastatic colorectal canc", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36912150"}, {"offsetInBeginSection": 162, "offsetInEndSection": 1410, "text": "The BRAF V600E mutation has been associated with worse survival in MSS CRC. This mutation occurs in 40% of MSI CRC and it is unclear whether it confers worse survival in this setting. The prognostic value of KRAS mutations in both MSS and MSI CRC remains unclear. We examined the effect of BRAF and KRAS mutations on survival in stage II and III MSI colon cancer patients. BRAF exon 15 and KRAS exon 2-3 mutation status was assessed in 143 stage II (n\u2009=\u200985) and III (n\u2009=\u200958) MSI colon cancers by high resolution melting analysis and sequencing. The relation between mutation status and cancer-specific (CSS) and overall survival (OS) was analyzed using Kaplan-Meier and Cox regression analysis. BRAF V600E mutations were observed in 51% (n\u2009=\u200973) and KRAS mutations in 16% of cases (n\u2009=\u200923). Patients with double wild-type cancers (dWT; i.e., BRAF and KRAS wild-type) had a highly favourable survival with 5-year CSS of 93% (95% CI 84-100%), while patients with cancers harbouring mutations in either BRAF or KRAS, had 5-year CSS of 76% (95% CI 67-85%). In the subgroup of stage II patients with dWT cancers no cancer-specific deaths were observed. On multivariate analysis, mutation in either BRAF or KRAS vs. dWT remained significantly prognostic.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26376292"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1097, "text": "BACKGROUND: BRAF gene encodes a serinethreonine kinase that inhibits the RAS/MAPK intracellular pathway. BRAF mutations occur at an early stage of colorectal cancer and their presence, 10-20% of colorectal cancer (CRC), is usually associated with inferior prognosis.MATERIALS AND METHODS: From 41 consecutive CRC confirmed referrals from 1,446 suspected cancer cases (mean age=67.99+13.451, male=21, female=20), we retrospectively analyzed collected data from haemoglobin (Hb) and symptoms at presentation, location of tumor and stage of the disease, including lymphovascular invasion (LVI). Gene profile analysis data (KRAS, BRAF) were retrospectively collected and associated with the presentation profile above.RESULTS: There was no significant correlation in presentation Hb levels and eventual disease staging (p>0.05 for all associations). Patients with right-sided tumours were found to have a lower Hb level than patients with either left-sided colonic or rectal tumours. Hb levels were also significantly lower in patients with the BRAF V600E mutation. KRAS status or LVI status did not h", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25862899"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1014, "text": "The BRAF(V600E) mutation confers worse prognosis to metastatic colorectal cancer (mCRC) patients. In addition, this mutation has a negative predictive value for response to treatment with monoclonal antibodies against EGFR in patients with KRAS wild-type (wt) mCRC. The utility of immunohistochemistry (IHC) as an alternative approach for detection of BRAF(V600E) in the thoracic metastases of sporadic mCRC patients has not been evaluated until now. The purpose of this study was to compare BRAF(V600E) IHC staining with molecular biology methods and to define the diagnostic value of the VE1 antibody for the detection of BRAF(V600E) in this population. BRAF mutations were analysed by two DNA sequencing methods (pyrosequencing and Sanger sequencing) in a Caucasian population of 310 sporadic mCRC with thoracic metastases patients expressing KRAS wt. Detection of the BRAF(V600E) mutation was performed in the corresponding tumours by IHC using the VE1 antibody and compared to results of the DNA-based assays.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24798160"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1422, "text": "PURPOSE: BRAF V600E mutation is seen in 5% to 8% of patients with metastatic colorectal cancer (CRC) and is associated with poor prognosis. Vemurafenib, an oral BRAF V600 inhibitor, has pronounced activity in patients with metastatic melanoma, but its activity in patients with BRAF V600E-positive metastatic CRC was unknown.PATIENTS AND METHODS: In this multi-institutional, open-label study, patients with metastatic CRC with BRAF V600 mutations were recruited to an expansion cohort at the previously determined maximum-tolerated dose of 960 mg orally twice a day.RESULTS: Twenty-one patients were enrolled, of whom 20 had received at least one prior metastatic chemotherapy regimen. Grade 3 toxicities included keratoacanthomas, rash, fatigue, and arthralgia. Of the 21 patients treated, one patient had a confirmed partial response (5%; 95% CI, 1% to 24%) and seven other patients had stable disease by RECIST criteria. Median progression-free survival was 2.1 months. Patterns of concurrent mutations, microsatellite instability status, CpG island methylation status, PTEN loss, EGFR expression, and copy number alterations were not associated with clinical benefit. In contrast to prior expectations, concurrent KRAS and NRAS mutations were detected at low allele frequency in a subset of the patients' tumors (median, 0.21% allele frequency) and were apparent mechanisms of acquired resistance in vemurafenib-sensi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26460303"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1494, "text": "PURPOSE: In colorectal cancer (CRC), the BRAF V600E mutation is an important biomarker for poor prognosis, while high microsatellite instability (MSI-H) indicates good prognosis. Using a commercial BRAF V600E-specific antibody, we investigated the BRAF V600E mutation according to immunohistochemistry (IHC) and the MSI status in Japanese patients with CRC.METHODS: In this retrospective study, tissue samples from 472 Japanese patients with CRC, stratified for MSI, were analyzed to determine the prognostic value of BRAF V600E, as assessed using IHC. Mutations in 254 patients were evaluated using the direct sequencing method to check for concordance.RESULTS: The frequency of MSI-H was 9.3\u00a0% (44/472), and BRAF V600E mutation was detected immunohistochemically in 8.7\u00a0% patients (41/472). The sensitivity and specificity for detection of BRAF V600E mutations by IHC were 100\u00a0% (17/17) and 98.7\u00a0% (234/237), respectively. BRAF V600E mutations were significantly correlated with the anatomical tumor site (P\u00a0=\u00a00.0035), histological type (P\u00a0<\u00a00.0001), and MSI status (P\u00a0<\u00a00.0001). Consistent with other published series, patients with BRAF V600E mutation exhibited a significantly shorter overall survival (hazard ratio\u00a0=\u00a01.500, P\u00a0=\u00a00.0432). In particular, the microsatellite stable/BRAF mutation group had inferior prognosis compared with the MSI-H/BRAF wild-type group (hazard ratio\u00a0=\u00a02.621, P\u00a0=\u00a00.0004).CONCLUSIONS: IHC using a BRAF V600E-specific antibody was useful for diagnosis and conc", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27672042"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1202, "text": "BACKGROUND: Patients with BRAFV600E-mutated metastatic colorectal cancer (mCRC) have a poorer prognosis as well as resistance to anti-EGFR antibodies. However, it is unclear whether BRAF mutations other than BRAFV600E (BRAFnon-V600E mutations) contribute to anti-EGFR antibody resistance.METHODS: This study was composed of exploratory and inference cohorts. Candidate biomarkers identified by whole exome sequencing from super-responders and nonresponders in the exploratory cohort were validated by targeted resequencing for patients who received anti-EGFR antibody in the inference cohort.RESULTS: In the exploratory cohort, 31 candidate biomarkers, including KRAS/NRAS/BRAF mutations, were identified. Targeted resequencing of 150 patients in the inference cohort revealed 40 patients with RAS (26.7%), 9 patients with BRAFV600E (6.0%), and 7 patients with BRAFnon-V600E mutations (4.7%), respectively. The response rates in RAS, BRAFV600E, and BRAFnon-V600E were lower than those in RAS/BRAF wild-type (2.5%, 0%, and 0% vs 31.9%). The median PFS in BRAFnon-V600E mutations was 2.4 months, similar to that in RAS or BRAFV600E mutations (2.1 and 1.6 months) but significantly worse than that in wild", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28972961"}, {"offsetInBeginSection": 0, "offsetInEndSection": 754, "text": "INTRODUCTION: Chemotherapy is the principal treatment in metastatic colorectal cancer (mCRC) patients. RAC1b, a RAC1 spliced variant, is over-expressed in colorectal cancer (CRC), and impairs apoptosis by activation of nuclear-factor-KB. Since RAC1b has been associated with the BRAF(V600E) mutation, associated with poor prognosis in CRC, we evaluated the role of RAC1b expression as a predictor of chemotherapy efficacy in mCRC.METHODS: We analysed KRAS and BRAF mutation, microsatellite instability and RAC1b expression in 157 mCRC patients treated with FOLFOX/XELOX in first-line therapy.RESULTS: KRAS mutations were detected in 46 patients (34%), 10 patients were BRAF mutant (7%) and 79 were WT for both, KRAS and BRAF (59%). RAC1b overexpression w", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24833563"}, {"offsetInBeginSection": 0, "offsetInEndSection": 931, "text": "BACKGROUND: Mutations in KRAS, BRAF and PIK3CA are the most common somatic alterations found in the colorectal cancer (CRC) patients from Western countries; but their prevalence and prognostic value have not been adequately assessed in Asian patients. The aim of this study was to determine the mutation frequencies of these genes in Chinese CRC patients and to investigate their impact on prognosis.METHODS: The sequences of exon 2 of KRAS, exon 15 of BRAF and exons 9 and 20 of PIK3CA were evaluated by PCR and direct sequencing using DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues from primary CRC tumors of 214 patients (colon/rectum: 126/88).RESULTS: KRAS, BRAF and PIK3CA mutations were identified in 44.9% (96/214), 4.2% (9/214) and 12.3% (26/212) CRCs, respectively. The most frequent mutations in KRAS, BRAF and PIK3CA were G12D, V600E and H1047R, respectively. All BRAF and 80.8% PIK3CA mutations were", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25367198"}, {"offsetInBeginSection": 685, "offsetInEndSection": 1052, "text": "In colorectal cancer, BRAFV600E mutations are associated with decreased overall survival, poor treatment responses, and different patterns of metastatic spread compared with tumors with wild-type BRAF Success in treating other BRAFV600E -mutant cancers with BRAF inhibitors as monotherapy has not translated into efficacious treatment of metastatic colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32253230"}, {"offsetInBeginSection": 93, "offsetInEndSection": 216, "text": "A particularly bad prognosis might be expected for colorectal tumors with the unique molecular subtype BRAF V600E mutation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37639010"}, {"offsetInBeginSection": 826, "offsetInEndSection": 1007, "text": "This review highlights the importance of the BRAF mutation occurring in colorectal cancer stratified for molecular background and discusses its prognostic and clinical significance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30598662"}, {"offsetInBeginSection": 732, "offsetInEndSection": 990, "text": "Although BRAF-mutant was revealed to be an independent negative prognostic factor in stage IV CRC (HR, 8.42; 95% confidence interval, 2.72-26.02), BRAF-mutant samples exhibited better prognoses if they were treated with chemotherapy prior to tumor resection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29434925"}, {"offsetInBeginSection": 708, "offsetInEndSection": 939, "text": "s: 83.2 vs 65.0%, P=0.004). Compared with BRAF wild type, BRAF(V600E) was a risk for poor survival (overall survival; 5 years: 62.3% vs 51.6%, P=0.014; HR 1.43, CI 1.07-1.90, P=0.009), especially in rectal cancer (for DSS, HR: 10.6", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25973534"}, {"offsetInBeginSection": 1066, "offsetInEndSection": 1266, "text": " BRAF(V600E) was associated with inferior overall survival in metastatic CRC (HR = 2.02; 95% CI 1.26-3.26), particularly evident in patients treated with chemotherapy, and is independent of MSI status", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20635392"}, {"offsetInBeginSection": 952, "offsetInEndSection": 1138, "text": "en with or without cetuximab.CONCLUSIONS: Thus, the BRAF VK600-601E mutation may lead to an aggressive clinical course in CRC patients suffering from rapid progression and potential resi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25636897"}, {"offsetInBeginSection": 142, "offsetInEndSection": 279, "text": "Although the frequency of BRAF V600E mutation in CRC is less than 10%, it is associated with poor responses to conventional chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34168268"}, {"offsetInBeginSection": 1057, "offsetInEndSection": 1217, "text": "MSI status (P\u00a0<\u00a00.0001). Consistent with other published series, patients with BRAF V600E mutation exhibited a significantly shorter overall survival (hazard ra", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27672042"}, {"offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "BACKGROUND: BRAF V600E+ microsatellite stable (MSS) metastatic colorectal cancer (mCRC) patients comprise up to 10% of advanced CRC. They have a poor prognosis with a median survival typica", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35567913"}, {"offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Background: Colorectal cancer (CRC) patients with BRAF mutation have very poo", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37409251"}, {"offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "In patients with colorectal cancer (CRC), the BRAF V600E mutation has been reported to be associated with several clinicopathological features and poor survival.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27914130"}, {"offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "PURPOSE: BRAF(V600E) mutations are associated with poor clinical prognosis in colorectal canc", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23549875"}, {"offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "BACKGROUND: BRAF V600E-mutant colorectal cancers (CRCs) are associated with shorter survival than BRAF wild-", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35461290"}]}
+{"question_id": "662cfadc187cba990d000006", "question": "Circular RNAs (circRNAs) are a distinct family of RNAs, how are they derived?", "answer": "Most of the circRNAs reported to date originate from back splicing of a pre-mRNA.", "relevant_passage_ids": ["37124497", "37762282", "33634138", "32972011", "29567830", "29804099", "32781555", "29182528", "27365365", "31001302", "30259367", "30259356", "36164985", "36875647", "37190069", "34571139", "29914009", "30894216", "29343298", "37139555", "31421281", "30356745", "32398477", "34195961", "37592109", "35609906", "30057200", "32399680", "27619342", "29655315", "27982727", "36494488", "33717126", "28634583", "31212038", "28418376", "30837568", "29359036", "37871444", "38089761", "36797245", "34277605", "31532701", "25259915", "30087459", "31343080", "31421856", "36270182", "28594838", "31077303", "29322444", "26908011", "36645925", "34944400", "29387208", "35453621"], "type": "summary", "snippets": [{"offsetInBeginSection": 206, "offsetInEndSection": 319, "text": "Circular RNAs (circRNAs) are generated by back-splicing and have a single-stranded continuous circular structure.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37124497"}, {"offsetInBeginSection": 141, "offsetInEndSection": 273, "text": " Circular RNAs (circRNAs) are produced by back-splicing and influence the interactive RNA network by microRNA and protein sponging. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37762282"}, {"offsetInBeginSection": 302, "offsetInEndSection": 443, "text": " Identified as a new class of RNAs, circular RNAs (circRNAs) derive from pre-mRNA back splicing with considerable stability and conservation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33634138"}, {"offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Most of the circRNAs reported to date originate from back splicing of a pre-mRNA, and these exonic circRNAs are termed canonical circRNAs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32972011"}, {"offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "Circular RNAs (circRNAs) are single-stranded and covalently closed non-coding RNA molecules originated from RNA splicing. Their functions include regulatory potential over other RNA species, such as microRNAs, messenger RNAs and RNA binding proteins.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37139555"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Circular RNAs (circRNAs) are 3'-5' covalently closed RNA rings produced from back-splicing of precursor mRNA in eukaryotes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30894216"}, {"offsetInBeginSection": 0, "offsetInEndSection": 391, "text": "Circular RNAs (circRNAs), which were discovered as a special class of endogenous non-coding RNAs, have recently shown huge capabilities as gene regulators in different species in a wide variety of organisms including viruses, plants, archaea and animals. These circRNAs mainly arise from exons or introns in different combinations by special selective splicing and are enriched in cytoplasm.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29914009"}, {"offsetInBeginSection": 0, "offsetInEndSection": 430, "text": "Unlike other non-coding RNAs (ncRNAs), circular RNA (circRNA) is generally presented as a covalently linked circle lacking both a 5' cap and a 3' tail. circRNAs were thought to be spliced intermediates, byproducts, or products of abnormal RNA splicing events. However, the high-throughput sequencing technology coupled with bioinformatics has recently uncovered thousands of endogenous circRNAs in cells of many different species.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29343298"}, {"offsetInBeginSection": 0, "offsetInEndSection": 633, "text": "Most of the circRNAs reported to date originate from back splicing of a pre-mRNA, and these exonic circRNAs are termed canonical circRNAs. Our objective was to provide an overview of all other (non-canonical) circRNAs that do not originate from the junction of two exons and to characterize their common properties. Those generated through a failure of intron lariat debranching are the best known, even though studies on them are rare. These circRNAs retain the 2'-5' bond derived from the intron lariat, and this feature probably explains the difficulties in obtaining efficient reverse transcription through the circular junction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32972011"}, {"offsetInBeginSection": 0, "offsetInEndSection": 348, "text": "Circular RNAs are a recently discovered class of RNAs formed by covalently linking the 5' and 3' end of an RNA. Pre-mRNAs generate circular RNAs through a back-splicing mechanism. Whereas in linear splicing a 5' splice site is connected to a downstream 3' splice site, in back-splicing the 5' splice site is connected to an upstream 3' splice site.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31421281"}, {"offsetInBeginSection": 0, "offsetInEndSection": 287, "text": "Circular RNAs (circRNAs) have recently been identified as a new class of long noncoding RNAs with gene regulatory roles. These covalently closed transcripts are generated when the pre-mRNA splicing machinery back splices to join a downstream 5' splice site to an upstream 3' splice site.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32398477"}, {"offsetInBeginSection": 0, "offsetInEndSection": 342, "text": "It has recently been reported that thousands of covalently linked circular RNAs (circRNAs) are expressed from human genomes. circRNAs emerge during RNA splicing. circRNAs are circularized in a reaction termed \"backsplicing,\" whereby the spliceosome fuses a splice donor site in a downstream exon to a splice acceptor site in an upstream exon.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30356745"}, {"offsetInBeginSection": 0, "offsetInEndSection": 471, "text": "Circular RNAs (circRNAs) have recently been identified as a new class of long noncoding RNAs with gene regulatory roles. These covalently closed transcripts are generated when the pre-mRNA splicing machinery back splices to join a downstream 5' splice site to an upstream 3' splice site. CircRNAs are naturally resistant to degradation by exonucleases and have long half-lives compared with their linear counterpart that potentially could serve as biomarkers for disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32398477"}, {"offsetInBeginSection": 0, "offsetInEndSection": 433, "text": "Splicing events do not always produce a linear transcript. Circular RNAs (circRNAs) are a class of RNA that are emerging as key new members of the gene regulatory milieu, which are produced by back-splicing events within genes. In circRNA formation, rather than being spliced in a linear fashion, exons can be circularised by use of the 3' acceptor splice site of an upstream exon, leading to the formation of a circular RNA species.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29182528"}, {"offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Circular RNAs (circRNAs) are covalently closed single-stranded RNA molecules derived from exons by alternative mRNA splicing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30259356"}, {"offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Circular RNAs (circRNAs) are covalently closed single-stranded RNA molecules derived from exons by alternative mRNA splicing. Circularization of single-stranded RNA molecules was already described in 1976 for viroids in plants.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30259356"}, {"offsetInBeginSection": 125, "offsetInEndSection": 342, "text": "circRNAs emerge during RNA splicing. circRNAs are circularized in a reaction termed \"backsplicing,\" whereby the spliceosome fuses a splice donor site in a downstream exon to a splice acceptor site in an upstream exon.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30356745"}, {"offsetInBeginSection": 125, "offsetInEndSection": 468, "text": "circRNAs emerge during RNA splicing. circRNAs are circularized in a reaction termed \"backsplicing,\" whereby the spliceosome fuses a splice donor site in a downstream exon to a splice acceptor site in an upstream exon. Although a young field of research, first studies indicate that backsplicing is not an erroneous reaction of the spliceosome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30356745"}, {"offsetInBeginSection": 0, "offsetInEndSection": 485, "text": "Circular RNAs (circRNAs) are covalently closed single-stranded RNA molecules derived from exons by alternative mRNA splicing. Circularization of single-stranded RNA molecules was already described in 1976 for viroids in plants. Since then several additional types of circular RNAs in many species\u00a0have been described such as the circular single-stranded RNA genome of the hepatitis delta virus (HDV) or circular RNAs as products or intermediates of tRNA and rRNA maturation in archaea.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30259356"}, {"offsetInBeginSection": 107, "offsetInEndSection": 231, "text": "Instead, they are derived in closed circle forms from pre-mRNAs by a non-canonical splicing mechanism named \"back-splicing.\"", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36164985"}, {"offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Circular RNAs (circRNAs) are a class of single-stranded RNAs derived from exonic, intronic, and intergenic regions from precursor messenger RNAs (pre-mRNA), where a noncanonical back-splicing event occurs, in which the 5' and 3' ends are attached by covalent bond.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34195961"}, {"offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Circular RNAs (circRNAs) are a novel category of covalently-closed non-coding RNAs mainly derived from the back-splicing of exons or introns of protein-coding genes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36875647"}, {"offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "A circular RNA (circRNA) is a non-coding RNA (ncRNA) derived from reverse splicing from pre-mRNA and is characterized by the absence of a cap structure at the 5' end and a poly-adenylated tail at the 3' end.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37592109"}, {"offsetInBeginSection": 0, "offsetInEndSection": 327, "text": "Circular RNAs (circRNAs) are a recently discovered class of RNAs derived from protein-coding genes that have important biological and pathological roles. They are formed through backsplicing during co-transcriptional alternative splicing; however, the unified mechanism that accounts for backsplicing decisions remains unclear.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37190069"}, {"offsetInBeginSection": 0, "offsetInEndSection": 412, "text": "Covalently closed, single-stranded circular RNAs can be produced from viral RNA genomes as well as from the processing of cellular housekeeping noncoding RNAs and precursor messenger RNAs. Recent transcriptomic studies have surprisingly uncovered that many protein-coding genes can be subjected to backsplicing, leading to widespread expression of a specific type of circular RNAs (circRNAs) in eukaryotic cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35609906"}, {"offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Covalently closed circular RNAs (circRNAs) are produced by precursor mRNA back-splicing of exons of thousands of genes in eukaryotes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30057200"}, {"offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Circular RNAs (circRNAs) are single-strand covalently closed circular noncoding RNAs that are endogenous transcripts generated from linear precursor mRNA through a backsplicing mechanism.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32399680"}, {"offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Circular RNAs (circRNAs) are novel endogenous non-coding RNAs characterized by the presence of a covalent bond linking the 3' and 5' ends generated by backsplicing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27619342"}, {"offsetInBeginSection": 369, "offsetInEndSection": 595, "text": "The pre-mRNA splicing machinery generates circRNAs via backsplicing reactions, which are often facilitated by intronic repeat sequences that base pair to one another and bring the intervening splice sites into close proximity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29655315"}, {"offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Circular RNAs (circRNAs) are a novel class of non-coding RNA characterized by a covalently closed-loop structure generated through a special type of alternative splicing termed backsplicing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27982727"}, {"offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Circular RNAs (CircRNAs) are a class of noncoding RNAs formed by backsplicing during cotranscriptional and posttranscriptional processes", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36494488"}, {"offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "Circular RNAs (circRNAs) are single-stranded, endogenous, non-coding RNA (ncRNA) molecules formed by the backsplicing of messenger RNA (mRNA) precursors and have covalently closed circular structures without 5'-end caps and 3'-end polyadenylation [poly(A)] tails.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33717126"}, {"offsetInBeginSection": 0, "offsetInEndSection": 606, "text": "Circular RNAs (circRNAs) are currently classed as non-coding RNA (ncRNA) that, unlike linear RNAs, form covalently closed continuous loops and act as gene regulators in mammals. They were originally thought to represent errors in splicing and considered to be of low abundance, however, there is now an increased appreciation of their important function in gene regulation. circRNAs are differentially generated by backsplicing of exons or from lariat introns. Unlike linear RNA, the 3' and 5' ends normally present in an RNA molecule have been joined together by covalent bonds leading to circularization.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28634583"}, {"offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Circular RNAs (circRNAs) are a distinct family of RNAs derived from alternative splicing which play a crucial role in regulating gene expression by acting as microRNA (miRNA) and RNA binding protein (RBP) sponges.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32781555"}, {"offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Circular RNAs (circRNAs) are a diverse and abundant class of hyper-stable, non-canonical RNAs that arise through a form of alternative splicing (AS) called back-splicing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28418376"}, {"offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Circular RNAs (circRNAs) are a novel class of noncoding RNAs present in all eukaryotic cells investigated so far and generated by a special mode of alternative splicing of pre-mRNAs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29359036"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Circular RNAs (circRNAs) are transcript isoforms generated by back-splicing of exons and circularisation of the transcript.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30837568"}, {"offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Circular RNAs (circRNAs) are a distinct family of RNAs derived from the non-regular process of alternative splicing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29804099"}, {"offsetInBeginSection": 59, "offsetInEndSection": 227, "text": "Circular RNAs (circRNAs) are a class of RNA that are emerging as key new members of the gene regulatory milieu, which are produced by back-splicing events within genes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29182528"}, {"offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Circular RNAs (circRNAs) are a class of RNA molecules that are characterized by their covalently closed structure, which is formed through a process of back splicing of the precursor mRNA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37871444"}, {"offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Circular RNAs (circRNAs) are a class of single-stranded closed RNAs that are produced by the back splicing of precursor mRNAs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38089761"}, {"offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Circular RNA (circRNAs) is a covalently closed circular non-coding RNA formed by reverse back-splicing from precursor messenger RNA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36797245"}, {"offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Circular RNAs (circRNAs) are a recently discovered type of covalently-closed circular non-coding RNAs, mainly formed by non-sequential back-splicing of precursor mRNAs (pre-mRNAs).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34277605"}, {"offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Formed by back splicing or back fusion of linear RNAs, circular RNAs (circRNAs) constitute a new class of non-coding RNAs of eukaryotes. Recent studies reveal a spliceosome-dependent biogenesis of circRNAs where circRNAs arise at the intron-exon junctions of mRNAs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31532701"}, {"offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Circular RNAs are generated during splicing through various mechanisms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25259915"}, {"offsetInBeginSection": 0, "offsetInEndSection": 335, "text": "Circular RNAs (circRNAs), a group of circular RNA molecules with a 3',5'-phosphodiester bond at the junction site, are generated by back-splicing of precursor mRNAs. Most of the circular RNAs originate from the exon region of the encoded protein, and some are derived from intron regions, antisense transcripts, or long noncoding RNAs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30259367"}, {"offsetInBeginSection": 0, "offsetInEndSection": 393, "text": "Circular RNAs (circRNAs) are covalently closed endogenous molecules with tissue- and disease-specific expression patterns, which have potential as diagnostic and prognostic biomarkers in cancer. The molecules are formed by a backsplicing event linking the 3'-end of an exon to the 5'-end of the same or an upstream exon, and they exert diverse regulatory functions important in carcinogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30087459"}, {"offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Exonic circular RNAs (circRNAs) are covalently closed RNA molecules generated by a process named back-splicing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31343080"}, {"offsetInBeginSection": 206, "offsetInEndSection": 326, "text": "Circular RNAs are covalently closed loop RNA species that are formed naturally through noncolinear splicing of pre-mRNA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31421856"}, {"offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Circular RNAs (circRNAs) are a recently identified class of RNAs produced via back-splicing and covalent linkage between RNA ends, resulting in a circularized RNA molecule.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36270182"}, {"offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Circular RNA (circRNA) is mainly generated by the splice donor of a downstream exon joining to an upstream splice acceptor, a phenomenon known as backsplicing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28594838"}, {"offsetInBeginSection": 0, "offsetInEndSection": 678, "text": "Circular RNAs (circRNAs) are a distinct family of RNAs derived from the non-regular process of alternative splicing. CircRNAs have recently gained interest in transcriptome research due to their potential regulatory functions during gene expression. CircRNAs can act as microRNA sponges and affect transcription through their complex involvement in regular transcriptional processes. Some early studies also suggested significant roles for circRNAs in human diseases, especially cancer, as biomarkers and potential clinical targets. Therefore, there is a great need for laboratory scientists to translate these findings into clinical tools to advance testing for human diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29804099"}, {"offsetInBeginSection": 59, "offsetInEndSection": 1026, "text": "Circular RNAs (circRNAs) are a class of RNA that are emerging as key new members of the gene regulatory milieu, which are produced by back-splicing events within genes. In circRNA formation, rather than being spliced in a linear fashion, exons can be circularised by use of the 3' acceptor splice site of an upstream exon, leading to the formation of a circular RNA species. circRNAs have been demonstrated across species and have the potential to present genetic information in new orientations distinct from their parent transcript. The importance of these RNA players in gene regulation and normal cellular homeostasis is now beginning to be recognised. They have several potential modes of action, from serving as sponges for micro RNAs and RNA binding proteins, to acting as transcriptional regulators. In accordance with an important role in the normal biology of the cell, perturbations of circRNA expression are now being reported in association with disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29182528"}, {"offsetInBeginSection": 0, "offsetInEndSection": 739, "text": "Circular RNAs (circRNAs) are a diverse and abundant class of hyper-stable, non-canonical RNAs that arise through a form of alternative splicing (AS) called back-splicing. These single-stranded, covalently-closed circRNA molecules have been identified in all eukaryotic kingdoms of life1, yet their functions have remained elusive. Here, we report that circRNAs can be used as bona fide biomarkers of functional, exon-skipped AS variants in Arabidopsis, including in the homeotic MADS-box transcription factor family. Furthermore, we demonstrate that circRNAs derived from exon 6 of the SEPALLATA3 (SEP3) gene increase abundance of the cognate exon-skipped AS variant (SEP3.3 which lacks exon 6), in turn driving floral homeotic phenotypes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28418376"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1055, "text": "Circular RNAs (circRNAs) are a distinct family of RNAs derived from alternative splicing which play a crucial role in regulating gene expression by acting as microRNA (miRNA) and RNA binding protein (RBP) sponges. However, recent studies have also reported the multifunctional potential of these particles. Under different conditions, circRNAs not only regulate protein synthesis, destination, and degradation but can serve as protein scaffolds or recruiters and are also able to produce short peptides with active biological functions. circRNAs are under ongoing investigation because of their close association with the development of diseases. Some circRNAs are reportedly expressed in a tissue- and development stage-specific manner. Furthermore, due to other features of circRNAs, including their stability, conservation, and high abundance in bodily fluids, they are believed to be potential biomarkers for various diseases, including cancers. In this review, we focus on providing a summary of the current knowledge on circRNA-protein interactions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32781555"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1352, "text": "Circular RNAs (circRNAs) are a relatively new class of RNA molecules, and knowledge about their biogenesis and function is still in its infancy. It was recently shown that alternative splicing underlies the formation of circular RNAs (circRNA) arising from the Titin (TTN) gene. Since the main mechanism by which circRNAs are formed is still unclear, we hypothesized that alternative splicing, and in particular exon skipping, is a major driver of circRNA production. We performed RNA sequencing on human and mouse hearts, mapped alternative splicing events, and overlaid these with expressed circRNAs at exon-level resolution. In addition, we performed RNA sequencing on hearts of Rbm20 KO mice to address how important Rbm20-mediated alternative splicing is in the production of cardiac circRNAs. In human and mouse hearts, we show that cardiac circRNAs are mostly (\u223c90%) produced from constitutive exons and less (\u223c10%) from alternatively spliced exons. In Rbm20 KO hearts, we identified 38 differentially expressed circRNAs of which 12 were produced from the Ttn gene. Even though Ttn appeared the most prominent target of Rbm20 for circularization, we also detected Rbm20-dependent circRNAs arising from other genes including Fan1, Stk39, Xdh, Bcl2l13, and Sorbs1 Interestingly, only Ttn circRNAs seemed to arise from Rbm20-mediated skipped exons.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29567830"}, {"offsetInBeginSection": 0, "offsetInEndSection": 552, "text": "Circular RNAs (circRNAs) differ structurally from other types of RNAs and are resistant against exoribonucleases. Although they have been detected in all domains of life, it remains unclear how circularization affects or changes functions of these ubiquitous nucleic acid circles. The biogenesis of circRNAs has been mostly described as a backsplicing event, but in archaea, where RNA splicing is a rare phenomenon, a second pathway for circRNA formation was described in the cases of rRNAs processing, tRNA intron excision, and Box C/D RNAs formation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31212038"}, {"offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Circular RNAs (circRNAs) are single-stranded and covalently closed non-coding RNA molecules originated from RNA splicing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37139555"}, {"offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Circular RNAs (circRNAs), a group of circular RNA molecules with a 3',5'-phosphodiester bond at the junction site, are generated by back-splicing of precursor mRNAs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30259367"}, {"offsetInBeginSection": 59, "offsetInEndSection": 433, "text": "Circular RNAs (circRNAs) are a class of RNA that are emerging as key new members of the gene regulatory milieu, which are produced by back-splicing events within genes. In circRNA formation, rather than being spliced in a linear fashion, exons can be circularised by use of the 3' acceptor splice site of an upstream exon, leading to the formation of a circular RNA species.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29182528"}, {"offsetInBeginSection": 59, "offsetInEndSection": 593, "text": "Circular RNAs (circRNAs) are a class of RNA that are emerging as key new members of the gene regulatory milieu, which are produced by back-splicing events within genes. In circRNA formation, rather than being spliced in a linear fashion, exons can be circularised by use of the 3' acceptor splice site of an upstream exon, leading to the formation of a circular RNA species. circRNAs have been demonstrated across species and have the potential to present genetic information in new orientations distinct from their parent transcript.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29182528"}, {"offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Circular RNAs (circRNAs) are new endogenous non-coding RNA family members that arise during pre-mRNA splicing in a reversed order in which the 3' and 5' ends are covalently closed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31001302"}, {"offsetInBeginSection": 0, "offsetInEndSection": 415, "text": "Circular RNAs (circRNAs) are new endogenous non-coding RNA family members that arise during pre-mRNA splicing in a reversed order in which the 3' and 5' ends are covalently closed. Compared to the comprehensive investigation of circRNAs in animals, circRNA research in plants is still in its infancy. Genome-wide identification and characterization of circRNAs have recently been performed in several plant species.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31001302"}, {"offsetInBeginSection": 0, "offsetInEndSection": 441, "text": "Circular RNAs (circRNAs), a group of circular RNA molecules with a 3',5'-phosphodiester bond at the junction site, are generated by back-splicing of precursor mRNAs. Most of the circular RNAs originate from the exon region of the encoded protein, and some are derived from intron regions, antisense transcripts, or long noncoding RNAs. Circular RNAs are abundantly in eukaryotic transcriptome and participate in various biological processes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30259367"}, {"offsetInBeginSection": 228, "offsetInEndSection": 715, "text": "In circRNA formation, rather than being spliced in a linear fashion, exons can be circularised by use of the 3' acceptor splice site of an upstream exon, leading to the formation of a circular RNA species. circRNAs have been demonstrated across species and have the potential to present genetic information in new orientations distinct from their parent transcript. The importance of these RNA players in gene regulation and normal cellular homeostasis is now beginning to be recognised.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29182528"}, {"offsetInBeginSection": 228, "offsetInEndSection": 593, "text": "In circRNA formation, rather than being spliced in a linear fashion, exons can be circularised by use of the 3' acceptor splice site of an upstream exon, leading to the formation of a circular RNA species. circRNAs have been demonstrated across species and have the potential to present genetic information in new orientations distinct from their parent transcript.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29182528"}, {"offsetInBeginSection": 374, "offsetInEndSection": 606, "text": "circRNAs are differentially generated by backsplicing of exons or from lariat introns. Unlike linear RNA, the 3' and 5' ends normally present in an RNA molecule have been joined together by covalent bonds leading to circularization.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28634583"}, {"offsetInBeginSection": 83, "offsetInEndSection": 230, "text": "and plants. During pre-RNA splicing, the 5' and 3' termini of exon(s) can be covalently ligated to form circRNAs through back-splicing (head-to-tai", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31077303"}, {"offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Circular RNAs (circRNAs) derived from back-spliced exons have been widely identified as being co-expressed with their linear counterparts.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27365365"}, {"offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Human transcriptome contains a large number of circular RNAs (circRNAs) that are mainly produced by back splicing of pre-mRNA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29322444"}, {"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Circular RNAs (circRNAs) are produced from precursor mRNA (pre-mRNA) back-splicing of thousands of genes in eukaryotes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26908011"}, {"offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Circular RNAs (circRNAs) are covalently closed RNA molecules generated from precursor RNAs by the head-to-tail backsplicing of exons.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36645925"}, {"offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Circular RNA (circRNA) is a group of highly stable RNA molecules with suggested roles in development and disease. They derive from linear pre-mRNAs when a 5'-splice site splices back to an upstream 3'-splice site in a process termed back-splicing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34571139"}, {"offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Circular RNA (circRNA) is a distinct class of non-coding RNA produced, in principle, using a back-splicing mechanism, conserved during evolution, with increased stability and a tissue-dependent expression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34944400"}, {"offsetInBeginSection": 176, "offsetInEndSection": 332, "text": "circRNAs are formed with covalently closed continuous loops and are mainly generated by back-splicing processes or lariat introns from exons and/or introns.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29387208"}, {"offsetInBeginSection": 180, "offsetInEndSection": 399, "text": "Whereas in linear splicing a 5' splice site is connected to a downstream 3' splice site, in back-splicing the 5' splice site is connected to an upstream 3' splice site. Both mechanisms use the spliceosome for catalysis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31421281"}, {"offsetInBeginSection": 205, "offsetInEndSection": 454, "text": "circRNAs are thought to be generated by back-splicing of pre-mRNA transcripts, which can be facilitated by reverse complementary sequences in the flanking introns and trans-acting factors, such as splicing regulatory factors and RNA-binding factors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35453621"}]}
+{"question_id": "66169f9bfdcbea915f000057", "question": "Transgender identity and mortality.", "answer": "Transgender people might have higher mortality than their cisgender counterparts.", "relevant_passage_ids": ["37367977", "36716027"], "type": "summary", "snippets": [{"offsetInBeginSection": 12, "offsetInEndSection": 140, "text": "Prior studies have suggested that transgender individuals may be a high-risk group with respect to suicide attempt and mortality", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37367977"}, {"offsetInBeginSection": 2594, "offsetInEndSection": 2784, "text": "transgender individuals had significantly higher rates of suicide attempt, suicide mortality, suicide-unrelated mortality, and all-cause mortality compared with the nontransgender population", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37367977"}, {"offsetInBeginSection": 12, "offsetInEndSection": 146, "text": "Limited prior research suggests that transgender and gender diverse (TGD) people may have higher mortality rates than cisgender people", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36716027"}, {"offsetInBeginSection": 2890, "offsetInEndSection": 2962, "text": "TGD persons had elevated mortality rates compared with cisgender persons", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36716027"}]}
+{"question_id": "663016bb187cba990d000023", "question": "Which genetic alteration is most commonly associated with the classical subtype of glioblastoma?", "answer": "Despite all of the progress in understanding its molecular biology and pathogenesis, glioblastoma (GBM) is one of the most aggressive types of cancer, and without an efficient treatment modality at the moment, it remains largely incurable. Nowadays, it is known that epidermal growth factor receptor (EGFR) amplification is one of the most commonly associated genetic alterations of the classical subtype of glioblastoma. However, targeted therapies against this type of receptor have not yet shown a clear clinical benefit.", "relevant_passage_ids": ["37446288", "33435537", "31733287", "26757882", "30680510", "24457079", "34608482", "20129251", "24410805", "22539962", "33053208", "32998960"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 598, "text": "Despite all of the progress in understanding its molecular biology and pathogenesis, glioblastoma (GBM) is one of the most aggressive types of cancers, and without an efficient treatment modality at the moment, it remains largely incurable. Nowadays, one of the most frequently studied molecules with important implications in the pathogenesis of the classical subtype of GBM is the epidermal growth factor receptor (EGFR). Although many clinical trials aiming to study EGFR targeted therapies have been performed, none of them have reported promising clinical results when used in glioma patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37446288"}, {"offsetInBeginSection": 463, "offsetInEndSection": 692, "text": "It is known that epidermal growth factor receptor (EGFR) amplification is a characteristic of the classical subtype of glioma. However, targeted therapies against this type of receptor have not yet shown a clear clinical benefit.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33435537"}, {"offsetInBeginSection": 370, "offsetInEndSection": 836, "text": "We tested this assumption by a multilevel analysis ranging from a detailed histopathological analysis to a genome-wide expression profiling by microarray and RNA-seq on gliomas induced by two distinct molecular alterations: the overstimulation of the PDGF- and the EGF- pathways. These alterations are landmarks of proneural and classical glioblastoma subtypes respectively. However, our results consistently showed a strong similarity between the two glioma models.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31733287"}, {"offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "EGFR amplification and classical subtype are associated with a poor response to bevacizumab in recurrent glioblastoma.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30680510"}, {"offsetInBeginSection": 587, "offsetInEndSection": 713, "text": "FHL1 is highly expressed and positively correlated with EGFR levels in human GBM, particularly those of the classical subtype.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33053208"}]}
+{"question_id": "66302487187cba990d000031", "question": "What is PUL-2 in Duchenne Muscular Dystrophy?", "answer": "PUL 2.0 is the performance of upper limb 2.0 (PUL) and is widely used to assess upper limb function in DMD patients.", "relevant_passage_ids": ["37066919"], "type": "factoid", "snippets": [{"offsetInBeginSection": 12, "offsetInEndSection": 113, "text": "The performance of upper limb 2.0 (PUL) is widely used to assess upper limb function in DMD patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37066919"}]}
+{"question_id": "65cfac201930410b13000013", "question": "What is the mechanism of action of Mezigdomide?", "answer": "Mezigdomide is a novel cereblon E3 ubiquitin ligase modulator with potent antiproliferative and tumoricidal activity in multiple myeloma.", "relevant_passage_ids": ["37646702", "37705327", "36342226", "37906232"], "type": "summary", "snippets": [{"offsetInBeginSection": 73, "offsetInEndSection": 292, "text": "Mezigdomide is a novel cereblon E3 ubiquitin ligase modulator with potent antiproliferative and tumoricidal activity in preclinical models of multiple myeloma, including those resistant to lenalidomide and pomalidomide.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37646702"}, {"offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Model based assessment of food and acid reducing agent effects on oral absorption of mezigdomide (CC-92480), a novel cereblon E3 ligase modulator.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37705327"}, {"offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Mezigdomide is a novel cereblon E3 ligase modulator (CELMoD) agent with enhanced autonomous cell-killing activity in multiple myeloma (MM) cells, and promising immunomodulatory and antitumor activity in patients with MM. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37705327"}, {"offsetInBeginSection": 355, "offsetInEndSection": 1018, "text": "AREAS COVERED: We review common toxicities associated with agents approved for RRMM in the past 5\u2009years, including the anti-CD38 monoclonal antibody isatuximab, the antibody-drug conjugate belantamab mafodotin, the bispecific antibody teclistamab, the chimeric antigen receptor (CAR) T cell products idecabtagene vicleucel and ciltacabtagene autoleucel, the selective inhibitor of nuclear export compound selinexor, and the drug-peptide conjugate melflufen, as well as toxicities associated with emerging agents for RRMM including additional bispecific antibodies, the BCL-2 inhibitor venetoclax, and the cereblon E3 ligase modulators iberdomide and mezigdomide. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37906232"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1292, "text": "Mezigdomide is a novel cereblon E3 ligase modulator (CELMoD) agent with enhanced autonomous cell-killing activity in multiple myeloma (MM) cells, and promising immunomodulatory and antitumor activity in patients with MM. We developed a population pharmacokinetics (PKs) model for mezigdomide in healthy subjects (HSs), and quantified effects of high-fat meal and proton pump inhibitor (PPI) on human disposition parameters. Plasma concentrations from 64 HS in two phase I clinical studies (NCT03803644 and NCT04211545) were used to develop a population PK model. The HSs received single oral doses of 0.4-3.2\u2009mg mezigdomide with full PK profiles collected. A two-compartment linear PK model with first-order absorption and lag time best described mezigdomide PK profiles in HSs. The population PK parameters of absorption rate constant, lag time, central volume of distribution, clearance, peripheral volume of distribution, and intercompartmental clearance were estimated to be 1.18\u2009h-1 (interoccasion variability [IOV]: 65%), 0.423\u2009h (IOV: 31%), 440\u2009L (interindividual variability [IIV]: 63%), 35.1\u2009L/h (IIV: 40%), 243\u2009L (IIV: 26%), and 36.8\u2009L/h (IIV: 26%), respectively. High-fat meal increased oral bioavailability by ~30% and PPI co-administration decreased oral bioavailability by ~64%.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37705327"}, {"offsetInBeginSection": 61, "offsetInEndSection": 2031, "text": " incurable. Mezigdomide is a novel cereblon E3 ubiquitin ligase modulator with potent antiproliferative and tumoricidal activity in preclinical models of multiple myeloma, including those resistant to lenalidomide and pomalidomide.METHODS: In this phase 1-2 study, we administered oral mezigdomide in combination with dexamethasone to patients with relapsed and refractory myeloma. The primary objectives of phase 1 (dose-escalation cohort) were to assess safety and pharmacokinetics and to identify the dose and schedule for phase 2. In phase 2 (dose-expansion cohort), objectives included the assessment of the overall response (partial response or better), safety, and efficacy of mezigdomide plus dexamethasone at the dose and schedule determined in phase 1.RESULTS: In phase 1, a total of 77 patients were enrolled in the study. The most common dose-limiting toxic effects were neutropenia and febrile neutropenia. On the basis of the phase 1 findings, investigators determined the recommended phase 2 dose of mezigdomide to be 1.0 mg, given once daily in combination with dexamethasone for 21 days, followed by 7 days off, in each 28-day cycle. In phase 2, a total of 101 patients received the dose identified in phase 1 in the same schedule. All patients in the dose-expansion cohort had triple-class-refractory multiple myeloma, 30 patients (30%) had received previous anti-B-cell maturation antigen (anti-BCMA) therapy, and 40 (40%) had plasmacytomas. The most common adverse events, almost all of which proved to be reversible, included neutropenia (in 77% of the patients) and infection (in 65%; grade 3, 29%; grade 4, 6%). No unexpected toxic effects were encountered. An overall response occurred in 41% of the patients (95% confidence interval [CI], 31 to 51), the median duration of response was 7.6 months (95% CI, 5.4 to 9.5; data not mature), and the median progression-free survival was 4.4 months (95% CI, 3.0 to 5.5), with a median follow-up of 7.5 ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37646702"}, {"offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Mezigdomide is a novel cereblon E3 ligase modulator (CELMoD) agent with enhanced autonomous cell-killing activity in multiple myeloma (MM) cells, and promising immunomodulatory and antitumor activity in patients with MM.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37705327"}, {"offsetInBeginSection": 72, "offsetInEndSection": 441, "text": " Mezigdomide is a novel cereblon E3 ubiquitin ligase modulator with potent antiproliferative and tumoricidal activity in preclinical models of multiple myeloma, including those resistant to lenalidomide and pomalidomide.METHODS: In this phase 1-2 study, we administered oral mezigdomide in combination with dexamethasone to patients with relapsed and refractory myeloma", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37646702"}, {"offsetInBeginSection": 73, "offsetInEndSection": 442, "text": "Mezigdomide is a novel cereblon E3 ubiquitin ligase modulator with potent antiproliferative and tumoricidal activity in preclinical models of multiple myeloma, including those resistant to lenalidomide and pomalidomide.METHODS: In this phase 1-2 study, we administered oral mezigdomide in combination with dexamethasone to patients with relapsed and refractory myeloma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37646702"}, {"offsetInBeginSection": 72, "offsetInEndSection": 594, "text": " Mezigdomide is a novel cereblon E3 ubiquitin ligase modulator with potent antiproliferative and tumoricidal activity in preclinical models of multiple myeloma, including those resistant to lenalidomide and pomalidomide.METHODS: In this phase 1-2 study, we administered oral mezigdomide in combination with dexamethasone to patients with relapsed and refractory myeloma. The primary objectives of phase 1 (dose-escalation cohort) were to assess safety and pharmacokinetics and to identify the dose and schedule for phase 2", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37646702"}, {"offsetInBeginSection": 0, "offsetInEndSection": 423, "text": "Mezigdomide is a novel cereblon E3 ligase modulator (CELMoD) agent with enhanced autonomous cell-killing activity in multiple myeloma (MM) cells, and promising immunomodulatory and antitumor activity in patients with MM. We developed a population pharmacokinetics (PKs) model for mezigdomide in healthy subjects (HSs), and quantified effects of high-fat meal and proton pump inhibitor (PPI) on human disposition parameters.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37705327"}, {"offsetInBeginSection": 0, "offsetInEndSection": 562, "text": "Mezigdomide is a novel cereblon E3 ligase modulator (CELMoD) agent with enhanced autonomous cell-killing activity in multiple myeloma (MM) cells, and promising immunomodulatory and antitumor activity in patients with MM. We developed a population pharmacokinetics (PKs) model for mezigdomide in healthy subjects (HSs), and quantified effects of high-fat meal and proton pump inhibitor (PPI) on human disposition parameters. Plasma concentrations from 64 HS in two phase I clinical studies (NCT03803644 and NCT04211545) were used to develop a population PK model.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37705327"}, {"offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "BACKGROUND: Despite recent progress, multiple myeloma remains incurable. Mezigdomide is a novel cereblon E3 ubiquitin ligase modulator with potent antiproliferative and tumoricidal activity in preclinical models of multiple myeloma, including those resistant to lenalidomide and pomalidomide", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37646702"}, {"offsetInBeginSection": 0, "offsetInEndSection": 441, "text": "BACKGROUND: Despite recent progress, multiple myeloma remains incurable. Mezigdomide is a novel cereblon E3 ubiquitin ligase modulator with potent antiproliferative and tumoricidal activity in preclinical models of multiple myeloma, including those resistant to lenalidomide and pomalidomide.METHODS: In this phase 1-2 study, we administered oral mezigdomide in combination with dexamethasone to patients with relapsed and refractory myeloma", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37646702"}]}
+{"question_id": "66099907fdcbea915f000015", "question": "What is the average median survival for advanced colorectal cancer patients?", "answer": "Median OS was roughly stable for patients diagnosed between 2004 and 2012 (22.6 months) but since has steadily improved for those diagnosed in 2013 to 2015 (28.8 months), and 2016 to 2019 (32.4 months)", "relevant_passage_ids": ["36781990", "22763194", "22848257", "15547753", "7008761", "30003196", "31933846", "16334762", "33206858", "30973370", "29516930", "32148114", "32638384", "37699362", "36630020", "29755763", "34380826", "11596040", "12482332", "38091773", "1588370", "14975808", "3435011", "36013160", "10826427"], "type": "factoid", "snippets": [{"offsetInBeginSection": 513, "offsetInEndSection": 713, "text": "Median OS was roughly stable for patients diagnosed between 2004 and 2012 (22.6 months) but since has steadily improved for those diagnosed in 2013 to 2015 (28.8 months), and 2016 to 2019 (32.4 months", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36781990"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1331, "text": "OBJECTIVES: The survival of patients with metastatic colorectal cancer (CRC) has been increasing over recent decades due to improvements in chemotherapy and surgery. There is a need to refine prognostic information to more accurately predict survival as patients survive for any given length of time to assist multidisciplinary cancer management teams in treatment decisions.MATERIALS AND METHODS: We performed a single center retrospective analysis of patients treated with metastatic CRC (unresectable and resectable) who survived >24 months between 2005 and 2015 (N=155). Patient tumor and treatment related variables were collected. Overall survival (OS) estimates conditional on surviving >24 months were compared with actuarial survival estimates of a cohort of patients (33,104 resected, 39,382 unresected) from the National Cancer Database (NCDB).RESULTS: With a median follow-up of 44.2 months, the median OS of resected patients (n=86) was not reached. The median OS of unresected patients was 75.9 months. The conditional survival probabilities of living 1, 2, or 3 years longer after 24 months of survival are 92%, 72%, and 52%, respectively, in unresectable patients and 98%, 92%, and 89% in patients who were resected. The corresponding NCDB 1, 2, and 3 year actuarial survival was 38%, 20%, and 11% for unresected pa", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30973370"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1227, "text": "CONTEXT: Colorectal cancers are frequent among cancers of gastrointestinal system. Whether there are any differences between survival in rectum and colon cancer patients is controversial.AIMS: In this study, we aimed to compare survival in surgically treated rectum and colon cancers and determine the factors affecting survival.SUBJECTS AND METHODS: The patients with colon and rectum cancer operated between 2009 and 2013 were examined retrospectively using prospective database. Patients were categorized as colon and rectum according to the tumor's location. Survival was identified as the primary outcome. Kaplan-Meier survival analysis and log-rank tests in survival assessment were used.RESULTS: One hundred and sixty-one patients with a mean age of 62.8 \u00b1 12.7 years were included in the study. Male/female ratio was 1.6. Colon and rectum patients were counted as 92 (%57.1) and 69 (%42.9), respectively. Both groups were similar in demographic data (P > 0.05). It was observed that in 46 months (mean) of follow-up, 39.7% (n: 64) died, and 60.3% (n: 97) survived. Median survival time was 79 months, and 5-year cumulative survival rate was 60.8%. Five-year cumulative survival rates in stages for 1, 2, 3 and 4 were 88", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29516930"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1223, "text": "Reported median overall survival (mOS) in metastatic colorectal cancer (mCRC) patients participating in systemic therapy trials has increased to over 30\u2009months. It is uncertain whether trial results translate to real-life populations. Moreover, patients prefer presentation of multiple survival scenarios. Population-based data of all stage IV CRC patients diagnosed between 2008 and 2016 were obtained from the Netherlands Cancer Registry, which has a case ascertainment completeness surpassing 95%. We calculated the following percentiles (scenarios) of OS per year of diagnosis for the total population, and for treatment subgroups: 10th (best-case), 25th (upper-typical), 50th (median), 75th (lower-typical) and 90th (worst-case). Twenty-five percent of patients did not receive any antitumor treatment. From 2008 to 2016, mOS of the total population (n = 27275) remained unchanged at approximately 12\u2009months. OS improved only for the upper-typical and best-case patients; by 4.2 to 29.1 months (P <\u2009.001), and by 6 to 62\u2009months (P <\u2009.001), respectively. No clinically relevant change was observed among patients who received systemic therapy, with mOS close to 15\u2009months and best-case scenario approximately 40\u2009months.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32638384"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1019, "text": "BACKGROUND: In this real-life practice study, we aimed to find whether elderly colorectal cancer (CRC) patients in our center were treated optimally and also if this has an effect on overall survival (OS) or not.METHODS: We have retrospectively screened 150 CRC patients older than 65 years, diagnosed in our institution between 2010 and 2018. As study variables, patient characteristics, tumor location, tumor, nodes, metastases stage, Eastern Cooperative Oncology Group performance status (ECOG PS), comorbidities, adjuvant or metastatic chemotherapy regimens, and treatment toxicity were recorded, and the OS rate of patients was assessed.RESULTS: The median age was 72 (range 65 - 89) years and 48 (32%) patients had metastatic disease at the time of diagnosis. The median OS (mOS) in the suboptimal adjuvant treatment group was 31.5 (range 20.7-42.3) months, whereas mOS was not reached during the median follow-up time in the optimal treatment group (P = 0.036). The addition of oxaliplatin to chemotherapy had no", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34380826"}, {"offsetInBeginSection": 0, "offsetInEndSection": 863, "text": "Background: The study aimed to assess the overall and stage-specific colorectal cancer (CRC) survival and to identify the prognostic factors for survival among Thai patients.Research design and methods: The retrospective data of CRC patients from a university hospital-based cancer registry from 2001 to 2014 were used to estimate five-year overall survival (OS). Kaplan-Meier method and log-rank tests were used to assess the differences in five-year OS by age at diagnosis, diagnostic period, tumor site, stage at diagnosis and treatment modalities. A multivariate Cox's proportional hazard model was used to identify independent prognostic factors for the OS.Results: A total of 1,507 (48%) colon and 1,648 (52%) rectal cancer patients were included. Five-year OS for CRC patients was 44%. It differed significantly by stage, age group, and treatment received.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32148114"}, {"offsetInBeginSection": 0, "offsetInEndSection": 758, "text": "BACKGROUND: Hospital-based studies recently have shown increases in colorectal cancer survival, and better survival for women, young people, and patients diagnosed at an early disease stage.OBJECTIVE: To describe the overall survival and analyze the prognostic factors of patients treated for colorectal cancer at an oncology center.METHODS: The analysis included patients diagnosed with colon and rectal adenocarcinoma between 2000 and 2013 and identified in the Hospital Cancer Registry at A.C.Camargo Cancer Center. Overall 5-year survival was estimated using the Kaplan-Meier method, and prognostic factors were evaluated in a Cox regression model. Hazard ratios (HR) are reported with 95% confidence intervals (CI).RESULTS: Of 2,279 colorectal cancer ca", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33206858"}, {"offsetInBeginSection": 0, "offsetInEndSection": 942, "text": "BACKGROUND: An aging population and a high incidence of colorectal cancer (CRC) in patients over the age of 80 make it important to understand survival times, hazard ratios and prognostic factors in this group. A better understanding of these factors will help clinicians determine appropriate therapeutic strategies for such patients, including when more aggressive treatment strategies may be preferred to palliative treatment.METHODS: A retrospective analysis of 619 CRC patients of \u226580 years of age from 1991-2010 at Baylor Scott & White Hospital in Temple, Texas. Twelve variables were analyzed through statistical analysis as potential prognostic factors for survival. Univariate and multivariate Cox proportional hazard models were used to determine hazard ratios. The elderly population was further stratified by age subgroup (80-84, 85-89, \u226590).RESULTS: Median survival time was 53.6, 30.0, and 11.3 months for age groups of 80-84, 8", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29755763"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1245, "text": "Introduction Survival of patients suffering from metastatic colorectal cancer (mCRC) has increased over the last decades. These benefits appear to be restricted to patients aged 50 and above. However, among the population aged < 50, CRC incidence and mortality rates are significantly rising. The clinical benefit of treatment in this population still is a matter of debate. We aim to compare the clinical outcome between patients aged 50 and younger. Methods In this retrospective, observational study, we analyzed data from 1077 patients treated for mCRC at three cancer centers in Austria from January 2005 to December 2019. Patients were divided into two groups based on age at diagnosis: <50 years (eo-CRC) and >50 years (regular-onset CRC, ro-CRC). Propensity score matching was used to control for potential biases, and survival outcomes were compared between the two groups. Results The differences in tumor characteristics between eo-CRC and ro-CRC in the overall population were primarily related to tumor sidedness and disease-free survival following intended curative resection. Our data show that eo-CRC patients underwent metastases resection more often and received significantly more lines of treatment in the palliative setting.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37699362"}, {"offsetInBeginSection": 0, "offsetInEndSection": 855, "text": "PURPOSE: The purpose of this study was to evaluate clinical outcomes of standard therapies in previously treated, advanced colorectal cancer (CRC) patients.METHODS: A systematic literature review was conducted in Embase, MEDLINE, and CENTRAL databases (January 2000-July 2021), annual oncology conferences (2019-2021), and clinicaltrials.gov to identify studies evaluating the use of licensed interventions in second-line or later settings. The primary outcome of interest was objective response rate (ORR) and secondary outcomes included progression-free survival (PFS) and overall survival (OS). ORR was pooled using the Freeman-Tukey double arcsine transformation. For survival outcomes, published Kaplan-Meier curves for OS and PFS were digitized to re-construct individual patient-level data and pooled following the methodology described by Combescu", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36630020"}, {"offsetInBeginSection": 1018, "offsetInEndSection": 1099, "text": "The results showed the median survival of patients to be 24 months (range 16-42).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22848257"}, {"offsetInBeginSection": 1018, "offsetInEndSection": 1184, "text": "The results showed the median survival of patients to be 24 months (range 16-42). One-year survival was found to be 65% while the 2-year survival was found to be 25%.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22848257"}, {"offsetInBeginSection": 748, "offsetInEndSection": 834, "text": " median survival from the diagnosis of advanced/metastatic disease was 34.3 months. On", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16334762"}, {"offsetInBeginSection": 1100, "offsetInEndSection": 1395, "text": "One-year survival was found to be 65% while the 2-year survival was found to be 25%. A satisfactory quality of life was also observed. In conclusion, colorectal cancer is a slow-going malignancy, as indicated by the long-term survival of patients and the biological characteristics of the tumor.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22848257"}, {"offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Survival of untreated advanced colorectal cancer patients.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22848257"}, {"offsetInBeginSection": 797, "offsetInEndSection": 998, "text": "Recent randomized trials of first-line chemotherapy for metastatic colorectal cancer in which patients were likely to have access to all 3 effective drugs demonstrated median survivals of 18-20 months.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12482332"}, {"offsetInBeginSection": 1112, "offsetInEndSection": 1195, "text": "Survival of all patients was as follows: median 25 months (range 16.1-33.9 months).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15547753"}, {"offsetInBeginSection": 928, "offsetInEndSection": 1032, "text": "Median follow-up was 33\u00a0months (range 5-61) with a response rate of 63.6% and stable disease rate of 75%", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38091773"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1350, "text": "Our primary objective was to determine the median and overall survival and secondarily the response rate to first- and second-line chemotherapy of patients with advanced colorectal metastatic disease. Three-hundred and seventy-nine patients (median age 60 years, range 30-87 years) were enrolled from April 1993 to March 2000. Median follow-up was 6 years (range 3-10 years), until July 2003. All patients were evaluable for survival and 342 were evaluable for response and toxicity. Thirty-seven patients did not undergo chemotherapy. All patients had confirmed histology as well as metastatic disease based on radiological tests. First-line treatment was administered to 342 patients: leucovorin (LV) 30 mg/m2 and 5-fluorouracil (5-FU) 425 mg/m2. Three different combinations were given as second-line treatment during different chronological periods: i) 5-FU, mitomycin-C and doxorubicin (FAM); ii) 5-FU and cisplatin (CDDP) and iii) 5-FU, LV and irinotecan (CPT-II). Responses were observed as follows: first-line treatment 16.37%, after FAM 25%, following 5-FU-CDDP 26.83% and after 5-FU-LV-CPT-II, 30.61%. Survival of all patients was as follows: median 25 months (range 16.1-33.9 months). The longest survival was of patients on 5-FU-LV-CPT-II. Median survival of patients with stable disease was 19 months and of untreated patients 12 months.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15547753"}, {"offsetInBeginSection": 171, "offsetInEndSection": 1589, "text": "The last ten years allowed a rapid evolution for colon chemotherapy with a switch from 5-FU modulated by leucovorin to poly-chemotherapy (fluoropyrimidines with oxaliplatin or irinotecan) integrated into therapeutic strategies, where surgery had a place more and more important in metastatic patients. In correlation with these advances, median survival of patient with metastatic colorectal cancer is between 17 and 22 months. Targeted therapeutics with monoclonal antibody such as EGF inhibitors (cetuximab) or VEGF inhibitors (bevacizumab) had for the first time demonstrated efficacy with encouraging results in randomised trials. In adjuvant situation, LV5FU2 is less toxic than monthly FUFOL and no statistically significant difference could be detected in disease-free or overall survival between the two schedules. Oxaliplatin combined with 5 fluorouracil and leucovorin (FOLFOX4) is the first combination to demonstrate significant superiority over 5 fluorouracil and leucovorin in adjuvant treatment of colorectal cancer. Fluorouracil-based adjuvant chemotherapy benefited to patients with stage II or III colon cancer with microsatellite-stable tumours or tumour exhibiting low-frequency microsatellite instability but may be not those with tumours exhibiting high-frequency microsatellite instability (MSI). These data need to be confirmed by prospective studies before changing our therapeutic references.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14975808"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1653, "text": "PURPOSE: The advantage of chemotherapy in asymptomatic patients with advanced colorectal cancer is debatable. Whether early chemotherapy improves survival and the length of the symptom-free period versus no therapy until symptoms appear was studied in a randomized trial.PATIENTS AND METHODS: A total of 183 patients with advanced, but asymptomatic colorectal cancer were randomly allocated to receive either initial treatment with sequential methotrexate 250 mg/m2 during the first 2 hours, and fluorouracil (5-FU) 500 mg/m2 at hours 3 and 23 followed by leucovorin rescue initiated at hour 24 (MFL) for 12 courses or to primary expectancy with chemotherapy not considered until symptoms appeared. One patient was ineligible and excluded from analysis. Nine patients did not fulfill the inclusion criteria and five patients refused treatment allocation; these patients were not excluded from the study population so as not to introduce bias. So far, 51 of 90 (60%) patients in the expectancy group have received chemotherapy.RESULTS: Overall survival was better in the MFL group than in the expectancy group (Breslow-Gehan, P less than .02; log-rank, P = .13) with a difference in median survival of approximately 5 months. Also the symptom-free period and the time to disease progression were longer in the MFL group (P less than .001), with median differences of 8 and 4 months, respectively. Toxicity to MFL treatment was low; however, three patients died because of toxicity--none of them should have received therapy because of poor performance or S-creatinine elevation. The patients maintained an excellent performance throughout the MFL treatme", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1588370"}, {"offsetInBeginSection": 1208, "offsetInEndSection": 1555, "text": " trend was most pronounced for patients with colorectal carcinoma. At 5 years after the initial diagnosis, the remaining median survival was longest for patients with colorectal carcinoma, almost 6 years (71.5 months), followed by patients with lung carcinoma (52.5 months), breast carcinoma (42.5 months), and prostate carcinoma (34.5 months). Al", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11596040"}, {"offsetInBeginSection": 1278, "offsetInEndSection": 1669, "text": "5 years after the initial diagnosis, the remaining median survival was longest for patients with colorectal carcinoma, almost 6 years (71.5 months), followed by patients with lung carcinoma (52.5 months), breast carcinoma (42.5 months), and prostate carcinoma (34.5 months). Although race was a correlate with initial survival, gender and age had more impact on late conditional survival.CON", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11596040"}, {"offsetInBeginSection": 1208, "offsetInEndSection": 1669, "text": " trend was most pronounced for patients with colorectal carcinoma. At 5 years after the initial diagnosis, the remaining median survival was longest for patients with colorectal carcinoma, almost 6 years (71.5 months), followed by patients with lung carcinoma (52.5 months), breast carcinoma (42.5 months), and prostate carcinoma (34.5 months). Although race was a correlate with initial survival, gender and age had more impact on late conditional survival.CON", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11596040"}, {"offsetInBeginSection": 1278, "offsetInEndSection": 1863, "text": "5 years after the initial diagnosis, the remaining median survival was longest for patients with colorectal carcinoma, almost 6 years (71.5 months), followed by patients with lung carcinoma (52.5 months), breast carcinoma (42.5 months), and prostate carcinoma (34.5 months). Although race was a correlate with initial survival, gender and age had more impact on late conditional survival.CONCLUSIONS: The conditional median survival provides useful and encouraging information for patients who survive with advanced disease and for healthcare professionals who treat these patients. Ho", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11596040"}, {"offsetInBeginSection": 216, "offsetInEndSection": 321, "text": "ctively. Systemic chemotherapy produces a modest improvement to 48, 21, and 3 percent and 12 months, resp", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10826427"}, {"offsetInBeginSection": 322, "offsetInEndSection": 434, "text": "ctively. Regional chemotherapy produces a further improvement to 64, 25, and 5 percent and 15 to 17 months, resp", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10826427"}]}
+{"question_id": "662cfa24187cba990d000005", "question": "What is the function of the mTORC1 kinase?", "answer": "The mammalian target of rapamycin (mTOR) is one of the most important signaling pathways that regulate nutrient sensing, cell growth, metabolism, and aging. The mTOR pathway, particularly mTOR complex 1 (mTORC1), has been shown to control aging, lifespan, and healthspan through the regulation of protein synthesis, autophagy, mitochondrial function, and metabolic health.", "relevant_passage_ids": ["37057673", "37274127", "17510057", "21576368", "31451768", "25457612", "30359581", "22168436", "24666346", "29515755", "31277692", "36858209", "34245780", "32854217", "29337437", "32122730", "35580586", "32899613", "28411448", "37507012", "23863160", "35948564", "37511253", "37225457", "19272448", "21138990", "28583723", "22576015", "18812319", "24558442", "19209957", "19995915", "30552228", "19270521", "25514416", "17956308", "20670887", "34965982", "25940091", "19297407", "21795849", "23416465", "32850834", "19166929", "36732624", "25263562", "36189922", "19143637", "23184942", "19690328", "23928304"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 372, "text": "The mammalian target of rapamycin (mTOR) is one of the most important signaling pathways that regulate nutrient sensing, cell growth, metabolism, and aging. The mTOR pathway, particularly mTOR complex 1 (mTORC1), has been shown to control aging, lifespan, and healthspan through the regulation of protein synthesis, autophagy, mitochondrial function, and metabolic health.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37274127"}, {"offsetInBeginSection": 9, "offsetInEndSection": 123, "text": "Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) regulates cell growth in response to nutritional status.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37057673"}, {"offsetInBeginSection": 0, "offsetInEndSection": 938, "text": "Mechanistic (or mammalian) target of rapamycin (mTOR) is a kinase that regulates almost all functions related to cell growth and metabolism in response to extra- and intracellular stimuli, such as availability of nutrients, the presence of growth factors, or the energy status of the cell. As part of two distinct protein complexes, mTORC1 and mTORC2, the kinase has been shown to influence cell growth and proliferation by controlling ribosome biogenesis, mRNA translation, carbohydrate and lipid metabolism, protein degradation, autophagy as well as microtubule and actin dynamics. In addition to these well-characterized functions, mTOR can also influence gene transcription. While most studies focused on investigating how canonical mTOR signaling regulates the activity of transcription factors outside the nucleus, recent findings point to a more direct role for mTOR as a transcription factor operating on chromatin in the nucleus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29337437"}, {"offsetInBeginSection": 0, "offsetInEndSection": 782, "text": "Mechanistic target of rapamycin (mTOR) is a protein kinase regulating cell growth, survival, metabolism, and immunity. mTOR is usually assembled into several complexes such as mTOR complex 1/2 (mTORC1/2). In cooperation with raptor, rictor, LST8, and mSin1, key components in mTORC1 or mTORC2, mTOR catalyzes the phosphorylation of multiple targets such as ribosomal protein S6 kinase \u03b2-1 (S6K1), eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), Akt, protein kinase C (PKC), and type-I insulin-like growth factor receptor (IGF-IR), thereby regulating protein synthesis, nutrients metabolism, growth factor signaling, cell growth, and migration. Activation of mTOR promotes tumor growth and metastasis. Many mTOR inhibitors have been developed to treat cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31277692"}, {"offsetInBeginSection": 313, "offsetInEndSection": 1116, "text": "mTORC1 and the less well studied mTORC2 respond to diverse cues to control cellular metabolism, proliferation, and survival. Although TBK1 has been linked to Akt phosphorylation, a direct relationship between TBK1 and mTORC2, an Akt kinase, has not been described. By studying MEFs lacking TBK1, as well as MEFs, macrophages, and mice bearing an Mtor S2159A knock-in allele (MtorA/A) using in\u00a0vitro kinase assays and cell-based approaches, we demonstrate here that TBK1 activates mTOR complex 2 (mTORC2) directly to increase Akt phosphorylation. We find that TBK1 and mTOR S2159 phosphorylation promotes mTOR-dependent phosphorylation of Akt in response to several growth factors and poly(I:C). Mechanistically, TBK1 coimmunoprecipitates with mTORC2 and phosphorylates mTOR S2159 within mTORC2 in cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34245780"}, {"offsetInBeginSection": 0, "offsetInEndSection": 498, "text": "The mammalian target of rapamycin (mTOR) is an evolutionary conserved Ser/Thr protein kinase that senses multiple upstream stimuli to control cell growth, metabolism, and autophagy. mTOR is the catalytic subunit of mTOR complex 1 (mTORC1). A significant amount of research has uncovered the signaling pathways regulated by mTORC1, and the involvement of these signaling cascades in human diseases like cancer, diabetes, and ageing. Here, we review advances in mTORC1 regulation by upstream stimuli.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32854217"}, {"offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "Mammalian target of rapamycin (mTOR), a serine/threonine protein kinase and a master regulator of cell growth and metabolism, forms two structurally and functionally distinct complexes, mTOR complex 1 (mTORC1) and mTORC2. While mTORC1 signaling is well characterized, mTORC2 is relatively poorly understood.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32899613"}, {"offsetInBeginSection": 0, "offsetInEndSection": 612, "text": "The mechanistic (or mammalian) Target of Rapamycin Complex 1 (mTORC1) is a central regulator of cell growth and metabolism. By integrating mitogenic signals, mTORC1-dependent phosphorylation of substrates dictates the balance between anabolic, pro-growth and catabolic, recycling processes in the cell. The discovery that amino acids activate mTORC1 by promoting its translocation to the lysosome was a fundamental advance in the understanding of mTORC1 signalling. It has since become clear that the lysosome-cytoplasm shuttling of mTORC1 represents just one layer of spatial control of this signalling pathway.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32122730"}, {"offsetInBeginSection": 0, "offsetInEndSection": 467, "text": "The mammalian target of rapamycin complex 1 (mTORC1) functions as an environmental sensor to promote critical cellular processes such as protein synthesis, cell growth, and cell proliferation in response to growth factors and nutrients. While diverse stimuli regulate mTORC1 signaling, the direct molecular mechanisms by which mTORC1 senses and responds to these signals remain poorly defined. Here we investigated the role of mTOR phosphorylation in mTORC1 function.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21576368"}, {"offsetInBeginSection": 0, "offsetInEndSection": 393, "text": "The mammalian target of rapamycin complex 1 (mTORC1) functions as an environmental sensor to promote critical cellular processes such as protein synthesis, cell growth, and cell proliferation in response to growth factors and nutrients. While diverse stimuli regulate mTORC1 signaling, the direct molecular mechanisms by which mTORC1 senses and responds to these signals remain poorly defined.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21576368"}, {"offsetInBeginSection": 377, "offsetInEndSection": 1098, "text": "mTORC1 [mammalian (or mechanistic) target of rapamycin complex 1] is often considered to be the master regulator of cell growth that enhances cellular biomass through up-regulation of protein translation. In order for cells to control cellular homoeostasis during growth, there is close signalling interplay between mTORC1 and two other protein kinases, AMPK (AMP-activated protein kinase) and ULK1 (Unc-51-like kinase 1). This kinase triad collectively senses the energy and nutrient status of the cell and appropriately dictates whether the cell will actively favour energy- and amino-acid-consuming anabolic processes such as cellular growth, or energy- and amino-acid-generating catabolic processes such as autophagy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23863160"}, {"offsetInBeginSection": 273, "offsetInEndSection": 799, "text": "Consequently, the energy and nutrient status of\u00a0the cell is acutely monitored and carefully maintained. mTORC1 [mammalian (or mechanistic) target of rapamycin complex 1] is often considered to be the master regulator of cell growth that enhances cellular biomass through up-regulation of protein translation. In order for cells to control cellular homoeostasis during growth, there is close signalling interplay between mTORC1 and two other protein kinases, AMPK (AMP-activated protein kinase) and ULK1 (Unc-51-like kinase 1).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23863160"}, {"offsetInBeginSection": 0, "offsetInEndSection": 569, "text": "mTOR [mechanistic target of rapamycin] is a serine/threonine protein kinase that, as part of mTORC1 (mTOR complex 1), acts as an important molecular connection between nutrient signals and the metabolic processes indispensable for cell growth. While there has been pronounced interest in the upstream mechanisms regulating mTORC1, the full range of downstream molecular targets through which mTORC1 signaling stimulates cell growth is only recently emerging. It is now evident that mTORC1 promotes cell growth primarily through the activation of key anabolic processes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28411448"}, {"offsetInBeginSection": 0, "offsetInEndSection": 458, "text": "mTOR [mechanistic target of rapamycin] is a serine/threonine protein kinase that, as part of mTORC1 (mTOR complex 1), acts as an important molecular connection between nutrient signals and the metabolic processes indispensable for cell growth. While there has been pronounced interest in the upstream mechanisms regulating mTORC1, the full range of downstream molecular targets through which mTORC1 signaling stimulates cell growth is only recently emerging.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28411448"}, {"offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "The conserved protein kinase mTOR (mechanistic target of rapamycin) responds to diverse environmental cues to control cell metabolism and promote cell growth, proliferation, and survival as part of two multiprotein complexes, mTOR complex 1 (mTORC1) and mTORC2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37507012"}, {"offsetInBeginSection": 273, "offsetInEndSection": 581, "text": "Consequently, the energy and nutrient status of\u00a0the cell is acutely monitored and carefully maintained. mTORC1 [mammalian (or mechanistic) target of rapamycin complex 1] is often considered to be the master regulator of cell growth that enhances cellular biomass through up-regulation of protein translation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23863160"}, {"offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "The mammalian target of rapamycin complex 1 (mTORC1) functions as an environmental sensor to promote critical cellular processes such as protein synthesis, cell growth, and cell proliferation in response to growth factors and nutrients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21576368"}, {"offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "mTORC1 signaling and the metabolic control of cell growth.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28411448"}, {"offsetInBeginSection": 974, "offsetInEndSection": 1141, "text": "Thus, the mTORC1-controlled phosphorylation status of SCYL1 is an important determinant regulating subcellular distribution and function of endolysosomal compartments.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35948564"}, {"offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "The mammalian (or mechanistic) target of rapamycin (mTOR) complex 1 (mTORC1) is a serine and threonine kinase that regulates cell growth, survival, and proliferation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24666346"}, {"offsetInBeginSection": 167, "offsetInEndSection": 237, "text": "mTORC1 is a master controller of the translation of a subset of mRNAs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24666346"}, {"offsetInBeginSection": 238, "offsetInEndSection": 383, "text": "In the central nervous system mTORC1 plays a crucial role in mechanisms underlying learning and memory by controlling synaptic protein synthesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24666346"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1762, "text": "The mammalian target of rapamycin (mTOR) pathway is implicated in a number of human diseases, but the pathway details are not fully understood. Here we elucidate the interactions between various proteins involved in mTOR complex 1 (mTORC1). An in vitro mTORC1 kinase assay approach was used to probe the role of the mTORC1 component Raptor and revealed that certain Raptor mutations disrupt binding to eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and prevent its subsequent phosphorylation by mTOR. Interestingly, we show that a point mutation in the highly conserved Raptor RNC domain still allows binding to mTOR but prevents Raptor association and mTOR-dependent phosphorylation of 4E-BP1, indicating that this Raptor domain facilitates substrate recognition by mTORC1. This Raptor RNC domain mutant also dominantly inhibits mTORC1 signalling to 4E-BP1, S6K1 and HIF1alpha in vivo. We further characterise the functions of the mTORC1 signalling (TOS) and RAIP motifs of 4E-BP1, which are involved in substrate recognition by Raptor and phosphorylation by mTORC1. We show that an mTOR mutant, L1460P, responds to insulin even in nutrient-deprived conditions and is resistant to inhibition by inactive RagB-RagC heterodimers that mimic nutrient withdrawal suggesting that this region of mTOR is involved in sensing the permissive amino acid input. We found that FKBP38 inhibits mTOR(L1460P), while the mTOR(E2419K) kinase domain mutant was resistant to FKBP38 inhibition. Finally, we show that activation of mTORC1 by both Rheb and RhebL1 is impaired by FKBP38. Our work demonstrates the value of an in vitro mTORC1 kinase assay to characterise cell signalling components of mTORC1 involved in recognition and phosphotransfer to mTORC1 substrates.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19272448"}, {"offsetInBeginSection": 1082, "offsetInEndSection": 1366, "text": "These results indicate that the activity of mTORC1 actually directs these cellular processes in response to nutrient status and confirm the biological functions of mTORC1, which had been proposed solely from loss-of-function analyses using rapamycin and (molecular)genetic techniques.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18812319"}, {"offsetInBeginSection": 1320, "offsetInEndSection": 1459, "text": "Our results unveil a novel role for MTORC1 in the maintenance of cellular homeostasis by regulating autophagy at the transcriptional level.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22576015"}, {"offsetInBeginSection": 732, "offsetInEndSection": 933, "text": "The results thus far indicate that the mTORC1-S6K1 axis controls fundamental cellular processes, including transcription, translation, protein and lipid synthesis, cell growth/size and cell metabolism.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22168436"}, {"offsetInBeginSection": 248, "offsetInEndSection": 337, "text": "mTORC1 transduces anabolic signals to stimulate protein synthesis and inhibits autophagy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29515755"}, {"offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "The mechanistic target of rapamycin (mTOR) functions as a component of two large complexes, mTORC1 and mTORC2, which play crucial roles in regulating cell growth and homeostasis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24558442"}, {"offsetInBeginSection": 0, "offsetInEndSection": 352, "text": "The mechanistic (or mammalian) target of rapamycin complex 1 (mTORC1) controls cell growth, proliferation, and metabolism in response to diverse stimuli. Two major parallel pathways are implicated in mTORC1 regulation including a growth factor-responsive pathway mediated via TSC2/Rheb and an amino acid-responsive pathway mediated via the Rag GTPases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30552228"}, {"offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "The mammalian target of rapamycin complex 1 (mTORC1) is involved in the cellular transcription and translation processes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25514416"}, {"offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Amino acids regulate signalling through the mTORC1 (mammalian target of rapamycin, complex 1) and thereby control a number of components of the translational machinery, including initiation and elongation factors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17956308"}, {"offsetInBeginSection": 390, "offsetInEndSection": 569, "text": "mTORC1 activation is sufficient to stimulate specific metabolic pathways, including glycolysis, the oxidative arm of the pentose phosphate pathway, and de novo lipid biosynthesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20670887"}, {"offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "The mammalian target of rapamycin complex 1 (mTORC1) is a critical regulator of protein synthesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25940091"}, {"offsetInBeginSection": 514, "offsetInEndSection": 647, "text": "mTORC1 plays an essential role in a wide array of cellular processes including translation, transcription, trafficking and autophagy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19297407"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "PURPOSE: Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) regulates cell growth in response to nutritional status.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37057673"}, {"offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "The protein kinase mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth and proliferation, supporting anabolic reactions and inhibiting catabolic pathways like autophagy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35948564"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1034, "text": "The mammalian target of rapamycin complex 1 (mTORC1) functions as an environmental sensor to promote critical cellular processes such as protein synthesis, cell growth, and cell proliferation in response to growth factors and nutrients. While diverse stimuli regulate mTORC1 signaling, the direct molecular mechanisms by which mTORC1 senses and responds to these signals remain poorly defined. Here we investigated the role of mTOR phosphorylation in mTORC1 function. By employing mass spectrometry and phospho-specific antibodies, we demonstrated novel phosphorylation on S2159 and T2164 within the mTOR kinase domain. Mutational analysis of these phosphorylation sites indicates that dual S2159/T2164 phosphorylation cooperatively promotes mTORC1 signaling to S6K1 and 4EBP1. Mechanistically, S2159/T2164 phosphorylation modulates the mTOR-raptor and raptor-PRAS40 interactions and augments mTORC1-associated mTOR S2481 autophosphorylation. Moreover, mTOR S2159/T2164 phosphorylation promotes cell growth and cell cycle progression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21576368"}, {"offsetInBeginSection": 0, "offsetInEndSection": 647, "text": "Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase originally discovered as the molecular target of the immunosuppressant rapamycin. mTOR forms two compositionally and functionally distinct complexes, mTORC1 and mTORC2, which are crucial for coordinating nutrient, energy, oxygen, and growth factor availability with cellular growth, proliferation, and survival. Recent studies have identified critical, non-redundant roles for mTORC1 and mTORC2 in controlling B cell development, differentiation, and functions, and have highlighted emerging roles of the Folliculin-Fnip protein complex in regulating mTOR and B cell development.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28583723"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1285, "text": "Mechanistic target of rapamycin (mTOR) kinase functions in two multiprotein complexes: lysosomal mTOR complex 1 (mTORC1) and mTORC2 at the plasma membrane. mTORC1 modulates the cell response to growth factors and nutrients by increasing protein synthesis and cell growth, and repressing the autophagy-lysosomal pathway1-4; however, dysfunction in mTORC1 is implicated in various diseases3,5,6. mTORC1 activity is regulated by phosphoinositide lipids7-10. Class I phosphatidylinositol-3-kinase (PI3K)-mediated production of phosphatidylinositol-3,4,5-trisphosphate6,11 at the plasma membrane stimulates mTORC1 signalling, while local synthesis of phosphatidylinositol-3,4-bisphosphate by starvation-induced recruitment of class II PI3K-\u03b2 (PI3KC2-\u03b2) to lysosomes represses mTORC1 activity12. How the localization and activity of PI3KC2-\u03b2 are regulated by mitogens is unknown. We demonstrate that protein kinase N (PKN) facilitates mTORC1 signalling by repressing PI3KC2-\u03b2-mediated phosphatidylinositol-3,4-bisphosphate synthesis downstream of mTORC2. Active PKN2 phosphorylates PI3KC2-\u03b2 to trigger PI3KC2-\u03b2 complex formation with inhibitory 14-3-3 proteins. Conversely, loss of PKN2 or inactivation of its target phosphorylation site in PI3KC2-\u03b2 represses nutrient signalling via mTORC1.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31451768"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1027, "text": "The mammalian target of rapamycin (mTOR) regulates cell growth and survival by integrating nutrient and hormonal signals. These signaling functions are distributed between at least two distinct mTOR protein complexes: mTORC1 and mTORC2. mTORC1 is sensitive to the selective inhibitor rapamycin and activated by growth factor stimulation via the canonical phosphoinositide 3-kinase (PI3K)-->Akt-->mTOR pathway. Activated mTORC1 kinase up-regulates protein synthesis by phosphorylating key regulators of mRNA translation. By contrast, mTORC2 is resistant to rapamycin. Genetic studies have suggested that mTORC2 may phosphorylate Akt at S473, one of two phosphorylation sites required for Akt activation; this has been controversial, in part because RNA interference and gene knockouts produce distinct Akt phospho-isoforms. The central role of mTOR in controlling key cellular growth and survival pathways has sparked interest in discovering mTOR inhibitors that bind to the ATP site and therefore target both mTORC2 and mTORC1.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19209957"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1342, "text": "The mechanistic target of rapamycin (mTOR) functions as a component of two large complexes, mTORC1 and mTORC2, which play crucial roles in regulating cell growth and homeostasis. However, the molecular mechanisms by which mTOR controls cell proliferation remain elusive. Here we show that the FoxO3a transcription factor is coordinately regulated by mTORC1 and mTORC2, and plays a crucial role in controlling cell proliferation. To dissect mTOR signaling, mTORC1 was specifically inactivated by depleting p18, an essential anchor of mTORC1 on lysosomes. mTORC1 inactivation caused a marked retardation of cell proliferation, which was associated with upregulation of cyclin-dependent kinase inhibitors (CDKIs). Although Akt was activated by mTORC1 inactivation, FoxO3a was upregulated via an epigenetic mechanism and hypophosphorylated at Ser314, which resulted in its nuclear accumulation. Consistently, mTORC1 inactivation induced downregulation of serum- and glucocorticoid-inducible kinase 1 (SGK1), the kinase responsible for Ser314 phosphorylation. Expression of FoxO3a mutated at Ser314 suppressed cell proliferation by inducing CDKI expression. SGK1 overexpression suppressed CDKI expression in p18-deficient cells, whereas SGK1 knockdown induced CDKI expression in wild-type cells, resulting in the suppression of cell proliferation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24558442"}, {"offsetInBeginSection": 0, "offsetInEndSection": 845, "text": "The mammalian target of rapamycin (mTOR) is a protein kinase that plays key roles in cellular regulation. It forms complexes with additional proteins. The best-understood one is mTOR complex 1 (mTORC1). The regulation and cellular functions of mTORC1 have been the subjects of intense study; despite this, many questions remain to be answered. They include questions about the actual mechanisms by which mTORC1 signaling is stimulated by hormones and growth factors, which involves the small GTPase Rheb, and by amino acids, which involves other GTPase proteins. The control of Rheb and the mechanism by which it activates mTORC1 remain incompletely understood. Although it has been known for many years that rapamycin interferes with some functions of mTORC1, it is not known how it does this, or why only some functions of mTORC1 are affected.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21138990"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1083, "text": "Mammalian target of rapamycin (mTOR) functions in two distinct signaling complexes, mTORC1 and mTORC2. In response to insulin and nutrients, mTORC1, consisting of mTOR, raptor (regulatory-associated protein of mTOR), and mLST8, is activated and phosphorylates eukaryotic initiation factor 4E-binding protein (4EBP) and p70 S6 kinase to promote protein synthesis and cell size. Previously we found that activation of mTOR kinase in response to insulin was associated with increased 4EBP1 binding to raptor. Here we identify prolinerich Akt substrate 40 (PRAS40) as a binding partner for mTORC1. A putative TOR signaling motif, FVMDE, is identified in PRAS40 and shown to be required for interaction with raptor. Insulin stimulation markedly decreases the level of PRAS40 bound by mTORC1. Recombinant PRAS40 inhibits mTORC1 kinase activity in vivo and in vitro, and this inhibition depends on PRAS40 association with raptor. Furthermore, decreasing PRAS40 expression by short hairpin RNA enhances 4E-BP1 binding to raptor, and recombinant PRAS40 competes with 4E-BP1 binding to raptor.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17510057"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1017, "text": "The mammalian target of rapamycin (mTOR) is a conserved Ser/Thr kinase that forms two functionally distinct complexes important for nutrient and growth factor signaling. While mTOR complex 1 (mTORC1) regulates mRNA translation and ribosome biogenesis, mTORC2 plays an important role in the phosphorylation and subsequent activation of Akt. Interestingly, mTORC1 negatively regulates Akt activation, but whether mTORC1 signaling directly targets mTORC2 remains unknown. Here we show that growth factors promote the phosphorylation of Rictor (rapamycin-insensitive companion of mTOR), an essential subunit of mTORC2. We found that Rictor phosphorylation requires mTORC1 activity and, more specifically, the p70 ribosomal S6 kinase 1 (S6K1). We identified several phosphorylation sites in Rictor and found that Thr1135 is directly phosphorylated by S6K1 in vitro and in vivo, in a rapamycin-sensitive manner. Phosphorylation of Rictor on Thr1135 did not affect mTORC2 assembly, kinase activity, or cellular localization.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19995915"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "The mechanistic (or mammalian) Target of Rapamycin Complex 1 (mTORC1) is a central regulator of cell growth and metabolism.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32122730"}, {"offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "The mechanistic target of rapamycin complex 1 (mTORC1) kinase is a sensor of different environmental conditions and regulator of cell growth, metabolism, and autophagy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25457612"}, {"offsetInBeginSection": 0, "offsetInEndSection": 357, "text": "The mechanistic target of rapamycin complex 1 (mTORC1) kinase is a sensor of different environmental conditions and regulator of cell growth, metabolism, and autophagy. mTORC1 is activated by Rag GTPases, working as RagA:RagB and RagC:RagD heterodimers. Rags control mTORC1 activity by tethering mTORC1 to the lysosomes where it is activated by Rheb GTPase.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25457612"}, {"offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "ULK1 (Unc51-like kinase, hATG1) is a Ser/Thr kinase that plays a key role in inducing autophagy in response to starvation. ULK1 is phosphorylated and negatively regulated by the mammalian target of rapamycin complex 1 (mTORC1).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21795849"}, {"offsetInBeginSection": 196, "offsetInEndSection": 296, "text": "Mammalian target of rapamycin complex 1 (mTORC1) plays a central role in cellular growth regulation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19270521"}, {"offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "The mechanistic target of rapamycin complex 1 (mTORC1) is a key regulator of cell growth and proliferation in response to various upstream signals.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23416465"}, {"offsetInBeginSection": 231, "offsetInEndSection": 400, "text": "Among the nutrient-sensing pathways, the mechanistic target of rapamycin complex 1 (mTORC1) acts as the central regulator of cellular functions, which include autophagy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32850834"}, {"offsetInBeginSection": 417, "offsetInEndSection": 553, "text": "mTORC1 signalling is classically known for its role in regulating cell growth and proliferation through modulation of protein synthesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19166929"}, {"offsetInBeginSection": 508, "offsetInEndSection": 747, "text": "The catalytic subunit of the mTORC1 kinase complex (Tor1 or Tor2 in budding yeast and mTor in mammals) phosphorylates several downstream effectors regulating transcriptional and translational responses controlling growth and proliferation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30359581"}, {"offsetInBeginSection": 597, "offsetInEndSection": 698, "text": "mTORC1 is a master regulator of many cellular processes and is often hyperactivated in human disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34965982"}, {"offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth in response to amino acid and glucose levels.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36732624"}, {"offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "The mechanistic target of rapamycin complex 1 (mTORC1) kinase is a major regulator of cell growth that responds to numerous environmental cues.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25263562"}, {"offsetInBeginSection": 148, "offsetInEndSection": 239, "text": "Accumulating evidence has suggested a role for mTORC1 signaling in the DNA damage response.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36189922"}, {"offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "The mechanistic (or mammalian) target of rapamycin complex 1 (mTORC1) controls cell growth, proliferation, and metabolism in response to diverse stimuli.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30552228"}, {"offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Signalling through mTORC1 (mammalian target of rapamycin complex 1) is important in controlling many cell functions, including protein synthesis, which it activates.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19143637"}, {"offsetInBeginSection": 311, "offsetInEndSection": 554, "text": "mTORC1 signalling regulates several components of the protein synthetic machinery, including initiation and elongation factors, protein kinases which phosphorylate the ribosome and/or translation factors, and the translation of specific mRNAs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19143637"}, {"offsetInBeginSection": 169, "offsetInEndSection": 298, "text": "mTORC1, which is directly inhibited by rapamycin, promotes cell growth by stimulating protein synthesis and inhibiting autophagy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23184942"}, {"offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "High nutrient availability stimulates the mammalian target of rapamycin complex 1 (mTORC1) to coordinately activate anabolic processes, such as protein synthesis, while inhibiting the cellular catabolism of autophagy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19690328"}, {"offsetInBeginSection": 414, "offsetInEndSection": 676, "text": "The complementary inhibitory mechanism in which mTORC1 phosphorylates the autophagy regulatory complex containing unc-51-like kinase 1 (ULK1), the mammalian Atg13 protein, and focal adhesion kinase interacting protein of 200 kD (FIP200) has also been elucidated.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19690328"}, {"offsetInBeginSection": 187, "offsetInEndSection": 620, "text": "Mechanistic target of rapamycin (mTOR) signaling is the essential nutrient-sensing pathway that controls anabolic processes in cells. The central component of this pathway is mTOR, a highly conserved and essential protein kinase that exists in two distinct functional complexes. The nutrient-sensitive mTOR complex 1 (mTORC1) controls cell growth and cell size by phosphorylation of the regulators of protein synthesis S6K1 and 4EBP1", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23928304"}]}
+{"question_id": "6616a122fdcbea915f000058", "question": "Has statin use been associated with a higher risk of dementia?", "answer": "No, there is no strong evidence to suggest that statin use is associated with a higher risk of dementia. In fact, some studies have found that statin use may be linked to a reduced risk of dementia, particularly among patients with stroke. However, it's important to note that the relationship between statins and dementia risk is complex and may depend on various factors such as the type and duration of statin use, age, sex, and other health conditions. Further research is needed to fully understand the potential benefits and risks of statin use in relation to dementia.", "relevant_passage_ids": ["34871380", "34756134", "30087076", "30045255", "30337635", "26080283", "24578458", "24681022", "31574510", "23461525", "16009757", "35305172", "29507718", "32583471", "25203109", "20413854", "21795660", "12084801", "24075740", "37291702", "34315986", "24504830", "29247073", "22269162", "22451317"], "type": "yesno", "snippets": [{"offsetInBeginSection": 23, "offsetInEndSection": 91, "text": "impact of statins on cognitive decline and dementia is still debated", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34871380"}, {"offsetInBeginSection": 1419, "offsetInEndSection": 1484, "text": "absence of a neurocognitive risk associated with statin treatment", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34871380"}, {"offsetInBeginSection": 687, "offsetInEndSection": 755, "text": "evidence in support of as well as against statin therapy in dementia", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34756134"}, {"offsetInBeginSection": 1079, "offsetInEndSection": 1166, "text": "Lowering cholesterol using statin may help prevent or delay the progression of dementia", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34756134"}, {"offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "BACKGROUND: The effect of statin use on dementia risk remains unclear", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24578458"}, {"offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "BACKGROUND: The effect of statin use on dementia risk remains unclear. This study aims to examine the association between long-term statin use and dementia risk", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24578458"}, {"offsetInBeginSection": 1521, "offsetInEndSection": 1623, "text": "S: In this cohort study, statin therapy was not associated with a decreased risk of dementia. Methodol", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16009757"}, {"offsetInBeginSection": 1150, "offsetInEndSection": 1424, "text": "Higher potency and longer cumulative duration of statin use were required for reducing the risk of incident dementia in male patients than in female patients.CONCLUSION: Statin use was associated with a significantly lower risk of dementia in the elderly patients in Taiwan.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24681022"}, {"offsetInBeginSection": 1344, "offsetInEndSection": 1622, "text": "A significant decrease in the risk of dementia with increasing statin duration was also demonstrated (P for trend\u2009=\u20090.002).CONCLUSIONS: Statin use in T2DM patients receiving ADT for PCa had decreased risk of dementia, with statin adherence and intensity augmenting this benefit.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30337635"}, {"offsetInBeginSection": 1047, "offsetInEndSection": 1394, "text": "The overall pooled reduction of Alzheimer disease in patients with statin use was RR 0.69 (95% CI 0.60-0.80, p < 0.0001), and the overall pooled RR of statin use and vascular dementia risk was RR 0.93 (95% CI 0.74-1.16, p = 0.54).CONCLUSION: This study suggests that the use of statin is significantly associated with a decreased risk of dementia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31574510"}, {"offsetInBeginSection": 1356, "offsetInEndSection": 1515, "text": "Statin initiation after stroke was associated with lower risk of dementia, with a potentially greater benefit in patients who persisted with statins over time.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35305172"}, {"offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "In a 2009 Cochrane review, the authors concluded that there is good evidence that statins, given in late life to people at risk of vascular disease, have no effect in preventing Alzheimer's disease or dementia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20413854"}, {"offsetInBeginSection": 298, "offsetInEndSection": 441, "text": "While some studies have shown a beneficial effect of statins on cognitive function, others have observed mild detrimental effects on cognition.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20413854"}, {"offsetInBeginSection": 1524, "offsetInEndSection": 1745, "text": "In this population-based sample, elderly participants treated with statins and untreated controls performed similarly in all tested cognitive areas. These results do not support a positive benefit of statins on cognition.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20413854"}, {"offsetInBeginSection": 1372, "offsetInEndSection": 1617, "text": "se events with simvastatin treatment.CONCLUSION: Simvastatin had no benefit on the progression of symptoms in individuals with mild to moderate AD despite significant lowering of cholesterol.CLASSIFICATION OF EVIDENCE: This study provides Class ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21795660"}, {"offsetInBeginSection": 1141, "offsetInEndSection": 1247, "text": "Findings of the present meta-analysis show that statin use was associated with a reduced risk of dementia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23461525"}, {"offsetInBeginSection": 1241, "offsetInEndSection": 1503, "text": "No significant effect modification for the relationship between statin use and the risk of dementia was found for either age or sex.CONCLUSION: In this nationwide cohort study, statin use was associated with decreased risk of dementia among patients with stroke.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30087076"}, {"offsetInBeginSection": 353, "offsetInEndSection": 487, "text": "Significant cognitive decline associated with statin use in elderly patients with Alzheimer's disease has also been reported recently.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25203109"}, {"offsetInBeginSection": 1309, "offsetInEndSection": 1463, "text": ".75; 95% CI: 0.61 to 0.94). Simvastatin and atorvastatin were both associated with a reduced risk of dementia, while no similar evidence was observed for ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24075740"}, {"offsetInBeginSection": 1500, "offsetInEndSection": 1638, "text": "e of 1.5 +/- 0.1, p =.036).CONCLUSIONS: The use of statins is associated with a lower prevalence of dementia and has a positive impact on ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12084801"}, {"offsetInBeginSection": 1006, "offsetInEndSection": 1288, "text": "The statin therapy group had a significantly lower dementia risk in a dose-dependent relationship compared with the non-statin therapy group (P for trend\u00a0<0.001).CONCLUSION: In NVAF patients who received OAC, statin therapy lowered the dementia risk compared with no statin therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37291702"}, {"offsetInBeginSection": 162, "offsetInEndSection": 352, "text": "The Food and Drug Administration recently published enhanced warnings for statin use, including the possible relationship between statins and cognitive impairment, especially in the elderly.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25203109"}, {"offsetInBeginSection": 1197, "offsetInEndSection": 1253, "text": "Statins use was associated with dementia risk decrement.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30045255"}, {"offsetInBeginSection": 1398, "offsetInEndSection": 1647, "text": "6), respectively, in women.CONCLUSIONS: Hypercholesterolaemic individuals exposed to statin had a lower risk of overall dementia and Alzheimer's disease and related dementia in both sexes, and a lower risk of other types of dementia in women, than s", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32583471"}, {"offsetInBeginSection": 398, "offsetInEndSection": 544, "text": "Paradoxically, statins have also been shown to decrease the risk of dementia, Alzheimer's disease, and improve cognitive impairment in some cases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29507718"}, {"offsetInBeginSection": 524, "offsetInEndSection": 804, "text": "Cognitive data from several large epidemiological studies have not reliably demonstrated a robust association between incident cognitive impairment and statin use, with some studies reporting a protective effect, some reporting an increased risk and others finding no association.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24504830"}, {"offsetInBeginSection": 484, "offsetInEndSection": 641, "text": " Overall, statin use was not associated with an increased risk of AD incidence [adjusted hazard ratio (aHR)\u2009=\u20091.04; 95% confidence interval (CI)\u2009=\u20090.99-1.10]", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34315986"}, {"offsetInBeginSection": 642, "offsetInEndSection": 825, "text": " When examined by level of statin exposure, statin prescription\u2009<\u2009540\u00a0days during a 2-year window time was associated with a higher risk for incidence of AD compared to statin non-use", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34315986"}, {"offsetInBeginSection": 1039, "offsetInEndSection": 1158, "text": "1] per 1,000 person-years). Compared to synthetic, fungus-derived statins were associated with an increased risk of AD ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29247073"}, {"offsetInBeginSection": 1159, "offsetInEndSection": 1368, "text": "HR 1.09, 95% CI 1.03-1.15). Lipophilic statins also were associated with higher AD risk (HR 1.18, 95% CI 1.09-1.27) compared to hydrophilic statins, while statin potency did not modify the risk of AD (adjusted", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29247073"}, {"offsetInBeginSection": 1423, "offsetInEndSection": 1558, "text": "ed in sensitivity analyses.CONCLUSION: Fungus-derived and lipophilic statins were not associated with decreased incidence of AD compare", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29247073"}, {"offsetInBeginSection": 542, "offsetInEndSection": 781, "text": "Although statin treatment has been shown to associate with a lower risk of dementia and cognitive decline in observational studies, randomized controlled trials show no beneficial effect of statin treatment on late-life cognitive function.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22269162"}, {"offsetInBeginSection": 1400, "offsetInEndSection": 1508, "text": " There is no evidence that treatment with statins in late-life has a beneficial effect on cognitive function", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22269162"}, {"offsetInBeginSection": 1275, "offsetInEndSection": 1437, "text": "For both genders, no significant associations were found between statins (irrespective of their lipophilicity) and either cognitive decline or dementia incidence.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22451317"}, {"offsetInBeginSection": 865, "offsetInEndSection": 1019, "text": "sed with incident dementia. Statin use was associated with a significantly lower incidence of dementia (adjusted hazard ratio, .81; 95% confidence interva", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30087076"}, {"offsetInBeginSection": 854, "offsetInEndSection": 1021, "text": " (1.89% vs. 2.20%; p<0.001). Statin use exhibited a protective effect on the occurrence of non-vascular dementia, with an adjusted hazard ratio (HR) of 0.832 (95% conf", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26080283"}, {"offsetInBeginSection": 1022, "offsetInEndSection": 1200, "text": "]. Our findings indicate that less persistent statin use is associated with increased risk of AD, whereas persistent and adherent statin use is associated with decreased risk of ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34315986"}]}
+{"question_id": "6630254b187cba990d000032", "question": "Is DNA methylation always associated with gene silencing?", "answer": "DNA methylation is frequently described as a 'silencing' epigenetic mark, and indeed this function of 5-methylcytosine was originally proposed in the 1970s. Now, thanks to improved genome-scale mapping of methylation, we can evaluate DNA methylation in different genomic contexts: transcriptional start sites with or without CpG islands, in gene bodies, at regulatory elements, and at repeat sequences. The emerging picture is that the function of DNA methylation seems to vary with context, and the relationship between DNA methylation and transcription is more nuanced than we realized at first. For example, in the standard model, methylation in gene promoters has received the most attention since it is generally associated with transcriptional silencing. In contrast, recent studies in human tissues reveal that methylation of the region downstream of the transcription start site is highly informative of gene expression. Also, in some cell types and specific genes, it has been found that methylation of the first intron is linked with gene expression. Therefore, improving our understanding of the functions of DNA methylation is necessary for interpreting changes in this mark that are observed in diseases such as cancer.", "relevant_passage_ids": ["31914996", "22641018", "29958539", "32348735", "36694897", "18288132", "26510177"], "type": "yesno", "snippets": [{"offsetInBeginSection": 459, "offsetInEndSection": 698, "text": "DNA methylation is most commonly associated with downregulation of gene expression. However, positive associations of DNA methylation to gene expression have also been reported, suggesting a more diverse mechanism of epigenetic regulation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31914996"}, {"offsetInBeginSection": 0, "offsetInEndSection": 757, "text": "DNA methylation is frequently described as a 'silencing' epigenetic mark, and indeed this function of 5-methylcytosine was originally proposed in the 1970s. Now, thanks to improved genome-scale mapping of methylation, we can evaluate DNA methylation in different genomic contexts: transcriptional start sites with or without CpG islands, in gene bodies, at regulatory elements and at repeat sequences. The emerging picture is that the function of DNA methylation seems to vary with context, and the relationship between DNA methylation and transcription is more nuanced than we realized at first. Improving our understanding of the functions of DNA methylation is necessary for interpreting changes in this mark that are observed in diseases such as cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22641018"}, {"offsetInBeginSection": 12, "offsetInEndSection": 617, "text": "DNA methylation is one of the main epigenetic mechanisms for the regulation of gene expression in eukaryotes. In the standard model, methylation in gene promoters has received the most attention since it is generally associated with transcriptional silencing. Nevertheless, recent studies in human tissues reveal that methylation of the region downstream of the transcription start site is highly informative of gene expression. Also, in some cell types and specific genes it has been found that methylation of the first intron, a gene feature typically rich in enhancers, is linked with gene expression. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29958539"}, {"offsetInBeginSection": 305, "offsetInEndSection": 712, "text": "Classically, dense promoter DNA methylation is associated with transcriptional repression. However, growing evidence suggests that this association may not always hold true, and promoter hypermethylation now also appears to be associated with high transcriptional activity. Furthermore, in a selection of contexts, increasing levels of promoter methylation correlate directly with increased gene expression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32348735"}, {"offsetInBeginSection": 1093, "offsetInEndSection": 1271, "text": "Lastly, the moderate expression of several genes proximal to hypermethylated CpG tracts suggests that DNA methylation assays are not always accurate predictors of gene silencing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18288132"}, {"offsetInBeginSection": 681, "offsetInEndSection": 892, "text": "Underscoring the complex relationships between CpG methylation and gene expression, here hypermethylation was never associated with gene silencing, nor was hypomethylation always associated with gene activation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26510177"}]}
+{"question_id": "66302174187cba990d00002e", "question": "Are there any digital biomarkers for Duchenne Muscular Dystrophy?", "answer": "Yes, digital biomarkers have been developed for Duchenne Muscular Dystrophy.", "relevant_passage_ids": ["36658421"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Wearable full-body motion tracking of activities of daily living predicts disease trajectory in Duchenne muscular dystrophy.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36658421"}, {"offsetInBeginSection": 950, "offsetInEndSection": 1145, "text": "we constructed a behavioral biomarker, termed the KineDMD ethomic biomarker, which is derived from daily-life behavioral data and whose value progresses with age in an S-shaped sigmoid curve form", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36658421"}, {"offsetInBeginSection": 1147, "offsetInEndSection": 1367, "text": "The biomarker developed in this study, derived from digital readouts of daily-life movement behavior, can predict disease progression in patients with muscular dystrophy and can potentially track the response to therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36658421"}]}
+{"question_id": "65cfd2681930410b1300001e", "question": "How should Insulin icodec be administered?", "answer": "Insulin icodec is administered as once weekly injection.", "relevant_passage_ids": ["36631720", "37354562", "37313230", "37249450", "33944562", "32960514", "34133152", "34413118", "36108418", "37356066", "33875485", "37148899", "37156252", "37748181", "37984730", "37863084", "37694740", "33875484"], "type": "summary", "snippets": [{"offsetInBeginSection": 136, "offsetInEndSection": 276, "text": "This trial investigated whether choice of injection region affects exposure and glucose-lowering effect of once-weekly basal insulin icodec.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36631720"}, {"offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes: The ONWARDS 3 Randomized Clinical Trial.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37354562"}, {"offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Importance: Once-weekly insulin icodec could provide a simpler dosing alternative to daily basal insulin in people with type 2 diabetes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37354562"}, {"offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Insulin Icodec Weekly: A Basal Insulin Analogue for Type 2 Diabetes.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37313230"}, {"offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Insulin icodec is a once-weekly basal insulin analogue in late-phase clinical development. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37313230"}, {"offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Once-Weekly Insulin Icodec vs. Once-Daily Insulin Glargine U100 for type 2 diabetes: a systematic review and meta-analysis of phase 2 randomized controlled trials.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37249450"}, {"offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Objective: Insulin Icodec is a novel basal insulin analogue designed for once-weekly administration, therefore might propitiate reduction in the frequency of injections and facilitate treatment adherence. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37249450"}, {"offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Once-weekly Insulin Icodec as Compared to Once-daily Basal Insulins: A Meta-analysis.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37984730"}, {"offsetInBeginSection": 12, "offsetInEndSection": 181, "text": "ONWARDS 6 compared the efficacy and safety of once-weekly subcutaneous insulin icodec (icodec) and once-daily insulin degludec (degludec) in adults with type 1 diabetes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37863084"}, {"offsetInBeginSection": 153, "offsetInEndSection": 282, "text": "Once-weekly insulin icodec (icodec) is a basal insulin analogue that is in development and is aimed at reducing treatment burden.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37748181"}, {"offsetInBeginSection": 0, "offsetInEndSection": 908, "text": "BACKGROUND AND AIMS: Insulin icodec is currently the most advanced candidate insulin suitable for once-weekly administration. We aim to conduct a systematic review of the literature to find out the efficacy and safety of insulin icodec in patients with diabetes mellitus.METHODS: We systematically searched the electronic database of PubMed, and Google Scholar from inception until August 20, 2022, using MeSH keywords. Ongoing trials of insulin icodec were additionally searched from the ClinicalTrials.Gov. We retrieved all the available granular details of phase 1 to phase 3 studies of insulin icodec in both type 1 and type 2 diabetes.RESULTS: Phase 1 study showed insulin icodec having a half-life of 196\u00a0h (>1 week) while a steady state is achieved after 3 to 4 weekly injections. Phase 2 studies compared once-weekly icodec to insulin glargine (U-100) and found a similar glucose control with no sign", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36108418"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1389, "text": "Objective: Insulin Icodec is a novel basal insulin analogue designed for once-weekly administration, therefore might propitiate reduction in the frequency of injections and facilitate treatment adherence. This study aimed to determine the glycemic control and safety profile of Insulin Icodec, compared with Glargine U100 in patients with diabetes mellitus type 2.Materials and methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCT) data comparing OnceWeekly Insulin Icodec and Once-Daily Insulin Glargine U100 in patients with type 2 diabetes mellitus. PubMed, Embase, and Cochrane databases were searched for trials published up to May 14, 2022. Data were extracted from published reports and quality assessment was performed per Cochrane recommendations.Results: Three studies were included comprising 453 patients, 230 (50.77%) using Once-Weekly Insulin Icodec and 223 (49.22%) using Once-Daily Insulin Glargine U100. In the pooled data, Glycated Hemoglobin (MD -0.20% CI -0.33 to -0.07%; P=0.002) change from baseline demonstrated a significantly higher reduction in the Icodec group. Time with Glucose in Range (MD 6.60% CI 3.63 to 9.57%; P < 0.0001) and Insulin Dose Difference (MD 0.97UI CI 0.76 to 1.18UI; P < 0.0001) were higher in the Icodec group. There was no significant difference in fasting plasma glucose, body weight change, hyp", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37249450"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1195, "text": "INTRODUCTION: Insulin icodec is a novel, long-acting insulin analog designed to cover basal insulin requirements with once-weekly subcutaneous administration. Here we describe the molecular engineering and the biological and pharmacological properties of insulin icodec.RESEARCH DESIGN AND METHODS: A number of in vitro assays measuring receptor binding, intracellular signaling as well as cellular metabolic and mitogenic responses were used to characterize the biological properties of insulin icodec. To evaluate the pharmacological properties of insulin icodec in individuals with type 2 diabetes, a randomized, double-blind, double-dummy, active-controlled, multiple-dose, dose escalation trial was conducted.RESULTS: The long half-life of insulin icodec was achieved by introducing modifications to the insulin molecule aiming to obtain a safe, albumin-bound circulating depot of insulin icodec, providing protracted insulin action and clearance. Addition of a C20 fatty diacid-containing side chain imparts strong, reversible albumin binding, while three amino acid substitutions (A14E, B16H and B25H) provide molecular stability and contribute to attenuating insulin receptor (IR) bindin", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34413118"}, {"offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "Insulin icodec is a once-weekly basal insulin analogue in late-phase clinical development. Similar efficacy and safety of icodec to once-daily basal insulin analogues have been reported in over 4,200 participants with type 2 diabetes from three phase II and five phase III trials.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37313230"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1614, "text": "AIMS: To characterize the pharmacokinetic and pharmacodynamic properties of once-weekly insulin icodec in type 2 diabetes (T2D).MATERIALS AND METHODS: In an open-label trial, 46 individuals with T2D (18-75\u2009years; body mass index 18.0-38.0\u2009kg/m2 ; glycated haemoglobin \u226475\u2009mmol/mol [\u22649%]; basal insulin-treated) received subcutaneous once-weekly icodec for \u22658\u2009weeks at individualized doses, aiming at a pre-breakfast plasma glucose concentration of 4.4 to 7.0\u2009mmol/L (80-126\u2009mg/dL) on the last three mornings of each weekly dosing interval. Frequent blood sampling to assess total serum icodec concentration (ie, albumin-bound and unbound) occurred from first icodec dose until 35\u2009days after last dose. Icodec trough concentrations following initiation of once-weekly dosing were predicted by pharmacokinetic modelling. During the final 3\u2009weeks of icodec treatment, while at steady state, the icodec glucose-lowering effect was assessed in three glucose clamps (target 7.5\u2009mmol/L [135\u2009mg/dL]): 0 to 36, 40 to 64 and 144 to 168\u2009h post-dose, thus covering the initial, middle and last part of the 1-week dosing interval. Glucose-lowering effect during a complete dosing interval was predicted by pharmacokinetic-pharmacodynamic modelling.RESULTS: Model-predicted icodec steady state was attained after 3 to 4\u2009weeks. At steady state, model-predicted daily proportions of glucose-lowering effect on days 1 to 7 of the 1-week dosing interval were 14.1%, 16.1%, 15.8%, 15.0%, 14.0%, 13.0% and 12.0%, respectively. Icodec duration of action was at least 1\u2009week in all participants. Once-weekly icodec was overall safe and ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37694740"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1376, "text": "OBJECTIVE: Insulin icodec (icodec) is a novel once-weekly basal insulin analog. This trial investigated two approaches for switching to icodec versus once-daily insulin glargine 100 units/mL (IGlar U100) in people with type 2 diabetes receiving daily basal insulin and one or more oral glucose-lowering medications.RESEARCH DESIGN AND METHODS: This multicenter, open-label, treat-to-target phase 2 trial randomized (1:1:1) eligible basal insulin-treated (total daily dose 10-50 units) people with type 2 diabetes (HbA1c 7.0-10.0% [53.0-85.8 mmol/mol]) to icodec with an initial 100% loading dose (in which only the first dose was doubled [icodec LD]), icodec with no loading dose (icodec NLD), or IGlar U100 for 16 weeks. Primary end point was percent time in range (TIR; 3.9-10.0 mmol/L [70-180 mg/dL]) during weeks 15 and 16, measured using continuous glucose monitoring. Key secondary end points included HbA1c, adverse events (AEs), and hypoglycemia.RESULTS: Estimated mean TIR during weeks 15 and 16 was 72.9% (icodec LD; n = 54), 66.0% (icodec NLD; n = 50), and 65.0% (IGlar U100; n = 50), with a statistically significant difference favoring icodec LD versus IGlar U100 (7.9%-points [95% CI 1.8-13.9]). Mean HbA1c reduced from 7.9% (62.8 mmol/mol) at baseline to 7.1% (54.4 mmol/mol icodec LD) and 7.4% (57.6 mmol/mol icodec NLD and IGlar U100); incidences and rates of", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33875485"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1603, "text": "BACKGROUND AND OBJECTIVE: Individuals with diabetes mellitus may prefer different body regions for subcutaneous insulin administration. This trial investigated whether choice of injection region affects exposure and glucose-lowering effect of once-weekly basal insulin icodec.METHODS: In a randomised, open-label, crossover trial, 25 individuals with type 2 diabetes received single subcutaneous icodec injections (5.6 U/kg) in the thigh, abdomen or upper arm (9-13 weeks' washout). Pharmacokinetic blood sampling occurred frequently until 35 days post-dose. Partial glucose-lowering effect was assessed 36-60 h post-dose in a glucose clamp (target 7.5 mmol/L). Steady-state pharmacokinetics following multiple once-weekly dosing were simulated using a two-compartment pharmacokinetic model.RESULTS: Total icodec exposure (area under the curve from zero to infinity after single dose; AUC0-\u221e,SD) was similar between injection in the thigh, abdomen and upper arm (estimated AUC0-\u221e,SD ratios [95% confidence interval]: abdomen/thigh 1.02 [0.96-1.09], p = 0.473; upper arm/thigh 1.04 [0.98-1.10], p = 0.162; abdomen/upper arm 0.98 [0.93-1.05], p = 0.610). Maximum icodec concentration (Cmax) after single dose was higher for abdomen (by 17%, p = 0.002) and upper arm (by 24%, p < 0.001) versus thigh. When simulated to steady state, smaller differences in Cmax were seen for abdomen (by 11%, p = 0.004) and upper arm (by 16%, p < 0.001) versus thigh. Geometric mean [coefficient of variation] glucose-lowering effect 36-60 h post-dose was comparable between the thigh (1961\u00a0mg/kg [51%]), abdomen (2130 mg/k", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36631720"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1503, "text": "OBJECTIVE: Insulin icodec is a novel once-weekly basal insulin analog. This trial investigated the efficacy and safety of icodec using different once-weekly titration algorithms.RESEARCH DESIGN AND METHODS: This was a phase 2, randomized, open-label, 16-week, treat-to-target study. Insulin-naive adults (n = 205) with type 2 diabetes and HbA1c 7-10% while treated with oral glucose-lowering medications initiated once-weekly icodec titrations A (prebreakfast self-measured blood glucose target 80-130 mg/dL; adjustment \u00b121 units/week; n = 51), B (80-130 mg/dL; \u00b128 units/week; n = 51), or C (70-108 mg/dL; \u00b128 units/week; n = 52), or once-daily insulin glargine 100 units/mL (IGlar U100) (80-130 mg/dL; \u00b14 units/day; n = 51), all titrated weekly. Percentage of time in range (TIR) (70-180 mg/dL) during weeks 15 and 16 was measured using continuous glucose monitoring.RESULTS: TIR improved from baseline (means: A, 57.0%; B, 55.2%; C, 51.0%; IGlar U100, 55.3%) to weeks 15 and 16 (estimated mean: A, 76.6%; B, 83.0%; C, 80.9%; IGlar U100, 75.9%). TIR was greater for titration B than for IGlar U100 (estimated treatment difference 7.08%-points; 95% CI 2.12 to 12.04; P = 0.005). No unexpected safety signals were observed. Level 2 hypoglycemia (<54 mg/dL) was low in all groups (0.05, 0.15, 0.38, 0.00 events per patient-year of exposure for icodec titrations A, B, and C and IGlar U100, respectively), with no episodes of severe hypoglycemia.CONCLUSIONS: Once-weekly icodec was efficacious and well to", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33875484"}, {"offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "BACKGROUND AND AIMS: Insulin icodec is currently the most advanced candidate insulin suitable for once-weekly administration. We aim to conduct a systematic review of the literature to find out the efficacy and safety of insulin icodec in patients with diabetes mellitus", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36108418"}, {"offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "BACKGROUND AND AIMS: Insulin icodec is currently the most advanced candidate insulin suitable for once-weekly administration", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36108418"}, {"offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "OBJECTIVE: Insulin icodec (icodec) is a novel once-weekly basal insulin analog. This trial investigated two approaches for switching to icodec versus once-daily insulin glargine 100 units/mL (IGlar U100) in people with type 2 diabetes receiving daily basal insulin and one or more oral glucose-lowering medications", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33875485"}, {"offsetInBeginSection": 827, "offsetInEndSection": 998, "text": "In phase-2 clinical trial, once-weekly insulin icodec provided safe and efficacious glycemic control comparable to once-daily insulin glargine in type 2 diabetes patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33944562"}, {"offsetInBeginSection": 827, "offsetInEndSection": 1085, "text": "In phase-2 clinical trial, once-weekly insulin icodec provided safe and efficacious glycemic control comparable to once-daily insulin glargine in type 2 diabetes patients. The structure-activity relationship study leading to insulin icodec is presented here.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33944562"}, {"offsetInBeginSection": 157, "offsetInEndSection": 365, "text": "Insulin icodec, a novel ultralong-acting lipidated analog validates the concept of a once-weekly basal injection that is less burdensome, yet equally safe and efficacious as conventional once-daily treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34133152"}, {"offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "INTRODUCTION: Insulin icodec is a novel, long-acting insulin analog designed to cover basal insulin requirements with once-weekly subcutaneous administration.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34413118"}, {"offsetInBeginSection": 177, "offsetInEndSection": 760, "text": "Insulin icodec is a basal insulin analogue designed for once-weekly administration that is in development for the treatment of diabetes.METHODS: We conducted a 26-week, randomized, double-blind, double-dummy, phase 2 trial to investigate the efficacy and safety of once-weekly insulin icodec as compared with once-daily insulin glargine U100 in patients who had not previously received long-term insulin treatment and whose type 2 diabetes was inadequately controlled (glycated hemoglobin level, 7.0 to 9.5%) while taking metformin with or without a dipeptidyl peptidase 4 inhibitor.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32960514"}, {"offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "BACKGROUND: Insulin icodec (icodec) is a basal insulin analogue suitable for once-weekly dosing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37156252"}, {"offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Objective: Insulin Icodec is a novel basal insulin analogue designed for once-weekly administration, therefore might propitiate reduction in the frequency of injections and facilitate treatment adherence.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37249450"}, {"offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "BACKGROUND AND AIMS: Insulin icodec is currently the most advanced candidate insulin suitable for once-weekly administration.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36108418"}, {"offsetInBeginSection": 2033, "offsetInEndSection": 2329, "text": "Most adverse events were mild, and no serious events were deemed to be related to the trial medications.CONCLUSIONS: Once-weekly treatment with insulin icodec had glucose-lowering efficacy and a safety profile similar to those of once-daily insulin glargine U100 in patients with type 2 diabetes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32960514"}, {"offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "INTRODUCTION: Insulin icodec is a novel, long-acting insulin analog designed to cover basal insulin requirements with once-weekly subcutaneous a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34413118"}, {"offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Objective: Insulin Icodec is a novel basal insulin analogue designed for once-weekly administration, therefore might propitiate reduction in the frequency of injections and facilitate treatment", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37249450"}, {"offsetInBeginSection": 165, "offsetInEndSection": 301, "text": "2 diabetes. Insulin icodec is a basal insulin analogue designed for once-weekly administration that is in development for the treatment ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32960514"}, {"offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "BACKGROUND: Insulin icodec is an investigational once-weekly basal insulin analogue for diabetes", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37356066"}, {"offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "BACKGROUND: Insulin icodec (icodec) is a once-weekly basal insulin currently under ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37148899"}, {"offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Insulin icodec is a once-weekly basal insulin analogue in late-phase clinical development.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37313230"}, {"offsetInBeginSection": 165, "offsetInEndSection": 2109, "text": "2 diabetes. Insulin icodec is a basal insulin analogue designed for once-weekly administration that is in development for the treatment of diabetes.METHODS: We conducted a 26-week, randomized, double-blind, double-dummy, phase 2 trial to investigate the efficacy and safety of once-weekly insulin icodec as compared with once-daily insulin glargine U100 in patients who had not previously received long-term insulin treatment and whose type 2 diabetes was inadequately controlled (glycated hemoglobin level, 7.0 to 9.5%) while taking metformin with or without a dipeptidyl peptidase 4 inhibitor. The primary end point was the change in glycated hemoglobin level from baseline to week 26. Safety end points, including episodes of hypoglycemia and insulin-related adverse events, were also evaluated.RESULTS: A total of 247 participants were randomly assigned (1:1) to receive icodec or glargine. Baseline characteristics were similar in the two groups; the mean baseline glycated hemoglobin level was 8.09% in the icodec group and 7.96% in the glargine group. The estimated mean change from baseline in the glycated hemoglobin level was -1.33 percentage points in the icodec group and -1.15 percentage points in the glargine group, to estimated means of 6.69% and 6.87%, respectively, at week 26; the estimated between-group difference in the change from baseline was -0.18 percentage points (95% CI, -0.38 to 0.02, P\u2009=\u20090.08). The observed rates of hypoglycemia with severity of level 2 (blood glucose level, <54 mg per deciliter) or level 3 (severe cognitive impairment) were low (icodec group, 0.53 events per patient-year; glargine group, 0.46 events per patient-year; estimated rate ratio, 1.09; 95% CI, 0.45 to 2.65). There was no between-group difference in insulin-related key adverse events, and rates of hypersensitivity and injection-site reactions were low. Most adverse events were mild, and no serious events were deemed to be relat", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32960514"}, {"offsetInBeginSection": 0, "offsetInEndSection": 2164, "text": "BACKGROUND: Insulin icodec is an investigational once-weekly basal insulin analogue for diabetes management.METHODS: We conducted a 78-week randomized, open-label, treat-to-target phase 3a trial (including a 52-week main phase and a 26-week extension phase, plus a 5-week follow-up period) involving adults with type 2 diabetes (glycated hemoglobin level, 7 to 11%) who had not previously received insulin. Participants were randomly assigned in a 1:1 ratio to receive once-weekly insulin icodec or once-daily insulin glargine U100. The primary end point was the change in the glycated hemoglobin level from baseline to week 52; the confirmatory secondary end point was the percentage of time spent in the glycemic range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter) in weeks 48 to 52. Hypoglycemic episodes (from baseline to weeks 52 and 83) were recorded.RESULTS: Each group included 492 participants. Baseline characteristics were similar in the two groups. The mean reduction in the glycated hemoglobin level at 52 weeks was greater with icodec than with glargine U100 (from 8.50% to 6.93% with icodec [mean change, -1.55 percentage points] and from 8.44% to 7.12% with glargine U100 [mean change, -1.35 percentage points]); the estimated between-group difference (-0.19 percentage points; 95% confidence interval [CI], -0.36 to -0.03) confirmed the noninferiority (P<0.001) and superiority (P\u2009=\u20090.02) of icodec. The percentage of time spent in the glycemic range of 70 to 180 mg per deciliter was significantly higher with icodec than with glargine U100 (71.9% vs. 66.9%; estimated between-group difference, 4.27 percentage points [95% CI, 1.92 to 6.62]; P<0.001), which confirmed superiority. Rates of combined clinically significant or severe hypoglycemia were 0.30 events per person-year of exposure with icodec and 0.16 events per person-year of exposure with glargine U100 at week 52 (estimated rate ratio, 1.64; 95% CI, 0.98 to 2.75) and 0.30 and 0.16 events per person-year of exposure, respectively, at week 83 (estimated rate ratio, 1.63; 95% CI, 1.02 to 2.61). No new safety signals were identified, and incidences of adverse events wer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37356066"}, {"offsetInBeginSection": 0, "offsetInEndSection": 2288, "text": "BACKGROUND: Insulin icodec (icodec) is a basal insulin analogue suitable for once-weekly dosing. ONWARDS 4 aimed to assess the efficacy and safety of once-weekly icodec compared with once-daily insulin glargine U100 (glargine U100) in individuals with long-standing type 2 diabetes on a basal-bolus regimen.METHODS: In this 26-week, phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trial, adults from 80 sites (outpatient clinics and hospital departments) across nine countries (Belgium, India, Italy, Japan, Mexico, the Netherlands, Romania, Russia, and the USA) with type 2 diabetes (glycated haemoglobin [HbA1c] 7\u00b70-10\u00b70%) were randomly assigned (1:1) to receive once-weekly icodec or once-daily glargine U100 combined with 2-4 daily bolus insulin aspart injections. The primary outcome was change in HbA1c from baseline to week 26 (non-inferiority margin of 0\u00b73 percentage points). The primary outcome was evaluated in the full analysis set (ie, all randomly assigned participants). Safety outcomes were evaluated in the safety analysis set (ie, all participants randomly assigned who received at least one dose of trial product). This trial is registered with ClinicalTrials.gov, NCT04880850.FINDINGS: Between May 14 and Oct 29, 2021, 746 participants were screened for eligibility, of whom 582 (78%) were randomly assigned (291 [50%] to icodec treatment and 291 [50%] to glargine U100 treatment). Participants had a mean duration of type 2 diabetes of 17\u00b71 years (SD 8\u00b74). At week 26, estimated mean change in HbA1c was -1\u00b716 percentage points in the icodec group (baseline 8\u00b729%) and -1\u00b718 percentage points in the glargine U100 group (baseline 8\u00b731%), showing non-inferiority for icodec versus glargine U100 (estimated treatment difference 0\u00b702 percentage points [95% CI -0\u00b711 to 0\u00b715], p<0\u00b70001). Overall, 171 (59%) of 291 participants in the icodec group and 167 (57%) of 291 participants in the glargine U100 group had an adverse event. 35 serious adverse events were reported in 22 (8%) of 291 participants in the icodec group and 33 serious adverse events were reported in 25 (9%) of 291 participants receiving glargine U100. Overall, combined level 2 and level 3 hypoglycaemia rates were similar between treatment groups. No new safety concern", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37156252"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1770, "text": "BACKGROUND: Inadequate dose titration and poor adherence to basal insulin can lead to suboptimal glycemic control in persons with type 2 diabetes (T2D). Once-weekly insulin icodec (icodec) is a basal insulin analogue that is in development and is aimed at reducing treatment burden.OBJECTIVE: To compare the effectiveness and safety of icodec titrated with a dosing guide app (icodec with app) versus once-daily basal insulin analogues (OD analogues) dosed per standard practice.DESIGN: 52-week, randomized, open-label, parallel-group, phase 3a trial with real-world elements. (ClinicalTrials.gov: NCT04760626).SETTING: 176 sites in 7 countries.PARTICIPANTS: 1085 insulin-naive adults with T2D.INTERVENTION: Icodec with app or OD analogue (insulin degludec, insulin glargine U100, or insulin glargine U300).MEASUREMENTS: The primary outcome was change in glycated hemoglobin (HbA1c) level from baseline to week 52. Secondary outcomes included patient-reported outcomes (Treatment Related Impact Measure for Diabetes [TRIM-D] compliance domain score and change in Diabetes Treatment Satisfaction Questionnaire [DTSQ] total treatment satisfaction score).RESULTS: The estimated mean change in HbA1c level from baseline to week 52 was greater with icodec with app than with OD analogues, with noninferiority (P < 0.001) and superiority (P = 0.009) confirmed in prespecified hierarchical testing (estimated treatment difference [ETD], -0.38 percentage points [95% CI, -0.66 to -0.09 percentage points]). At week 52, patient-reported outcomes were more favorable with icodec with app than with OD analogues (ETDs, 3.04 [CI, 1.28 to 4.81] for TRIM-D and 0.78 [CI, 0.10 to 1.47] for DTSQ). Rates of clinically significant or severe hypoglycemia were low and similar with both tr", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37748181"}, {"offsetInBeginSection": 0, "offsetInEndSection": 2655, "text": "BACKGROUND: Insulin icodec (icodec) is a once-weekly basal insulin currently under development. ONWARDS 2 aimed to assess the efficacy and safety of once-weekly icodec versus once-daily insulin degludec (degludec) in basal insulin-treated type 2 diabetes.METHODS: This 26-week, randomised, open-label, active-controlled, multicentre, treat-to-target phase 3a trial was conducted in 71 sites in nine countries. Eligible participants with type 2 diabetes inadequately controlled on once-daily or twice-daily basal insulin, with or without non-insulin glucose-lowering agents, were randomly assigned (1:1) to once-weekly icodec or once-daily degludec. The primary outcome was change from baseline to week 26 in HbA1c; the margin used to establish non-inferiority of icodec compared with degludec was 0\u00b73 percentage points. Safety outcomes (hypoglycaemic episodes and adverse events) and patient-reported outcomes were also assessed. The primary outcome was evaluated in all randomly assigned participants; safety outcomes were evaluated descriptively based on all randomly assigned participants who received at least one dose of trial product, with statistical analyses based on all randomly assigned participants. This trial is registered with ClinicalTrials.gov, NCT04770532, and is now complete.FINDINGS: Between March 5 and July 19, 2021, 635 participants were screened, of whom 109 were ineligible or withdrew, and 526 were randomly assigned to icodec (n=263) or degludec (n=263). From a mean baseline of 8\u00b717% (icodec; 65\u00b78 mmol/mol) and 8\u00b710% (degludec; 65\u00b70 mmol/mol), HbA1c was reduced to a greater extent with icodec than degludec (7\u00b720% vs 7\u00b742% [55\u00b72 vs 57\u00b76 mmol/mol], respectively) at week 26. This translates to an estimated treatment difference (ETD) of -0\u00b722 percentage points (95% CI -0\u00b737 to -0\u00b708) or -2\u00b74 mmol/mol (95% CI -4\u00b71 to -0\u00b78), demonstrating non-inferiority (p<0\u00b70001) and superiority (p=0\u00b70028). The estimated mean change from baseline to week 26 in bodyweight was +1\u00b740 kg for icodec and -0\u00b730 kg for degludec (ETD 1\u00b770 [95% CI 0\u00b776 to 2\u00b763]). Overall rates of combined level 2 or level 3 hypoglycaemia were less than one event per patient-year of exposure for both groups (0\u00b773 [icodec] vs 0\u00b727 [degludec]; estimated rate ratio 1\u00b793 [95% CI 0\u00b793 to 4\u00b702]). Overall, 161 (61%) of 262 participants receiving icodec and 134 (51%) of 263 participants receiving degludec experienced an adverse event; 22 (8%) and 16 (6%), respectively, experienced a serious adverse event. One serious adverse event (degludec) was assessed as being possibly related to treatment. No new safety issues were identified in relation to icodec compared", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37148899"}, {"offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "INTRODUCTION: Insulin icodec is a novel, long-acting insulin analog designed to cover basal insulin requirements with once-weekly subcutaneous administration", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34413118"}, {"offsetInBeginSection": 152, "offsetInEndSection": 575, "text": " Once-weekly insulin icodec (icodec) is a basal insulin analogue that is in development and is aimed at reducing treatment burden.OBJECTIVE: To compare the effectiveness and safety of icodec titrated with a dosing guide app (icodec with app) versus once-daily basal insulin analogues (OD analogues) dosed per standard practice.DESIGN: 52-week, randomized, open-label, parallel-group, phase 3a trial with real-world elements", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37748181"}, {"offsetInBeginSection": 152, "offsetInEndSection": 478, "text": " Once-weekly insulin icodec (icodec) is a basal insulin analogue that is in development and is aimed at reducing treatment burden.OBJECTIVE: To compare the effectiveness and safety of icodec titrated with a dosing guide app (icodec with app) versus once-daily basal insulin analogues (OD analogues) dosed per standard practice", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37748181"}, {"offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "INTRODUCTION: Insulin icodec is a novel, long-acting insulin analog designed to cover basal insulin requirements with once-weekly subcutaneous administration. Here we describe the molecular engineering and the biological and pharmacological properties of insulin icodec", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34413118"}, {"offsetInBeginSection": 0, "offsetInEndSection": 418, "text": "BACKGROUND AND AIMS: Insulin icodec is currently the most advanced candidate insulin suitable for once-weekly administration. We aim to conduct a systematic review of the literature to find out the efficacy and safety of insulin icodec in patients with diabetes mellitus.METHODS: We systematically searched the electronic database of PubMed, and Google Scholar from inception until August 20, 2022, using MeSH keywords", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36108418"}, {"offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Once-weekly basal insulin icodec: Looking ONWARDS from pharmacology to clinical trials.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36108418"}, {"offsetInBeginSection": 0, "offsetInEndSection": 365, "text": "Basal glucose control is commonly maintained by a single, once-daily administration of insulin through subcutaneous injection or a continuous pump-infusion. Insulin icodec, a novel ultralong-acting lipidated analog validates the concept of a once-weekly basal injection that is less burdensome, yet equally safe and efficacious as conventional once-daily treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34133152"}]}
+{"question_id": "66099ba9fdcbea915f000022", "question": "Is FOLFIRI plus Aflibercept a cost-effective treatment in patients with advanced colorectal caner?", "answer": "Compared with FOLFIRI treatment, aflibercept combined with FOLFIRI for the second-line treatment of mCRC patients has better efficacy, worse safety, and is not cost-effective", "relevant_passage_ids": ["36110513", "25616671", "32616433", "25137165", "29804191", "34816395", "31863550", "24011538", "29605592", "27551256"], "type": "yesno", "snippets": [{"offsetInBeginSection": 2539, "offsetInEndSection": 2715, "text": "Compared with FOLFIRI treatment, aflibercept combined with FOLFIRI for the second-line treatment of mCRC patients has better efficacy, worse safety, and is not cost-effective. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36110513"}, {"offsetInBeginSection": 2758, "offsetInEndSection": 3443, "text": "After consideration of the manufacturer's submission and the ERG's critique, and submissions from other stakeholders, the NICE Appraisal Committee concluded that aflibercept in combination with irinotecan and fluorouracil-based therapy could not be considered a cost effective use of National Health Service resources for treating metastatic colorectal cancer that is resistant to or has progressed after an oxaliplatin-containing regimen. Aflibercept in combination with irinotecan and fluorouracil-based therapy is not recommended for the treatment of metastatic colorectal cancer that is resistant to or has progressed after an oxaliplatin-containing regimen in NICE guidance TA307.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25616671"}, {"offsetInBeginSection": 2236, "offsetInEndSection": 2359, "text": "Adding AFL or RAM to FOLFIRI in the second line of mCRC treatment was not cost-effective in the Japanese health care system", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32616433"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1648, "text": "PURPOSE: The addition of aflibercept (AFL) or ramucirumab (RAM) to folinic acid, fluorouracil, and irinotecan (FOLFIRI) prolongs overall survival and progression-free survival compared with FOLFIRI alone in patients with metastatic colorectal cancer (mCRC) as second-line therapy. Although these combination regimens are recommended among the standard therapies, significant additional cost is a concern. The comparative cost-effectiveness of AFL and RAM was examined from the perspective of the Japanese health care payer.METHODS: A partitioned survival analysis was constructed. The data sources were the VELOUR (Aflibercept Versus Placebo in Combination With Irinotecan and 5-FU in the Treatment of Patients With Metastatic Colorectal Cancer After Failure of an Oxaliplatin Based Regimen) and RAISE (Ramucirumab Versus Placebo in Combination With Second-Line FOLFIRI in Patients With Metastatic Colorectal Carcinoma That Progressed During or After First-Line Therapy With Bevacizumab, Oxaliplatin, and a Fluoropyrimidine) trials, which compared FOLFIRI alone with AFL or RAM in second-line treatment for mCRC. The cost and effectiveness of the combination of AFL or RAM with FOLFIRI were compared with those of FOLFIRI alone and examined between both agents in a 10-year time horizon. The health outcomes were life-years (LYs) and quality-adjusted life-years (QALYs). The costs were 2019 revisions to the drug prices and medical fees. The robustness of the model was verified by 1-way sensitivity analyses and a probability sensitivity analysis. A 2% annual discount was applied to the expenses and QALYs. A willingness-to-pay threshold of \u00a57.5 ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32616433"}, {"offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "[Cost-effectiveness analysis of aflibercept in combination with FOLFIRI in the treatment of patients with metastatic colorectal cancer].", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25137165"}, {"offsetInBeginSection": 772, "offsetInEndSection": 1184, "text": "Dividing the costs of therapy by the measure of efficacy represented by PFS, we found out that the lowest cost per month of PFS gained (4581 \u20ac) was associated with the use of FOLFIRI plus aflibercept.CONCLUSIONS: Combining pharmacological costs of drugs with the measure of efficacy represented by the PFS, aflibercept in combination with FOLFIRI is a cost-effective second-line treatment for patients with mCRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29804191"}, {"offsetInBeginSection": 1213, "offsetInEndSection": 1503, "text": "In the cost-effectiveness analysis Euros 38,931/LYG was obtained with aflibercept in combination with FOLFIRI versus FOLFIRI.CONCLUSION: Aflibercept in combination with FOLFIRI increased overall survival versus FOLFIRI, so it is an effective strategy in the treatment of patients with mCRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25137165"}, {"offsetInBeginSection": 2527, "offsetInEndSection": 2714, "text": "Conclusion: Compared with FOLFIRI treatment, aflibercept combined with FOLFIRI for the second-line treatment of mCRC patients has better efficacy, worse safety, and is not cost-effective.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36110513"}, {"offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "The Clinical and Cost Effectiveness of Aflibercept in Combination with Irinotecan and Fluorouracil-Based Therapy (FOLFIRI) for the Treatment of Metastatic Colorectal Cancer Which has Progressed Following Prior Oxaliplatin-Based Chemotherapy: a Critique of the Evidence.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25616671"}, {"offsetInBeginSection": 0, "offsetInEndSection": 472, "text": "The National Institute for Health and Care Excellence (NICE) invited the manufacturer of aflibercept (Sanofi) to submit clinical and cost-effectiveness evidence for aflibercept in combination with irinotecan and fluorouracil-based therapy [irinotecan/5-fluorouracil/folinic acid (FOLFIRI)] for the treatment of metastatic colorectal cancer which has progressed following prior oxaliplatin-based chemotherapy, as part of the Institute's Single Technology Appraisal process.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25616671"}, {"offsetInBeginSection": 770, "offsetInEndSection": 1603, "text": "est model robustness.RESULTS: Administration of aflibercept + FOLFIRI as second-line treatment provided 1.78 LYG (21 life-months gained). With FOLFIRI 1.43 LYG (17 months) were obtained. The cost of the clinical management of aflibercept + FOLFIRI implied an additional investment of Euros 13,564 compared with FOLFIRI for a lifetime horizon, being total costs for aflibercept + FOLFIRI of Euros 38,346, compared to Euros 24,782 with FOLFIRI. In the cost-effectiveness analysis Euros 38,931/LYG was obtained with aflibercept in combination with FOLFIRI versus FOLFIRI.CONCLUSION: Aflibercept in combination with FOLFIRI increased overall survival versus FOLFIRI, so it is an effective strategy in the treatment of patients with mCRC. Aflibercept in combination with FOLFIRI is an efficient strategy for second-line mCRC treatment fro", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25137165"}, {"offsetInBeginSection": 2150, "offsetInEndSection": 2500, "text": "The base-case incremental cost-effectiveness ratio (ICER) for the overall population was reported by the manufacturer to be \u00a336,294 per quality-adjusted life-year (QALY). After correcting the model programming and updating the model to include the ERG's preferred parameter estimates, the ICER from the ERG's alternative base case was \u00a354,368 per QAL", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25616671"}, {"offsetInBeginSection": 1648, "offsetInEndSection": 2315, "text": "million was used.FINDINGS: Compared with FOLFIRI alone, combination AFL or RAM with FOLFIRI had incremental effects of 0.173 QALYs (0.253 LYs) and 0.137 QALYs (0.197 LYs), incremental costs of \u00a53,423,481 (US $31,010) and \u00a55,766,106 (US $52,229), and incremental cost-effectiveness ratios of \u00a519, 836, 504 (US $179,678) and \u00a541, 947, 989 (US $379,964) per QALY, respectively. Results of 1-way sensitivity analyses and probability sensitivity analysis all exceeded a willingness-to-pay threshold of \u00a57.5 million. In the comparison of the 2 agents, AFL was a dominant over RAM.IMPLICATIONS: Adding AFL or RAM to FOLFIRI in the second line of mCRC treatment was not cost-", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32616433"}, {"offsetInBeginSection": 747, "offsetInEndSection": 1146, "text": "including 3938 patients. Dividing the costs of therapy by the measure of efficacy represented by PFS, we found out that the lowest cost per month of PFS gained (4581 \u20ac) was associated with the use of FOLFIRI plus aflibercept.CONCLUSIONS: Combining pharmacological costs of drugs with the measure of efficacy represented by the PFS, aflibercept in combination with FOLFIRI is a cost-effective second-", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29804191"}, {"offsetInBeginSection": 725, "offsetInEndSection": 907, "text": "Sensitivity analyses (SA) were performed to test model robustness.RESULTS: Administration of aflibercept + FOLFIRI as second-line treatment provided 1.78 LYG (21 life-months gained).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25137165"}, {"offsetInBeginSection": 957, "offsetInEndSection": 1212, "text": "The cost of the clinical management of aflibercept + FOLFIRI implied an additional investment of Euros 13,564 compared with FOLFIRI for a lifetime horizon, being total costs for aflibercept + FOLFIRI of Euros 38,346, compared to Euros 24,782 with FOLFIRI.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25137165"}, {"offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Efficacy, safety, and cost-effectiveness analysis of aflibercept in metastatic colorectal cancer: A rapid health technology assessment.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36110513"}, {"offsetInBeginSection": 2300, "offsetInEndSection": 2415, "text": "Aflibercept was superior to ramucirumab and costed less, but neither were cost-effective compared to standard care.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34816395"}, {"offsetInBeginSection": 772, "offsetInEndSection": 1464, "text": "t model robustness.RESULTS: Administration of aflibercept + FOLFIRI as second-line treatment provided 1.78 LYG (21 life-months gained). With FOLFIRI 1.43 LYG (17 months) were obtained. The cost of the clinical management of aflibercept + FOLFIRI implied an additional investment of Euros 13,564 compared with FOLFIRI for a lifetime horizon, being total costs for aflibercept + FOLFIRI of Euros 38,346, compared to Euros 24,782 with FOLFIRI. In the cost-effectiveness analysis Euros 38,931/LYG was obtained with aflibercept in combination with FOLFIRI versus FOLFIRI.CONCLUSION: Aflibercept in combination with FOLFIRI increased overall survival versus FOLFIRI, so it is an effective strategy ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25137165"}, {"offsetInBeginSection": 0, "offsetInEndSection": 3197, "text": "The National Institute for Health and Care Excellence (NICE) invited the manufacturer of aflibercept (Sanofi) to submit clinical and cost-effectiveness evidence for aflibercept in combination with irinotecan and fluorouracil-based therapy [irinotecan/5-fluorouracil/folinic acid (FOLFIRI)] for the treatment of metastatic colorectal cancer which has progressed following prior oxaliplatin-based chemotherapy, as part of the Institute's Single Technology Appraisal process. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and the resulting NICE guidance TA307 issued in March 2014. The ERG critically reviewed the evidence presented in the manufacturer's submission and identified areas requiring clarification, for which the manufacturer provided additional evidence. The clinical effectiveness data were derived from one good-quality double-blind randomised controlled trial (RCT), the VELOUR trial, which compared aflibercept plus FOLFIRI with placebo plus FOLFIRI. This RCT found a small but statistically significant increase in overall survival (OS); the difference in median OS was 1.44 months (13.5 months in the aflibercept group and 12.06 months in the placebo group). There was also a statistically significant increase in progression-free survival (PFS) with aflibercept; the difference in median PFS was 2.23 months (6.9 months in the aflibercept group and 4.67 months in the placebo group). However, grade 3-4 adverse events were more frequent in the aflibercept group than the placebo group: 83.5% compared with 62.5%. Treatment-emergent adverse events led to permanent discontinuation of treatment in 26.8% of patients in the aflibercept group and 12.1% of patients in the placebo group. The manufacturer's submission included an estimation of mean OS benefit based on extrapolation of the data, which was considerably longer than the median OS benefit reported (4.7 vs. 1.44 months). The ERG considered this to be an over estimate. The base-case incremental cost-effectiveness ratio (ICER) for the overall population was reported by the manufacturer to be \u00a336,294 per quality-adjusted life-year (QALY). After correcting the model programming and updating the model to include the ERG's preferred parameter estimates, the ICER from the ERG's alternative base case was \u00a354,368 per QALY. The extrapolation of the OS curves was the key cost-effectiveness driver and a major source of uncertainty in the model. Additional scenarios related to the extrapolation of OS undertaken by the ERG resulted in ICERs between \u00a362,894 and \u00a392,089 per QALY. After consideration of the manufacturer's submission and the ERG's critique, and submissions from other stakeholders, the NICE Appraisal Committee concluded that aflibercept in combination with irinotecan and fluorouracil-based therapy could not be considered a cost effective use of National Health Service resources for treating metastatic colorectal cancer that is resistant to or has progressed after an oxaliplatin-containing regimen.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25616671"}, {"offsetInBeginSection": 960, "offsetInEndSection": 1506, "text": " cost of the clinical management of aflibercept + FOLFIRI implied an additional investment of Euros 13,564 compared with FOLFIRI for a lifetime horizon, being total costs for aflibercept + FOLFIRI of Euros 38,346, compared to Euros 24,782 with FOLFIRI. In the cost-effectiveness analysis Euros 38,931/LYG was obtained with aflibercept in combination with FOLFIRI versus FOLFIRI.CONCLUSION: Aflibercept in combination with FOLFIRI increased overall survival versus FOLFIRI, so it is an effective strategy in the treatment of patients with mCRC. Af", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25137165"}, {"offsetInBeginSection": 0, "offsetInEndSection": 395, "text": "PURPOSE: The addition of aflibercept (AFL) or ramucirumab (RAM) to folinic acid, fluorouracil, and irinotecan (FOLFIRI) prolongs overall survival and progression-free survival compared with FOLFIRI alone in patients with metastatic colorectal cancer (mCRC) as second-line therapy. Although these combination regimens are recommended among the standard therapies, significant additional cost is a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32616433"}, {"offsetInBeginSection": 1183, "offsetInEndSection": 1308, "text": "to Euros 24,782 with FOLFIRI. In the cost-effectiveness analysis Euros 38,931/LYG was obtained with aflibercept in combinatio", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25137165"}, {"offsetInBeginSection": 747, "offsetInEndSection": 946, "text": "including 3938 patients. Dividing the costs of therapy by the measure of efficacy represented by PFS, we found out that the lowest cost per month of PFS gained (4581 \u20ac) was associated with the use of", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29804191"}, {"offsetInBeginSection": 1060, "offsetInEndSection": 1230, "text": "Questions regarding optimal treatment setting, predictive biomarkers of response, and cost effectiveness of these anti-angiogenic agents and others are as yet unanswered.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27551256"}, {"offsetInBeginSection": 1648, "offsetInEndSection": 1991, "text": "million was used.FINDINGS: Compared with FOLFIRI alone, combination AFL or RAM with FOLFIRI had incremental effects of 0.173 QALYs (0.253 LYs) and 0.137 QALYs (0.197 LYs), incremental costs of \u00a53,423,481 (US $31,010) and \u00a55,766,106 (US $52,229), and incremental cost-effectiveness ratios of \u00a519, 836, 504 (US $179,678) and \u00a541, 947, 989 (US $3", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32616433"}]}
+{"question_id": "662cf96f187cba990d000004", "question": "Please list some treatment options for bone marrow edema syndrome,", "answer": "BME can be related to trauma or a variety of non-traumatic diseases, and current treatment modalities include non-steroidal anti-inflammatory drugs (NSAIDS), bisphosphonates, denosumab, extracorporeal shockwave therapy (ESWT), the vasoactive prostacyclin analogue iloprost, zoledronic acid, and surgical decompression.", "relevant_passage_ids": ["37047734", "36573724", "33880304", "33413520", "23460121", "19358909", "37005106", "37056599", "34780382", "35987803", "28287351", "27587374", "32982099", "23263544", "25901618", "33573900", "16228105", "22933125", "25783691", "16904599", "23053191"], "type": "list", "snippets": [{"offsetInBeginSection": 219, "offsetInEndSection": 521, "text": "BME can be related to trauma or a variety of non-traumatic diseases, and current treatment modalities include non-steroidal anti-inflammatory drugs (NSAIDS), bisphosphonates, denosumab, extracorporeal shockwave therapy (ESWT), the vasoactive prostacyclin analogue iloprost, and surgical decompression. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37047734"}, {"offsetInBeginSection": 1, "offsetInEndSection": 88, "text": "he Use of Iloprost in the Treatment of Bone Marrow Edema Syndrome of the Proximal Femur", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36573724"}, {"offsetInBeginSection": 11, "offsetInEndSection": 212, "text": "The aim of this meta-analysis was to investigate the impact of intravenous iloprost therapy on pain, function, edema changes, and follow-up surgery in bone marrow edema syndrome of the proximal femur. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36573724"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Single-Dose Therapy of Zoledronic Acid for the Treatment of Primary Bone Marrow Edema Syndrome.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33880304"}, {"offsetInBeginSection": 11, "offsetInEndSection": 137, "text": "o review the patients diagnosed with bone marrow edema syndrome who had been treated with one single dose of zoledronic acid. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33880304"}, {"offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Extracorporeal shock wave therapy for bone marrow edema syndrome in patients with osteonecrosis of the femoral head: a retrospective cohort study.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33413520"}, {"offsetInBeginSection": 12, "offsetInEndSection": 195, "text": "There is now ample evidence suggesting that extracorporeal shock wave therapy (ESWT) can improve hip mobility and reduce pain in patients with osteonecrosis of the femoral head (ONFH)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33413520"}, {"offsetInBeginSection": 198, "offsetInEndSection": 428, "text": "he ability of ESWT to cure bone marrow edema syndrome (BMES) in patients with ONFH, 12\u2009weeks after the initial course of ESWT, needs to be verified further and more relevant clinical research-based evidence should be consolidated.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33413520"}, {"offsetInBeginSection": 1375, "offsetInEndSection": 1471, "text": "ESWT should be included in the classic physical therapy regimen for patients with ONFH and BMES.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33413520"}, {"offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Subchondroplasty - A Viable Treatment Option for Transient Bone Marrow Edema Syndrome of the Navicular in an Adolescent: A Case Report.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37056599"}, {"offsetInBeginSection": 137, "offsetInEndSection": 1530, "text": "Methods The data of 54 patients with bone marrow edema syndrome treated with a single dose of intravenous zoledronic acid and partial weight-bearing were included in the study. The diagnosis was based on clinical examination, the existence of prolonged pain, the presence of bone marrow edema on magnetic resonance imaging, and the patient's medical history. The efficacy was assessed using changes in symptoms, visual analogue scale, and changes in magnetic resonance imaging. Results Overall, 54 patients (35.2% male) were included with bone marrow edema syndrome, with a mean age of 52.7 \u00b1 9.77 years (range: 35 - 74 years). The most commonly affected joint was the knee in 32 patients (59.2%), followed by the foot/ankle in 13 patients (24.1%), and the hip in nine patients (16.7%). Improved mobility was reported by 29 patients (53.7%) among the total number of the patients at the six-month\u00a0follow-up visit. The mean visual analogue scale was 6.77 \u00b1 0.83, 7.25 \u00b1 1.19, and 7.46 \u00b1 0.96 at baseline and 5.11 \u00b1 2.14, 4.25 \u00b1 1.84 and 5.15 \u00b1 2.03 at the six-month\u00a0follow-up for the hip, knee and foot/ankle, respectively (p\u00a0= 0.098, p\u00a0< 0.001, p\u00a0= 0.002). At the six-month\u00a0follow-up, the MRI showed resolution of the edema in 20 out of 54 patients (approximately 37%). Only 7.4% of the patients reported minor adverse events which were resolved through a single administration of paracetamol.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33880304"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1404, "text": "PURPOSE: The purpose of this review was to conduct a literature search assessing the efficacy of various conservative treatments of BMES.METHODS: According to the PRISMA guidelines, a literature search was conducted in April 2021 in MEDLINE database via PubMed and Embase to identify original articles describing the results of conservative treatments for BMES of hip and knee published in the last ten years. For each study, information regarding study characteristics, description of the treatment, patient's demographic and clinical data, length of follow-up, clinical outcome measure, disability, adverse events, classification, and extent and of edema on MRI, were extracted.RESULTS: A total of 12 studies were identified. Two studies described treatment with iloprost, three with hyperbaric oxygen (HBO), two with bisphosphonates, five with extracorporeal shockwave therapy (ESWT). The total number of patients was 351: 34 treated with iloprost, 64 with hyperbaric oxygen, 37 with bisphosphonates, 216 with ESWT. In ESWT studies, treatment with a higher flux density and a higher number of therapy sessions lead to better clinical and radiological scores. In iloprost studies, a more remarkable improvement in the VAS scale was observed in the study on hip patients.CONCLUSIONS: The treatment of idiopathic bone marrow edema is currently not standardized, making it difficult to find data that can ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35987803"}, {"offsetInBeginSection": 359, "offsetInEndSection": 821, "text": "This paper reviews the literature and summarizes the treatment options for bone marrow edema syndrome, such as symptomatic treatment, extracorporeal shock waves therapy (ESWT), pulsed electromagnetic fields (PEFs), hyperbaric oxygen (HBO), vitamin D, iloprost, bisphosphonates, denosumab, and surgery, etc. This informs clinicians in treating bone marrow edema syndrome, hopefully improving patients' quality of life and shortening the duration of their disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37005106"}, {"offsetInBeginSection": 359, "offsetInEndSection": 665, "text": "This paper reviews the literature and summarizes the treatment options for bone marrow edema syndrome, such as symptomatic treatment, extracorporeal shock waves therapy (ESWT), pulsed electromagnetic fields (PEFs), hyperbaric oxygen (HBO), vitamin D, iloprost, bisphosphonates, denosumab, and surgery, etc.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37005106"}, {"offsetInBeginSection": 126, "offsetInEndSection": 821, "text": "Hence, doctors are not sufficiently aware of the disease and are prone to misdiagnosis and mistreatment, which can undoubtedly prolong the course of the disease, reduce the quality of life of patients and even affect their function. This paper reviews the literature and summarizes the treatment options for bone marrow edema syndrome, such as symptomatic treatment, extracorporeal shock waves therapy (ESWT), pulsed electromagnetic fields (PEFs), hyperbaric oxygen (HBO), vitamin D, iloprost, bisphosphonates, denosumab, and surgery, etc. This informs clinicians in treating bone marrow edema syndrome, hopefully improving patients' quality of life and shortening the duration of their disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37005106"}, {"offsetInBeginSection": 126, "offsetInEndSection": 665, "text": "Hence, doctors are not sufficiently aware of the disease and are prone to misdiagnosis and mistreatment, which can undoubtedly prolong the course of the disease, reduce the quality of life of patients and even affect their function. This paper reviews the literature and summarizes the treatment options for bone marrow edema syndrome, such as symptomatic treatment, extracorporeal shock waves therapy (ESWT), pulsed electromagnetic fields (PEFs), hyperbaric oxygen (HBO), vitamin D, iloprost, bisphosphonates, denosumab, and surgery, etc.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37005106"}, {"offsetInBeginSection": 79, "offsetInEndSection": 665, "text": "It has been poorly reported in the literature. Hence, doctors are not sufficiently aware of the disease and are prone to misdiagnosis and mistreatment, which can undoubtedly prolong the course of the disease, reduce the quality of life of patients and even affect their function. This paper reviews the literature and summarizes the treatment options for bone marrow edema syndrome, such as symptomatic treatment, extracorporeal shock waves therapy (ESWT), pulsed electromagnetic fields (PEFs), hyperbaric oxygen (HBO), vitamin D, iloprost, bisphosphonates, denosumab, and surgery, etc.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37005106"}, {"offsetInBeginSection": 0, "offsetInEndSection": 401, "text": "To determine the validity and safety of extracorporeal shock wave therapy (ESWT) in the treatment of bone marrow edema syndrome (BMES) of the foot. Twenty patients diagnosed as foot BMES in our Center were followed and treated by ESWT for 1 to 2 courses. The target of the ESWT treatment was the most obvious foot tenderness, or the most obvious part of bone edema on magnetic resonance imaging (MRI).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33573900"}, {"offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "To determine the validity and safety of extracorporeal shock wave therapy (ESWT) in the treatment of bone marrow edema syndrome (BMES) of the foot. Twenty patients diagnosed as foot BMES in our Center were followed and treated by ESWT for 1 to 2 courses.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33573900"}, {"offsetInBeginSection": 1432, "offsetInEndSection": 1969, "text": "On magnetic resonance imaging (MRI), bone marrow edema improved in all patients during the follow-up period. After extracorporeal shock wave therapy, all patients remained pain-free and had normal findings on posttreatment radiographs and MRI scans. Extracorporeal shock wave therapy appears to be a valid, reliable, and noninvasive tool for rapidly resolving intractable bone marrow edema syndrome of the hip, and it has a low complication rate and relatively low cost compared with other conservative and surgical treatment approaches.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25901618"}, {"offsetInBeginSection": 915, "offsetInEndSection": 1001, "text": "Ischemic BME and early stages of ON can be successfully treated by core decompression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23460121"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Effective and rapid treatment of painful localized transient osteoporosis (bone marrow edema) with intravenous ibandronate.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16228105"}, {"offsetInBeginSection": 713, "offsetInEndSection": 1068, "text": "Conservative or surgical treatment is considered, depending on the etiology of BME. BME syndrome is generally treated conservatively. Infusion of prostacycline or bisphosphonates is a promising option. Ischemic BME and early stages of ON can be successfully treated by core decompression. A combination of both treatment options may also offer advantages.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23460121"}, {"offsetInBeginSection": 782, "offsetInEndSection": 964, "text": "The goal of BMES treatment is to relieve pain and shorten disease duration. Treatment options are limited and may include symptomatic treatment, pharmacologic treatment, and surgery.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27587374"}, {"offsetInBeginSection": 1052, "offsetInEndSection": 1180, "text": " Zoledronic acid is a option in the management of BMES, since 75% of patients treated with it presented with a complete response", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28287351"}, {"offsetInBeginSection": 154, "offsetInEndSection": 512, "text": "ervatively.AIM: This case report describes the clinical history of a patient with BMES and a therapy attempt with denosumab.RESULTS AND DISCUSSION: Complete restitution of the bone marrow edema in the knee and the disappearance of clinical complaints were observed 8 weeks after a single therapy with 60\u00a0mg denosumab (Prolia\u00ae) as a subcutaneous injection. No", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25783691"}, {"offsetInBeginSection": 524, "offsetInEndSection": 711, "text": "We treated 6 patients with bone marrow edema in MRI and suspected osteonecrosis of the hip joint with calcium dobesilate, a vasoactive agent used in the treatment of diabetic retinopathy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32982099"}, {"offsetInBeginSection": 0, "offsetInEndSection": 529, "text": "\u27a4: Bone marrow edema (BME) is a nonspecific but relevant finding, usually indicating the presence of an underlying pathology.\u27a4: The gold standard technique for detecting BME is magnetic resonance imaging (MRI), as it allows for a correct diagnosis to be made, which is extremely important given the heterogeneity of BME-related diseases.\u27a4: Depending on the severity of painful symptomatology and the MRI evidence, different treatment strategies can be followed: physical modalities, pharmacological options, and surgical therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34780382"}, {"offsetInBeginSection": 1531, "offsetInEndSection": 1781, "text": "Conclusion Our data show that the combination treatment of a single dose of zoledronic acid and partial weight-bearing for one month improves mobility and reduces edema in patients with bone marrow edema syndrome in the primary weight-bearing joints.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33880304"}, {"offsetInBeginSection": 797, "offsetInEndSection": 1068, "text": "BME syndrome is generally treated conservatively. Infusion of prostacycline or bisphosphonates is a promising option. Ischemic BME and early stages of ON can be successfully treated by core decompression. A combination of both treatment options may also offer advantages.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23460121"}, {"offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "BACKGROUND: In this pilot study, we investigated the therapeutic efficacy of intravenous Ibandronate compared to pain medication on the outcome of bone marrow edemas (BME) of the kne", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23053191"}, {"offsetInBeginSection": 795, "offsetInEndSection": 1222, "text": "MRI at the third monthly visit showed nearly complete resolution of bone marrow edema. The patient was followed for 2 years and 6 months and was completely asymptomatic. This case report suggests the need for orthopaedic surgeons to know about BMES. Before all-arthroscopic interventions are performed, MRI views should be evaluated carefully. Iloprost infusion therapy seems to be effective and safe in the management of BMES.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16904599"}, {"offsetInBeginSection": 0, "offsetInEndSection": 762, "text": "Transient osteoporosis of the hip (TOH), also referred to as transient bone marrow edema syndrome, is most common in middle-aged men and often after trivial trauma or sport-related injuries. Diagnosis is usually made by eliminating other possible causes of hip pain. Magnetic resonance imaging (MRI) plays an important role in diagnosis and demonstrates a typical pattern of bone marrow edema (BME) in the form of diffuse low signal on T1-weighted images and high signal on T2 fat-suppressed or short T1 inversion recovery images. No consensus exists about the management of TOH, as it may progress to avascular necrosis. We describe eight cases of TOH treated with alendronate resulting in improvement of pain and function and complete resolution of BME on MRI.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22933125"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1026, "text": "An increase in interstitial fluid is an expression of bone marrow edema (BME) and osteonecrosis (ON). The exact pathogenetic processes still remain unknown. Treatment options are mainly symptomatic with core decompression as surgical golden standard with immediate pain relief. Recently, it has been shown that intravenous iloprost can be used to achieve a reduction in BME and ON with a considerable improvement in the accompanying symptoms. The effect of intraveneously applied iloprost alone (12 patients) was studied against core decompression alone (12 patients) as well as iloprost following core decompression (12 patients). We could find a significant improvement in HHS, WOMAC score, SF-36 score and VAS 3 months and 1 year after therapeutical intervention in all treatment groups; however, statistically best results were obtained by combination. Concerning the MRI scans, we found a distinct reduction in BME in all groups again favoring the combination. Concerning ON, the results were not as promising as for BME.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23263544"}, {"offsetInBeginSection": 0, "offsetInEndSection": 386, "text": "Bone marrow edema syndrome of the femoral head in pregnant women is a rare disease resulting in disabling coxalgia, beginning in the last 3 months of pregnancy and persisting for several months after parturition. The parenteral administration of the vasoactive drug iloprost constitutes a new approach to the treatment of painful bone marrow edema syndrome of the hip of pregnant women.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19358909"}, {"offsetInBeginSection": 137, "offsetInEndSection": 313, "text": "Methods The data of 54 patients with bone marrow edema syndrome treated with a single dose of intravenous zoledronic acid and partial weight-bearing were included in the study.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33880304"}, {"offsetInBeginSection": 0, "offsetInEndSection": 542, "text": "Bone marrow edema syndrome of the femoral head in pregnant women is a rare disease resulting in disabling coxalgia, beginning in the last 3 months of pregnancy and persisting for several months after parturition. The parenteral administration of the vasoactive drug iloprost constitutes a new approach to the treatment of painful bone marrow edema syndrome of the hip of pregnant women. Six postpartal women (8 hips) with bone marrow edema syndrome of the femoral head were treated with iloprost followed by 3 weeks of partial weight-bearing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19358909"}, {"offsetInBeginSection": 213, "offsetInEndSection": 713, "text": "The parenteral administration of the vasoactive drug iloprost constitutes a new approach to the treatment of painful bone marrow edema syndrome of the hip of pregnant women. Six postpartal women (8 hips) with bone marrow edema syndrome of the femoral head were treated with iloprost followed by 3 weeks of partial weight-bearing. Relief from pain, restoration of functional capacity, and normalization of the MRI signal pattern were rapidly achieved, thus avoiding the need for surgical intervention.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19358909"}]}
+{"question_id": "66150639fdcbea915f000047", "question": "What is the immediate treatment after a sexual assault?", "answer": "The immediate treatment after a sexual assault includes ensuring the victim's safety and privacy, treating physical injuries, and preventing unwanted pregnancy and sexually transmitted infections (STIs). This may involve administering emergency contraception, prophylaxis for bacterial and viral STIs, and offering post-exposure prophylaxis for human immunodeficiency virus (HIV) infection in high-risk cases. Additionally, psychological support and risk assessment for self-harm or suicide should be provided. The healthcare provider should also collect evidence for a \"rape kit\" if trained to do so, while being sensitive to the victim's emotional well-being. Overall, the goal of immediate treatment is to address the victim's physical and emotional needs, prevent long-term health consequences, and provide support during this traumatic experience.", "relevant_passage_ids": ["37977653", "36940194"], "type": "list", "snippets": [{"offsetInBeginSection": 792, "offsetInEndSection": 815, "text": "Emergency contraception", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37977653"}, {"offsetInBeginSection": 877, "offsetInEndSection": 921, "text": "postexposure prophylaxis (PEP) for chlamydia", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37977653"}, {"offsetInBeginSection": 959, "offsetInEndSection": 966, "text": "for HIV", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37977653"}, {"offsetInBeginSection": 990, "offsetInEndSection": 1013, "text": "Hepatitis B vaccination", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37977653"}, {"offsetInBeginSection": 1036, "offsetInEndSection": 1094, "text": "presumptive gonorrhea and chlamydia treatment was provided", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36940194"}, {"offsetInBeginSection": 1188, "offsetInEndSection": 1201, "text": "contraception", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36940194"}]}
+{"question_id": "6630562c187cba990d000036", "question": "What is the potential role of the tumor microenvironment and factors like stem cells in contributing to the recurrence of glioblastoma?", "answer": "Glioblastoma (GBM) tumor microenvironment (TME) is a highly heterogeneous and complex system, which in addition to cancer cells, consists of various resident brain and immune cells as well as cells in transit through the tumor such as marrow-derived immune cells. The TME is a dynamic environment that is heavily influenced by alterations in cellular composition, cell-to-cell contact, and cellular metabolic products as well as other chemical factors, such as pH and oxygen levels. Emerging evidence suggests that GBM cells - especially glioma stem cells (GSCs) - appear to reprogram the TME, and hijack microenvironmental elements to facilitate rapid proliferation, invasion, migration, and survival thus generating treatment resistance and recurrence.", "relevant_passage_ids": ["37237548", "36968288", "22996727", "24834433", "32545571", "36338705", "22379614", "23063412", "21446047", "24904289", "31147872", "35920986", "35228161", "34687436", "28630875", "37218976", "37108208", "34439159", "35805138", "28740831", "30619286", "35311140", "29204831", "35456984", "35269652", "28003805", "33799798", "35141013", "30577488", "22614016", "37088298", "32952746", "28670569", "26880981", "32942567", "19770585"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 705, "text": "Glioblastoma (GBM) tumor microenvironment (TME) is a highly heterogeneous and complex system, which in addition to cancer cells, consists of various resident brain and immune cells as well as cells in transit through the tumor such as marrow-derived immune cells. The TME is a dynamic environment which is heavily influenced by alterations in cellular composition, cell-to-cell contact and cellular metabolic products as well as other chemical factors, such as pH and oxygen levels. Emerging evidence suggests that GBM cells appear to reprogram their the TME, and hijack microenvironmental elements to facilitate rapid proliferation, invasion, migration, and survival thus generating treatment resistance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36968288"}, {"offsetInBeginSection": 0, "offsetInEndSection": 468, "text": "The invasive nature of glioblastoma is problematic in a radical surgery approach and can be responsible for tumor recurrence. In order to create new therapeutic strategies, it is imperative to have a better understanding of the mechanisms behind tumor growth and invasion. The continuous cross-talk between glioma stem cells (GSCs) and the tumor microenvironment (TME) contributes to disease progression, which renders research in this field difficult and challenging.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37237548"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1014, "text": "Glioma is the most common primary intracranial tumor and has the greatest prevalence of all brain tumors. Treatment resistance and tumor recurrence in GBM are mostly explained by considerable alterations within the tumor microenvironment, as well as extraordinary cellular and molecular heterogeneity. Soluble factors, extracellular matrix components, tissue-resident cell types, resident or newly recruited immune cells together make up the GBM microenvironment. Regardless of many immune cells, a profound state of tumor immunosuppression is supported and developed, posing a considerable hurdle to cancer cells' immune-mediated destruction. Several studies have suggested that various GBM subtypes present different modifications in their microenvironment, although the importance of the microenvironment in treatment response has yet to be determined. Understanding the microenvironment and how it changes after therapies is critical because it can influence the remaining invasive GSCs and lead to recurrence.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35269652"}, {"offsetInBeginSection": 0, "offsetInEndSection": 652, "text": "Glioblastoma multiforme (GBM) is the most incurable tumor (due to the difficulty in complete surgical resection and the resistance to conventional chemo/radiotherapies) that displays a high relapse frequency. Cancer stem cells (CSCs) have been considered as a promising target responsible for therapy resistance and cancer recurrence. CSCs are known to organize a self-advantageous microenvironment (niche) for their maintenance and expansion. Therefore, understanding how the microenvironment is reconstructed by the remaining CSCs after conventional treatments and how it eventually causes recurrence should be essential to inhibit cancer recurrence.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35805138"}, {"offsetInBeginSection": 0, "offsetInEndSection": 335, "text": "The tumor microenvironment (TME) of glioblastoma malforms (GBMs) contains tumor invasiveness factors, microvascular proliferation, migratory cancer stem cells and infiltrative tumor cells, which leads to tumor recurrence in the absence of effective drug delivery in a Blood Brain Barrier (BBB)-intact TME and radiological invisibility.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35141013"}, {"offsetInBeginSection": 0, "offsetInEndSection": 392, "text": "Glioblastoma multiforme (GBM) is a devastating disease with high mortality and poor prognosis. Cancer stem cells (CSCs) have recently been defined as a fraction of tumor cells highly resistant to therapy and subsequently considered to be responsible for tumor recurrence. These cells have been characterized in GBM and suggested to reside in and be supported by the tumor microvascular niche.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22614016"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1047, "text": "It has been recently suggested that many types of cancer, including glioblastoma (GBM), contain functionally subsets of cells with stem-like properties named \"cancer stem cells\" (CSCs). These are characterized by chemotherapy resistance and considered one of the key determinants driving tumor relapse. Many studies demonstrated that Glioma stem cells (GSCs) reside in particular tumor niches, that are necessary to support their behavior. A hypoxic microenvironment has been reported to play a crucial role in controlling GSC molecular and phenotypic profile and in promoting the recruitment of vascular and stromal cells in order to sustain tumor growth. Recent advances in the field allow researches to generate models able to recapitulate, at least in part, the extreme heterogeneity found within GBM tumors. These models try to account for the presence of GSCs and more differentiated cells, the influence of different microenvironments enclosed within the mass, heterotypic interactions between GBM and stromal cells and genetic aberrations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23063412"}, {"offsetInBeginSection": 201, "offsetInEndSection": 415, "text": "In addition to heterogenous populations of tumor cells, the glioma stem cells (GSCs) and other nontumor cells present in the glioma microenvironment serve as critical regulators of tumor progression and recurrence.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30619286"}, {"offsetInBeginSection": 553, "offsetInEndSection": 883, "text": "The reciprocal interaction between glioma stem cells (GSCs) and cells from the microenvironment, such as endothelial cells, immune cells, and other parenchymal cells, may also promote angiogenesis, invasion, proliferation, and stemness of the GSCs and be likely to have an underappreciated role in their responsiveness to therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28630875"}, {"offsetInBeginSection": 106, "offsetInEndSection": 301, "text": "Treatment resistance and tumor recurrence in GBM are mostly explained by considerable alterations within the tumor microenvironment, as well as extraordinary cellular and molecular heterogeneity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35269652"}, {"offsetInBeginSection": 1109, "offsetInEndSection": 1461, "text": "The microenvironment contribution in GBM development is increasingly emphasized. An interplay exists between CSCs, differentiated GBM cells, and the microenvironment, mainly through secreted chemokines (e.g., CXCL12) causing recruitment of fibroblasts, endothelial, mesenchymal and inflammatory cells to the tumor, via specific receptors such as CXCR4.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24904289"}]}
+{"question_id": "663020d7187cba990d00002b", "question": "Is there an association between specific genotypes and the risk of ADHD for Duchenne Muscular Dystrophy?", "answer": "Yes, ADHD might be associated with the Dp71 genotype in DMD.", "relevant_passage_ids": ["36565132"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1530, "offsetInEndSection": 1584, "text": "ADHD might be associated with the Dp71 genotype in DMD", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36565132"}]}
+{"question_id": "65cfd8551930410b13000023", "question": "Is vemurafenib\u2013cobimetinib promising for craniopharyngioma?", "answer": "Yes. Vemurafenib\u2013cobimetinib showed promising for craniopharyngioma", "relevant_passage_ids": ["37437144", "37477404", "35169097"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1973, "offsetInEndSection": 2187, "text": "CONCLUSIONS: In this small, single-group study involving patients with papillary craniopharyngiomas, 15 of 16 patients had a partial response or better to the BRAF-MEK inhibitor combination vemurafenib-cobimetinib.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37437144"}, {"offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Vemurafenib plus cobimetinib is effective in patients with BRAF-mutant papillary craniopharyngioma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37477404"}, {"offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "BRAF-MEK Inhibition Is Effective in BRAFV600E-Mutant Papillary Craniopharyngioma.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37477404"}, {"offsetInBeginSection": 726, "offsetInEndSection": 1028, "text": "Several case reports have illustrated dramatic response of the residual or recurrent papillary craniopharyngioma to molecularly targeted therapy with a BRAF inhibitor(vemurafenib or dabrafenib)and a MEK inhibitor(trametinib), which are currently approved for melanoma and non-small cell lung carcinoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35169097"}]}
+{"question_id": "66214db9b9f8b89d7e000004", "question": "What is the molecular mechanism by which Bacteroides Fragilis is associated to colorectal cancer development?", "answer": "B. fragilis (BFT) had a higher abundance in the tumor samples than in healthy tissues, and this bacterium may lead to CRC by making changes in cellular signaling pathways and genes, including the WNT/Beta-catenin pathway.  Intestinal inflammation is mediated by BFT, as yet the only known virulence factor of ETBF. Recent experimental evidence demonstrating that ETBF-driven colitis promotes colon tumorigenesis has generated interest in the potential contribution of ETBF to human colon carcinogenesis", "relevant_passage_ids": ["37644520", "25105360", "30429227", "32038097", "32010637", "31378159", "27846243", "16842574", "32863742", "34627951", "31515468", "35587635", "32684087", "34371001", "37828235", "37806638", "37612266", "37554340", "37066368", "31857085", "35461079", "30151274", "27323816", "21876161", "35166235", "36465770", "36578036", "10075957", "19366918", "28144586", "28151975", "25305284", "35468857", "33981848", "34273006", "36790675", "32604093", "30279518", "35104632", "34108031", "35317317", "27686415", "23534358", "33492552", "27112830", "27607555", "36173175", "19188353", "26173688", "21233422"], "type": "summary", "snippets": [{"offsetInBeginSection": 172, "offsetInEndSection": 288, "text": "Bacteroides fragilis can lead to tumorigenesis by changing signaling pathways, including the WNT/\u03b2-catenin pathway. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37644520"}, {"offsetInBeginSection": 1465, "offsetInEndSection": 1640, "text": " B. fragilis had a higher abundance in the tumor samples than in healthy tissues, and this bacterium may lead to CRC by making changes in cellular signaling pathways and genes", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37644520"}, {"offsetInBeginSection": 662, "offsetInEndSection": 941, "text": "Intestinal inflammation is mediated by BFT, as yet the only known virulence factor of ETBF. Recent experimental evidence demonstrating that ETBF-driven colitis promotes colon tumorigenesis has generated interest in the potential contribution of ETBF to human colon carcinogenesis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25105360"}, {"offsetInBeginSection": 384, "offsetInEndSection": 684, "text": "This study compared the interaction of CRC-associated species Enterotoxigenic Bacteroides fragilis, Enterococcus faecalis and Fusobacterium nucleatum and one probiotic species, Escherichia coli Nissle 1917 with a colorectal adenoma (S/RG/C2) and a colorectal adenocarcinoma (HCT116) derived cell line", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37828235"}, {"offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Clinical significance of Bacteroides fragilis as a potential prognostic factor in colorectal cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37806638"}, {"offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Evaluation of enterotoxigenic Bacteroides fragilis correlation with the expression of cellular signaling pathway genes in Iranian patients with colorectal cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37644520"}, {"offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Bacterial lipopolysaccharide modulates immune response in the colorectal tumor microenvironment.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37612266"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1859, "text": "Many patients with chronic inflammation of the gut, such as that observed in inflammatory bowel disease (IBD), develop colorectal cancer (CRC). Recent studies have reported that the development of IBD and CRC partly results from an imbalanced composition of intestinal microbiota and that intestinal inflammation in these diseases can be modulated by the microbiota. The human commensal Bacteroides fragilis is best exemplified playing a protective role against the development of experimental colitis in several animal disease models. In this study, we found that gut inflammation caused by dextran sulfate sodium (DSS) treatment was inhibited by B. fragilis colonization in mice. Further, we reveal a protective role of B. fragilis treatment against colon tumorigenesis using an azoxymethane (AOM)/DSS-induced model of colitis-associated colon cancer in mice and demonstrate that the decreased tumorigenesis by B. fragilis administration is accompanied by inhibited expression of C-C chemokine receptor 5 (CCR5) in the gut. We show direct evidence that the inhibition of tumor formation provided by B. fragilis in colitis-associated CRC animals was dependent on the production of polysaccharide A (PSA) from B. fragilis and that Toll-like receptor 2 (TLR2) signaling was responsible for the protective function of B. fragilisIMPORTANCE The incidence of colorectal cancer (CRC) is rapidly growing worldwide, and there is therefore a greater emphasis on studies of the treatment or prevention of CRC pathogenesis. Recent studies suggested that consideration of the microbiota is unavoidable to understand inflammation and tumorigenesis in the gastrointestinal tract. We demonstrate, using a mouse model of colitis-associated CRC, that human commensal B. fragilis protects against colon tumorigenesis. The protective role against tumor formation provided by B.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30429227"}, {"offsetInBeginSection": 0, "offsetInEndSection": 920, "text": "The importance of the microbiota in the development of colorectal cancer (CRC) is increasingly evident, but identifying specific microbial features that influence CRC initiation and progression remains a central task for investigators. Studies determining the microbial mechanisms that directly contribute to CRC development or progression are revealing bacterial factors such as toxins that contribute to colorectal carcinogenesis. However, even when investigators have identified bacteria that express toxins, questions remain about the host determinants of a toxin's cancer-potentiating effects. For other cancer-correlating bacteria that lack toxins, the challenge is to define cancer-relevant virulence factors. Herein, we evaluate three CRC-correlating bacteria, colibactin-producing Escherichia coli, enterotoxigenic Bacteroides fragilis, and Fusobacterium nucleatum, for their virulence features relevant to CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35166235"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1415, "text": "BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers all over the world, and dysbiosis in the gut microbiota may play a role in colorectal carcinogenesis. Bacteroides fragilis can lead to tumorigenesis by changing signaling pathways, including the WNT/\u03b2-catenin pathway. Therefore, in the present study, we investigated the correlation between the enterotoxigenic B. fragilis amount and the expression of signaling pathway genes involved in CRC.MATERIALS AND METHODS: B. fragilis was determined in 30 tumors and adjacent healthy tissues by the qPCR method. Next, the relationship between enterotoxigenic B. fragilis and the expression of signaling pathway genes, including CCND1, TP53, BCL2, BAX, WNT, TCF, AXIN, APC, and CTNNB1 was investigated. Additionally, possible correlations between clinicopathological features of the tumor samples and the abundance of B. fragilis were analyzed.RESULTS: The results showed that B. fragilis was detected in 100% of tumor samples and 86% of healthy tissues. Additionally, enterotoxigenic B. fragilis colonized 47% of all samples, and bft-1 toxin was the most frequently found isotype among the samples. The analysis showed that the high level of B. fragilis has a significant relationship with the high expression of AXIN, CTNNB1, and BCL2 genes. On the other hand, our results did not show any possible correlation between this bacterium and the clinicopat", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37644520"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1478, "text": "BACKGROUND: Colorectal cancer (CRC) is the third most diagnosed cancer and the second most common cause of cancer deaths worldwide. CRC patients present with an increase in pathogens in their gut microbiota, such as polyketide synthase-positive bacteria (pks\u2009+) and enterotoxigenic Bacteroides fragilis (ETBF). The pks\u2009+\u2009Escherichia coli promotes carcinogenesis and facilitates CRC progression through the production of colibactin, a genotoxin that induces double-strand DNA breaks (DSBs). ETBF is a procarcinogenic bacterium producing the B. fragilis toxin (bft) that promotes colorectal carcinogenesis by modulating the mucosal immune response and inducing epithelial cell changes.METHODS: Fecal samples were collected from healthy controls (N\u2009=\u200962) and CRC patients (N\u2009=\u200994) from the province of Qu\u00e9bec (Canada), and a bacterial DNA extraction was performed. Fecal DNA samples were then examined for the presence of the pks island gene and bft using conventional qualitative PCR.RESULTS: We found that a high proportion of healthy controls are colonized by pks\u2009+\u2009bacteria (42%) and that these levels were similar in CRC patients (46%). bft was detected in 21% of healthy controls and 32% of CRC patients, while double colonization by both pks\u2009+\u2009bacteria and ETBF occurred in 8% of the healthy controls and 13% of the CRC patients. Most importantly, we found that early-onset CRC (<\u200950\u00a0years) patients were significantly less colonized with pks\u2009+\u2009bacteria (20%) compared to la", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36578036"}, {"offsetInBeginSection": 0, "offsetInEndSection": 997, "text": "The Bacteroides fragilis (B. fragilis) produce biofilm for colonisation in the intestinal tract can cause a series of inflammatory reactions due to B. fragilis toxin (BFT) which can lead to chronic intestinal inflammation and tissue injury and play a crucial role leading to colorectal cancer (CRC). The enterotoxigenic B. fragilis (ETBF) forms biofilm and produce toxin and play a role in CRC, whereas the non-toxigenic B. fragilis (NTBF) does not produce toxin. The ETBF triggers the expression of cyclooxygenase (COX)-2 that releases PGE2 for inducing inflammation and control cell proliferation. From chronic intestinal inflammation to cancer development, it involves signal transducers and activators of transcription (STAT)3 activation. STAT3 activates by the interaction between epithelial cells and BFT. Thus, regulatory T-cell (Tregs) will activates and reduce interleukin (IL)-2 amount. As the level of IL-2 drops, T-helper (Th17) cells are generated leading to increase in IL-17 levels.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32863742"}, {"offsetInBeginSection": 0, "offsetInEndSection": 969, "text": "Enterotoxigenic Bacteroides fragilis (ETBF) has received significant attention for a possible association with, or causal role in, colorectal cancer (CRC). The goal of this review was to assess the status of the published evidence supporting (i) the association between ETBF and CRC and (ii) the causal role of ETBF in CRC. PubMed and Scopus searches were performed in August 2021 to identify human, animal, and cell studies pertaining to the role of ETBF in CRC. Inclusion criteria included the use of cell lines, mice, exposure to BFT or ETBF, and detection of bft. Review studies were excluded, and studies were limited to the English language. Quality of study design and risk of bias analysis was performed on the cell, animal, and human studies using ToxRTools, SYRCLE, and NOS, respectively. Ninety-five eligible studies were identified, this included 22 human studies, 24 animal studies, 43 cell studies, and 6 studies that included both cells and mice studies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35461079"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1534, "text": "INTRODUCTION: Bacteroides fragilis (B. fragilis) is considered to act in an anti-inflammatory manner on the intestinal tract. On the contrary, enterotoxigenic B. fragilis (ETBF), a subtype of B. fragilis, produces an enterotoxin (BFT; B. fragilis toxin), leading to asymptomatic chronic infections and colonic tumor formation. However, the impact of B. fragilis and ETBF on the clinical outcome of colorectal cancer (CRC) remains unclear. We aim to assess whether their presence affects the outcome in patients with CRC after curative resection.METHODS: We obtained 197 pairs of matched formalin-fixed paraffin-embedded samples from cancerous and adjacent non-cancerous tissues of patients with pathological stage (pstage) II and III CRC after curative resection. The presence of B. fragilis and ETBF were estimated using real-time polymerase chain reaction, and recurrence-free survival (RFS) and overall survival (OS) of the patients were analyzed.RESULTS: 16\u00a0S rRNA for B. fragilis and bft DNA were detected in 120 (60.9%) and 12 (6.1%) of the 197 patients, respectively. B. fragilis-positive patients had better RFS than B. fragilis-negative patients, although that was not statistically significant. In subgroup analysis, better outcomes on RFS were observed in the presence of B. fragilis in pstage II and left-sided CRC. The association of B. fragilis positivity on OS was accentuated in the depth of T4 subgroup. No significant differences were observed in RFS and OS between ETBF and non-toxigenic B. fragilis.CONCLUSIONS: Ou", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37806638"}, {"offsetInBeginSection": 0, "offsetInEndSection": 463, "text": "The Bacteroides fragilis (B. fragilis) produce biofilm for colonisation in the intestinal tract can cause a series of inflammatory reactions due to B. fragilis toxin (BFT) which can lead to chronic intestinal inflammation and tissue injury and play a crucial role leading to colorectal cancer (CRC). The enterotoxigenic B. fragilis (ETBF) forms biofilm and produce toxin and play a role in CRC, whereas the non-toxigenic B. fragilis (NTBF) does not produce toxin.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32863742"}, {"offsetInBeginSection": 0, "offsetInEndSection": 599, "text": "The Bacteroides fragilis (B. fragilis) produce biofilm for colonisation in the intestinal tract can cause a series of inflammatory reactions due to B. fragilis toxin (BFT) which can lead to chronic intestinal inflammation and tissue injury and play a crucial role leading to colorectal cancer (CRC). The enterotoxigenic B. fragilis (ETBF) forms biofilm and produce toxin and play a role in CRC, whereas the non-toxigenic B. fragilis (NTBF) does not produce toxin. The ETBF triggers the expression of cyclooxygenase (COX)-2 that releases PGE2 for inducing inflammation and control cell proliferation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32863742"}, {"offsetInBeginSection": 0, "offsetInEndSection": 299, "text": "The Bacteroides fragilis (B. fragilis) produce biofilm for colonisation in the intestinal tract can cause a series of inflammatory reactions due to B. fragilis toxin (BFT) which can lead to chronic intestinal inflammation and tissue injury and play a crucial role leading to colorectal cancer (CRC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32863742"}, {"offsetInBeginSection": 0, "offsetInEndSection": 434, "text": "BACKGROUND: Strains of Bacteroides fragilis producing a 20 kDa protein toxin (B fragilis toxin (BFT) or fragilysin) are associated with diarrhoea in animals and humans. Although in vitro results indicate that BFT damages intestinal epithelial cells in culture, the effects of BFT on native human colon are not known.AIMS: To examine the electrophysiological and morphological effects of purified BFT-2 on human colonic mucosa in vitro", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10075957"}, {"offsetInBeginSection": 0, "offsetInEndSection": 315, "text": "BACKGROUND: Strains of Bacteroides fragilis producing a 20 kDa protein toxin (B fragilis toxin (BFT) or fragilysin) are associated with diarrhoea in animals and humans. Although in vitro results indicate that BFT damages intestinal epithelial cells in culture, the effects of BFT on native human colon are not known", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10075957"}, {"offsetInBeginSection": 0, "offsetInEndSection": 486, "text": "Enterotoxigenic Bacteroides fragilis (ETBF) strains are strains of B. fragilis that secrete a 20-kDa heat-labile zinc-dependent metalloprotease toxin termed the B. fragilis toxin (BFT). BFT is the only recognized virulence factor specific for ETBF. ETBF strains are associated with inflammatory diarrheal disease in children older than 1 year of age and in adults; limited data suggest an association of ETBF colonization with inflammatory bowel disease flare-ups and colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19366918"}, {"offsetInBeginSection": 395, "offsetInEndSection": 663, "text": "A subset of B. fragilis strains carry a genetic element that encodes a metalloprotease enterotoxin named Bacteroides fragilis toxin, or BFT. Toxin-bearing strains, or Enterotoxigenic B. fragilis (ETBF) cause acute and chronic intestinal disease in children and adults.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31857085"}, {"offsetInBeginSection": 395, "offsetInEndSection": 792, "text": "A subset of B. fragilis strains carry a genetic element that encodes a metalloprotease enterotoxin named Bacteroides fragilis toxin, or BFT. Toxin-bearing strains, or Enterotoxigenic B. fragilis (ETBF) cause acute and chronic intestinal disease in children and adults. Despite this association with disease, around twenty percent of the human population appear to be asymptomatic carriers of ETBF.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31857085"}, {"offsetInBeginSection": 395, "offsetInEndSection": 535, "text": "A subset of B. fragilis strains carry a genetic element that encodes a metalloprotease enterotoxin named Bacteroides fragilis toxin, or BFT.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31857085"}, {"offsetInBeginSection": 1026, "offsetInEndSection": 1513, "text": "We show direct evidence that the inhibition of tumor formation provided by B. fragilis in colitis-associated CRC animals was dependent on the production of polysaccharide A (PSA) from B. fragilis and that Toll-like receptor 2 (TLR2) signaling was responsible for the protective function of B. fragilisIMPORTANCE The incidence of colorectal cancer (CRC) is rapidly growing worldwide, and there is therefore a greater emphasis on studies of the treatment or prevention of CRC pathogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30429227"}, {"offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "BACKGROUND: Enterotoxigenic Bacteroides fragilis (ETBF) has been implicated in colorectal carcinogenesis through the actions of its toxin, B. fragilis toxin (BFT).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35468857"}, {"offsetInBeginSection": 2112, "offsetInEndSection": 2298, "text": "Our results suggest that the commensal microorganism B. fragilis can be used to prevent inflammation-associated CRC development and may provide an effective therapeutic strategy for CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30429227"}, {"offsetInBeginSection": 682, "offsetInEndSection": 1025, "text": "Further, we reveal a protective role of B. fragilis treatment against colon tumorigenesis using an azoxymethane (AOM)/DSS-induced model of colitis-associated colon cancer in mice and demonstrate that the decreased tumorigenesis by B. fragilis administration is accompanied by inhibited expression of C-C chemokine receptor 5 (CCR5) in the gut.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30429227"}, {"offsetInBeginSection": 1105, "offsetInEndSection": 1316, "text": "These findings support a role for Fn and ETBF in potentiating tumorigenesis via the induction of a cancer stem cell-like transit-amplifying and enterocyte population and the disruption of CTL cytotoxic function.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37066368"}, {"offsetInBeginSection": 1801, "offsetInEndSection": 1957, "text": "The protective role against tumor formation provided by B. fragilis is associated with inhibition of expression of the chemokine receptor CCR5 in the colon.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30429227"}, {"offsetInBeginSection": 428, "offsetInEndSection": 726, "text": "However, a link between E-cadherin, IL-8 and Stat3 has not been investigated in the context of ETBF infection.RESULTS: We found that co-culture of HT-29 and HCT116 colorectal cell lines with ETBF, had a similar effect on activation of IL8 gene and protein expression as treatment with purified BFT.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35468857"}, {"offsetInBeginSection": 269, "offsetInEndSection": 420, "text": "Changes in microbiota, like Fusobacterium nucleatum and Bacteroides fragilis, also alter the metabolic activity of the host, promoting CRC development.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36790675"}, {"offsetInBeginSection": 356, "offsetInEndSection": 841, "text": "a in the human gut. A disturbance of this balance towards increased levels of the bacteria Fusobacterium nucleatum and Bacteroides fragilis is associated with an increased risk of colorectal cancer. The mechanisms involved include the release of toxins which activate inflammation and the regulation of specific miRNAs (with an increase in the expression of oncogenic miRNAs and a decrease in the expression of tumour suppressor miRNAs), thereby increasing cell proliferation and leadi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32604093"}, {"offsetInBeginSection": 327, "offsetInEndSection": 502, "text": "Fusobacterium nucleatum and Bacteroides fragilis were more abundant in worse prognosis groups, while Faecalibacterium prausnitzii displayed higher abundance in survival group.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27323816"}, {"offsetInBeginSection": 661, "offsetInEndSection": 763, "text": "high abundance of F. nucleatum and B. fragilis were independent indicators of poor patient's survival.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27323816"}, {"offsetInBeginSection": 1213, "offsetInEndSection": 1342, "text": " that KRAS and BRAF expression were prominent in F. nucleatum and B. fragilis high abundance group, while MLH1 showed lower expre", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27323816"}, {"offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Gut colonization with enterotoxigenic Bacteroides fragilis (ETBF) appears to be associated with the development of colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27686415"}, {"offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "BACKGROUND: Enterotoxigenic Bacteroides fragilis (ETBF) is a toxin-producing bacteria thought to possibly promote colorectal carcinogenesis by modulating the mucosal immune response and inducing epithelial c", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28151975"}, {"offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "BACKGROUND: Enterotoxigenic Bacteroides fragilis (ETBF) produces the Bacteroides fragilis toxin, which has been associated with acute diarrheal disease, inflammatory bowel disease, and colorectal c", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25305284"}, {"offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "Fusobacterium nucleatum (Fn) and enterotoxigenic Bacteroides fragilis (ETBF) are two pathobionts consistently enriched in the gut microbiomes of patients with colorectal cancer (CRC) compared to healthy counterparts and frequently observed for their direct association within tumors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37066368"}, {"offsetInBeginSection": 205, "offsetInEndSection": 418, "text": "In the context of gastrointestinal disease, the bacterium enterotoxigenic Bacteroides fragilis (ETBF) is a significant source of chronic inflammation and has been implicated as a risk factor for colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21876161"}, {"offsetInBeginSection": 415, "offsetInEndSection": 620, "text": "In this study, we produced recombinant Bacteroides fragilis enterotoxin-1 (rBFT1) and demonstrate that rBFT1 could promote cell proliferation in colorectal cancer cells and accelerate tumor growth in vivo.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33981848"}, {"offsetInBeginSection": 159, "offsetInEndSection": 444, "text": "In this review, we highlight the various gut and oral microbiota associated with CRC and colorectal adenomas, and their proposed molecular mechanisms in relation to the processes of \"the hallmarks of cancer\", and differences in microbial diversity and abundance between race/ethnicity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35317317"}, {"offsetInBeginSection": 476, "offsetInEndSection": 687, "text": "In the present study, we revealed the mechanism by which a lncRNA participates in gut bacteria-induced carcinogenesis: Bacteroides fragilis-associated lncRNA1 (BFAL1) in CRC tissues mediates ETBF carcinogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31515468"}, {"offsetInBeginSection": 731, "offsetInEndSection": 922, "text": "Our view is that in the precancerous stage of colorectal cancer, ETBF causes inflammation, leading to potential changes in intestinal ecology that may provide the basic conditions for pks+ E.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37554340"}, {"offsetInBeginSection": 1305, "offsetInEndSection": 1641, "text": "On the other hand, our results did not show any possible correlation between this bacterium and the clinicopathological features of the tumor sample.CONCLUSION: B. fragilis had a higher abundance in the tumor samples than in healthy tissues, and this bacterium may lead to CRC by making changes in cellular signaling pathways and genes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37644520"}, {"offsetInBeginSection": 1340, "offsetInEndSection": 1667, "text": "In contrast to ETBF diarrheal disease where bft-1 detection dominates, bft-2 was the most frequent toxin isotype identified in both cases and controls, whereas multiple bft isotypes were detected more frequently in cases (P \u2264 .02).CONCLUSIONS: The bft gene is associated with colorectal neoplasia, especially in late-stage CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25305284"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Enterotoxigenic Bacteroides fragilis activates IL-8 expression through Stat3 in colorectal cancer cells.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35468857"}, {"offsetInBeginSection": 727, "offsetInEndSection": 845, "text": "Inhibition of Stat3 resulted in a decrease in IL-8 gene and protein expression in response to ETBF in both cell lines.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35468857"}, {"offsetInBeginSection": 910, "offsetInEndSection": 1186, "text": "Collectively, our results indicate that rBFT1 serves as a tumor promoter and plays a crucial role in inducing the proliferation of CRC via accelerating CCL3-related molecular pathway, thus giving insights into mechanistic underpinnings for the prevention and treatment of CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33981848"}, {"offsetInBeginSection": 336, "offsetInEndSection": 427, "text": "Stat3 activation has also been associated with ETBF-related colitis and tumour development.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35468857"}, {"offsetInBeginSection": 160, "offsetInEndSection": 274, "text": "inogenesis. Bacteroides fragilis can lead to tumorigenesis by changing signaling pathways, including the WNT/\u03b2-cat", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37644520"}, {"offsetInBeginSection": 871, "offsetInEndSection": 1261, "text": "ance of B. fragilis were analyzed.RESULTS: The results showed that B. fragilis was detected in 100% of tumor samples and 86% of healthy tissues. Additionally, enterotoxigenic B. fragilis colonized 47% of all samples, and bft-1 toxin was the most frequently found isotype among the samples. The analysis showed that the high level of B. fragilis has a significant relationship with the high ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37644520"}, {"offsetInBeginSection": 254, "offsetInEndSection": 1467, "text": "Here, we investigate the relationships between the most commonly studied CRC-associated bacteria (Enterotoxigenic Bacteroides fragilis, pks+ Escherichia coli, Fusobacterium spp., afaC+ E. coli, Enterococcus faecalis & Enteropathogenic E. coli) and altered transcriptomic and methylation profiles of CRC patients, in order to gain insight into the potential contribution of these bacteria in the aetiopathogenesis of CRC. We show that colonisation by E. faecalis and high levels of Fusobacterium is associated with a specific transcriptomic subtype of CRC that is characterised by CpG island methylation, microsatellite instability and a significant increase in inflammatory and DNA damage pathways. Analysis of the significant, bacterially-associated changes in host gene expression, both at the level of individual genes as well as pathways, revealed a transcriptional remodeling that provides a plausible mechanistic link between specific bacterial colonisation and colorectal cancer disease development and progression in this subtype; these included upregulation of REG3A, REG1A and REG1P in the case of high-level colonization by Fusobacterium, and CXCL10 and BMI1 in the case of colonisation by E. faecalis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27846243"}, {"offsetInBeginSection": 539, "offsetInEndSection": 655, "text": "The abundance of Bacteroides fragilis reduced significantly in the process of colitis associated cancer development.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34627951"}, {"offsetInBeginSection": 914, "offsetInEndSection": 1290, "text": "B. fragilis promotes the secretion of short-chain fatty acids (SCFAs). Subsequently, SCFAs, especially butyrate, negatively regulate the inflammatory signaling pathway mediated by NLRP3 to inhibit the activation of macrophages and the secretion of proinflammatory mediators such as IL-18 and IL-1\u03b2, reducing the level of intestinal inflammation and restricting CAC development", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34627951"}, {"offsetInBeginSection": 514, "offsetInEndSection": 610, "text": "Particular focus is given to the oncogenic capabilities of enterotoxigenic Bacteroides fragilis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23534358"}, {"offsetInBeginSection": 249, "offsetInEndSection": 486, "text": "ETBF strains are associated with inflammatory diarrheal disease in children older than 1 year of age and in adults; limited data suggest an association of ETBF colonization with inflammatory bowel disease flare-ups and colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19366918"}, {"offsetInBeginSection": 836, "offsetInEndSection": 1003, "text": "Mechanistically, ETBF promoted tumor growth via BFAL1 by activating the Ras homolog, which is the MTORC1 binding/mammalian target of the rapamycin (RHEB/mTOR) pathway.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31515468"}, {"offsetInBeginSection": 390, "offsetInEndSection": 655, "text": "Gut microbiota in the process of colorectal cancer development in UC patients was analyzed using the gutMEGA database and verified in fecal samples. The abundance of Bacteroides fragilis reduced significantly in the process of colitis associated cancer development.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34627951"}, {"offsetInBeginSection": 889, "offsetInEndSection": 1033, "text": " BRAF genes were analyzed.RESULTS: In studied samples, B. fragilis was the most abundant bacteria that was detected in 66 and 60% of paired tumo", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34108031"}, {"offsetInBeginSection": 284, "offsetInEndSection": 1437, "text": " causation. Gut microbial metabolites are functional output of the host-microbiota interactions and produced by anaerobic fermentation of food components in the diet. They contribute to influence variety of biological mechanisms including inflammation, cell signaling, cell-cycle disruption which are majorly disrupted in carcinogenic activities.PURPOSE: In this review, we intend to discuss recent updates and possible molecular mechanisms to provide the role of bacterial metabolites, gut bacteria and diet in the colorectal carcinogenesis. Recent evidences have proposed the role of bacteria, such as Fusobacterium nucleaturm, Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis and Clostridium septicum, in the carcinogenesis of CRC. Metagenomic study confirmed that these bacteria are in increased abundance in CRC patient as compared to healthy individuals and can cause inflammation and DNA damage which can lead to development of cancer. These bacteria produce metabolites, such as secondary bile salts from primary bile salts, hydrogen sulfide, trimethylamine-N-oxide (TMAO), which are likely to promote inflammation and subsequently", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34273006"}, {"offsetInBeginSection": 0, "offsetInEndSection": 633, "text": "Dysbiosis of the gut microbiome has been associated with the development of colorectal cancer (CRC). Gut microbiota is involved in the metabolic transformations of dietary components into oncometabolites and tumor-suppressive metabolites that in turn affect CRC development. In a healthy colon, the major of microbial metabolism is saccharolytic fermentation pathways. The alpha-bug hypothesis suggested that oncogenic bacteria such as enterotoxigenic Bacteroides fragilis (ETBF) induce the development of CRC through direct interactions with colonic epithelial cells and alterations of microbiota composition at the colorectal site.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33492552"}, {"offsetInBeginSection": 0, "offsetInEndSection": 952, "text": "The relevance of specific microbial colonisation to colorectal cancer (CRC) disease pathogenesis is increasingly recognised, but our understanding of possible underlying molecular mechanisms that may link colonisation to disease in vivo remains limited. Here, we investigate the relationships between the most commonly studied CRC-associated bacteria (Enterotoxigenic Bacteroides fragilis, pks+ Escherichia coli, Fusobacterium spp., afaC+ E. coli, Enterococcus faecalis & Enteropathogenic E. coli) and altered transcriptomic and methylation profiles of CRC patients, in order to gain insight into the potential contribution of these bacteria in the aetiopathogenesis of CRC. We show that colonisation by E. faecalis and high levels of Fusobacterium is associated with a specific transcriptomic subtype of CRC that is characterised by CpG island methylation, microsatellite instability and a significant increase in inflammatory and DNA damage pathways.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27846243"}, {"offsetInBeginSection": 0, "offsetInEndSection": 909, "text": "Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide and stands among the leading causes of cancer-related deaths. Although deregulation of the microbiota in the gastrointestinal tract has been frequently described in CRC, very little is known about the precise molecular mechanisms by which bacteria and their toxins modulate the process of tumorigenesis and behavior of cancer cells. In this study, we produced recombinant Bacteroides fragilis enterotoxin-1 (rBFT1) and demonstrate that rBFT1 could promote cell proliferation in colorectal cancer cells and accelerate tumor growth in vivo. To identify the mechanisms, we further investigated CCL3/CCR5 and NF-\u03baB pathway. We found that CCL3, CCR5, NF-\u03baB, and TRAF-6 were dramatically upregulated after rBFT1 treatment, thus suggesting that the role of rBFT1 in CRC progression may be associated with CCL3/CCR5 and NF-\u03baB pathways.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33981848"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1104, "text": "Fusobacterium nucleatum (Fn) and enterotoxigenic Bacteroides fragilis (ETBF) are two pathobionts consistently enriched in the gut microbiomes of patients with colorectal cancer (CRC) compared to healthy counterparts and frequently observed for their direct association within tumors. Although several molecular mechanisms have been identified that directly link these organisms to features of CRC in specific cell types, their specific effects on the epithelium and local immune compartment are not well-understood. To fill this gap, we leveraged single-cell RNA sequencing (scRNA-seq) on wildtype mice and mouse model of CRC. We find that Fn and ETBF exacerbate cancer-like transcriptional phenotypes in transit-amplifying and mature enterocytes in a mouse model of CRC. We also observed increased T cells in the pathobiont-exposed mice, but these pathobiont-specific differences observed in wildtype mice were abrogated in the mouse model of CRC. Although there are similarities in the responses provoked by each organism, we find pathobiont-specific effects in Myc-signaling and fatty acid metabolism.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37066368"}, {"offsetInBeginSection": 159, "offsetInEndSection": 835, "text": "Although the role of lncRNAs in tumor formation is becoming clear, whether lncRNAs mediate gut microbiota-induced colorectal cancer (CRC) is largely unknown. Enterotoxigenic Bacteroides fragilis (ETBF) is a well-known tumor-inducing bacterium in the human gut; however, its tumorigenic effect remains to be explored. In the present study, we revealed the mechanism by which a lncRNA participates in gut bacteria-induced carcinogenesis: Bacteroides fragilis-associated lncRNA1 (BFAL1) in CRC tissues mediates ETBF carcinogenesis. BFAL1 was highly expressed in CRC tissues compared with that in adjacent normal tissues. In vitro, BFAL1 was upregulated in ETBF-treated CRC cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31515468"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1543, "text": "BACKGROUND: Enterotoxigenic Bacteroides fragilis (ETBF) produces the Bacteroides fragilis toxin, which has been associated with acute diarrheal disease, inflammatory bowel disease, and colorectal cancer (CRC). ETBF induces colon carcinogenesis in experimental models. Previous human studies have demonstrated frequent asymptomatic fecal colonization with ETBF, but no study has investigated mucosal colonization that is expected to impact colon carcinogenesis.METHODS: We compared the presence of the bft gene in mucosal samples from colorectal neoplasia patients (cases, n = 49) to a control group undergoing outpatient colonoscopy for CRC screening or diagnostic workup (controls, n = 49). Single bacterial colonies isolated anaerobically from mucosal colon tissue were tested for the bft gene with touch-down polymerase chain reaction.RESULTS: The mucosa of cases was significantly more often bft-positive on left (85.7%) and right (91.7%) tumor and/or paired normal tissues compared with left and right control biopsies (53.1%; P = .033 and 55.5%; P = .04, respectively). Detection of bft was concordant in most paired mucosal samples from individual cases or controls (75% cases; 67% controls). There was a trend toward increased bft positivity in mucosa from late- vs early-stage CRC patients (100% vs 72.7%, respectively; P = .093). In contrast to ETBF diarrheal disease where bft-1 detection dominates, bft-2 was the most frequent toxin isotype identified in both cases and controls, whereas multiple bft isotypes were detected more fr", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25305284"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1359, "text": "Various studies have shown the interplay between the intestinal microbiome, environmental factors, and genetic changes in colorectal cancer (CRC) development. In this review, we highlight the various gut and oral microbiota associated with CRC and colorectal adenomas, and their proposed molecular mechanisms in relation to the processes of \"the hallmarks of cancer\", and differences in microbial diversity and abundance between race/ethnicity. Patients with CRC showed increased levels of Bacteroides, Prevotella, Escherichia coli, enterotoxigenic Bacteroides fragilis, Streptococcus gallolyticus, Enterococcus faecalis, Fusobacterium nucleatum (F. nucleatum) and Clostridium difficile. Higher levels of Bacteroides have been found in African American (AA) compared to Caucasian American (CA) patients. Pro-inflammatory bacteria such as F. nucleatum and Enterobacter species were significantly higher in AAs. Also, AA patients have been shown to have decreased microbial diversity compared to CA patients. Some studies have shown that using microbiome profiles in conjunction with certain risk factors such as age, race and body mass index may help predict healthy colon vs one with adenomas or carcinomas. Periodontitis is one of the most common bacterial infections in humans and is more prevalent in Non-Hispanic-Blacks as compared to Non-Hispanic Whites.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35317317"}, {"offsetInBeginSection": 0, "offsetInEndSection": 656, "text": "Gut colonization with enterotoxigenic Bacteroides fragilis (ETBF) appears to be associated with the development of colorectal cancer. However, differences in carriage rates are seen with various testing methods and sampling sites. We compared standard PCR, SYBR green and TaqMan quantitative PCR (qPCR) and digital PCR (dPCR) in detecting the B. fragilis toxin (bft) gene from cultured ETBF, and from matched luminal and faecal stool samples from 19 colorectal cancer patients. Bland-Altman analysis found that all three quantitative methods performed comparably in detecting bft from purified bacterial DNA, with the same limits of detection (<1\u2009copy/\u03bcl).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27686415"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1281, "text": "BACKGROUND: Enterotoxigenic Bacteroides fragilis (ETBF) is a toxin-producing bacteria thought to possibly promote colorectal carcinogenesis by modulating the mucosal immune response and inducing epithelial cell changes. Here, we aim to examine the association of colonic mucosal colonization with ETBF and the presence of a range of lesions on the colonic neoplastic spectrum.METHODS: Mucosal tissue from up to four different colonic sites was obtained from a consecutive series of 150 patients referred for colonoscopy. The presence and relative abundance of the B. fragilis toxin gene (bft) in each tissue sample was determined using quantitative PCR, and associations with clinicopathological characteristics were analysed.FINDINGS: We found a high concordance of ETBF between different colonic sites (86%). Univariate analysis showed statistically significant associations between ETBF positivity and the presence of low-grade dysplasia (LGD), tubular adenomas (TA), and serrated polyps (P-values of 0.007, 0.027, and 0.007, respectively). A higher relative abundance of ETBF was significantly associated with LGD and TA (P-values of < 0.0001 and 0.025, respectively). Increased ETBF positivity and abundance was also associated with left-sided biopsies, compared to those from", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28151975"}, {"offsetInBeginSection": 0, "offsetInEndSection": 627, "text": "It is estimated that the etiology of 20-30% of epithelial cancers is directly associated with inflammation, although the direct molecular events linking inflammation and carcinogenesis are poorly defined. In the context of gastrointestinal disease, the bacterium enterotoxigenic Bacteroides fragilis (ETBF) is a significant source of chronic inflammation and has been implicated as a risk factor for colorectal cancer. Spermine oxidase (SMO) is a polyamine catabolic enzyme that is highly inducible by inflammatory stimuli resulting in increased reactive oxygen species (ROS) and DNA damage. We now demonstrate that purified B.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21876161"}, {"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Enterotoxigenic Bacteroides fragilis (ETBF) has received significant attention for a possible association with, or causal role in, colorectal cancer (CRC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35461079"}, {"offsetInBeginSection": 1219, "offsetInEndSection": 1430, "text": "Enterotoxigenic Bacteroides fragilis (ETBF), Clostridium and Salmonella, and Peptostreptococcus showed links with colorectal cancer and described pathways that could explain its implication in colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36465770"}, {"offsetInBeginSection": 531, "offsetInEndSection": 671, "text": "cing the B. fragilis toxin (bft) that promotes colorectal carcinogenesis by modulating the mucosal immune response and inducing epithelial c", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36578036"}, {"offsetInBeginSection": 1860, "offsetInEndSection": 1957, "text": "fragilis is associated with inhibition of expression of the chemokine receptor CCR5 in the colon.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30429227"}, {"offsetInBeginSection": 151, "offsetInEndSection": 299, "text": "fragilis toxin (BFT) which can lead to chronic intestinal inflammation and tissue injury and play a crucial role leading to colorectal cancer (CRC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32863742"}, {"offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Recombinant Bacteroides fragilis enterotoxin-1 (rBFT-1) promotes proliferation of colorectal cancer via CCL3-related molecular pathways.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33981848"}, {"offsetInBeginSection": 144, "offsetInEndSection": 701, "text": "Although deregulation of the microbiota in the gastrointestinal tract has been frequently described in CRC, very little is known about the precise molecular mechanisms by which bacteria and their toxins modulate the process of tumorigenesis and behavior of cancer cells. In this study, we produced recombinant Bacteroides fragilis enterotoxin-1 (rBFT1) and demonstrate that rBFT1 could promote cell proliferation in colorectal cancer cells and accelerate tumor growth in vivo. To identify the mechanisms, we further investigated CCL3/CCR5 and NF-\u03baB pathway.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33981848"}, {"offsetInBeginSection": 144, "offsetInEndSection": 620, "text": "Although deregulation of the microbiota in the gastrointestinal tract has been frequently described in CRC, very little is known about the precise molecular mechanisms by which bacteria and their toxins modulate the process of tumorigenesis and behavior of cancer cells. In this study, we produced recombinant Bacteroides fragilis enterotoxin-1 (rBFT1) and demonstrate that rBFT1 could promote cell proliferation in colorectal cancer cells and accelerate tumor growth in vivo.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33981848"}, {"offsetInBeginSection": 415, "offsetInEndSection": 701, "text": "In this study, we produced recombinant Bacteroides fragilis enterotoxin-1 (rBFT1) and demonstrate that rBFT1 could promote cell proliferation in colorectal cancer cells and accelerate tumor growth in vivo. To identify the mechanisms, we further investigated CCL3/CCR5 and NF-\u03baB pathway.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33981848"}, {"offsetInBeginSection": 539, "offsetInEndSection": 794, "text": "The abundance of Bacteroides fragilis reduced significantly in the process of colitis associated cancer development. Broad-spectrum antibiotics (BSAB) intervene with the intestinal microbiota of mice and accelerate the process of colon cancer development.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34627951"}, {"offsetInBeginSection": 539, "offsetInEndSection": 888, "text": "The abundance of Bacteroides fragilis reduced significantly in the process of colitis associated cancer development. Broad-spectrum antibiotics (BSAB) intervene with the intestinal microbiota of mice and accelerate the process of colon cancer development. However, gavage transplantation with B. fragilis can effectively reverse the effects of BSAB.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34627951"}, {"offsetInBeginSection": 390, "offsetInEndSection": 794, "text": "Gut microbiota in the process of colorectal cancer development in UC patients was analyzed using the gutMEGA database and verified in fecal samples. The abundance of Bacteroides fragilis reduced significantly in the process of colitis associated cancer development. Broad-spectrum antibiotics (BSAB) intervene with the intestinal microbiota of mice and accelerate the process of colon cancer development.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34627951"}, {"offsetInBeginSection": 415, "offsetInEndSection": 909, "text": "In this study, we produced recombinant Bacteroides fragilis enterotoxin-1 (rBFT1) and demonstrate that rBFT1 could promote cell proliferation in colorectal cancer cells and accelerate tumor growth in vivo. To identify the mechanisms, we further investigated CCL3/CCR5 and NF-\u03baB pathway. We found that CCL3, CCR5, NF-\u03baB, and TRAF-6 were dramatically upregulated after rBFT1 treatment, thus suggesting that the role of rBFT1 in CRC progression may be associated with CCL3/CCR5 and NF-\u03baB pathways.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33981848"}, {"offsetInBeginSection": 0, "offsetInEndSection": 334, "text": "BACKGROUND: Enterotoxigenic Bacteroides fragilis (ETBF) has been implicated in colorectal carcinogenesis through the actions of its toxin, B. fragilis toxin (BFT). Studies on colorectal cell lines have shown that treatment with BFT causes disruption of E-cadherin leading to increased expression of the pro-inflammatory cytokine, IL-8", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35468857"}, {"offsetInBeginSection": 0, "offsetInEndSection": 426, "text": "BACKGROUND: Enterotoxigenic Bacteroides fragilis (ETBF) has been implicated in colorectal carcinogenesis through the actions of its toxin, B. fragilis toxin (BFT). Studies on colorectal cell lines have shown that treatment with BFT causes disruption of E-cadherin leading to increased expression of the pro-inflammatory cytokine, IL-8. Stat3 activation has also been associated with ETBF-related colitis and tumour development", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35468857"}, {"offsetInBeginSection": 615, "offsetInEndSection": 1049, "text": "Although the mechanism of action of BFT is incompletely understood, available data suggest that BFT binds to a specific intestinal epithelial cell receptor, stimulating intestinal cell signal transduction pathways that result in cell morphology changes, cleavage of E-cadherin, reduced colonic barrier function, and increased epithelial cell proliferation and cytokine expression (such as the proinflammatory chemokine interleukin-8).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19366918"}, {"offsetInBeginSection": 369, "offsetInEndSection": 633, "text": "The alpha-bug hypothesis suggested that oncogenic bacteria such as enterotoxigenic Bacteroides fragilis (ETBF) induce the development of CRC through direct interactions with colonic epithelial cells and alterations of microbiota composition at the colorectal site.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33492552"}, {"offsetInBeginSection": 692, "offsetInEndSection": 785, "text": "both in\u00a0vitro and in\u00a0vivo.RESULTS: ETBF promoted CRC cell proliferation by down-regulating mi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34371001"}, {"offsetInBeginSection": 1744, "offsetInEndSection": 1916, "text": "In summary, ETBF upregulated JMJD2B levels in a TLR4-NFAT5-dependent pathway, and played an important role in stemness regulation, which promoted colorectal carcinogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32684087"}, {"offsetInBeginSection": 1244, "offsetInEndSection": 1364, "text": "Thus, BFAL1 is a mediator of ETBF-induced carcinogenesis and may be a potential therapeutic target for ETBF-induced CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31515468"}, {"offsetInBeginSection": 325, "offsetInEndSection": 548, "text": "ETBF's only recognized specific virulence factor is a zinc-dependent metallopeptidase (MP) called B. fragilis toxin (BFT) or fragilysin, which damages the intestinal mucosa and triggers disease-related signaling mechanisms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36173175"}, {"offsetInBeginSection": 132, "offsetInEndSection": 304, "text": "The only known ETBF virulence factor is the Bacteroides fragilis toxin (BFT), which induces E-cadherin cleavage, interleukin-8 secretion, and epithelial cell proliferation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19188353"}, {"offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "Bacteroides fragilis is an abundant commensal component of the healthy human colon. However, under dysbiotic conditions, enterotoxigenic B. fragilis (ETBF) may arise and elicit diarrhea, anaerobic bacteremia, inflammatory bowel disease, and colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36173175"}, {"offsetInBeginSection": 198, "offsetInEndSection": 391, "text": "Through its primary virulence factor, B. fragilis toxin (BFT), ETBF causes asymptomatic, chronic colitis in C57BL/6 mice and increased colon tumorigenesis in multiple intestinal neoplasia mice.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26173688"}, {"offsetInBeginSection": 0, "offsetInEndSection": 434, "text": "Enterotoxigenic Bacteroides fragilis is the most frequent disease-causing anaerobe in the intestinal tract of humans and livestock and its specific virulence factor is fragilysin, also known as B. fragilis toxin. This is a 21-kDa zinc-dependent metallopeptidase existing in three closely related isoforms that hydrolyze E-cadherin and contribute to secretory diarrhea, and possibly to inflammatory bowel disease and colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21233422"}, {"offsetInBeginSection": 1185, "offsetInEndSection": 1362, "text": "The recent observation of ETBF-bearing biofilms in colon biopsies from humans with colon cancer susceptibility loci strongly suggests that ETBF is a driver of colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31857085"}]}
+{"question_id": "662cfbf5187cba990d000007", "question": "Where in the body would the globus pallidus be found?", "answer": "The globus pallidus is found deep within the brain", "relevant_passage_ids": ["36724759", "36719479", "36418626", "36378365", "36309960", "1401259", "34129267", "31778724", "37532091", "37660542", "37492559", "37403078", "31927758", "30262639", "32906651", "33409084", "30822586", "14614896", "26706479", "37336974", "2579980", "15322674", "18688722", "26917269", "3469674", "4063830", "1380517", "7133405", "12764086", "36895960", "15169693", "2428943", "20107133", "30077619", "2153714"], "type": "factoid", "snippets": [{"offsetInBeginSection": 277, "offsetInEndSection": 522, "text": "This pilot study was conducted in 4 patients with Parkinson's disease (PD) who underwent MRI-guided deep brain stimulation of the globus pallidus internus (GPi). CSF was obtained via lumbar puncture after general anesthesia and prior to incision", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36724759"}, {"offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "We and others have observed reduced volumes of brain regions, including the nucleus accumbens, globus pallidus, hypothalamus, and habenula in opioid addiction. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36719479"}, {"offsetInBeginSection": 355, "offsetInEndSection": 731, "text": "Quantitative susceptibility mapping (QSM) was performed, and magnetic susceptibility was measured using three-dimensional volumes of interest (VOIs) for the caudate nucleus (CN), globus pallidus (GP), putamen (PT), and ventrolateral thalamic nucleus (VL). Cross-sectional analysis was performed for 99 patients with normal development and 39 patients with delayed development.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36418626"}, {"offsetInBeginSection": 169, "offsetInEndSection": 298, "text": " Several reports have shown that deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) might be effective in TD,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36378365"}, {"offsetInBeginSection": 10, "offsetInEndSection": 235, "text": " Progressive supranuclear palsy (PSP) is a 4R-tauopathy showing heterogeneous tau cytopathology commencing in the globus pallidus (GP) and the substantia nigra (SN), regions also associated with age-related iron accumulation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36309960"}, {"offsetInBeginSection": 103, "offsetInEndSection": 265, "text": "The clinical significance of weight changes following deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) is unclear.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37660542"}, {"offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "The external globus pallidus (GPe) is an essential component of the basal ganglia, a group of subcortical nuclei that are involved in control of action", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37532091"}, {"offsetInBeginSection": 897, "offsetInEndSection": 1098, "text": "These regions include the left inferior frontal gyrus, left ventral premotor cortex, left anterior insula, left posterior cerebellum (crus II), and bilateral basal ganglia (putamen and globus pallidus)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37492559"}, {"offsetInBeginSection": 1040, "offsetInEndSection": 1367, "text": "Autopsy of his brain revealed (i) tumor cells with atypical nuclei and small lymphocytes, (ii) neuronal cytoplasmic inclusions and Lewy bodies that were positive for \u03b1-synuclein in the midbrain, pons, amygdala, putamen and globus pallidus, and (iii) no amyloid plaques and only rare neurofibrillary tangles near the hippocampi.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37403078"}, {"offsetInBeginSection": 417, "offsetInEndSection": 779, "text": "There are sparse reports on the localization of functions in humans. This paper attempts to provide such localization of function with a focus on the globus pallidus externus of the basal ganglia. We present the case of a young man who had impairment in mixed cognitive, perceptual, and mood disturbances. No significant motor symptoms were noted in the patient.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33409084"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1743, "text": "BACKGROUND AND PURPOSE: Electrophysiologic abnormalities of the globus pallidus externus have been shown in several disease processes including Parkinson disease, dystonia, and Huntington disease. However, the connectivity, nuclear structure, and function of the globus pallidus externus are still not well-understood. Increasing evidence for the existence of direct corticopallidal connections challenges traditional understanding of the connectivity of the globus pallidus externus; nevertheless, these corticopallidal connections have yet to be fully characterized in humans. The objective of this study was to assess the corticopallidal connections of the globus pallidus externus by means of probabilistic diffusion-weighted MR imaging tractography using high-resolution, multishell data.MATERIALS AND METHODS: Imaging data from the open-access Human Connectome Project data base were used to perform probabilistic tractography between the globus pallidus externus and the cerebral cortex using 34 distinct cortical regions. Group averages were calculated for normalized percentages of tracts reaching each of the cortical targets, and side-to-side comparison was made.RESULTS: Cortical connectivity was demonstrated between the globus pallidus externus and multiple cortical regions, including direct connection to putative sensorimotor, associative, and limbic areas. Connectivity patterns were not significantly different between the right and left hemispheres with the exception of the frontal pole, which showed a greater number of connections on the right (P = .004).CONCLUSIONS: Our in vivo study of the human globus pallidus externus using probabilistic tractography supports the existence of extensive corticopallidal connections", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30262639"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1124, "text": "BACKGROUND: The globus pallidus internus (Gpi) is a major target in functional neurosurgery. Anatomical studies are crucial for correct planning and good surgical outcomes in this region. The present study described the anatomical coordinates of the Gpi and its relationship with other brain structures and compared the findings with those from previous anatomical studies.METHODS: We obtained 35 coronal and 5 horizontal brain specimens from the Department of Anatomy and stained them using the Robert, Barnard, and Brown technique. After excluding defective samples, 60 nuclei were analyzed by assessing their distances to the anatomical references and the trajectories to these nuclei.RESULTS: The barycenter of the Gpi was identified at the level of the mammillary bodies and 1 cm above the intercommissural plane. Thereafter, the distances to other structures were found. The mean \u00b1 standard deviation distance was 15.62 \u00b1 2.66 mm to the wall of the third ventricle and 17.02 \u00b1 2.69 mm to its midline, 4.74 \u00b1 1.12 mm to the optic tract, 2.51 \u00b1 0.8 mm and 13.56 \u00b1 2 mm to the internal and external capsule, and 21.3 \u00b1 2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30822586"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1239, "text": "Background and objectives: The internal (GPi) and external segments (GPe) of the globus pallidus represent key nodes in the basal ganglia system. Connections to and from pallidal segments are topographically organized, delineating limbic, associative and sensorimotor territories. The topography of pallidal afferent and efferent connections with brainstem structures has been poorly investigated. In this study we sought to characterize in-vivo connections between the globus pallidus and the pedunculopontine nucleus (PPN) via diffusion tractography. Materials and Methods: We employed structural and diffusion data of 100 subjects from the Human Connectome Project repository in order to reconstruct the connections between the PPN and the globus pallidus, employing higher order tractography techniques. We assessed streamline count of the reconstructed bundles and investigated spatial relations between pallidal voxels connected to the PPN and pallidal limbic, associative and sensorimotor functional territories. Results: We successfully reconstructed pallidotegmental tracts for the GPi and GPe in all subjects. The number of streamlines connecting the PPN with the GPi was greater than the number of those joining it with the GPe.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32906651"}, {"offsetInBeginSection": 0, "offsetInEndSection": 694, "text": "Although the localization and role of kainate receptors in the CNS remain poorly known, complex, and rather unusual, pre-synaptic auto- and heteroreceptor functions have been disclosed in various brain regions. Basal ganglia nuclei, including the globus pallidus, are enriched in GluR6/7 immunoreactivity. Using electron microscopic immunocytochemistry for GluR6/7 combined with post-embedding immunogold labeling for GABA, we demonstrate that GluR6/7 immunoreactivity is enriched in a large subpopulation of small unmyelinated, presumably pre-terminal, axons as well as GABAergic and putative glutamatergic axon terminals in the internal and external segments of the globus pallidus in monkey.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14614896"}, {"offsetInBeginSection": 780, "offsetInEndSection": 1170, "text": "Brain imaging demonstrated dense bilateral calcifications in the basal ganglia, bilaterally localizing to the anterior region of the globus pallidus externus. We discuss our findings in light of recent studies that imply that isolated pathology in the anterior region of the globus pallidus externus may be associated with behavioral, mood, and cognitive disturbance without motor symptoms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33409084"}, {"offsetInBeginSection": 486, "offsetInEndSection": 722, "text": "This paper attempts to provide such localization of function with a focus on the globus pallidus externus of the basal ganglia. We present the case of a young man who had impairment in mixed cognitive, perceptual, and mood disturbances.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33409084"}, {"offsetInBeginSection": 486, "offsetInEndSection": 779, "text": "This paper attempts to provide such localization of function with a focus on the globus pallidus externus of the basal ganglia. We present the case of a young man who had impairment in mixed cognitive, perceptual, and mood disturbances. No significant motor symptoms were noted in the patient.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33409084"}, {"offsetInBeginSection": 780, "offsetInEndSection": 938, "text": "Brain imaging demonstrated dense bilateral calcifications in the basal ganglia, bilaterally localizing to the anterior region of the globus pallidus externus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33409084"}, {"offsetInBeginSection": 723, "offsetInEndSection": 1170, "text": "No significant motor symptoms were noted in the patient. Brain imaging demonstrated dense bilateral calcifications in the basal ganglia, bilaterally localizing to the anterior region of the globus pallidus externus. We discuss our findings in light of recent studies that imply that isolated pathology in the anterior region of the globus pallidus externus may be associated with behavioral, mood, and cognitive disturbance without motor symptoms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33409084"}, {"offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "The Anterior Globus Pallidus Externus of Basal Ganglia as Primarily a Limbic and Associative Territory.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33409084"}, {"offsetInBeginSection": 486, "offsetInEndSection": 613, "text": "This paper attempts to provide such localization of function with a focus on the globus pallidus externus of the basal ganglia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33409084"}, {"offsetInBeginSection": 773, "offsetInEndSection": 1139, "text": "LTS: Thirteen studies specified the involved basal ganglia nuclei (subthalamic nucleus, caudate, putamen, globus pallidus, or lentiform nuclei, comprised by the putamen and globus pallidus). Studies investigating the lentiform nuclei (without distinguishing between the putamen and globus pallidus) showed that all subjects (19 of 19) had lentiform nuclei damage. St", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26706479"}, {"offsetInBeginSection": 723, "offsetInEndSection": 938, "text": "No significant motor symptoms were noted in the patient. Brain imaging demonstrated dense bilateral calcifications in the basal ganglia, bilaterally localizing to the anterior region of the globus pallidus externus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33409084"}, {"offsetInBeginSection": 142, "offsetInEndSection": 230, "text": "The globus pallidus is an area of major iron metabolism and storage in the brain tissue.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34129267"}, {"offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "The external globus pallidus (GPe) of the basal ganglia has been underappreciated owing to poor understanding of its cells and circuits.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37336974"}, {"offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "The external globus pallidus (GPe) is an essential component of the basal ganglia, a group of subcortical nuclei that are involved in control of action.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37532091"}, {"offsetInBeginSection": 51, "offsetInEndSection": 247, "text": "The basal ganglia are recognized for their role in reward processes; however, specific roles of the different nuclei (e.g., nucleus accumbens, caudate, putamen and globus pallidus) remain unclear.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31927758"}, {"offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "BACKGROUND: Hyperintense signals in the basal ganglia, namely the globus pallidus, have been reported on magnetic resonance imaging (MRI) in 70-100% of patients with cirrhosis of the liver.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18688722"}, {"offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "The globus pallidus in the basal ganglia plays an important role in movement regulation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31778724"}, {"offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The globus pallidus occupies a critical position in the 'indirect' pathway of the basal ganglia and, as such, plays an important role in the modulation of movement.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15322674"}, {"offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "The anatomical structure of the basal ganglia indicates that the input from the cerebral cortex is funnelled through the striatum to the globus pallidus and substantia nigra.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4063830"}, {"offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "The globus pallidus is characterized by a high iron content and the distribution of the ferric iron in the rat brain provides evidence that globus pallidus extends rostroventrally below the anterior commissure and into the olfactory tubercle.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7133405"}, {"offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "The anatomical structure of the basal ganglia displays topographical organization and massive funneling of neuronal projections toward the globus pallidus as well as an axonal collateral system within this nucleus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12764086"}, {"offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Globus pallidus internus deep brain stimulation is an established therapy for patients with medication-refractory Parkinson's disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36895960"}, {"offsetInBeginSection": 184, "offsetInEndSection": 755, "text": "der (OCD).METHOD: Volumes of the caudate nucleus, putamen, and globus pallidus and gray and white matter volumes of the anterior cingulate gyrus and superior frontal gyrus were computed from contiguous 1.5-mm magnetic resonance images from 23 psychotropic drug-naive pediatric patients with OCD (seven male patients and 16 female patients) and 27 healthy volunteers (12 male subjects and 15 female subjects).RESULTS: Patients had smaller globus pallidus volumes than healthy volunteers, but the two groups did not differ in volumes of the caudate nucleus, putamen, or fro", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15169693"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1103, "text": "Previous immunohistochemical studies have provided evidence that the external segment of the globus pallidus extends ventrally beneath the transverse limb of the anterior commissure into the area of the substantia innominata. Enkephalin-positive staining in the form of \"woolly fibers\" has been used as a marker for the globus pallidus and its ventral extension. Acetylcholinesterase staining of both fibers and cell bodies, frequently used as a marker for the basal nucleus of Meynert, is also found in the area of the substantia innominata. This study describes the differential distribution of enkephalin-positive woolly fibers and acetylcholinesterase staining on adjacent sections in both the monkey and human basal forebrain area in an attempt to define the relationship between the basal ganglia and the basal nucleus of Meynert. The results show that while both occupy large regions of the basal forebrain, they overlap very little. In both species investigated, dense concentrations of acetylcholinesterase-positive neurons lie, for the most part, outside the boundaries of the pallidal fibers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3469674"}, {"offsetInBeginSection": 564, "offsetInEndSection": 1328, "text": "The globus pallidus was injected with Phaseolus vulgaris-leucoagglutinin (PHA-L), and on the same side of the brain, the striatum was injected with biocytin. The entopeduncular nuclei of these animals were then examined for anterogradely labelled pallidal and striatal terminals. Rich plexuses of PHA-L-labelled pallidal terminals and biocytin-labelled striatal terminals were identified throughout the entopeduncular nucleus. At the electron microscopic level, the pallidal boutons were classified as two types. The majority (Type 1), were large boutons that formed symmetrical synapses with the dendrites and perikarya of neurones in the entopeduncular nucleus. Type 2 PHA-L-labelled terminals were much rarer, slightly smaller, and formed asymmetrical synapses.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1380517"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1637, "text": "The anatomical structure of the basal ganglia indicates that the input from the cerebral cortex is funnelled through the striatum to the globus pallidus and substantia nigra. This structure implies integration of the information as it is transferred through the basal ganglia. In order to investigate this integration, we studied the collateralization of striatal efferents to the globus pallidus and the substantia nigra-ventral tegmental area. Retrogradely transported fluorescent tracers were injected into the target areas of striatal efferents. Nuclear yellow or propidium iodide was injected into the substantia nigra-ventral tegmental area (SN-VTA) and 4-acetamido, 4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) into the globus pallidus (GP) of adult albino rats. SITS was chosen for the pallidal injections because it is not taken up by fibers-of-passage. The pressure injections resulted in large injection sites which covered the majority of each efferent target area, and as a result retrogradely labeled cell bodies were found throughout the entire extent of the striatum. Cell bodies double-labeled with both dyes were found intermingled with single-labeled cell bodies. In rats injected with propidium iodide in the SN-VTA and SITS in the GP, 70% of all neurons (as revealed by Nissl staining) were labeled. Of these labeled cells, 40% were double labeled, 20% contained only SITS and 40% contained only propidium iodide. Thus a substantial number of the striatal neurons that project to the SN-VTA also possess collateral axons to the GP. Some striatal neurons appear to project to only the SN-VTA or only to the GP.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4063830"}, {"offsetInBeginSection": 211, "offsetInEndSection": 305, "text": "Basal ganglia nuclei, including the globus pallidus, are enriched in GluR6/7 immunoreactivity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14614896"}, {"offsetInBeginSection": 1812, "offsetInEndSection": 2354, "text": "Fewer, but still ample numbers, of SP-reactive axons are present also in the ventral tegmental and retrorubral areas of the midbrain tegmentum and in the ventral pallidum of the basal forebrain, but only sparse ME-reactive axons are present in these areas. This differential distribution of SP- and ME-containing axons in the pallidal and nigral structures stands in contrast to the relatively homogeneous and dense distribution of GAD-containing axons throughout the dorsal and ventral pallidum, entopeduncular nucleus, and substantia nigra.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2579980"}, {"offsetInBeginSection": 0, "offsetInEndSection": 323, "text": "Immunocytochemical studies of the human forebrain have shown that enkephalin-like, dynorphin-like and substance-P-like immunoreactivity (respectively ELI, DLI, and SPI) normally present in unique pattern (now termed woolly fibers) in the globus pallidus and substantia nigra, in which their concentration is at its densest.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2428943"}, {"offsetInBeginSection": 200, "offsetInEndSection": 536, "text": "The distribution of choline acetyltransferase-immunoreactive axons and varicosities and their relationship to regional perikarya showed that the caudate, putamen, nucleus accumbens, olfactory tubercle, globus pallidus, substantia nigra, red nucleus, and subthalamic nucleus of the human brain receive widespread cholinergic innervation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1401259"}, {"offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "The basal ganglia are a subcortical assembly of nuclei involved in many aspects of behavior. Three of the nuclei have high firing rates and inhibitory influences: the substantia nigra pars reticulata (SNr), globus pallidus interna (GPi), and globus pallidus externa (GPe).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20107133"}, {"offsetInBeginSection": 947, "offsetInEndSection": 1142, "text": "In the basal ganglia, they were found in the caudate putamen, core part of accumbens nucleus, lateral globus pallidus, subthalamic nucleus, and substantia nigra pars compacta and pars reticulata.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30077619"}, {"offsetInBeginSection": 708, "offsetInEndSection": 904, "text": "In the basal ganglia, high levels of binding of 125I-351A are found in the caudate nucleus, putamen, nucleus accumbens, both divisions of the globus pallidus, and substantia nigra pars reticulata.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2153714"}, {"offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Deep brain stimulation in the globus pallidus externa promotes sleep.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26917269"}]}
+{"question_id": "66151045fdcbea915f000048", "question": "What is the approximate prevalence of autoimmune diseases?", "answer": "There is an approximate incidence of 10% autoimmune diseases affecting the general population.", "relevant_passage_ids": ["37156255"], "type": "factoid", "snippets": [{"offsetInBeginSection": 243, "offsetInEndSection": 313, "text": "incidence and prevalence of 19 of the most common autoimmune diseases ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37156255"}, {"offsetInBeginSection": 1813, "offsetInEndSection": 1862, "text": "63\u00b79%) of these diagnosed individuals were female", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37156255"}, {"offsetInBeginSection": 2964, "offsetInEndSection": 3112, "text": "Autoimmune disorders were commonly associated with each other, particularly Sj\u00f6gren's syndrome, systemic lupus erythematosus, and systemic sclerosis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37156255"}, {"offsetInBeginSection": 3500, "offsetInEndSection": 3563, "text": "Autoimmune diseases affect approximately one in ten individuals", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37156255"}]}
+{"question_id": "662ee24a187cba990d00000d", "question": "What is the role of Isocitrate dehydrogenase (IDH) mutations in glioma?", "answer": "Isocitrate dehydrogenase (IDH) is a key rate-limiting enzyme in the Krebs cycle that plays an important role in energy metabolism. In recent years, it has been found that IDH mutations are closely related to the occurrence and development of glioma, and it is a notable potential therapeutic target. First, IDH mutations can produce high levels of 2-hydroxyglutaric acid (2-HG), thereby inhibiting glioma stem cell differentiation. At the same time, IDH mutations can upregulate vascular endothelial growth factor (VEGF) to promote the formation of the tumor microenvironment. In addition, IDH mutations can also induce high levels of hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) to promote glioma invasion. Ultimately, these changes will lead to the development of glioma. Finally, in addition to affecting gliomas directly, mutations in IDH can also alter their immune microenvironment and can change immune-cell function in direct and indirect ways. Currently, a large number of IDH inhibitors and vaccines have entered clinical trials, representing progress in the treatment of glioma patients.", "relevant_passage_ids": ["35670952", "31263678", "28705010", "26834160", "30006485", "29031038", "21527585", "34356864", "22002076", "32291392", "35769466", "22399191", "21284999", "32825279", "34904924", "25078896", "26220714", "30427756", "28980701", "33981605", "35267433", "30857299", "30194083", "31485826", "37296846", "22105553", "36286062", "30149878", "28782849", "27355333", "28319047", "26188014", "36367045", "37287696", "37324217", "19228619", "25495392", "24460285", "22136423", "19915484", "19996293", "23877318", "27014635", "32965568", "21955197", "21294161", "21752797", "27005468", "25155243", "23532369", "20692206", "19554337", "21442241", "20142433", "27621679", "20615753", "24295421", "24880135", "30102604", "26960449", "21289278"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 911, "text": "Isocitrate dehydrogenase (IDH) is a key rate-limiting enzyme in the Krebs cycle that plays an important role in energy metabolism. In recent years, it has been found that IDH mutations are closely related to the occurrence and development of glioma, and it is a notable potential therapeutic target. First, IDH mutations can produce high levels of 2-hydroxyglutaric acid (2-HG), thereby inhibiting glioma stem cell differentiation. At the same time, IDH mutations can upregulate vascular endothelial growth factor (VEGF) to promote the formation of the tumor microenvironment. In addition, IDH mutations can also induce high levels of hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) to promote glioma invasion. Ultimately, these changes will lead to the development of glioma. Currently, a large number of IDH inhibitors and vaccines have entered clinical trials, representing progress in the treatment of glioma patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31263678"}, {"offsetInBeginSection": 184, "offsetInEndSection": 486, "text": "In addition to affecting gliomas directly, mutations in IDH can also alter their immune microenvironment and can change immune-cell function in direct and indirect ways. IDH mutations mediate immune-cell infiltration and function by modulating immune-checkpoint gene expression and chemokine secretion.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35670952"}, {"offsetInBeginSection": 0, "offsetInEndSection": 576, "text": "Isocitrate dehydrogenase (IDH) is a key rate-limiting enzyme in the Krebs cycle that plays an important role in energy metabolism. In recent years, it has been found that IDH mutations are closely related to the occurrence and development of glioma, and it is a notable potential therapeutic target. First, IDH mutations can produce high levels of 2-hydroxyglutaric acid (2-HG), thereby inhibiting glioma stem cell differentiation. At the same time, IDH mutations can upregulate vascular endothelial growth factor (VEGF) to promote the formation of the tumor microenvironment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31263678"}, {"offsetInBeginSection": 0, "offsetInEndSection": 408, "text": "Mutations in isocitrate dehydrogenase (IDH) are commonly observed in lower-grade glioma and secondary glioblastomas. IDH mutants confer a neomorphic enzyme activity that converts \u03b1-ketoglutarate to an oncometabolite D-2-hydroxyglutarate, which impacts cellular epigenetics and metabolism. IDH mutation establishes distinctive patterns in metabolism, cancer biology, and the therapeutic sensitivity of glioma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32825279"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1222, "text": "Isocitrate dehydrogenases (IDH) are important enzymes that catalyze the oxidative decarboxylation of isocitrate to \u03b1-ketoglutarate (\u03b1-KG), producing NADPH in the process. More than 80% of low-grade gliomas and secondary glioblastoma (GBM) harbor an IDH mutation. IDH mutations involve the catalytic pocket of the enzyme and lead to a neomorphic ability to produce 2-hydroxyglutarate (2HG) while oxidizing NADPH to NADP+. 2HG is considered as an 'oncometabolite' which is thought to be responsible for many, if not all, biologic effects of IDH mutations. 2HG accumulation competitively inhibits \u03b1-KG-dependent dioxygenases, including histone lysine demethylases and DNA demethylases, resulting in a hypermethylation phenotype with alterations in cellular epigenetic status as well as a block in cellular differentiation. IDH mutations have been suggested as an important early event in tumorigenesis, however it remains unclear whether IDH mutation by itself causes cancer or if it requires other oncogenic events to initiate tumorigenesis. Significant efforts have been made to better understand the mechanisms of IDH mutations in tumor initiation and progression, and to develop targeted therapies for IDH-mutated tumors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28705010"}, {"offsetInBeginSection": 0, "offsetInEndSection": 657, "text": "Isocitrate dehydrogenases 1 and 2 (IDH1/2) are enzymes that play a major role in the Krebs cycle. Mutations in these enzymes are found in the majority of lower gliomas and secondary glioblastomas, but also in myeloid malignancies and other cancers. IDH1 and IDH2 mutations are restricted to specific arginine residues in the active site of the enzymes and are gain-of-function, i.e. they confer a neomorphic enzyme activity resulting in the accumulation of D-2-hydroxyglutarate (2-HG). 2-HG is an oncometabolite causing profound metabolic dysregulation which, among others, results in methylator phenotypes and in defects in homologous recombination repair.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30194083"}, {"offsetInBeginSection": 168, "offsetInEndSection": 544, "text": "Isocitrate dehydrogenase (IDH) is mutated in many gliomas and other cancers. Physiologically, IDH converts isocitrate to \u03b1-ketoglutarate (\u03b1-KG), but when mutated, IDH reduces \u03b1-KG to D2-hydroxyglutarate (D2-HG). D2-HG accumulates at elevated levels in IDH mutant tumours, and in the last decade, a massive effort has been made to develop small inhibitors targeting mutant IDH.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37296846"}, {"offsetInBeginSection": 0, "offsetInEndSection": 671, "text": "The metabolic genes isocitrate dehydrogenase 1 (IDH1) and IDH2 are commonly mutated in low-grade glioma and in a subset of glioblastoma. These mutations co-occur with other recurrent molecular alterations, including 1p/19q codeletions and tumor suppressor protein 53 (TP53) and alpha thalassemia/mental retardation (ATRX) mutations, which together help to define a molecular signature that aids in the classification of gliomas and helps to better predict clinical behavior. A confluence of research suggests that glioma development in IDH-mutant and IDH wild-type tumors is driven by different oncogenic processes and responds differently to current treatment paradigms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28980701"}, {"offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "BACKGROUND: Recurrent mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes, which are frequent in gliomas, result in marked accumulation of the metabolic by-product 2-hydroxyglutarate (2-HG) within tumors", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26834160"}, {"offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "Mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 are among the first genetic alterations observed during the development of lower-grade glioma (LGG). LGG-associated IDH mutations confer gain-of-function activity by converting \u03b1-ketoglutarate to the oncometabolite R-2-hydroxyglutarate (2HG).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28319047"}, {"offsetInBeginSection": 0, "offsetInEndSection": 444, "text": "Isocitrate dehydrogenase (IDH) is an essential enzyme for cellular respiration in the tricarboxylic acid (TCA) cycle. Recurrent mutations in IDH1 or IDH2 are prevalent in several cancers including glioma, acute myeloid leukemia (AML), cholangiocarcinoma and chondrosarcoma. The mutated IDH1 and IDH2 proteins have a gain-of-function, neomorphic activity, catalyzing the reduction of \u03b1-ketoglutarate (\u03b1-KG) to 2-hydroxyglutarate (2-HG) by NADPH.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27355333"}, {"offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "Isocitrate dehydrogenase (IDH) is an essential enzyme for cellular respiration in the tricarboxylic acid (TCA) cycle. Recurrent mutations in IDH1 or IDH2 are prevalent in several cancers including glioma, acute myeloid leukemia (AML), cholangiocarcinoma and chondrosarcoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27355333"}, {"offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 are among the first genetic alterations observed during the development of lower-grade glioma (LGG).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28319047"}, {"offsetInBeginSection": 184, "offsetInEndSection": 353, "text": "In addition to affecting gliomas directly, mutations in IDH can also alter their immune microenvironment and can change immune-cell function in direct and indirect ways.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35670952"}, {"offsetInBeginSection": 202, "offsetInEndSection": 550, "text": "Mutations in two isocitrate dehydrogenase (IDH) genes, IDH1 and IDH2, commonly occur in low-grade gliomas and secondary high-grade gliomas, but are rare in primary GBMs. These mutations alter the catalytic activity of IDH proteins, promoting gliomagenesis. Gliomas with IDH1 or IDH2 mutation have better outcomes than do gliomas with wild-type IDH.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25495392"}, {"offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are found frequently in malignant gliomas and are likely involved in early gliomagenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22136423"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "IDH1/2 mutations target a key hallmark of cancer by deregulating cellular metabolism in glioma.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23877318"}, {"offsetInBeginSection": 414, "offsetInEndSection": 582, "text": "IDH1 and IDH2 mutations may serve as prognostic factors because patients with an IDH-mutated glioma survive significantly longer than those with an IDH-wild-type tumor.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23877318"}, {"offsetInBeginSection": 452, "offsetInEndSection": 627, "text": "Mutations in IDH genes are thought to occur early in tumorigenesis and define a subgroup of glioma that are characterized by specific metabolic changes and improved prognosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21955197"}, {"offsetInBeginSection": 303, "offsetInEndSection": 413, "text": "Gliomas with IDH1/2 mutations always harbor other molecular aberrations, such as TP53 mutation or 1p/19q loss.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23877318"}, {"offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Mutations in isocitrate dehydrogenase (IDH) are commonly observed in lower-grade glioma and secondary glioblastomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32825279"}, {"offsetInBeginSection": 859, "offsetInEndSection": 1066, "text": "Elucidating the pathogenesis of IDH mutations will improve understanding of the molecular mechanisms of gliomagenesis and may lead to development of a new molecular classification system and novel therapies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23877318"}, {"offsetInBeginSection": 133, "offsetInEndSection": 302, "text": "IDH1 and IDH2 are mutated in 50%-80% of astrocytomas, oligodendrogliomas, oligoastrocytomas, and secondary glioblastomas but are seldom mutated in primary glioblastomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23877318"}, {"offsetInBeginSection": 808, "offsetInEndSection": 1009, "text": "IDH1/2 mutations are tightly associated with grade II and III gliomas and secondary glioblastomas, with better prognosis and production of a recently described oncometabolite, 2-hydroxyglutarate (2HG).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25078896"}, {"offsetInBeginSection": 675, "offsetInEndSection": 976, "text": "Most intriguingly, IDH mutations are observed in \u223c70-80% of grade II/III gliomas and the majority of secondary glioblastomas, but only 10% of primary glioblastomas, suggesting a different cellular origin of the gliomas, which had previously been viewed as a multistep process of malignant progression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21294161"}, {"offsetInBeginSection": 726, "offsetInEndSection": 885, "text": "IDH mutations are highly common in lower grade gliomas (LGG) and secondary glioblastomas, and they are among the earliest genetic events driving tumorigenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34356864"}, {"offsetInBeginSection": 996, "offsetInEndSection": 1187, "text": "On the other hand, the metabolic consequences derived from IDH mutations lead to selective vulnerabilities within tumor cells, making them more sensitive to several therapeutic interventions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34356864"}, {"offsetInBeginSection": 309, "offsetInEndSection": 457, "text": "Mutations of IDH1 and IDH2 led to simultaneous loss and gain of activities in the production of \u03b1-ketoglutarate and 2-hydroxyglutarate, respectively", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22105553"}, {"offsetInBeginSection": 166, "offsetInEndSection": 351, "text": "These mutations, which occur early in gliomagenesis, change the function of the enzymes, causing them to produce 2-hydroxyglutarate, a possible oncometabolite, and to not produce NADPH.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23532369"}, {"offsetInBeginSection": 0, "offsetInEndSection": 346, "text": "Somatic mutations in the IDH1 gene encoding cytosolic NADP+-dependent isocitrate dehydrogenase have been shown in the majority of astrocytomas, oligodendrogliomas and oligoastrocytomas of WHO grades II and III. IDH2 encoding mitochondrial NADP+-dependent isocitrate dehydrogenase is also mutated in these tumors, albeit at much lower frequencies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19554337"}, {"offsetInBeginSection": 0, "offsetInEndSection": 320, "text": "Recent genome wide sequencing has identified mutations in IDH1/IDH2 predominantly in grade II-III gliomas and secondary glioblastomas which are associated with favorable clinical outcome. These mutations have become molecular markers of significant diagnostic and prognostic relevance in the assessment of human gliomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24460285"}, {"offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Low-grade diffuse gliomas WHO grade II (diffuse astrocytoma, oligoastrocytoma, oligodendroglioma) are characterized by frequent IDH1/2 mutations (>80%) that occur at a very early stage.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21442241"}, {"offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2), are present in most gliomas and secondary glioblastomas, but are rare in other neoplasms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20142433"}, {"offsetInBeginSection": 118, "offsetInEndSection": 226, "text": " IDH1/2 mutations define distinct subsets of cancers, including low-grade gliomas and secondary glioblastoma", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27621679"}, {"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Isocitrate dehydrogenase (IDH) mutations are biomarkers to classify diffuse gliomas into biologically similar subgroups.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30149878"}, {"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Isocitrate dehydrogenase (IDH1/IDH2) mutations in gliomas of WHO grade II/III and secondary glioblastoma are almost always heterozygous missense mutations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28782849"}, {"offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Both IDH1 (isocitrate dehydrogenase 1) and IDH2 (isocitrate dehydrogenase 2) mutations play a vital role in the development of gliomas through disruption of normal cellular metabolic processes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36286062"}, {"offsetInBeginSection": 131, "offsetInEndSection": 299, "text": "In recent years, it has been found that IDH mutations are closely related to the occurrence and development of glioma, and it is a notable potential therapeutic target.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31263678"}, {"offsetInBeginSection": 242, "offsetInEndSection": 529, "text": "IDH mutations in glioma can inhibit tumor-associated immune system evasion of NK cell immune surveillance. Meanwhile, mutant IDH can inhibit classical and alternative complement pathways and directly inhibit T-cell responses by metabolizing isocitrate to D-2-Hydroxyglutaric acid (2-HG).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35769466"}, {"offsetInBeginSection": 339, "offsetInEndSection": 507, "text": "IDH1 and IDH2 mutations define a specific subtype of gliomas and may have significant utility for the diagnosis, prognosis, and treatment of patients with these tumors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19996293"}, {"offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Point mutations of the NADP(+)-dependent isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) occur early in the pathogenesis of gliomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21289278"}, {"offsetInBeginSection": 1235, "offsetInEndSection": 1403, "text": "Since IDH mutations are associated with good prognosis, their use in routine clinical practice will enable better risk stratification and management of glioma patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24460285"}]}
+{"question_id": "66301fcb187cba990d000029", "question": "Is there an association between specific genotypes and the risk of neurodevelopmental disorders for Becker Muscular Dystrophy?", "answer": "Yes, in Becker Muscular Dystrophy, Dp140 and Dp71 could be associated with developmental disorders.", "relevant_passage_ids": ["36565132", "36440509"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1451, "offsetInEndSection": 1522, "text": "In BMD, Dp140 and Dp71 could be associated with developmental disorders", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36565132"}, {"offsetInBeginSection": 5, "offsetInEndSection": 271, "text": "To estimate the global prevalence of intellectual developmental disorder (IDD) and the IDD prevalence-genotype association in Becker muscular dystrophy (BMD) or Duchenne muscular dystrophy (DMD) according to the affected isoforms of the DMD gene: Dp427, Dp140, Dp71.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36440509"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1400, "text": "BACKGROUND: Dystrophinopathies are associated with neuropsychiatric disorders due to alterations in dystrophin/DMD expression.OBJECTIVE: The objective was to estimate the association of developmental disorders, autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), depression, anxiety disorders, and obsessive-compulsive disorder with the dystrophin/DMD genotype in population with dystrophinopathies.METHODS: Systematic searches of Medline, Scopus, Web of Science, and Cochrane Library were performed from inception to September 2022. We included observational studies in the population with Becker or Duchenne muscular dystrophies (BMD, DMD) that estimated the prevalence of these disorders according to Dp140 and/or Dp71 genotype. Meta-analysis of the prevalence ratio (PR) of genotype comparisons was conducted for each disorder.RESULTS: Ten studies were included in the systematic review. In BMD, Dp140+ vs. Dp140- and Dp71+ vs. Dp71- were associated with developmental disorders with a PR of 0.11 (0.04, 0.34) and 0.22 (0.07, 0.67), respectively. In DMD, Dp140+/Dp71+ vs. Dp140- /Dp71- had a PR of 0.40 (0.28, 0.57), and Dp71+ vs. Dp71- had a PR of 0.47 (0.36, 0.63) for ADHD. However, there was no association of genotype with ASD, only a trend was observed for Dp71+ vs. Dp71-, with a PR of 0.61 (0.35, 1.06). Moreover, the data showed no association of these isof", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36565132"}, {"offsetInBeginSection": 1346, "offsetInEndSection": 1585, "text": "Moreover, the data showed no association of these isoforms with emotional-related disorders.CONCLUSIONS: In BMD, Dp140 and Dp71 could be associated with developmental disorders, while ADHD might be associated with the Dp71 genotype in DMD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36565132"}]}
+{"question_id": "65d375b31930410b1300004b", "question": "What medication are included in the Juvisync pill?", "answer": "Juvisync pill included sitagliptin and simvastatin.", "relevant_passage_ids": ["25709467"], "type": "list", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "BACKGROUND: The purpose of this study was to review the current literature and information on the combination product Juvisync\u2122 (sitagliptin + simvastatin), which was approved by the US Food and Drug Administration in October 2011.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25709467"}, {"offsetInBeginSection": 1448, "offsetInEndSection": 1540, "text": "CONCLUSION: Juvisync should be used in patients requiring both sitagliptin and simvastatin. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25709467"}, {"offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "BACKGROUND: The purpose of this study was to review the current literature and information on the combination product Juvisync\u2122 (sitagliptin + simvastatin), which was approved by the US Food and Drug Administration in October 2011", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25709467"}, {"offsetInBeginSection": 1454, "offsetInEndSection": 1544, "text": "SION: Juvisync should be used in patients requiring both sitagliptin and simvastatin. Both", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25709467"}, {"offsetInBeginSection": 1454, "offsetInEndSection": 1613, "text": "SION: Juvisync should be used in patients requiring both sitagliptin and simvastatin. Both agents have shown good efficacy and acceptable safety profiles. Sita", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25709467"}, {"offsetInBeginSection": 0, "offsetInEndSection": 420, "text": "BACKGROUND: The purpose of this study was to review the current literature and information on the combination product Juvisync\u2122 (sitagliptin + simvastatin), which was approved by the US Food and Drug Administration in October 2011.METHODS: PubMed (2001-2014) was searched for primary and review articles on sitagliptin, simvastatin, or the combination product. Drug manufacturing data and product labeling were also used", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25709467"}, {"offsetInBeginSection": 1302, "offsetInEndSection": 1611, "text": "ever, caution is needed when coadministering with any drug that may increase simvastatin levels to reduce the risk of myopathy and rhabdomyolysis.CONCLUSION: Juvisync should be used in patients requiring both sitagliptin and simvastatin. Both agents have shown good efficacy and acceptable safety profiles. Si", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25709467"}, {"offsetInBeginSection": 1227, "offsetInEndSection": 1542, "text": "h medications have also demonstrated an acceptable side effect profile. However, caution is needed when coadministering with any drug that may increase simvastatin levels to reduce the risk of myopathy and rhabdomyolysis.CONCLUSION: Juvisync should be used in patients requiring both sitagliptin and simvastatin. Bo", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25709467"}, {"offsetInBeginSection": 0, "offsetInEndSection": 360, "text": "BACKGROUND: The purpose of this study was to review the current literature and information on the combination product Juvisync\u2122 (sitagliptin + simvastatin), which was approved by the US Food and Drug Administration in October 2011.METHODS: PubMed (2001-2014) was searched for primary and review articles on sitagliptin, simvastatin, or the combination product.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25709467"}, {"offsetInBeginSection": 1299, "offsetInEndSection": 1539, "text": "However, caution is needed when coadministering with any drug that may increase simvastatin levels to reduce the risk of myopathy and rhabdomyolysis.CONCLUSION: Juvisync should be used in patients requiring both sitagliptin and simvastatin.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25709467"}, {"offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "BACKGROUND: The purpose of this study was to review the current literature and information on the combination product Juvisync\u2122 (sitagliptin + simvastatin), which was approved by the US Food and Drug Administration in Oc", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25709467"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1420, "text": "BACKGROUND: The purpose of this study was to review the current literature and information on the combination product Juvisync\u2122 (sitagliptin + simvastatin), which was approved by the US Food and Drug Administration in October 2011.METHODS: PubMed (2001-2014) was searched for primary and review articles on sitagliptin, simvastatin, or the combination product. Drug manufacturing data and product labeling were also used. Studies of simvastatin, sitagliptin, or the combination were screened and analyzed to include relevant and recent papers. Selected English language trials were limited to those with human subjects and included both safety and efficacy outcomes.RESULTS: When compared with glipizide as add-on therapy to metformin, sitagliptin was noninferior but had lower rates of hypoglycemia and weight gain. In addition, when compared with insulin glargine, sitagliptin was less effective in decreasing glycosylated hemoglobin, but was associated with significantly lower rates of hypoglycemia. Further, trials have shown a beneficial effect of using statins in patients with diabetes mellitus with regard to decreasing cardiovascular risk, regardless of baseline lipid levels or the presence of a cardiac disease. Both medications have also demonstrated an acceptable side effect profile. However, caution is needed when coadministering with any drug that may increase simvastatin levels to reduce the risk of ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25709467"}, {"offsetInBeginSection": 106, "offsetInEndSection": 220, "text": "ion product Juvisync\u2122 (sitagliptin + simvastatin), which was approved by the US Food and Drug Administration in Oc", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25709467"}]}
+{"question_id": "66214cc6b9f8b89d7e000003", "question": "Is fish intake a protective factor against colorectal cancer?", "answer": "Individuals in the highest (vs. lowest) category of fish consumption had a significantly reduced risk of CRC (SRR 0.94, 95%CI 0.89-0.99). In dose-response meta-analysis, a 50-g increment in the daily consumption of fish was associated with a statistically significant 4% reduction in CRC risk (SRR 0.96, 95%CI 0.92-0.99)", "relevant_passage_ids": ["35158907", "7549825", "24615521", "18483335", "24706410", "22513196", "26264963", "29399003", "15956652", "37572059", "19169007", "19553301", "12671534", "21888535", "17419892", "31252190", "32138465", "36014940", "32537063", "35458225", "33998355", "36092326", "28804436", "17425596", "10443950", "23878344", "15456633", "25619144", "16201848", "19638981", "17823383"], "type": "yesno", "snippets": [{"offsetInBeginSection": 874, "offsetInEndSection": 1195, "text": " Individuals in the highest (vs. lowest) category of fish consumption had a significantly reduced risk of CRC (SRR 0.94, 95%CI 0.89-0.99). In dose-response meta-analysis, a 50-g increment in the daily consumption of fish was associated with a statistically significant 4% reduction in CRC risk (SRR 0.96, 95%CI 0.92-0.99)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35158907"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1196, "text": "Background: Epidemiological studies on the association between fish consumption and colorectal cancer (CRC) risk have yielded inconsistent results, despite evidence from preclinical studies that long-chain \u03c9-3 polyunsaturated fatty acids inhibit colorectal carcinogenesis. We conducted a meta-analysis of prospective epidemiological studies investigating the association between fish consumption and CRC risk among humans and reviewed studies examining the link between fish components and colorectal carcinogenesis in animal models. Methods: We included studies published until November 2020. We calculated the summary risk ratio (SRR) and 95% confidence intervals (CI) through random effects meta-analysis models in order to summarize evidence from studies among humans. Results: Twenty-five prospective epidemiological studies encompassing 25,777 CRC cases were included. Individuals in the highest (vs. lowest) category of fish consumption had a significantly reduced risk of CRC (SRR 0.94, 95%CI 0.89-0.99). In dose-response meta-analysis, a 50-g increment in the daily consumption of fish was associated with a statistically significant 4% reduction in CRC risk (SRR 0.96, 95%CI 0.92-0.99).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35158907"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1739, "text": "BACKGROUND & AIMS: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.METHODS: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs.RESULTS: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80-0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82-0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83-1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78-0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was\u00a0associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18-1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal co", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31252190"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1122, "text": "Fish is among the foods exerting favourable effects on colorectal cancer (CRC), but the possible role of canned fish has been insufficiently investigated. We aimed to investigate the relationship between canned fish consumption and CRC risk. We analysed data from two case\u2212control studies conducted between 1992 and 2010 in several Italian areas, comprising a total of 2419 incident cases and 4723 hospital controls. Canned fish consumption was analysed according to the weekly frequency of consumption as <1 serving per week (s/w) (reference category), 1 < 2 s/w, and \u22652 s/w. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression models, adjusting for several recognised confounding factors. Overall, canned fish consumption was lower among cases than among controls (23.8% vs. 28.6%). An inverse association was found between canned fish consumption and CRC risk with a significant trend in risk (OR = 0.81, 95% CI: 0.71\u22120.92 for intermediate consumption and OR = 0.66, 95% CI: 0.51\u22120.85 for the highest one), which was consistent across strata of several covariates.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35458225"}, {"offsetInBeginSection": 0, "offsetInEndSection": 629, "text": "PURPOSE: We aimed to assess the association between the dietary intake of fish-derived omega-3 polyunsaturated fatty acids and the risk of colorectal cancer among Swedish women.MATERIALS AND METHODS: A total of 48,233 women with information on dietary intake were included in the analysis. Participants were followed for incident colorectal cancer until 31 December 2012. Cox proportional hazard models were used to assess the association between baseline fatty acid intake and colorectal cancer risk. All analyses were stratified by colon and rectal cancers.RESULTS: During a median of 21.3 years of follow-up, a total of 344 co", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32138465"}, {"offsetInBeginSection": 0, "offsetInEndSection": 907, "text": "Background : Colorectal cancer (CRC) is considered one of the most common forms of cancer in the Western world. High intake of red and processed meat is considered to increase CRC development. Objective : This study examined associations between intake of red meats, poultry, and fish and incident CRC, and if weight status modifies the associations. Design : In the Malm\u00f6 Diet and Cancer Study, dietary data was collected through a modified diet history method. Via the Swedish Cancer Registry, 728 cases of CRC were identified during 428\u00a0924 person-years of follow-up of 16\u00a0944 women and 10\u00a0987 men. Results : Beef intake was inversely associated with colon cancer. However, in men high intake of beef was associated with increased risk of rectal cancer. High intake of pork was associated with increased incidence of CRC, and colon cancer. Processed meat was associated with increased risk of CRC in men.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28804436"}, {"offsetInBeginSection": 86, "offsetInEndSection": 953, "text": "alth problem. Diet plays a key role in preventing this type of cancer. The purpose of our study was to determine dietary risk factors for colorectal cancer in our Moroccan context.METHODS: we conducted a case-control study including patients with colorectal cancer compared with controls. The statistical analysis of results was carried out using R software.RESULTS: our study included 225 patients treated for cancer at the Mohammed VI Hospital Center and 225 controls. The average age of our study population at the time of diagnosis was 55.49\u00b114.06 years, including 119 men (52.9%) and 106 women (47.1%) with a sex ratio of 1.12. Associations were found between the highest intakes of red meats, cold meats, sausages and the risk of colorectal cancer (p = 0.0001) with F4 (4-7 times / week) vs F1 (never): OR = 4.4 (1.6-11.9); (p = 0.001), OR = 1.7 (0.5-5.7); (p =", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32537063"}, {"offsetInBeginSection": 0, "offsetInEndSection": 900, "text": "The incidence and mortality rates of colorectal cancer (CRC) in Northeast Brazil are increasing. To study the association between CRC and diet, data were obtained from 64 patients with CRC and 123 sex- and age-matched controls. The dietary details were recorded using a validated food frequency questionnaire. Nutrient intake was calculated using Dietsys software (National Cancer Institute, Maryland, USA). In a binary logistic regression model of dietary components (model 1), the chance of CRC increased by 0.2% (odds ratio [OR]\u2009=\u20091.002; 95% confidence interval [CI]: 1.000-1.004) for each gram of processed meat intake per week (p\u2009<\u20090.010). Consumption of eggs decreased the chance by 0.1% per gram (OR = 0.999; 95% CI: 0.998-1.000; p\u2009<\u20090.050). The use of oil (including olive oil) for served food decreased the chance by 1.8% (OR = 0.982; 95% CI: 0.970-0.992) for each time consumed (p\u2009<\u20090.010).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33998355"}, {"offsetInBeginSection": 0, "offsetInEndSection": 772, "text": "There is limited evidence to support the relationship between the consumption of animal-source foods other than red meat and processed meat and colorectal cancer (CRC) risk. We aimed to examine the recent available evidence from observational studies about the association between these food groups\u2019 intake and CRC risk. For this systematic review, we searched the PubMed database for the last five years. A total of fourteen cohort studies and seven case\u2212control studies comprising a total of >60,000 cases were included. The studies showed a consistent significant decrease in CRC risk, overall and by subsites, associated with a high consumption of total dairy products. Less strong effects associated with the consumption of any subtype of dairy product were observed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36014940"}, {"offsetInBeginSection": 0, "offsetInEndSection": 514, "text": "Colorectal cancer (CRC) accounts for considerable mortalities worldwide. Several modifiable risk factors, including a high intake of certain foods and beverages can cause CRC. This review summarized the latest findings on the intake of various foods, nutrients, ingredients, and beverages on CRC development, with the objective of classifying them as a risk or protective factor. High-risk food items include red meat, processed meat, eggs, high alcohol consumption, sugar-sweetened beverages, and chocolate candy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37572059"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1521, "text": "Background and Objective: Colorectal cancer (CRC) is the third most common cancer worldwide, and the incidence and mortality rates continue to increase annually. Many factors, including genetic, immune, and environmental factors, influence the occurrence and development of CRC. Along with the economic development, changes in lifestyle, especially dietary factors, have been shown to greatly affect the progression of CRC. Increasing evidence showed that dietary patterns influence the risk of CRC and affect CRC treatment. The present review describes the role of diet in the prevention and treatment of CRC with the hope that doctors attach importance to dietary patterns in educating patients with CRC or at risk of CRC and that diet may be regarded as an auxiliary treatment strategy to improve patients' outcomes.Methods: English language articles published from 2000 to December 2021 in PubMed and Embase were identified by searching titles for keywords including \"diet\", \"colorectal cancer\", \"dietary pattern\", and \"dietary factor\"; 101 articles were selected for review.Key Content and Findings: The present review describes the role of different dietary patterns and factors in the prevention and treatment of CRC. We found that dietary intervention is closely related to the occurrence, development, and prognosis of CRC. Adherence to the Mediterranean diet (MD), the Dietary Approaches to Stop Hypertension (DASH) diet, fasting, vegetarian diets and the ketogenic diet (KD) were found to reduce the risk of CR", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36092326"}, {"offsetInBeginSection": 453, "offsetInEndSection": 874, "text": "The hypothesis linking fish consumption and low cancer incidence appears to be supported by little epidemiological data. However, there are several factors that may mask potential protective associations with fish intake. The type and the amount of fish eaten, the cooking method, the stage of the cancer and, amongst women, menopausal status may all be important factors that relate to whether fish is protective or not.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21888535"}, {"offsetInBeginSection": 453, "offsetInEndSection": 674, "text": "The hypothesis linking fish consumption and low cancer incidence appears to be supported by little epidemiological data. However, there are several factors that may mask potential protective associations with fish intake.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21888535"}, {"offsetInBeginSection": 242, "offsetInEndSection": 399, "text": " We examined the association between intakes of fish and n-3 fatty acids from fish and colorectal cancer risk in men enrolled in the Physicians' Health Study", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18483335"}, {"offsetInBeginSection": 0, "offsetInEndSection": 402, "text": "The association between specific fish intake and colorectal cancer risk remains controversial. This study aimed to examine the association between specific fish intake and colorectal cancer risk in Chinese population in a large case control study. During July 2010 to November 2014, 1189 eligible colorectal cancer cases and 1189 frequency-matched controls (age and sex) completed in-person interviews.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26264963"}, {"offsetInBeginSection": 1217, "offsetInEndSection": 1638, "text": "Our findings for n-3 fatty acids were similar to those for fish; the multivariate relative risk (95% confidence interval) of total colorectal cancer for the highest versus lowest quartile of n-3 fatty acids was 0.74 (0.57-0.95; P trend = 0.01).CONCLUSIONS: Our results from this long-term prospective study suggest that intakes of fish and long-chain n-3 fatty acids from fish may decrease the risk for colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18483335"}, {"offsetInBeginSection": 1684, "offsetInEndSection": 1845, "text": "This study had no publication bias.CONCLUSION: Our findings from this meta-analysis suggest that fish consumption is inversely associated with colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22513196"}, {"offsetInBeginSection": 672, "offsetInEndSection": 943, "text": "Cox proportional hazards models were used to estimate multivariate relative risks for colorectal cancer for the categories of fish intake and quartiles of n-3 fatty acid intake.RESULTS: During 22 years of follow-up, 500 men had a confirmed diagnosis of colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18483335"}, {"offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "BACKGROUND: Fish consumption may protect against colorectal cancer, but results from observational studies are inconsistent; therefore, a systematic review with a meta-analysis wa", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22513196"}, {"offsetInBeginSection": 1130, "offsetInEndSection": 1329, "text": ", 0.88; 95% CI, 0.80-0.95). The pooled ORs of colorectal cancer for the highest versus lowest fish consumption in case-control studies and cohort studies were 0.83 (95% CI, 0.72-0.95) and 0.93 (95% C", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22513196"}, {"offsetInBeginSection": 1420, "offsetInEndSection": 1655, "text": "t not among cohort studies. A significant inverse association was found between fish intake and rectal cancer (summary OR, 0.79; 95% CI, 0.65-0.97), and there was a modest trend seen between fish consumption and colon cancer (summary O", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22513196"}, {"offsetInBeginSection": 643, "offsetInEndSection": 739, "text": "l studies were identified. Fish consumption was not significantly associated with colorectal, co", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23878344"}, {"offsetInBeginSection": 1688, "offsetInEndSection": 1822, "text": "ion and intake of meat products.CONCLUSIONS: The study results indicate that increased fish intake may have a preventive effect on CRC", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19169007"}, {"offsetInBeginSection": 445, "offsetInEndSection": 596, "text": "Prospective and case-control studies either do not show an association between fish intake and cancer risks or show reduced risks at high fish intakes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10443950"}, {"offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "BACKGROUND/AIMS: Current epidemiologic studies investigating the effect of fish intake on colorectal cancer (CRC)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19169007"}, {"offsetInBeginSection": 308, "offsetInEndSection": 529, "text": "According to our results, the consumption of vegetables, fruits, fish, as well as coffee seems to be protective against digestive cancer, while the consumption of citrus and olive oil is protective against gastric cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24615521"}, {"offsetInBeginSection": 515, "offsetInEndSection": 824, "text": "Food items that are protective include milk, cheese and other dairy products, fruits, vegetables (particularly cruciferous), whole grains, legumes (particularly soy beans), fish, tea (particularly green tea), coffee (particularly among Asians), chocolate, and moderate alcohol consumption (particularly wine).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37572059"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1310, "text": "Although long-chain n-3 polyunsaturated fatty acids (Ln-3 PUFA), which are abundant in fish, have shown protective effects on colorectal cancer in laboratory studies, epidemiological studies to date have not been consistent. We evaluated the relationship of consumption of fish and Ln-3 PUFA to the colon and rectal cancer risk in the two cohorts of the Japan Public Health Center-based prospective study of 42,525 men and 46,133 women. Dietary and other exposure data were obtained between 1990 and 1994. Through December 1999, 705 cases of colon and rectal cancer were documented. When data from the two cohorts were pooled, multivariable relative risks (RRs) for the highest quartile compared with the lowest quartile of fish consumption were 1.07 (95% confidence interval, CI = 0.77-1.48) for colon cancer and 0.95 (95% CI = 0.63-1.43) for rectal cancer with no dose-risk trend. RRs for the highest quartile compared with the lowest quartile of eicosapentaenoic acid consumption were 1.05 (95% CI = 0.76-1.46) for colon cancer and 0.91 (95% CI = 0.60-1.38) for rectal cancer with no dose-risk trend. This study does not support the role of fish and Ln-3 PUFA in the etiology of colon and rectal cancer in this population whose fish consumption was high and the variation in Ln-3 PUFA consumption was large.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15456633"}, {"offsetInBeginSection": 0, "offsetInEndSection": 444, "text": "Recent studies have shown a decreased risk of colon cancer with consumption of fish. However, most studies on fish consumption do not distinguish between lean and fatty fish, or between poached and fried fish. The aim of this study was to investigate any association between fish consumption and colon cancer in The Norwegian Women and Cancer (NOWAC) study. We focused mainly on lean fish, which was further divided into poached and fried fish.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17419892"}, {"offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "BACKGROUND: Fish is the main dietary source of long-chain n-3 fatty acids, which have been suggested to play a protective role in colorectal cancer development in laboratory and animal studies. Human studies have not shown consist", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18483335"}, {"offsetInBeginSection": 1189, "offsetInEndSection": 1433, "text": "h colon and rectal cancers. Our findings for n-3 fatty acids were similar to those for fish; the multivariate relative risk (95% confidence interval) of total colorectal cancer for the highest versus lowest quartile of n-3 fatty acids was 0.74 ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18483335"}, {"offsetInBeginSection": 300, "offsetInEndSection": 452, "text": "Among 273 estimates of association reported by these studies, 53 indicated decreased risk while 12 indicated increased risk associated with fish intake.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21888535"}, {"offsetInBeginSection": 916, "offsetInEndSection": 980, "text": "nosis of colorectal cancer. Fish intake was inversely associated", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18483335"}, {"offsetInBeginSection": 547, "offsetInEndSection": 728, "text": "Fish oil feeding resulted in lower 8-OHdG levels (P = 0.038), higher levels of apoptosis (P = 0.035), and a lower cell proliferative index (P = 0.05) compared with corn oil feeding.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16201848"}, {"offsetInBeginSection": 0, "offsetInEndSection": 852, "text": "Breast and colorectal cancer are main causes of death in industrialized countries. In these cancers dietary factors appear to play beneficial or adverse roles. One of the possible beneficial factors may be fish intake or the n-3 polyunsaturated fatty acids from fish, as found in epidemiological and clinical studies. In population studies, high intake of fish during many years is associated with reduced risks of breast and colorectal cancer. Prospective and case-control studies either do not show an association between fish intake and cancer risks or show reduced risks at high fish intakes. In these studies, fish consumption may have been too low or may not reflect fish consumption over a longer period. In population, case-control, and prospective studies, fish and fish n-3 polyunsaturated fatty acids were not found to increase cancer risks.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10443950"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1419, "text": "BACKGROUND: Fish consumption may protect against colorectal cancer, but results from observational studies are inconsistent; therefore, a systematic review with a meta-analysis was conducted.METHODS: Relevant studies were identified by a search of MEDLINE and EMBASE databases to May 2011, with no restrictions. Reference lists from retrieved articles also were reviewed. Studies that reported odds ratio (OR) or relative risk estimates with 95% confidence intervals (CIs) for the association between the consumption of fish and the risk of colorectal, colon, or rectal cancer were included. Two authors independently extracted data and assessed study quality. The risk estimate (hazard ratio, relative risk, or OR) of the highest and lowest reported categories of fish intake were extracted from each study and analyzed using a random-effects model.RESULTS: Twenty-two prospective cohort and 19 case-control studies on fish consumption and colorectal cancer risk met the inclusion criteria and were included in the meta-analysis. Our analysis found that fish consumption decreased the risk of colorectal cancer by 12% (summary OR, 0.88; 95% CI, 0.80-0.95). The pooled ORs of colorectal cancer for the highest versus lowest fish consumption in case-control studies and cohort studies were 0.83 (95% CI, 0.72-0.95) and 0.93 (95% CI, 0.86-1.01), respectively. There was heterogeneity among case-control studies (P<.001) b", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22513196"}, {"offsetInBeginSection": 0, "offsetInEndSection": 915, "text": "BACKGROUND: Fish is the main dietary source of long-chain n-3 fatty acids, which have been suggested to play a protective role in colorectal cancer development in laboratory and animal studies. Human studies have not shown consistent results. We examined the association between intakes of fish and n-3 fatty acids from fish and colorectal cancer risk in men enrolled in the Physicians' Health Study.METHODS: The Physicians' Health Study began as a randomized trial to examine the effect of aspirin and beta-carotene supplementation on cancer and cardiovascular disease. Fish intake was assessed at the 12-month follow-up with an abbreviated food-frequency questionnaire. Cox proportional hazards models were used to estimate multivariate relative risks for colorectal cancer for the categories of fish intake and quartiles of n-3 fatty acid intake.RESULTS: During 22 years of follow-up, 500 men had a confirmed dia", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18483335"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1687, "text": "BACKGROUND/AIMS: Current epidemiologic studies investigating the effect of fish intake on colorectal cancer (CRC) risk are scarce. Therefore, the aim of this study was to elucidate the relationship between fish consumption and CRC risk.METHODS: This hospital-based case-control study was performed in 548 CRC patients (Surgery Clinic, University Hospital in Krakow, Poland) between November 2000 and May 2008. Histological findings, information on anatomic location and stage of cancer were available for all the patients enrolled in this study. The control group consisted of 745 patients of the same hospital with no history of cancer admitted for treatment of non-neoplastic conditions. During the 5-year study period, the food frequency questionnaire used focused on the reference period that was defined as 1-5 years prior to CRC diagnosis for the CRC cases and the date of hospital admission for the controls.RESULTS: The crude odds ratio (OR) was inversely related to fish consumption (z for trend in quartiles of intake= -2.31, p=0.021; OR=0.89; 95% confidence interval, CI: 0.81-0.98). The risk of CRC increased with intake of stewed or cooked meat (z for trend in quartiles of intake=2.14; p=0.032; OR=1.11; 95% CI: 1.01-1.23). The adjusted OR showed a significant reduction in CRC already at the moderate fish intake of one or two servings per week (OR=0.70; 95% CI: 0.51-0.94), but it was even lower at higher fish intake (OR=0.56; 95% CI: 0.39-0.86). All multivariate statistical models employed in the analysis considered potential confounders, such as demographic characteristics of subjects, body mass index, smoking status, leisure time physical activity, energy consump", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19169007"}, {"offsetInBeginSection": 0, "offsetInEndSection": 810, "text": "The association between fish, \u03c9-3 and \u03c9-6 polyunsaturated fatty acid (PUFA) intake and risk of colorectal cancer (CRC) remains inconclusive. Recent prospective studies suggest that the relationship may vary by gender, subsite and duration of follow-up. We followed 123,529 US adults (76,386 women and 47,143 men) without a history of cancer at baseline for 24 to 26 years. Fish and PUFA intake was assessed at baseline and updated every 4 years by using a validated food-frequency questionnaire. We found no overall association between fish, \u03c9-3 and \u03c9-6 PUFA intake and CRC risk with hazard ratio (HR) of 1.03 [95% confidence interval (CI): 0.89-1.20] comparing marine \u03c9-3 intake of \u2265 0.30 g/d versus <0.15 g/d among women and 1.05 (95% CI: 0.85-1.30) comparing intake of \u2265 0.41 g/d versus <0.16 g/d among men.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24706410"}, {"offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Background: Epidemiological studies on the association between fish consumption and colorectal cancer (CRC) risk have yielded inconsistent results, despite evidence from preclinical studies that long-chain \u03c9-3 polyunsaturated fatty acids inhibit colorectal carcinogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35158907"}, {"offsetInBeginSection": 908, "offsetInEndSection": 972, "text": "Fish intake was inversely associated with risk of rectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28804436"}, {"offsetInBeginSection": 0, "offsetInEndSection": 399, "text": "BACKGROUND: Fish is the main dietary source of long-chain n-3 fatty acids, which have been suggested to play a protective role in colorectal cancer development in laboratory and animal studies. Human studies have not shown consistent results. We examined the association between intakes of fish and n-3 fatty acids from fish and colorectal cancer risk in men enrolled in the Physicians' Health Study", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18483335"}, {"offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "BACKGROUND: Fish is the main dietary source of long-chain n-3 fatty acids, which have been suggested to play a protective role in colorectal cancer development in laboratory and animal studies. Human studies have not shown consistent results", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18483335"}, {"offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "BACKGROUND: Fish is the main dietary source of long-chain n-3 fatty acids, which have been suggested to play a protective role in colorectal cancer development in laboratory and animal studies", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18483335"}, {"offsetInBeginSection": 1544, "offsetInEndSection": 1748, "text": "Our findings do not support the hypothesis that consumption of red meat increases colorectal cancer risk but do suggest that high intake of fish may decrease the risk, particularly of distal colon cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17425596"}, {"offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Higher freshwater fish and sea fish intake is inversely associated with colorectal cancer risk among Chinese population: a case-control study.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26264963"}, {"offsetInBeginSection": 160, "offsetInEndSection": 596, "text": "One of the possible beneficial factors may be fish intake or the n-3 polyunsaturated fatty acids from fish, as found in epidemiological and clinical studies. In population studies, high intake of fish during many years is associated with reduced risks of breast and colorectal cancer. Prospective and case-control studies either do not show an association between fish intake and cancer risks or show reduced risks at high fish intakes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10443950"}, {"offsetInBeginSection": 712, "offsetInEndSection": 976, "text": "In population, case-control, and prospective studies, fish and fish n-3 polyunsaturated fatty acids were not found to increase cancer risks. Clinical studies on markers of colorectal cancer indicate that fish n-3 polyunsaturated fatty acids may reduce cancer risk.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10443950"}, {"offsetInBeginSection": 597, "offsetInEndSection": 976, "text": "In these studies, fish consumption may have been too low or may not reflect fish consumption over a longer period. In population, case-control, and prospective studies, fish and fish n-3 polyunsaturated fatty acids were not found to increase cancer risks. Clinical studies on markers of colorectal cancer indicate that fish n-3 polyunsaturated fatty acids may reduce cancer risk.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10443950"}, {"offsetInBeginSection": 712, "offsetInEndSection": 1253, "text": "In population, case-control, and prospective studies, fish and fish n-3 polyunsaturated fatty acids were not found to increase cancer risks. Clinical studies on markers of colorectal cancer indicate that fish n-3 polyunsaturated fatty acids may reduce cancer risk. In several studies in which the effect of fish consumption on cancer risk was investigated, meat and meat products were positively related to cancer risk, suggesting that cancer risks might be reduced more effectively when meat and meat products in meals are replaced by fish.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10443950"}, {"offsetInBeginSection": 160, "offsetInEndSection": 444, "text": "One of the possible beneficial factors may be fish intake or the n-3 polyunsaturated fatty acids from fish, as found in epidemiological and clinical studies. In population studies, high intake of fish during many years is associated with reduced risks of breast and colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10443950"}, {"offsetInBeginSection": 853, "offsetInEndSection": 1473, "text": "Clinical studies on markers of colorectal cancer indicate that fish n-3 polyunsaturated fatty acids may reduce cancer risk. In several studies in which the effect of fish consumption on cancer risk was investigated, meat and meat products were positively related to cancer risk, suggesting that cancer risks might be reduced more effectively when meat and meat products in meals are replaced by fish. In conclusion, the existing knowledge suggests that an increase in the consumption of fish and fish n-3 polyunsaturated fatty acids in industrialized countries may contribute to lower breast and colorectal cancer risks.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10443950"}, {"offsetInBeginSection": 853, "offsetInEndSection": 976, "text": "Clinical studies on markers of colorectal cancer indicate that fish n-3 polyunsaturated fatty acids may reduce cancer risk.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10443950"}]}
+{"question_id": "6616b259fdcbea915f00005a", "question": "What is the exposome?", "answer": "The exposome, defined as the totality of an individual's exposures over the life course. The concept of the Exposome is a compilation of diseases and one's lifetime exposure to chemicals, whether the exposure comes from environmental, dietary, or occupational exposures; or endogenous chemicals that are formed from normal metabolism, inflammation, oxidative stress, lipid peroxidation, infections, and other natural metabolic processes such as alteration of the gut microbiom", "relevant_passage_ids": ["26012316", "26339073", "24906490", "24767943", "26475350", "28669935", "29295136", "25378312", "34886409", "31953830", "30095351", "34629184", "32619912", "35004129", "26358001", "31009264", "35493396", "34465170", "32191165", "37979229", "37229681", "22136338", "34746906", "31960937", "22080817", "28867821", "29221465", "35964886", "35310334", "36436753", "34792619", "28125387", "30772495", "35108405", "28494538", "21081972", "32221742", "38058436", "26231368", "36424935", "29916594", "37138645", "31194890", "37431591", "27720464", "36983182", "22713677", "22199396"], "type": "summary", "snippets": [{"offsetInBeginSection": 688, "offsetInEndSection": 846, "text": "The term 'exposome' was proposed to reflect a life-course of environmental influences beginning in-utero and proceeding right through childhood to adulthood. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26012316"}, {"offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "The exposome, defined as the totality of an individual's exposures over the life course, is a seminal concept in the environmental health science", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26339073"}, {"offsetInBeginSection": 407, "offsetInEndSection": 604, "text": "The 'exposome' has therefore been proposed as a new paradigm to encompass the totality of human environmental (meaning all non-genetic) exposures from conception onwards, complementing the genome. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24906490"}, {"offsetInBeginSection": 0, "offsetInEndSection": 387, "text": "The concept of the Exposome is a compilation of diseases and one's lifetime exposure to chemicals, whether the exposure comes from environmental, dietary, or occupational exposures; or endogenous chemicals that are formed from normal metabolism, inflammation, oxidative stress, lipid peroxidation, infections, and other natural metabolic processes such as alteration of the gut microbiom", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24767943"}, {"offsetInBeginSection": 286, "offsetInEndSection": 1009, "text": "The exposome is the analogue to the genome, from an environmental exposure perspective; research on the exposome has gained momentum only since 2011. In this work, we propose a generally applicable methodology that aims to characterise the landscape of a new research area based on linguistic analysis of its associated publications. Using abstracts of 261 exposome research articles, we illustrate a methodology that combines (1) inductive analysis based on word frequency counts, and term analysis to identify the topics, methods and applications of the new field and (2) deductive analysis using the NCBO Ontology Recommender to identify to what extent this new area is covered by current knowledge representation tools.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29295136"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1016, "text": "The exposome concept arises from the need to integrate different disciplines of public health and environmental sciences, mainly including environmental epidemiology, exposure science, and toxicology. The role of the exposome is to understand how the totality of an individual's exposures throughout the lifetime can impact human health. The etiology of a health condition is rarely explained by a single exposure. Therefore, examining the human exposome as a whole becomes relevant to simultaneously consider multiple risk factors and more accurately estimate concurrent causes of different health outcomes. Generally, the exposome is explained through three domains: general external exposome, specific external exposome, and internal exposome. The general external exposome includes measurable population-level exposures such as air pollution or meteorological factors. The specific external exposome includes information on individual exposures, such as lifestyle factors, typically obtained from questionnaires.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37229681"}, {"offsetInBeginSection": 105, "offsetInEndSection": 838, "text": "While extensive research has been conducted on the human genome and microbiome, little is known about the human exposome. The exposome comprises the totality of chemical, biological, and physical exposures that individuals encounter over their lifetimes. Traditional environmental and biological monitoring only targets specific substances, whereas exposomic approaches identify and quantify thousands of substances simultaneously using nontargeted high-throughput and high-resolution analyses. The quantified self (QS) aims at enhancing our understanding of human health and disease through self-tracking. QS measurements are critical in exposome research, as external exposures impact an individual's health, behavior, and biology.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34465170"}, {"offsetInBeginSection": 0, "offsetInEndSection": 670, "text": "Derived from the term exposure, the exposome is an omic-scale characterization of the nongenetic drivers of health and disease. With the genome, it defines the phenome of an individual. The measurement of complex environmental factors that exert pressure on our health has not kept pace with genomics and historically has not provided a similar level of resolution. Emerging technologies make it possible to obtain detailed information on drugs, toxicants, pollutants, nutrients, and physical and psychological stressors on an omic scale. These forces can also be assessed at systems and network levels, providing a framework for advances in pharmacology and toxicology.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30095351"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1532, "text": "Complementing the human genome with an exposome reflects the increasingly obvious impact of environmental exposure, which far exceeds the role of genetics, on human health. Considering the complexity of exposures and, in addition, the reactions of the body to exposures - i.e., the exposome - reverses classical exposure science where the precise measurement of single or few exposures is associated with specific health or environmental effects. The complete description of an individual's exposome is impossible; even less so is that of a population. We can, however, cast a wider net by foregoing some rigor in assessment and compensating with the statistical power of rich datasets. The advent of omics technologies enables a relatively cheap, high-content description of the biological effects of substances, especially in tissues and biofluids. They can be combined with many other rich data-streams, creating big data of exposure and effect. Computational methods increasingly allow data integration, discerning the signal from the noise and formulating hypotheses of exposure-effect relationships. These can be followed up in a targeted way. With a better exposure element in the risk equation, exposomics - new kid on the block of risk assessment - promises to identify novel exposure (interactions) and health/environment effect associations. This may also create opportunities to prioritize the more relevant chemicals for risk assessment, thereby lowering the burden on hazard assessment in an expo-sure-driven approach.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31960937"}, {"offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "The current human exposome primarily emphasizes the total environmental exposure during an entire life. The characteristics of \"lifelong\" and \"all environmental factors\" make it very challenging to bring the exposomic study into real-life applications.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34746906"}, {"offsetInBeginSection": 301, "offsetInEndSection": 450, "text": "The exposome has been proposed to complement the genome and be the totality of all environmental exposures of an individual over his or her lifetime.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22080817"}, {"offsetInBeginSection": 301, "offsetInEndSection": 590, "text": "The exposome has been proposed to complement the genome and be the totality of all environmental exposures of an individual over his or her lifetime. However, if measurements of the exposome in biological samples are the sole tool for exposure assessment there are a number of limitations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22080817"}, {"offsetInBeginSection": 301, "offsetInEndSection": 741, "text": "The exposome has been proposed to complement the genome and be the totality of all environmental exposures of an individual over his or her lifetime. However, if measurements of the exposome in biological samples are the sole tool for exposure assessment there are a number of limitations. First, it has limited utility for fully capturing the impact of complex mixtures such environmental tobacco smoke or particulate matter air pollution.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22080817"}, {"offsetInBeginSection": 0, "offsetInEndSection": 590, "text": "Environmental exposures affecting human health range from complex mixtures, such as environmental tobacco smoke, ambient particulate matter air pollution and chlorination by products in drinking water, to hazardous chemicals, such as lead, and polycyclic aromatic hydrocarbons, such as benz(a)pyrene. The exposome has been proposed to complement the genome and be the totality of all environmental exposures of an individual over his or her lifetime. However, if measurements of the exposome in biological samples are the sole tool for exposure assessment there are a number of limitations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22080817"}, {"offsetInBeginSection": 0, "offsetInEndSection": 414, "text": "The exposome concept arises from the need to integrate different disciplines of public health and environmental sciences, mainly including environmental epidemiology, exposure science, and toxicology. The role of the exposome is to understand how the totality of an individual's exposures throughout the lifetime can impact human health. The etiology of a health condition is rarely explained by a single exposure.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37229681"}, {"offsetInBeginSection": 454, "offsetInEndSection": 965, "text": "In contemporary terminology, the cumulative measure of environmental influences and associated biological responses throughout the life span is termed the \"exposome.\" This includes all external exposures from the environment, diet, behavior, societal influences and infections, and also cumulative biological responses to exposures and endogenous processes. Pursuit of a Human Exposome Project is a vision worthy of our youth: development of strategies and tools will require the brightest and most imaginative.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28867821"}, {"offsetInBeginSection": 138, "offsetInEndSection": 310, "text": "In 2005, Christopher Wild introduced the concept of the exposome, which encompasses environmental exposures and concomitant biological responses throughout the life course.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28669935"}, {"offsetInBeginSection": 0, "offsetInEndSection": 447, "text": "The environment plays a major role in human health, yet tools to study the health impacts of complex environmental exposures are lacking. In 2005, Christopher Wild introduced the concept of the exposome, which encompasses environmental exposures and concomitant biological responses throughout the life course. Exposome-based approaches have the potential to enable novel insights into numerous research questions in environmental health sciences.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28669935"}, {"offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "The exposome integrates the variety and accumulation of exposures (external and internal) to which an individual is submitted to from conception to death.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35964886"}, {"offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "The exposome is the cumulative measure of environmental influences and associated biological responses throughout the lifespan, including those from the environment, diet, behaviour, and endogenous processes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36436753"}, {"offsetInBeginSection": 404, "offsetInEndSection": 521, "text": "The 'exposome' represents the (measurable) totality of environmental, i.e. nongenetic, drivers of health and disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34792619"}, {"offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "The exposome, which is defined as the cumulative effect of environmental exposures and corresponding biological responses, aims to provide a comprehensive measure for evaluating non-genetic causes of disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35004129"}, {"offsetInBeginSection": 0, "offsetInEndSection": 365, "text": "The influence of environmental factors on an individual, from conception onwards, is defined as the exposome. It can be categorized into the external exposome, which includes external factors such as air pollution, chemical contaminants, and diet, and the internal exposome, which is unique to an individual, and involves age, physiology, and their genetic profile.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34629184"}, {"offsetInBeginSection": 186, "offsetInEndSection": 426, "text": "The exposome, defined as the totality of environmental exposures from conception onward, may advance our understanding of environmental contributors to disease by more fully assessing the multitude of human exposures across the life course.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28125387"}, {"offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "The exposome is the cumulative measure of environmental influences and associated biological responses across the\u00a0life span, with critical relevance for understanding how exposures can impact human health.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31953830"}, {"offsetInBeginSection": 499, "offsetInEndSection": 636, "text": "The exposome comprises the cumulative environmental influences on an individual and associated biological responses through the lifespan.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30772495"}, {"offsetInBeginSection": 83, "offsetInEndSection": 363, "text": "The exposome can be classified into internal (e.g., aging, hormones, and metabolic processes), specific external (e.g., chemical pollutants or lifestyle factors), and general external (e.g., broader socioeconomic and psychological contexts) domains, all of which are interrelated.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35108405"}, {"offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "The \"exposome\" is an individual's lifetime spectrum of chemical exposures beginning at conception.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32191165"}, {"offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "The exposome is defined as \"the totality of environmental exposures encountered from birth to death\" and was developed to address the need for comprehensive environmental exposure assessment to better understand disease etiology.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29221465"}, {"offsetInBeginSection": 99, "offsetInEndSection": 406, "text": "An exposome includes general external influences such as pollution and weather; external individual-specific factors (diet, infections, self-selected chemical intake); and internal individual-specific constituents (metabolic byproducts, microbiome derivatives, inflammatory mediators, stress hormones, etc).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32191165"}, {"offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "The exposome concept refers to the totality of exposures from a variety of external and internal sources including chemical agents, biological agents, or radiation, from conception onward, over a complete lifetime.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32619912"}, {"offsetInBeginSection": 454, "offsetInEndSection": 620, "text": "In contemporary terminology, the cumulative measure of environmental influences and associated biological responses throughout the life span is termed the \"exposome.\"", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28867821"}, {"offsetInBeginSection": 838, "offsetInEndSection": 1095, "text": "The concept of the exposome, representing the totality of exposures received by a person during life, encompasses all sources of toxicants and, therefore, offers scientists an agnostic approach for investigating the environmental causes of chronic diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21081972"}, {"offsetInBeginSection": 407, "offsetInEndSection": 603, "text": "The 'exposome' has therefore been proposed as a new paradigm to encompass the totality of human environmental (meaning all non-genetic) exposures from conception onwards, complementing the genome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24906490"}, {"offsetInBeginSection": 357, "offsetInEndSection": 444, "text": "The exposome represents the totality of exposures in a lifetime from conception onward.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36424935"}, {"offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "The exposome represents the totality of life course environmental exposures (including lifestyle and other non-genetic factors), from the prenatal period onwards.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32221742"}, {"offsetInBeginSection": 732, "offsetInEndSection": 994, "text": "We propose a reattribution of \"exposome\" to exclusively represent the totality of contact with external factors that a biological entity experiences, and introduce the term \"functional exposomics\" to denote the systematic study of exposure-phenotype interaction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35310334"}, {"offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "OBJECTIVES: As Genomics aims at the collective characterization and quantification of genes, exposomics refers to the totality of lifetime environmental exposures, consisting in a novel approach to studying the role of the environment in hu", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29916594"}, {"offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "The current human exposome primarily emphasizes the total environmental exposure during an entire life.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34746906"}, {"offsetInBeginSection": 0, "offsetInEndSection": 409, "text": "Under the exposome paradigm all nongenetic factors contributing to disease are considered to be 'environmental' including chemicals, drugs, infectious agents, and psychosocial stress. We can consider these collectively as environmental stressors. Exposomics is the comprehensive analysis of exposure to all environmental stressors and should yield a more thorough understanding of chronic disease development.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26475350"}, {"offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "The concept of the exposome encompasses the totality of exposures from a variety of external and internal sources across an individual's life course.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37138645"}, {"offsetInBeginSection": 131, "offsetInEndSection": 241, "text": "The sum of external factors that an individual is exposed to throughout their lifetime is termed the exposome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31194890"}, {"offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "The exposome represents the totality of life course environmental exposures (including lifestyle and other non-genetic factors), from the prenatal period onwards. This holistic concept of exposure provides a new framework to advance the understanding of complex and multifactorial diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32221742"}, {"offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "The term \"exposome\" is defined as a comprehensive study of life-course environmental exposures and the associated biological responses.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37431591"}, {"offsetInBeginSection": 0, "offsetInEndSection": 960, "text": "The exposome represents the totality of life course environmental exposures (including lifestyle and other non-genetic factors), from the prenatal period onwards. This holistic concept of exposure provides a new framework to advance the understanding of complex and multifactorial diseases. Prospective pregnancy and birth cohort studies provide a unique opportunity for exposome research as they are able to capture, from prenatal life onwards, both the external (including lifestyle, chemical, social and wider community-level exposures) and the internal (including inflammation, metabolism, epigenetics, and gut microbiota) domains of the exposome. In this paper, we describe the steps required for applying an exposome approach, describe the main strengths and limitations of different statistical approaches and discuss their challenges, with the aim to provide guidance for methodological choices in the analysis of exposome data in birth cohort studies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32221742"}, {"offsetInBeginSection": 0, "offsetInEndSection": 781, "text": "The exposome concept takes a holistic approach facilitated by new and emerging technologies to describe 'the totality of human environmental (i.e. non-genetic) exposures from conception onwards, complementing the genome'. It provides a framework to advance the environmental epidemiology field that has until now focused almost exclusively on single-exposure health effects. The exposome includes an external domain, measured by methods including geo-spatial modelling, questionnaire and biomonitoring of external exposures while the internal domain is commonly assessed through molecular omics platforms. The internal domain, in part, reflects the biological response to the external domain. New statistical frameworks are required to integrate and assess exposome-health effects.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26231368"}, {"offsetInBeginSection": 324, "offsetInEndSection": 1017, "text": "To emphasize the importance of more complete evaluation of environmental exposure, the concept of the exposome, which indicates the entirety of environmental exposure from conception onwards, was introduced in 2005. Since the 2010s several epidemiological studies, such as the Human Early-Life Exposome project, have applied the exposome concept. The exposome consists of three overlapping domains: the general external, the specific external, and the internal environments. General external factors include the broader socioeconomic environment, and specific external factors include lifestyles, occupations, and pollutant exposures. Internal factors include biological effects and responses.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28494538"}, {"offsetInBeginSection": 249, "offsetInEndSection": 951, "text": "The exposome concept also aimed at to completing the genome, that describes the genetic predisposition as a determinant of disease and death as well as potential targets of intervention. The exposome can be subdivided into multiple pollutomes related to specific chemical and physical pollutants (or other forms of environmental risks), periods of life (infancy, childhood, adolescence, adulthood, and old age) or geographical locations. While exposome research and, in general, health research of the last decades has predominantly focused on what factors contribute to and initiate morbidity and mortality, little is done on factors that will help to develop, maintain, or even increase human health.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37979229"}, {"offsetInBeginSection": 357, "offsetInEndSection": 1487, "text": "The exposome represents the totality of exposures in a lifetime from conception onward. The framework offers a solution to handle the complexity of all \"non-genetic\" factors. The exposome approach has recently been adopted to construct an exposome score for schizophrenia (ES-SCZ). Findings demonstrate that ES-SCZ can be used for risk stratification, adjusting for cumulative environmental load in statistical testing, and collecting risk enriched cohorts. Increasing data availability will help improve ES-SCZ that can be used in staging models to enhance clinical characterization and outcome forecasting. Although an ES-SCZ already provides several practical benefits for research practice, the exposome paradigm offers much more. Agnostic exposure-wide analyses might be the first step to mapping the exposome of mental disorders. These analyses help distinguish genuine signals from selective reporting and uncover novel risk and resilience factors. The exposome approach will also increase our understanding of the differential impact of the environment on mental health across geographical settings and ethnic communities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36424935"}, {"offsetInBeginSection": 0, "offsetInEndSection": 2353, "text": "The exposome concept refers to the totality of exposures from a variety of external and internal sources including chemical agents, biological agents, or radiation, from conception onward, over a complete lifetime. It encompasses also \"psychosocial components\" including the impact of social relations and socio-economic position on health. In this review we provide examples of recent contributions from exposome research, where we believe their application will be of the greatest value for moving forward. So far, environmental epidemiology has mainly focused on hard outcomes, such as mortality, disease exacerbation and hospitalizations. However, there are many subtle outcomes that can be related to environmental exposures, and investigations can be facilitated by an improved understanding of internal biomarkers of exposure and response, through the application of omic technologies. Second, though we have a wealth of studies on environmental pollutants, the assessment of causality is often difficult because of confounding, reverse causation and other uncertainties. Biomarkers and omic technologies may allow better causal attribution, for example using instrumental variables in triangulation, as we discuss here. Even more complex is the understanding of how social relationships (in particular socio-economic differences) influence health and imprint on the fundamental biology of the individual. The identification of molecular changes that are intermediate between social determinants and disease status is a way to fill the gap. Another field in which biomarkers and omics are relevant is the study of mixtures. Epidemiology often deals with complex mixtures (e.g. ambient air pollution, food, smoking) without fully disentangling the compositional complexity of the mixture, or with rudimentary approaches to reflect the overall effect of multiple exposures or components. From the point of view of disease mechanisms, most models hypothesize that several stages need to be transitioned through health to the induction of disease, but very little is known about the characteristics and temporal sequence of such stages. Exposome models reinforce the idea of a biography-to-biology transition, in that everyone's disease is the product of the individual history of exposures, superimposed on their underlying genetic susceptibilities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32619912"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1695, "text": "Introduction: The exposome concept provides a framework to better incorporate the environment into the study of health and disease and has been defined by academics to encompass all lifetime exposures including toxicants, diet, and lifestyle choices. However, initial applications of the exposome concept have been less apt at measuring social determinants of health, focusing primarily on conventional environmental exposures and lifestyle choices that do not reflect the complex lived experience of many communities. To bring community voice into the exposome concept, the HERCULES Exposome Research Center and its Stakeholder Advisory Board co-developed the Exposome Roadshow. We present and discuss the resulting community-exposome definition to inform and improve exposome research.Materials and Methods: Four communities from distinct areas across metro-Atlanta participated in separate 2-day Exposome Roadshow workshops with concept mapping. Aligned with a popular education approach in which community knowledge is used to work collectively for change, concept mapping provided a systematic method to collect and visualize community members' knowledge and create a shared understanding to take action. Community members brainstormed, sorted, and rated their responses to the prompt: \"What in your environment is affecting your and your community's health?\" Responses were analyzed and visually depicted by concept maps consisting of separate but interrelated clusters of ideas. Community members discussed and validated the maps, selecting a final map illustrating their community's exposome.Results: A total of 118 community members completed concept mapping. On average communities ide", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35493396"}, {"offsetInBeginSection": 0, "offsetInEndSection": 731, "text": "The exposome concept encourages holistic consideration of the non-genetic factors (environmental exposures including lifestyle) that influence an individual's health over their life course. However, disconnect between the concept and practical application has promoted divergent interpretations of the exposome across disciplines and reinforced separation of the environmental (emphasizing exposures) and biological (emphasizing responses) research communities. In particular, while knowledge of biological responses can help to distinguish actual (i.e. experienced) from potential exposures, the inclusion of endogenous processes has generated confusion about the position of the exposome in a multi-omics systems biology context.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35310334"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1285, "text": "The \"exposome\" covers all disease determinants across a lifetime. Many exposome factors could induce epigenetic changes, especially in DNA methylation. Yet, the role of these modifications in disease development remains partly understood. Although the possible relationship among the exposome factors, epigenetic modifications, and health/disease has been investigated extensively, all previous studies start from the assumption that epigenetic changes are always detrimental to (or represent an adverse effect on) the health of the affected individual. We hereby propose a new approach to investigate these modifications, and their possible relation with human health, in the context of the exposome. Our hypothesis is based on the possibility that some environmentally-induced changes are plastic entities, responding physiologically to the environment to allow individual adaptation. Briefly, after evaluating the association between environmental exposure and the variation of a given biological parameter through regression models, we use the estimated regression function to predict values for each study subject. We then calculated the relative percent difference (PD) between the measured (i.e., observed) biological parameter and the predicted (i.e., expected) from the model.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38058436"}, {"offsetInBeginSection": 227, "offsetInEndSection": 359, "text": "The exposome comprises the totality of chemical, biological, and physical exposures that individuals encounter over their lifetimes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34465170"}, {"offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "The term \"exposome\" describes the totality of exposures to which an individual is subjected from conception to death.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27720464"}, {"offsetInBeginSection": 0, "offsetInEndSection": 427, "text": "The term \"exposome\" describes the totality of exposures to which an individual is subjected from conception to death. It includes both external and internal factors as well as the human body's response to these factors. Current exposome research aims to understand the effects all factors have on specific organs, yet today, the exposome of human skin has not received major attention and a corresponding definition is lacking.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27720464"}, {"offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "The term \"exposome\" describes the totality of exposures to which an individual is subjected from conception to death. It includes both external and internal factors as well as the human body's response to these factors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27720464"}, {"offsetInBeginSection": 138, "offsetInEndSection": 728, "text": "In 2005, Christopher Wild introduced the concept of the exposome, which encompasses environmental exposures and concomitant biological responses throughout the life course. Exposome-based approaches have the potential to enable novel insights into numerous research questions in environmental health sciences. To promote and develop the concept of the exposome, the Health and Exposome Research Center: Understanding Lifetime Exposures (HERCULES) Exposome Research Center at Emory University held the first Emory Exposome Summer Course from 13-17 June 2016. https://doi.org/10.1289/EHP1712.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28669935"}, {"offsetInBeginSection": 0, "offsetInEndSection": 374, "text": "The exposome concept takes a holistic approach facilitated by new and emerging technologies to describe 'the totality of human environmental (i.e. non-genetic) exposures from conception onwards, complementing the genome'. It provides a framework to advance the environmental epidemiology field that has until now focused almost exclusively on single-exposure health effects.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26231368"}, {"offsetInBeginSection": 0, "offsetInEndSection": 404, "text": "The exposome integrates the variety and accumulation of exposures (external and internal) to which an individual is submitted to from conception to death. Exposome may therefore be a useful tool for understanding the diversity of these factors and their role in the pathophysiology of rheumatoid arthritis (RA). Life is perceived as a continuum of cumulative changes, with key periods of disruption (e.g.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35964886"}, {"offsetInBeginSection": 0, "offsetInEndSection": 311, "text": "The exposome integrates the variety and accumulation of exposures (external and internal) to which an individual is submitted to from conception to death. Exposome may therefore be a useful tool for understanding the diversity of these factors and their role in the pathophysiology of rheumatoid arthritis (RA).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35964886"}, {"offsetInBeginSection": 691, "offsetInEndSection": 914, "text": "The exposome is defined as the cumulative measure of external exposures on an organism (external exposome), and the associated biological responses (endogenous exposome) throughout the lifespan, from conception and onwards.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34886409"}, {"offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "The exposome is defined as the totality of all human environmental exposures from conception to death.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25378312"}, {"offsetInBeginSection": 502, "offsetInEndSection": 650, "text": "The exposome can be defined as the measure of all the exposures of an individual during their lifetime and how these exposures relate to well-being.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36983182"}, {"offsetInBeginSection": 755, "offsetInEndSection": 905, "text": "The word exposome refers to the totality of environmental exposures from conception onwards, comprising factors in external and internal environments.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22136338"}, {"offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "The exposome is the cumulative measure of environmental influences and associated biological responses throughout the lifespan, including exposures from the environment, diet, behavior, and endogenous processes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26358001"}, {"offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "BACKGROUND: The exposome is defined as the totality of environmental exposures from conception onwards. It calls for providing a holistic view of environmental exposures and their effects on human health by evaluating multiple environmental exposures simultaneously during critical peri", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31009264"}, {"offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "BACKGROUND: The 'exposome' represents the accumulation of all environmental exposures across a lifetime. Top-down strategies are required to assess something this comprehensive, and could transform our understanding of how environmental factors affect h", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22713677"}, {"offsetInBeginSection": 1066, "offsetInEndSection": 1249, "text": "The concept of the 'exposome'-representing the totality of exposures from gestation onwards-has recently been introduced as a complement to the genome in studies of disease aetiology.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22199396"}]}
+{"question_id": "66156200fdcbea915f00004d", "question": "What is the gold standard for a diagnosis of narcolepsy?", "answer": "The gold standard for diagnosing narcolepsy is a combination of overnight polysomnography (PSG) followed by a multiple sleep latency test (MSLT). PSG is used to rule out other sleep disorders, while the MSLT assesses daytime sleepiness and the presence of sleep-onset REM periods, which are characteristic of narcolepsy. Measuring cerebrospinal fluid hypocretin-1 levels can provide additional diagnostic information.", "relevant_passage_ids": ["12659360", "37672382"], "type": "factoid", "snippets": [{"offsetInBeginSection": 688, "offsetInEndSection": 839, "text": "referral to an accredited sleep laboratory for a formal sleep study including overnight polysomnography is necessary for a positive narcolepsy diagnosi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12659360"}, {"offsetInBeginSection": 186, "offsetInEndSection": 350, "text": "Polysomnography (PSG) recordings, a gold standard for sleep monitoring and quality measurement, can provide abundant and objective cues for the narcolepsy diagnosis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37672382"}, {"offsetInBeginSection": 1093, "offsetInEndSection": 1169, "text": "end-to-end framework for automatic narcolepsy diagnosis using PSG recordings", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37672382"}]}
+{"question_id": "6630390b187cba990d000035", "question": "Which receptor tyrosine kinase is commonly mutated or amplified in pediatric glioma cases?", "answer": "Pediatric high-grade glioma (pHGG), including both diffuse midline glioma (DMG) and non-midline tumors, continues to be one of the deadliest oncologic diagnoses. Targeted therapy options aimed at key oncogenic receptor tyrosine kinase (RTK) drivers using small-molecule RTK inhibitors have been extensively studied, but the absence of proper in vivo modeling that recapitulates pHGG biology has historically been a research challenge. Over 20% of pHGG have been found in sequencing studies to have alterations in platelet derived growth factor-alpha (PDGFRA), making growth factor modeling and inhibition via targeted tyrosine kinases a promising research direction.", "relevant_passage_ids": ["35978801", "27582545", "26744350", "23970477", "20479398", "23438035", "26727948"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Pediatric high-grade glioma (pHGG), including both diffuse midline glioma (DMG) and non-midline tumors, continues to be one of the deadliest oncologic diagnoses", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35978801"}, {"offsetInBeginSection": 201, "offsetInEndSection": 473, "text": " Targeted therapy options aimed at key oncogenic receptor tyrosine kinase (RTK) drivers using small-molecule RTK inhibitors has been extensively studied, but the absence of proper in vivo modeling that recapitulate pHGG biology has historically been a research challenge. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35978801"}, {"offsetInBeginSection": 710, "offsetInEndSection": 934, "text": "Over 20% of pHGG have been found in sequencing studies to have alterations in platelet derived growth factor-alpha (PDGFRA), making growth factor modeling and inhibition via targeted tyrosine kinases a rich vein of interest.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35978801"}, {"offsetInBeginSection": 693, "offsetInEndSection": 773, "text": "PDGFRA amplification was frequent in pediatric (29.3%) and adult (20.9%) tumors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23438035"}, {"offsetInBeginSection": 244, "offsetInEndSection": 450, "text": "Genome-wide analyses of copy number imbalances previously showed that platelet-derived growth factor receptor \u03b1 (PDGFRA) is the most frequent target of focal amplification in pediatric HGGs, including DIPGs", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23970477"}]}
+{"question_id": "66300c23187cba990d00001a", "question": "Can procalcitonin be used as a predictor for mortality in paediatric sepsis?", "answer": "Yes, procalcitonin can be used as a predictor for mortality in paediatric sepsis.", "relevant_passage_ids": ["36715265"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1310, "offsetInEndSection": 1496, "text": "Procalcitonin, along with clinical evaluation, can guide the identification of children at higher risk of morbidity and mortality, allowing the most appropriate monitoring and treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36715265"}]}
+{"question_id": "66214c5db9f8b89d7e000002", "question": "What is the race with the highest incidence of colorectal cancer?", "answer": "Black Americans demonstrating the highest incidence and mortality from this disease", "relevant_passage_ids": ["34148614", "34325062", "16532978", "10826010", "9698125", "31701261", "12716038", "24574761", "30524961", "36047055", "15184825", "33616738", "38082093", "35936740", "33389864", "35504786", "16835912", "29128568", "31392043", "34568072", "15743345", "18300824", "22791544", "37963221", "34193094", "26703651", "28248415", "15052704", "30521807", "10826011"], "type": "factoid", "snippets": [{"offsetInBeginSection": 123, "offsetInEndSection": 206, "text": "Black Americans demonstrating the highest incidence and mortality from this disease", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34148614"}, {"offsetInBeginSection": 1247, "offsetInEndSection": 1321, "text": "blacks continued to have the highest incidence of CRC for every age group.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34325062"}, {"offsetInBeginSection": 1247, "offsetInEndSection": 1321, "text": "blacks continued to have the highest incidence of CRC for every age group.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34325062"}, {"offsetInBeginSection": 1216, "offsetInEndSection": 1478, "text": "Compared to Whites, Blacks (AOR: 1.99; 95% CI: 1.64-2.41), Hispanics (AOR: 2.49; 95% CI: 1.94-3.19) and colorectal cancer patients in the other category (AOR: 1.72; 95% CI: 1.35-2.18) were more likely to receive inpatient treatment with chemotherapy/radiotherapy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38082093"}, {"offsetInBeginSection": 0, "offsetInEndSection": 526, "text": "Colorectal cancer (CRC) is the third most prevalent and second deadliest cancer in the U.S. with 140,250 cases and 50,630 deaths for 2018. Prevention of CRC through screening is effective. Among categorized races in the U.S., African Americans (AAs) show the highest incidence and death rates per 100,000 when compared to Non-Hispanic Whites (NHWs), American Indian/Alaskan Natives, Hispanics, and Asian/Pacific Islanders, with an overall AA:NHW ratio of 1.13 for incidence and 1.32 for mortality (2010-2014, seer.cancer.gov).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30524961"}, {"offsetInBeginSection": 0, "offsetInEndSection": 424, "text": "Colorectal cancer (CRC) incidence and mortality vary by race and ethnicity in the United States, with the highest burden of disease among Black and American Indian/Alaska Native individuals. There are multiple contributors to these disparities, including lifestyle and environmental risk factors that result from adverse social determinants of health and are more prevalent in minority and medically underserved communities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35504786"}, {"offsetInBeginSection": 161, "offsetInEndSection": 1752, "text": "for the US.METHODS: Age-standardized incidence rates (ASIR, per 100,000) of CRC were calculated using the US Cancer Statistics Database's high-quality population-based cancer registry data from the entire US population. Results were cross-classified by age (20-49 [early-onset] and 50-74 years [late-onset]), race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, American Indian/Alaskan Native, Asian/Pacific Islander), sex, anatomic location (proximal, distal, rectal), and histology (adenocarcinoma, neuroendocrine).RESULTS: During 2001 through 2018, early-onset CRC rates significantly increased among American Indians/Alaskan Natives, Hispanics, and Whites. Compared to Whites, early-onset CRC rates are now 21% higher in American Indians/Alaskan Natives and 6% higher in Blacks. Rates of early-onset colorectal neuroendocrine tumors have increased in Whites, Blacks, and Hispanics; early-onset colorectal neuroendocrine tumor rates are 2-times higher in Blacks compared to Whites. Late-onset colorectal adenocarcinoma rates are decreasing, while late-onset colorectal neuroendocrine tumor rates are increasing, in all racial/ethnic groups. Late-onset CRC rates remain 29% higher in Blacks and 15% higher in American Indians/Alaskan Natives compared to Whites. Overall, CRC incidence was higher in men than women, but incidence of early-onset distal colon cancer was higher in women.CONCLUSIONS: The early-onset CRC disparity between Blacks and Whites has decreased, due to increasing rates in Whites-rates in Blacks have remained stable. However, rates of colorectal neuroen", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34568072"}, {"offsetInBeginSection": 0, "offsetInEndSection": 523, "text": "Black Americans have the highest colorectal cancer incidence and mortality rates of any U.S. racial/ethnic group. Warren Andersen and colleagues report that sociocultural, lifestyle, and healthcare factors did not explain the racial disparity in colorectal cancer incidence, but colorectal cancer screening lessened the disparity. While screening is a cornerstone of colorectal cancer prevention, an improved understanding of etiologic factors may inform additional strategies for primary prevention or risk stratification.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36047055"}, {"offsetInBeginSection": 186, "offsetInEndSection": 1234, "text": "Colorectal cancer (CRC) is one of the leading causes of cancer deaths in the United States and it disproportionately affects the non-Hispanic Black or African American (AA) population. When compared to the non-Hispanic White (nHW) population, incidence and death rates in AAs are 28% and 60% higher, respectively. Hispanics have an overall lower CRC incidence rate than nHWs (Hispanics: 35.5 per 100,000 population; nHWs: 40.2 per 100,000 population), but their incidence continues to rise, unlike nHWs, who are experiencing a decline. This disparity between Hispanics and nHWs is further highlighted in the younger Hispanic population. While the cause of the disparities is associated with CRC-related genetic and environmental factors, the role of specific genes/mutations in each population are still not fully unraveled. However, because CRC is a slowly progressing disease, routine screening and/or early intervention are key to achieving better outcomes in CRC patients and ultimately in closing the disparity gap among different populations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33389864"}, {"offsetInBeginSection": 0, "offsetInEndSection": 636, "text": "BACKGROUND: Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer related deaths in the United States. Racial disparities between Hispanics and Whites exist for incidence of late-onset (LO) CRC. However, not much is known about potential disparities between colon cancer (CC) and rectal cancer (RC) incidence queried individually.METHODS: Using the SEER database data from 2000 to 2010, we obtained the national estimates of CC and RC for Hispanics and Whites. We analyzed trends in incidence, mortality, gender and stage of disease for early-onset (EO) (<50 years old) and LO (>50 y", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31392043"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1042, "text": "The occurrence of colorectal cancer (CRC) shows a large disparity among recognized races and ethnicities in the U.S., with Black Americans demonstrating the highest incidence and mortality from this disease. Contributors for the observed CRC disparity appear to be multifactorial and consequential that may be initiated by structured societal issues (e.g., low socioeconomic status and lack of adequate health insurance) that facilitate abnormal environmental factors (through use of tobacco and alcohol, and poor diet composition that modifies one's metabolism, microbiome and local immune microenvironment) and trigger cancer-specific immune and genetic changes (e.g., localized inflammation and somatic driver gene mutations). Mitigating the disparity by prevention through CRC screening has been demonstrated; this has not been adequately shown once CRC has developed. Acquiring additional knowledge into the science behind the observed disparity will inform approaches towards abating both the incidence and mortality of CRC between U.S.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34148614"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1022, "text": "African Americans have the highest incidence and mortality rates of colorectal cancer (CRC) of any ethnic group in the United States. Although some of these disparities can be explained by differences in access to care, cancer screening, and other socioeconomic factors, disparities remain after adjustment for these factors. Consequently, an examination of recent advances in the understanding of ethnicity-specific factors, including genetic and environmental factors relating to risk of CRC, the biology of CRC progression, and the changes in screening and mortality, is important for evaluating our progress toward eliminating the disparities. An overarching limitation in this field is the number and sample size of studies performed to characterize the etiological bases of CRC incidence and mortality in African Americans. Despite this limitation, significant differences in etiology are manifest in many studies. These differences need validation, and their impacts on disparities need more detailed investigation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29128568"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1116, "text": "BACKGROUND & AIMS: Colorectal cancer (CRC) incidence has decreased overall in the last several decades, but it has increased among younger adults. Prior studies have characterized this phenomenon in the United States (U.S.) using only a small subset of cases. We describe CRC incidence trends using high-quality data from 92% of the U.S. population, with an emphasis on those younger than 50 years.METHODS: We obtained 2001 to 2016 data from the U.S. Cancer Statistics database and analyzed CRC incidence for all age groups, with a focus on individuals diagnosed at ages 20 to 49 years (early-onset CRC). We compared incidence trends stratified by age, as well as by race/ethnicity, sex, region, anatomic site, and stage at diagnosis.RESULTS: We observed 191,659 cases of early-onset and 1,097,765 cases of late-onset CRC during the study period. Overall, CRC incidence increased in every age group from 20 to 54 years. Whites were the only racial group with a consistent increase in incidence across all younger ages, with the steepest rise seen after 2012. Hispanics also experienced smaller increases in incidence", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34325062"}, {"offsetInBeginSection": 0, "offsetInEndSection": 549, "text": "INTRODUCTION: The incidence of CRC is higher in minority racial and ethnic groups. However, studies assessing trends among sex and racial groups on the incidence and mortality of CRC are lacking. We aim to investigate disparities in CRC by reviewing a large national cancer registry.METHODS: This is a retrospective cross-sectional study of the Surveillance, Epidemiology, and End Results Registry (SEER) of individuals aged 45-79 years from 2000-2017.RESULTS: During the study period, the incidence of CRC decreased for both males and females, resp", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33616738"}, {"offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "In the United States, African Americans have the highest incidence of colorectal cancer of any racial or ethnic group. Compared with whites, African Americans have a younger mean age at colorectal cancer diagnosis and a greater proportion have proximal cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15184825"}, {"offsetInBeginSection": 0, "offsetInEndSection": 339, "text": "In the United States, African Americans have the highest incidence of colorectal cancer of any racial or ethnic group. Compared with whites, African Americans have a younger mean age at colorectal cancer diagnosis and a greater proportion have proximal cancers. Survival in African Americans with colorectal cancer is lower than in whites.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15184825"}, {"offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "African Americans have the greatest incidence of colorectal cancer than any other racial or ethnic group.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18300824"}, {"offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "African Americans have the greatest incidence of colorectal cancer than any other racial or ethnic group. This population's survival from colorectal cancer is lower than that in the White population.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18300824"}, {"offsetInBeginSection": 0, "offsetInEndSection": 454, "text": "African Americans have the greatest incidence of colorectal cancer than any other racial or ethnic group. This population's survival from colorectal cancer is lower than that in the White population. Increased incidence and mortality can be attributed to barriers such as lower screening rates, less use of diagnostic testing, decreased access to healthcare, cultural beliefs, and lack of education regarding healthcare practices and preventable disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18300824"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "African-Americans have higher incidence and mortality from colorectal cancer than non-African-Americans.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22791544"}, {"offsetInBeginSection": 0, "offsetInEndSection": 39, "text": "Colorectal cancer in African Americans.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15184825"}, {"offsetInBeginSection": 0, "offsetInEndSection": 39, "text": "Colorectal cancer in African Americans.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15743345"}, {"offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Colorectal cancer in African Americans has an increased incidence and mortality relative to Whites.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15743345"}, {"offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "The occurrence of colorectal cancer (CRC) shows a large disparity among recognized races and ethnicities in the U.S., with Black Americans demonstrating the highest incidence and mortality from this disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34148614"}, {"offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Racial and ethnic disparities in colorectal cancer incidence and mortality.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34148614"}, {"offsetInBeginSection": 1012, "offsetInEndSection": 1335, "text": "increase from 2002 to 2007. In 2016, CRC incidence was higher among Blacks (42.5 per 100,000) than Whites (38.0), Latinos (31.7) and Asians (30.0). In 2016, Blacks had higher mortality rates (17.9), than Whites (15.2), Latinos (10.4) and Asians (8.8). In 2016, colonoscopy rates among Blacks were 72.2%, Latinos 71.1%, Whit", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34193094"}, {"offsetInBeginSection": 118, "offsetInEndSection": 323, "text": "In the US, CRC incidence and mortality differ among racial/ethnic groups, with non-Hispanic Blacks (NHB) and American Indian/Alaska Natives showing highest incidence and mortality and earlier presentation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35936740"}, {"offsetInBeginSection": 948, "offsetInEndSection": 1040, "text": "100,000 persons/year (age 30-39). CRC incidence was significantly higher in African American", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31701261"}, {"offsetInBeginSection": 410, "offsetInEndSection": 554, "text": "Age-adjusted incidence rates for men with colorectal cancer are highest for Alaskan native men, followed by Japanese, then African-American men.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10826010"}, {"offsetInBeginSection": 99, "offsetInEndSection": 219, "text": "There are significant differences in CRC incidence and mortality by race with the highest burden occurring among blacks.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24574761"}, {"offsetInBeginSection": 0, "offsetInEndSection": 604, "text": "BACKGROUND & AIMS: Increasing rates of young-onset colorectal cancer (CRC) have attracted substantial research and media attention, but we know little about racial disparities among younger adults with CRC. We examined racial disparities in young-onset CRC by comparing CRC incidence and relative survival among younger (<50-year-old) adults in 2 time periods.METHODS: Using data from the Surveillance, Epidemiology, and End Results program of cancer registries, we estimated CRC incidence rates (per 100,000 persons 20-49 years old) from 1992 through 2014 for different periods (1992-1996 vs 2010-2014) ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30521807"}, {"offsetInBeginSection": 165, "offsetInEndSection": 867, "text": "Racial and ethnic disparities in incidence, mortality and survival rates, and trends exist for this disease. Differences in colorectal cancer screening, early detection, and treatment in minority communities are related to therapeutic outcomes. Age-adjusted incidence rates for men with colorectal cancer are highest for Alaskan native men, followed by Japanese, then African-American men. For women, the incidence is highest for Alaskan native women, followed by African-American, then Japanese women. Mortality rates in men are highest for African Americans, followed by Alaskan natives and then Hawaiians. In women, mortality rates are highest for Alaskan natives, then African Americans and whites.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10826010"}, {"offsetInBeginSection": 0, "offsetInEndSection": 886, "text": "Worldwide, colorectal carcinoma (CRC) varies by race-ethnicity. The highest incidence occurs in whites of European descent. Rates in blacks of South Africa are much lower, but rise with migration to westernized countries, i.e. African Americans (blacks) in the US. In the US, CRC age-specific incidence rates increased dramatically with biologic aging for black and white men and women. For all ages, rates were slightly higher for black than for whites. Among whites, overall annual rates peaked in the 1980s then declined. Stage- and subsite-specific rate shifts suggested earlier detection of cancers through screening, particularly in the distal colon. Blacks have not experienced the same stage- and subsite temporal shifts, which were observed in whites. CRC racial differences have been attributed to biologic and/or non-biologic factors as well as to routine screening patterns.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12716038"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1346, "text": "Colorectal cancer (CRC) is one of the most common malignancies in the United States. Every 3 years, the American Cancer Society provides an update of CRC incidence, survival, and mortality rates and trends. Incidence data through 2013 were provided by the Surveillance, Epidemiology, and End Results program, the National Program of Cancer Registries, and the North American Association of Central Cancer Registries. Mortality data through 2014 were provided by the National Center for Health Statistics. CRC incidence rates are highest in Alaska Natives and blacks and lowest in Asian/Pacific Islanders, and they are 30% to 40% higher in men than in women. Recent temporal patterns are generally similar by race and sex, but differ by age. Between 2000 and 2013, incidence rates in adults aged \u226550 years declined by 32%, with the drop largest for distal tumors in people aged \u226565 years (incidence rate ratio [IRR], 0.50; 95% confidence interval [95% CI], 0.48-0.52) and smallest for rectal tumors in ages 50 to 64 years (male IRR, 0.91; 95% CI, 0.85-0.96; female IRR, 1.00; 95% CI, 0.93-1.08). Overall CRC incidence in individuals ages \u226550 years declined from 2009 to 2013 in every state except Arkansas, with the decrease exceeding 5% annually in 7 states; however, rectal tumor incidence in those ages 50 to 64 years was stable in most states.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28248415"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1850, "text": "BACKGROUND: Although colorectal cancer rates are low among most groups of Native Americans in North America, rates for Alaska Natives have been substantially elevated compared with US rates for all races combined.METHODS: To better describe the epidemiology of colorectal cancer incidence and survival among Alaska Natives, stratified by gender and tribal/ethnic affiliation, we examined data collected by the Alaska Native Cancer Registry 1969-1993. We calculated age-adjusted and age-specific incidence as well as actuarial survival rates, and examined histological type, site, stage at diagnosis, and treatment. We compared these data to colorectal cancer data from whites living in western Washington.RESULTS: In all, 587 colorectal cancer cases were identified among Alaska Natives over the 25-year period, for an age-adjusted annual incidence rate of 71.4/100000 in women, and 69.3/100000 in men. Compared to Alaska Indians, colon cancer rates were significantly higher in Aleuts (relative risk [RR] = 1.6, 95% CI: 1.2-2.2) and in Eskimos (RR = 1.5, 95% CI: 1.2-1.8), while rectal cancer rates did not differ by race/ethnicity. Alaska Natives experienced a 50% higher incidence rate of colorectal cancer overall compared to western Washington whites (RR = 1.5, 95% CI: 1.3-1.6), although rectal cancer rates were similar in the two populations. The highest RR were seen among Alaska Native women; Aleuts and Eskimos had colon cancer rates more than twice that of western Washington white women. No unusual qualitative features were found in the cancers occurring in Alaska Natives. Actuarial colorectal cancer survival rates for Alaska Natives overall were 74% at one year and 42% at 5 years; these rates were very similar to those observed for the western Washington population. Both one and 5-year survival rates showed a significant trend to", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9698125"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1918, "text": "OBJECTIVE: National and state data document racial differences in colorectal cancer (CRC) mortality and incidence. Screening for CRC reduces cancer incidence and deaths. Racial differences in colorectal cancer screening behavior may contribute to the racial disparity in incidence and mortality. The purpose of this study was to determine if colorectal cancer screening rates are different between blacks and whites while controlling for potential confounders.STUDY DESIGN: Cross-sectional survey. DATA SOURCE(S)/STUDY SETTING: We used data from the North Carolina Colon Cancer Study, a population-based case-control study conducted in 33 counties of North Carolina. We analyzed data from 598 control subjects who were eligible for colorectal cancer screening.METHODS: Trained nurses conducted face-to-face interviews from October 1996 through October 2000.RESULTS: Overall, 50% of the respondents were compliant with CRC screening guidelines. In the multivariable logistic regression model having a regular doctor and participation in a general medical exam were significantly associated with current screening status with odds ratios (OR) (95% confidence interval (CI)) of 3.8 (1.7-8.3) and 3.7 (2.1-6.7), respectively. Older age was a significant predictor of current screening status with an OR (95% CI) of 2.9 (1.7-4.8) for those 60-69 compared to respondents 50-59 and OR 3.2 (1.9-5.5) for those 70 and older compared to respondents 50-59. After adjusting for age, having a regular doctor and participation in general medical exams, race was not significantly associated with current CRC screening status, with an OR of 1.1 (95% CI 0.7-1.6).CONCLUSION: CRC screening rates in North Carolina were low. Race was not a significant determinant of screening behavior and therefore does not explain the racial disparity in incidence or survival. Older age, having a regular doctor and participating in general medical ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15052704"}, {"offsetInBeginSection": 0, "offsetInEndSection": 737, "text": "BACKGROUND AND AIMS: Colorectal cancer screening beginning at age 50 is recommended for all Americans considered at average risk for the development of colorectal cancer regardless of gender or race/ethnicity. We determined the influence of gender and race/ethnicity on the cost-effectiveness of recommended colorectal cancer screening regimens.METHODS: We determined age-specific colorectal cancer incidence rates; the proportion of left-sided cancers; and the proportion of localized cancers in Asian, black, Latino and white men and women using the California Cancer Registry. We incorporated these data and available data for life expectancy and colorectal cancer survival to model the cost-effectiveness of two 35-year colorectal ca", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16532978"}, {"offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "African Americans have the highest incidence and mortality rates of colorectal cancer (CRC) of any ethnic group in the United States.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29128568"}, {"offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Black Americans have the highest colorectal cancer incidence and mortality rates of any U.S.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36047055"}, {"offsetInBeginSection": 1069, "offsetInEndSection": 1313, "text": "Although non-Hispanic Black service members have historically had the highest incidence of colorectal cancer within the U.S. military, this study observed similar rates of colorectal cancer for all races and ethnicities after adjusting for age.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37963221"}, {"offsetInBeginSection": 713, "offsetInEndSection": 1313, "text": "Age-adjusted colorectal cancer rates were similar for males and females (4.46 and 4.33 cases per 100,000 person-years, respectively) and rates were relatively similar by service as well as race and ethnicity. This finding could be attributed to the small number of cases in this study due to better screening practices in the Military Health System (MHS). Although non-Hispanic Black service members have historically had the highest incidence of colorectal cancer within the U.S. military, this study observed similar rates of colorectal cancer for all races and ethnicities after adjusting for age.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37963221"}, {"offsetInBeginSection": 0, "offsetInEndSection": 514, "text": "BACKGROUND: Cancers of the colon and rectum are the third most common malignancy among males and females in the United States, although incidence and mortality have declined in recent years. We evaluated recent trends in colorectal cancer incidence in the United States by subsite and stage at diagnosis.METHODS: Data for this analysis included all cases of colorectal cancer diagnosed between 1992 and 2001 and reported to the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16835912"}, {"offsetInBeginSection": 922, "offsetInEndSection": 1555, "text": "This finding could be attributed to the small number of cases in this study due to better screening practices in the Military Health System (MHS). Although non-Hispanic Black service members have historically had the highest incidence of colorectal cancer within the U.S. military, this study observed similar rates of colorectal cancer for all races and ethnicities after adjusting for age. Incident rates of colorectal cancer within the U.S. military increase monotonically with age, with service members over the age of 45 with the highest incidence, re-enforcing the need to promote wellness screening among military populations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37963221"}, {"offsetInBeginSection": 1069, "offsetInEndSection": 1668, "text": "Although non-Hispanic Black service members have historically had the highest incidence of colorectal cancer within the U.S. military, this study observed similar rates of colorectal cancer for all races and ethnicities after adjusting for age. Incident rates of colorectal cancer within the U.S. military increase monotonically with age, with service members over the age of 45 with the highest incidence, re-enforcing the need to promote wellness screening among military populations. The importance of the DHA guideline changes that decreased colorectal screenings to age 45 years is significant.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37963221"}, {"offsetInBeginSection": 770, "offsetInEndSection": 1169, "text": "LTS: Age-specific colorectal cancer incidence rates were highest in black men and lowest in Latino women. Screening beginning at age 50 was most cost-effective in black men and least cost-effective in Latino women (measured as dollars spent per year of life saved) using annual fecal occult blood testing combined with flexible sigmoidoscopy every five years and using colonoscopy every 10 years. Th", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16532978"}, {"offsetInBeginSection": 347, "offsetInEndSection": 876, "text": "THODS: We determined age-specific colorectal cancer incidence rates; the proportion of left-sided cancers; and the proportion of localized cancers in Asian, black, Latino and white men and women using the California Cancer Registry. We incorporated these data and available data for life expectancy and colorectal cancer survival to model the cost-effectiveness of two 35-year colorectal cancer-screening interventions.RESULTS: Age-specific colorectal cancer incidence rates were highest in black men and lowest in Latino women. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16532978"}, {"offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "Colorectal cancer (CRC) is the second most common cancer among African American women and the third most common cancer for African American men. The mortality rate from CRC is highest among African Americans compared to any other racial or ethnic group.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26703651"}, {"offsetInBeginSection": 522, "offsetInEndSection": 824, "text": "In American blacks, there is evidence for a higher prevalence of right-sided colonic tumors and an earlier age of onset of colorectal cancer. In addition, blacks have the highest colon cancer incidence in the United States among ethnic groups and have poorer 5-year survival rates compared with whites.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10826011"}, {"offsetInBeginSection": 1012, "offsetInEndSection": 1131, "text": "increase from 2002 to 2007. In 2016, CRC incidence was higher among Blacks (42.5 per 100,000) than Whites (38.0), Latin", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34193094"}]}
+{"question_id": "662cfd21187cba990d000009", "question": "LRP6 is a member of what  superfamily of cell-surface receptors?", "answer": "LRP6 is a member of the low-density lipoprotein receptor superfamily of cell-surface receptors", "relevant_passage_ids": ["35052459", "16390319", "16263759", "20543981", "31679626", "26046396", "9704021", "15516984", "17326769", "22615920", "32661084", "34026761", "34490514", "28966723", "29312635", "15064719", "30038821"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "LRP6 is a member of the low-density lipoprotein receptor superfamily of cell-surface receptors. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35052459"}, {"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "LRP5, along with LRP6 and their Drosophila homolog, Arrow, constitute a novel subclass of the LDL receptor superfamily.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16390319"}, {"offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "LRP6 is a member of the low-density lipoprotein receptor superfamily of cell-surface receptors", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35052459"}, {"offsetInBeginSection": 12, "offsetInEndSection": 204, "text": "LGR6 (leucine-rich repeat containing, G protein-coupled receptor 6) is a member of the rhodopsin-like seven transmembrane domain receptor superfamily with the highest homology to LGR4 and LGR5", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22615920"}, {"offsetInBeginSection": 0, "offsetInEndSection": 623, "text": "LRP6 is a member of the low-density lipoprotein receptor superfamily of cell-surface receptors. It is required for the activation of the Wnt/\u03b2-catenin signalling pathway. LRP6 is detected in different tissue types and is involved in numerous biological activities such as cell proliferation, specification, metastatic cancer, and embryonic development. LRP6 is essential for the proper development of different organs in vertebrates, such as Xenopus laevis, chickens, and mice. In human, LRP6 overexpression and mutations have been reported in multiple complex diseases including hypertension, atherosclerosis, and cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35052459"}, {"offsetInBeginSection": 760, "offsetInEndSection": 1392, "text": "Although the low-density-lipoprotein-receptor-related-protein (LRP) family is best known for its role in binding and endocytosis of lipoproteins, specific members appear to have additional roles in cellular communication. Indeed, for WNT/\u03b2-catenin signalling one apparently universal requirement is the presence of either LRP5 or LRP6 in combination with one of the ten Frizzled (FZD) WNT receptors (FZD1-10). In the 20\u00a0years since their discovery as WNT/FZD co-receptors, research on the LRP family has contributed greatly to our understanding of WNT signalling and LRPs have emerged as central players in WNT/\u03b2-catenin signalling.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34490514"}, {"offsetInBeginSection": 0, "offsetInEndSection": 817, "text": "The LOW-density lipoprotein related protein 6 (LRP6) receptor is an important effector of canonical Wnt signaling, a developmental pathway, whose dysregulation has been implicated in various diseases including cancer. The membrane proximal low-density lipoprotein (LDL) receptor repeats in LRP6 exhibit homology to ligand binding repeats in the LDL receptor (LDLR), but lack known function. We generated single amino acid substitutions of LRP6-LDLR repeat residues, which are highly conserved in the human LDLR and mutated in patients with Familial Hypercholesteremia (FH). These substitutions negatively impacted LRP6 internalization and activation of Wnt signaling. By mass spectrometry, we observed that the Itch E3 ubiquitin ligase associated with and ubiquitinated wild type LRP6 but not the LDLR repeat mutants.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28966723"}, {"offsetInBeginSection": 154, "offsetInEndSection": 840, "text": "In vertebrates, low density lipoprotein receptor-related proteins 5 and 6 (LRP5 and LRP6), the single-pass transmembrane proteins, act as coreceptors of Wnt ligands and are indispensable for Wnt signal transduction. LRP5 and LRP6 are highly homologous and widely co-expressed in embryonic and adult tissues, and they share similar function in mediating Wnt signaling. However, they also exhibit distinct characteristics by interacting with different protein partners. As such, each of them possesses its own unique functions. In this review, we systematically discuss the similarity and divergence of LRP5 and LRP6 in mediating Wnt and other signaling in the context of kidney diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34026761"}, {"offsetInBeginSection": 0, "offsetInEndSection": 744, "text": "Low density lipoprotein (LDL) receptor-related protein-6 (LRP6) is an important co-receptor of Wnt pathway, which plays a predominant role in development and progression of colorectal cancer. Recently, dysregulation of LRP6 has proved to be involved in the progression of cancers, but its biological role and clinical significance in colorectal cancer remain unclear. In present study, we revealed that phosphorylation of LRP6 was aberrantly upregulated in colorectal carcinoma correlating with TNM or Dukes staging and worse prognosis. In addition, phosphorylated LRP6 was positively correlated with nuclear accumulation of \u03b2-catenin. Overexpression or activation of LRP6 could activate Wnt signaling and promote tumor cell migration in vitro.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29312635"}, {"offsetInBeginSection": 72, "offsetInEndSection": 983, "text": "Internalization of the low-density lipoprotein receptor-related protein 6 (LRP6) receptor complex can either promote or attenuate canonical WNT signaling, depending on the employed internalization pathway. Detailed analysis of the mechanism of LRP6 internalization and its temporal regulation is crucial for understanding the different cellular responses to WNT stimulation under varying conditions and in various cell types. Here, we elucidate the mechanisms involved in the internalization of LRP6 and re-evaluate existing, partly contradicting, theories on the regulation of LRP6 receptor internalization. We utilize a computational approach that aims at finding a set of mechanisms that accounts for the temporal dynamics of LRP6 receptor internalization upon WNT stimulation. Starting with a simple simulation model, we successively extend and probe the model's behavior based on quantitative measurements.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32661084"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "LRP6 is a member of the low-density lipoprotein receptor superfamily of cell-surface receptors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35052459"}, {"offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "LRP6 is a member of the low-density lipoprotein receptor superfamily of cell-surface receptors. It is required for the activation of the Wnt/\u03b2-catenin signalling pathway.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35052459"}, {"offsetInBeginSection": 0, "offsetInEndSection": 352, "text": "LRP6 is a member of the low-density lipoprotein receptor superfamily of cell-surface receptors. It is required for the activation of the Wnt/\u03b2-catenin signalling pathway. LRP6 is detected in different tissue types and is involved in numerous biological activities such as cell proliferation, specification, metastatic cancer, and embryonic development.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35052459"}, {"offsetInBeginSection": 137, "offsetInEndSection": 415, "text": "Lipoprotein receptor-related protein 6 (LRP6) is a member of the low-density lipoprotein receptor (LDLR) family composed of structurally related cell surface receptors and acts, in consort with Frizzled receptors, as a coreceptor to mediate the Wnt/\u03b2-catenin signalling pathway.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31679626"}, {"offsetInBeginSection": 137, "offsetInEndSection": 575, "text": "Lipoprotein receptor-related protein 6 (LRP6) is a member of the low-density lipoprotein receptor (LDLR) family composed of structurally related cell surface receptors and acts, in consort with Frizzled receptors, as a coreceptor to mediate the Wnt/\u03b2-catenin signalling pathway. Impaired LRP6 signalling in humans has been associated with multiple cardiovascular risk factors such as elevated serum LDL, triglycerides, and glucose levels.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31679626"}, {"offsetInBeginSection": 137, "offsetInEndSection": 829, "text": "Lipoprotein receptor-related protein 6 (LRP6) is a member of the low-density lipoprotein receptor (LDLR) family composed of structurally related cell surface receptors and acts, in consort with Frizzled receptors, as a coreceptor to mediate the Wnt/\u03b2-catenin signalling pathway. Impaired LRP6 signalling in humans has been associated with multiple cardiovascular risk factors such as elevated serum LDL, triglycerides, and glucose levels. Considerable efforts have been deployed to better understand the underlying mechanisms of LRP6-associated disorders, and the therapeutic targeting of LRP6 has been demonstrated to have positive effects in various animal models of cardiovascular disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31679626"}, {"offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "BACKGROUND: The low density lipoprotein receptor-related protein-6 (LRP6) is an essential co-receptor for canonical Wnt signaling", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20543981"}, {"offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "BACKGROUND: The low density lipoprotein receptor-related protein-6 (LRP6) is an essential co-receptor for canonical Wnt signaling. Dickkopf 1 (Dkk1), a major secreted Wnt signaling antagonist, binds to LRP6 with high affinity and prevents the Frizzled-Wnt-LRP6 complex formation in response to Wnts", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20543981"}, {"offsetInBeginSection": 0, "offsetInEndSection": 460, "text": "BACKGROUND: The low density lipoprotein receptor-related protein-6 (LRP6) is an essential co-receptor for canonical Wnt signaling. Dickkopf 1 (Dkk1), a major secreted Wnt signaling antagonist, binds to LRP6 with high affinity and prevents the Frizzled-Wnt-LRP6 complex formation in response to Wnts. Previous studies have demonstrated that Dkk1 promotes LRP6 internalization and degradation when it forms a ternary complex with the cell surface receptor Kremen", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20543981"}, {"offsetInBeginSection": 0, "offsetInEndSection": 406, "text": "A novel member of the low density lipoprotein receptor (LDLR) gene family has been identified and characterized. This gene, termed LDL receptor-related protein 6 (LRP6), encodes a transmembrane protein which has 71% identity and is structurally similar to the protein encoded by LRP5, a proposed candidate gene for type 1 diabetes located on human chromosome 11q13. LRP6 maps to human chromosome 12p11-p13.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9704021"}, {"offsetInBeginSection": 83, "offsetInEndSection": 277, "text": "The low-density lipoprotein (LDL) receptor-related protein-6 (LRP6), a novel member of the expanding LDL receptor family, functions as an indispensable co-receptor for the Wnt signaling pathway.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15516984"}, {"offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Low-density lipoprotein receptor-related protein 6 (LRP6) is a member of low-density lipoprotein receptor (LDLR) family which cooperates with Frizzled receptors to transduce the canonical Wnt signal.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17326769"}, {"offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Wnt co-receptors LRP5 and LRP6 are two members of the low-density lipoprotein receptor family.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16263759"}, {"offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "LRP6 Receptor Plays Essential Functions in Development and Human Diseases.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35052459"}, {"offsetInBeginSection": 171, "offsetInEndSection": 352, "text": "LRP6 is detected in different tissue types and is involved in numerous biological activities such as cell proliferation, specification, metastatic cancer, and embryonic development.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35052459"}, {"offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Isolation and characterization of LRP6, a novel member of the low density lipoprotein receptor gene family.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9704021"}, {"offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "BACKGROUND: LGR6 (leucine-rich repeat containing, G protein-coupled receptor 6) is a member of the rhodopsin-like seven transmembrane domain receptor superfamily with the highest homology to LG", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22615920"}, {"offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Low-density lipoprotein receptor-related protein 6 (LRP6) is a member of the low-density lipoprotein receptor family", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26046396"}, {"offsetInBeginSection": 17, "offsetInEndSection": 94, "text": "LRP5 and LRP6 are two members of the low-density lipoprotein receptor family.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16263759"}, {"offsetInBeginSection": 137, "offsetInEndSection": 908, "text": "Lipoprotein receptor-related protein 6 (LRP6) is a member of the low-density lipoprotein receptor (LDLR) family composed of structurally related cell surface receptors and acts, in consort with Frizzled receptors, as a coreceptor to mediate the Wnt/\u03b2-catenin signalling pathway. Impaired LRP6 signalling in humans has been associated with multiple cardiovascular risk factors such as elevated serum LDL, triglycerides, and glucose levels. Considerable efforts have been deployed to better understand the underlying mechanisms of LRP6-associated disorders, and the therapeutic targeting of LRP6 has been demonstrated to have positive effects in various animal models of cardiovascular disease. This review presents a synthetic summary highlighting the major roles of LRP6.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31679626"}, {"offsetInBeginSection": 0, "offsetInEndSection": 873, "text": "Wnt co-receptors LRP5 and LRP6 are two members of the low-density lipoprotein receptor family. Receptor-associated protein is not only a specialized chaperone but also a universal antagonist for members of the low-density lipoprotein receptor family. Here we test whether Mesd, a newly identified chaperone for members of the low-density lipoprotein receptor family, also binds to mature receptors at the cell surface and antagonizes ligand binding. We found that Mesd binds to cell surface LRP5 and LRP6, but not to other members of the low-density lipoprotein receptor family. Scatchard analysis revealed that Mesd binds cell surface LRP6 with high affinity (K(d) approximately 3.3 nM). Interestingly, the C-terminal region of Mesd, which is absent in sequences from invertebrates, is necessary and sufficient for binding to mature LRP6, and is required for LRP6 folding.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16263759"}, {"offsetInBeginSection": 0, "offsetInEndSection": 521, "text": "LRP5, along with LRP6 and their Drosophila homolog, Arrow, constitute a novel subclass of the LDL receptor superfamily. The arrangement of structural motifs in these receptors is different from the other members of the superfamily, and only recently have we begun to understand the functional importance of human LRP5 (and LRP6). Whole genome positional cloning studies have identified a number of mutations in LRP5 that underlie inherited human diseases/phenotypes, particularly those involving the skeleton and the eye.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16390319"}, {"offsetInBeginSection": 83, "offsetInEndSection": 520, "text": "The low-density lipoprotein (LDL) receptor-related protein-6 (LRP6), a novel member of the expanding LDL receptor family, functions as an indispensable co-receptor for the Wnt signaling pathway. Although the role of LRP6 in embryonic development is now well established, its role in tumorigenesis is unclear. We report that LRP6 is readily expressed at the transcript level in several human cancer cell lines and human malignant tissues.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15516984"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1489, "text": "BACKGROUND: LGR6 (leucine-rich repeat containing, G protein-coupled receptor 6) is a member of the rhodopsin-like seven transmembrane domain receptor superfamily with the highest homology to LGR4 and LGR5. LGR6 was found as one of the novel genes mutated in colon cancer through total exon sequencing and its promoter region is hypermethylated in 20-50% of colon cancer cases. In the skin, LGR6 marks a population of stem cells that can give rise to all cell lineages. Recently, we and others demonstrated that LGR4 and LGR5 function as receptors of R-spondins to potentiate Wnt/\u03b2-catenin signaling. However, the binding affinity and functional response of LGR6 to R-spondins, and the activity of colon cancer mutants of LGR6 have not been determined.PRINCIPAL FINDINGS: We found that LGR6 also binds and responds to R-spondins 1-3 with high affinity to enhance Wnt/\u03b2-catenin signaling through increased LRP6 phosphorylation. Similar to LGR4 and LGR5, LGR6 is not coupled to heterotrimeric G proteins or to \u03b2-arrestin following R-spondin stimulation. Functional and expression analysis of three somatic mutations identified in colon cancer samples indicates that one mutant fails to bind and respond to R-spondin (loss-of-function), but the other two have no significant effect on receptor function. Overexpression of wild-type LGR6 in HeLa cells leads to increased cell migration following co-treatment with R-spondin1 and Wnt3a when compared to vector control cells or cells overexpressi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22615920"}, {"offsetInBeginSection": 196, "offsetInEndSection": 1078, "text": "The identification of both Frizzled and LRP5/6 (LRP: low-density lipoprotein receptor-related protein) proteins as components of cell-surface receptors for Wnt proteins has raised questions about their individual functions. We have investigated this issue through a structure-function analysis of Frizzled and LRP proteins that have been implicated in Wnt1 signaling. Consistent with other reports, we find that LRP6/Arrow proteins deleted for their extracellular domain are able to activate the Wnt/beta-catenin signaling pathway. Importantly, our results demonstrate that this signaling from LRP6/Arrow derivatives can occur in a Frizzled- and ligand-independent manner. Furthermore, we show that the PPSP motifs within the intracellular domain of LRP6 are required for signaling. In contrast to results with LRP6, overexpression of Frizzled proteins did not activate the pathway.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15064719"}, {"offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "The LOW-density lipoprotein related protein 6 (LRP6) receptor is an important effector of canonical Wnt signaling, a developmental pathway, whose dysregulation has been implicated in various diseases including cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28966723"}, {"offsetInBeginSection": 154, "offsetInEndSection": 369, "text": "In vertebrates, low density lipoprotein receptor-related proteins 5 and 6 (LRP5 and LRP6), the single-pass transmembrane proteins, act as coreceptors of Wnt ligands and are indispensable for Wnt signal transduction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34026761"}, {"offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Low density lipoprotein (LDL) receptor-related protein-6 (LRP6) is an important co-receptor of Wnt pathway, which plays a predominant role in development and progression of colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29312635"}, {"offsetInBeginSection": 0, "offsetInEndSection": 415, "text": "Coronary artery disease (CAD), often related to dyslipidemia, is a major cause of death worldwide, highlighting unmet therapeutic needs. Lipoprotein receptor-related protein 6 (LRP6) is a member of the low-density lipoprotein receptor (LDLR) family composed of structurally related cell surface receptors and acts, in consort with Frizzled receptors, as a coreceptor to mediate the Wnt/\u03b2-catenin signalling pathway.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31679626"}, {"offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "Low-density lipoprotein receptor-related protein 6 (LRP6) is a co-receptor for Wnt signaling and can be recruited by multiple growth factors/hormones to their receptors facilitating intracellular signaling activation. The ligands that bind directly to LRP6 have not been identified.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30038821"}, {"offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Low-density lipoprotein receptor-related protein 6 (LRP6) is a co-receptor for Wnt signaling and can be recruited by multiple growth factors/hormones to their receptors facilitating intracellular signaling activation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30038821"}, {"offsetInBeginSection": 0, "offsetInEndSection": 406, "text": "Low-density lipoprotein receptor-related protein 6 (LRP6) is a co-receptor for Wnt signaling and can be recruited by multiple growth factors/hormones to their receptors facilitating intracellular signaling activation. The ligands that bind directly to LRP6 have not been identified. Here, we report that bioactive oxidized phospholipids (oxPLs) are native ligands of LRP6, but not the closely related LRP5.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30038821"}, {"offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "BACKGROUND: LGR6 (leucine-rich repeat containing, G protein-coupled receptor 6) is a member of the rhodopsin-like seven transmembrane domain receptor superfamily with the highest homology to LGR4 and LGR5.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22615920"}, {"offsetInBeginSection": 137, "offsetInEndSection": 304, "text": "Lipoprotein receptor-related protein 6 (LRP6) is a member of the low-density lipoprotein receptor (LDLR) family composed of structurally related cell surface receptors", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31679626"}]}
+{"question_id": "661686e4fdcbea915f000052", "question": "List of major risks of intrauterine device.", "answer": "Risks of using IDU for contraception are unwanted pregnancy, anemia, heavy bleeding, infection, PID, perforation, IUD expulsion, and deleterious effect on vaginal microbial environment.", "relevant_passage_ids": ["36717556", "27771475"], "type": "list", "snippets": [{"offsetInBeginSection": 1056, "offsetInEndSection": 1225, "text": "Total bacterial loads of women using Cu-IUD increase 5.5 fold after six months, predominantly driven by increases in the concentrations of several inflammatory anaerobes", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36717556"}, {"offsetInBeginSection": 1375, "offsetInEndSection": 1509, "text": "deleterious effects on the vaginal environment induced by Cu-IUD initiation, which may adversely impact sexual and reproductive health", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36717556"}, {"offsetInBeginSection": 476, "offsetInEndSection": 485, "text": "pregnancy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27771475"}, {"offsetInBeginSection": 487, "offsetInEndSection": 496, "text": "infection", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27771475"}, {"offsetInBeginSection": 320, "offsetInEndSection": 333, "text": "IUD expulsion", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27771475"}, {"offsetInBeginSection": 338, "offsetInEndSection": 349, "text": "perforation", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27771475"}, {"offsetInBeginSection": 498, "offsetInEndSection": 525, "text": "pelvic inflammatory disease", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27771475"}, {"offsetInBeginSection": 537, "offsetInEndSection": 551, "text": "heavy bleeding", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27771475"}, {"offsetInBeginSection": 555, "offsetInEndSection": 561, "text": "anemia", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27771475"}]}
+{"question_id": "66301e04187cba990d000027", "question": "What are episignatures?", "answer": "Episignatures are unique genomic DNA methylation patterns that can be used for diagnostic testing and as disease biomarkers in genetic syndromes.", "relevant_passage_ids": ["36572586"], "type": "factoid", "snippets": [{"offsetInBeginSection": 548, "offsetInEndSection": 744, "text": "A growing number of genetic syndromes have been associated with unique genomic DNA methylation patterns (called \"episignatures\") that can be used for diagnostic testing and as disease biomarkers. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36572586"}]}
+{"question_id": "66215690b9f8b89d7e00000a", "question": "Is chemotherapy an effective treatment for patients with advance colorectal cancer and poor performance status (ECOG/PS >1)", "answer": "Treatment with chemotherapy was associated with longer median overall survival across Performance Status (PS) groups. Exploratory analysis based on comorbidity score and tumor burden subgroups demonstrated a consistently positive overall survival association with treatment. Benefit was observed where poor overall survival was attributable to medical comorbidities and to tumor burden. Chemotherapy might benefit selected metastatic colorectal cancer (mCRC) patients with poor PS. With up-front dose reduction and close monitoring for toxicity, the risk of serious adverse events is minimized.", "relevant_passage_ids": ["32919889", "25442812", "31987521", "37336705", "32999176", "31060020", "15456953", "31732876", "37754536", "37668815", "30281700", "20016228", "37966630", "36630020", "34761596", "37133585", "32369650", "12667306", "21347194", "33068283", "37950903", "20100144"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1186, "offsetInEndSection": 1551, "text": " Treatment with chemotherapy was associated with longer median overall survival across PS groups. Exploratory analysis based on comorbidity score and tumor burden subgroups demonstrated a consistently positive overall survival association with treatment. Benefit was observed where poor overall survival was attributable to medical comorbidities and to tumor burden", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32919889"}, {"offsetInBeginSection": 2461, "offsetInEndSection": 2849, "text": "Our data indicate that relatively fit elderly patients with advanced cancer safely tolerate modern chemotherapy and enjoy disease control in a manner comparable to younger patients. Our GAP score, if further validated, offers promise for geriatric application in combination to comprehensive geriatric assessment tools for the optimisation of palliative therapy on an individualised basis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18243010"}, {"offsetInBeginSection": 1730, "offsetInEndSection": 1944, "text": "Our retrospective study suggests that chemotherapy might benefit selected mCRC patients with poor PS. With up-front dose reduction and close monitoring for toxicity, the risk of serious adverse events is minimized.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25442812"}, {"offsetInBeginSection": 1166, "offsetInEndSection": 1299, "text": "The two groups were statistically comparable in terms of sex, Eastern Cooperative Oncology Group Performance Status (ECOG PS) and TNM", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37754536"}, {"offsetInBeginSection": 12, "offsetInEndSection": 147, "text": "Data regarding treatment sequence for vulnerable patients with metastatic colorectal cancer (mCRC) in a real-world setting are lacking.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37668815"}, {"offsetInBeginSection": 127, "offsetInEndSection": 1303, "text": "While the evidence guiding cancer-directed treatment of this disease comes from phase III trials that have mostly enrolled patients with good performance status, some patients present with poor clinical conditions. The best treatment for these patients remains to be determined. We performed a systematic review of the treatment outcomes of patients with metastatic colorectal cancer and poor performance status, defined as Eastern Cooperative Oncology Group performance status \u22652. Eligible articles were prospective or retrospective studies or case reports published in English, Portuguese or Spanish. We searched PubMed, EMBASE, LILACS and the Cochrane Library from onset until October 2017 using specific keywords for each search. We found a total of 18 publications, mostly case reports and retrospective studies (14 articles). One was an uncontrolled prospective trial, two were observational studies and one was an individual patient meta-analysis. Although some studies suggested benefits in terms of symptomatic response with standard chemotherapy, with good safety profiles when dose-reduced regimens were administered, a true survival gain could not be demonstrated.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30281700"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1387, "text": "INTRODUCTION: Colorectal cancer is the second most common cancer in both genders and often presents as a metastatic, unresectable, or recurrent disease in early follow-up. It is uncertain the benefit of oxaliplatin-based palliative chemotherapy (CT) in the first line of treatment in patients with compromised performance status (PS), Eastern Cooperative Oncology Group (ECOG) 3 and 4. These patients are systematically excluded from clinical trials but may be treated in clinical practice.METHODS: We conducted a prospective observational cohort whose primary outcome was improving at least 2 points in the worst symptom in the Edmonton Symptom Assessment System Scale (ESAS-r), without grade 3 to 4 toxicity, comparing baseline and fourth week of treatment. Secondary endpoints included quality of life using the European Quality of Life-5 dimensions questionnaire, toxicity, response rate, clinical improvement of ECOG PS, and overall survival (OS).RESULTS: We included 28 patients, and 12 (42.8%) achieved the primary endpoint. Median overall survival was 86 days, 46% of patients did not respond to the fourth-week reevaluation due to clinical deterioration, and 17.8% presented toxicity grade \u22653, with 5 patients dying from toxicity. In addition, ECOG PS 4 or cholestasis had poorer overall survival. Finally, 25% and 53.6% of patients received these treatments in the last 14 and ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37336705"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1412, "text": "INTRODUCTION: Chemotherapy is difficult to administer in patients with poor performance status (PS), advanced metastatic lesion, and unresectable colon cancer. We report herein our experience of a patient who showed complete response to chemotherapy and marked PS improvement. The patient presented with the following adverse factors poor PS, advanced progression of metastatic lesions, advanced unresectable colorectal cancer with severe stricture, and old age.PRESENTATION OF CASE: The patient was an 80-year-old male diagnosed with occlusive cancer of the descending colon with multiple metastases in the liver, Stage \u2163b (National Comprehensive Cancer Network guidelines version 2. 2018). A 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6)\u2009+\u2009panitumumab (Pmab) regimen was successfully administered and led to decreased tumor marker levels; oral intake also became possible. Additional examinations showed that the primary lesion and distant metastatic lesions had almost disappeared; the patient had achieved a near complete response (CR). Currently, 35 cycles of mFOLFOX6\uff0bPmab have been administered, and his near CR has been maintained for 32 months.DISCUSSION: Best supportive care (BSC) is the recommended option for elderly patients with advanced unresectable colon cancer. This is the first case in which an elderly patient with poor PS and advanced unresectable colorectal cancer was treated wit", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31060020"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1145, "text": "BACKGROUND: The management of metastatic colorectal cancer patients with a poor performance status (PS) continues to be a clinical dilemma, with the potential activity and safety of treating this population remaining poorly understood. Few of these patients are enrolled onto clinical trials, and poor PS is often multifactorial.PATIENTS AND METHODS: We analyzed the Treatment of Recurrent and Advanced Colorectal Cancer registry to describe treatment practices and outcomes in poor (Eastern Cooperative Oncology Group [ECOG] PS 2) and very poor PS (ECOG PS > 2) patients to explore the relationship between age, tumor burden, comorbidities, and PS, and to evaluate the benefit of systemic therapy. Standard descriptive statistical methods, Kaplan-Meier analysis, and a multivariate Cox regression model were used.RESULTS: Of 2769 registry patients (diagnosed January 2009 to June 2018), 329 (12%) and 182 (7%) patients had a poor and very poor PS, respectively. Good PS patients were more likely to receive systemic therapy than poor and very poor PS patients (85%, 55%, and 21.5%, P\u00a0< .0001), but clinician assessed response was observed in al", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32919889"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1904, "text": "BACKGROUND: Within the context of metastatic colorectal cancer, patients with Eastern Cooperative Oncology Group (ECOG) performance score 0-1 are usually pooled together in clinical practice guidelines and clinical trials' reports. The current study aims to delineate potential differences in outcomes between metastatic colorectal cancer patients with ECOG score 0 versus 1 who are treated with currently accepted first-line fluorouracil (5FU)-based chemotherapy.METHODS: The current study is based on a pooled dataset from five clinical trials of 5FU-based treatment for metastatic colorectal cancer (NCT00272051; NCT00115765; NCT00305188; NCT00364013; and NCT00384176). Patients with metastatic colorectal cancer and ECOG score of 0-1 were eligible for the current study. Multivariable logistic regression analysis was used to assess the relationship between ECOG performance status and the development of different toxicities. Kaplan-Meier survival estimates were used to clarify the impact of the ECOG score on overall and progression-free survivals. Multivariable Cox regression analysis was then used to evaluate the impact of ECOG score on overall and progression-free survivals.RESULTS: A total of 3143 patients were included in the current analysis. Within multivariable logistic regression analysis, patients with an ECOG score of 0 have a lower probability of serious adverse events (OR 0.678; 95% CI 0.583-0.788; P\u2009<\u20090.001), fatal adverse events (OR 0.552; 95% CI 0.397-0.766; P\u2009<\u20090.001), high-grade anemia (OR 0.426; 95% CI 0.252-0.721; P\u2009=\u20090.001), and high-grade nausea/vomiting (OR 0.697; 95% CI 0.509-0.955; P\u2009=\u20090.024). Through Kaplan-Meier survival analysis, patients with an ECOG score of 0 have better overall and progression-free survivals (P\u2009<\u20090.001 for both endpoints). Median overall survival was 27.63\u00a0months among patients with an ECOG score of 0 versus 20.00\u00a0months among patie", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31732876"}, {"offsetInBeginSection": 0, "offsetInEndSection": 620, "text": "BACKGROUND: The benefit of chemotherapy for patients with metastatic colorectal cancer has not been established.METHODS: We retrospectively evaluated the effectiveness of chemotherapy with capecitabine and bevacizumab for patients with a performance status (PS) of 3.RESULTS: Seven patients were included; median age was 82 years (range, 65-91 years). Response was not ascertained; however, the disease control rate was 83.3%. Median PFS and OS were 10.0 and 25.8 months, respectively. Hand-foot syndrome was the most common toxicity observed (3 patients; 42.9%). Grade 3 toxicity was observed in 1 patient with proteinu", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32999176"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1250, "text": "PURPOSE: In this study, we aimed to determine the factors which affect post-progression survival (PPS) and overall survival (OS) in patients with metastatic colorectal cancer.METHODS: 87 patients with metastatic colorectal cancer had been followed up with palliative care due to disease progression or ECOG performance status after receiving at least two cycles of chemotherapy. PPS was estimated as the time between the last progression date and last control or death date in patients who were followed up with palliative care.RESULTS: 87 patients with metastatic colorectal cancer were included in the study. Evaluation with multivariate analysis of factors affecting PPS revealed a significantly longer PPS (10.8 weeks) in patients with ECOG score 0 or 1 than the PPS of patients with ECOG score 2-5 (3 weeks) (p=0.01). It was also found that PPS was 14.4 weeks in patients with CEA levels <5ng/ml,while it was 6.7 weeks in patients with CEA levels \u22655 ng/ml (p=0.001) and PPS was 13.7 weeks in patients with controlled disease after first-line chemotherapy while it was 8 weeks in patients with progression (p=0.03); both were statistically significant. No significant association was found between PPS and age, gender, tumor location, sites of me", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34761596"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1440, "text": "BACKGROUND: Performance status (PS) is a variable derived from the assessment of a patient's functional status, originally proposed to predict drug toxicity. However, despite its characteristic of being subjective and unidimensional, it has become one of the most important prognostic variables for patients with metastatic colorectal cancer (mCRC). In light of the considerable progressive prolongation of median overall survival (OS) of patients with mCRC, it is unclear whether PS continues to be a valid prognostic factor. This article aims to perform a meta-analysis to verify the current prognostic role of PS.METHODS: A search on two databases of prospective trials of first-line chemotherapy in mCRC patients, published in English from 1991 to 2020, was done by predefined criteria. After the selection of phase III trials evaluating the prognostic role of PS, a meta-analysis has been performed.RESULTS: Thirteen trials were included in the meta-analysis. They reported a reduction in the risk of death with a PS 0 compared to a PS 1 or more (HR 0.63, CI 0.54-0.72; 13 studies), which was confirmed for the comparison between PS 0 and PS 1. However, the study found significant heterogeneity (Q\u2009=\u200968.10; p-value\u2009<\u20090.001) and high-grade inconsistency (I2\u2009=\u200982.38%). Therefore, to explore the reasons for the heterogeneity, a univariate meta-regression was performed, which suggested a possible moderating activity for liver metastas", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37966630"}, {"offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "BACKGROUND: Although chemotherapy is standard for patients with mCRC and ECOG PS of 0/1, the real benefit for patients with ECOG PS > 2 remains uncertain, because they are generally excluded from clinical trials", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25442812"}, {"offsetInBeginSection": 0, "offsetInEndSection": 359, "text": "BACKGROUND: Although chemotherapy is standard for patients with mCRC and ECOG PS of 0/1, the real benefit for patients with ECOG PS > 2 remains uncertain, because they are generally excluded from clinical trials. Our objectives were to compare the survival and safety of ECOG PS 3/4 patients who were administered chemotherapy with those who received BSC only", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25442812"}, {"offsetInBeginSection": 0, "offsetInEndSection": 513, "text": "BACKGROUND: Although chemotherapy is standard for patients with mCRC and ECOG PS of 0/1, the real benefit for patients with ECOG PS > 2 remains uncertain, because they are generally excluded from clinical trials. Our objectives were to compare the survival and safety of ECOG PS 3/4 patients who were administered chemotherapy with those who received BSC only.PATIENTS AND METHODS: We retrospectively analyzed all consecutive mCRC patients who started first-line chemotherapy at our institution in a 4-year period", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25442812"}, {"offsetInBeginSection": 0, "offsetInEndSection": 489, "text": "INTRODUCTION: Colorectal cancer is the second most common cancer in both genders and often presents as a metastatic, unresectable, or recurrent disease in early follow-up. It is uncertain the benefit of oxaliplatin-based palliative chemotherapy (CT) in the first line of treatment in patients with compromised performance status (PS), Eastern Cooperative Oncology Group (ECOG) 3 and 4. These patients are systematically excluded from clinical trials but may be treated in clinical practice", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37336705"}, {"offsetInBeginSection": 0, "offsetInEndSection": 384, "text": "INTRODUCTION: Colorectal cancer is the second most common cancer in both genders and often presents as a metastatic, unresectable, or recurrent disease in early follow-up. It is uncertain the benefit of oxaliplatin-based palliative chemotherapy (CT) in the first line of treatment in patients with compromised performance status (PS), Eastern Cooperative Oncology Group (ECOG) 3 and 4", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37336705"}, {"offsetInBeginSection": 171, "offsetInEndSection": 489, "text": " It is uncertain the benefit of oxaliplatin-based palliative chemotherapy (CT) in the first line of treatment in patients with compromised performance status (PS), Eastern Cooperative Oncology Group (ECOG) 3 and 4. These patients are systematically excluded from clinical trials but may be treated in clinical practice", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37336705"}, {"offsetInBeginSection": 235, "offsetInEndSection": 697, "text": " Few of these patients are enrolled onto clinical trials, and poor PS is often multifactorial.PATIENTS AND METHODS: We analyzed the Treatment of Recurrent and Advanced Colorectal Cancer registry to describe treatment practices and outcomes in poor (Eastern Cooperative Oncology Group [ECOG] PS 2) and very poor PS (ECOG PS > 2) patients to explore the relationship between age, tumor burden, comorbidities, and PS, and to evaluate the benefit of systemic therapy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32919889"}, {"offsetInBeginSection": 1307, "offsetInEndSection": 1710, "text": "Finally, 25% and 53.6% of patients received these treatments in the last 14 and 30 days of life, respectively.CONCLUSION: In the present study, palliative multiagent chemotherapy in poor performance status patients with non-molecularly selected colorectal cancer tended to impact tumor symptoms control; however, there is no benefit in OS and a considerable risk of toxicity and treatment-related death.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37336705"}, {"offsetInBeginSection": 172, "offsetInEndSection": 385, "text": "It is uncertain the benefit of oxaliplatin-based palliative chemotherapy (CT) in the first line of treatment in patients with compromised performance status (PS), Eastern Cooperative Oncology Group (ECOG) 3 and 4.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37336705"}, {"offsetInBeginSection": 386, "offsetInEndSection": 759, "text": "These patients are systematically excluded from clinical trials but may be treated in clinical practice.METHODS: We conducted a prospective observational cohort whose primary outcome was improving at least 2 points in the worst symptom in the Edmonton Symptom Assessment System Scale (ESAS-r), without grade 3 to 4 toxicity, comparing baseline and fourth week of treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37336705"}, {"offsetInBeginSection": 1032, "offsetInEndSection": 1239, "text": "Median overall survival was 86 days, 46% of patients did not respond to the fourth-week reevaluation due to clinical deterioration, and 17.8% presented toxicity grade \u22653, with 5 patients dying from toxicity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37336705"}, {"offsetInBeginSection": 760, "offsetInEndSection": 1031, "text": "Secondary endpoints included quality of life using the European Quality of Life-5 dimensions questionnaire, toxicity, response rate, clinical improvement of ECOG PS, and overall survival (OS).RESULTS: We included 28 patients, and 12 (42.8%) achieved the primary endpoint.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37336705"}, {"offsetInBeginSection": 1387, "offsetInEndSection": 1668, "text": "30 days of life, respectively.CONCLUSION: In the present study, palliative multiagent chemotherapy in poor performance status patients with non-molecularly selected colorectal cancer tended to impact tumor symptoms control; however, there is no benefit in OS and a considerable ris", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37336705"}, {"offsetInBeginSection": 1081, "offsetInEndSection": 1302, "text": " Although some studies suggested benefits in terms of symptomatic response with standard chemotherapy, with good safety profiles when dose-reduced regimens were administered, a true survival gain could not be demonstrated", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30281700"}, {"offsetInBeginSection": 107, "offsetInEndSection": 286, "text": "Combined surgery, chemotherapy, and radiotherapy improved survival, but the side effects and the poor performance status of the patients seriously affect the use of these methods.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12667306"}, {"offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "BACKGROUND: Although chemotherapy is standard for patients with mCRC and ECOG PS of 0/1, the real benefit for patients with ECOG PS > 2 remains uncertain, because they are generally excluded from clinical trials.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25442812"}, {"offsetInBeginSection": 0, "offsetInEndSection": 351, "text": "BACKGROUND: The benefit of chemotherapy for patients with metastatic colorectal cancer has not been established.METHODS: We retrospectively evaluated the effectiveness of chemotherapy with capecitabine and bevacizumab for patients with a performance status (PS) of 3.RESULTS: Seven patients were included; median age was 82 years (range, 65-91 years).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32999176"}, {"offsetInBeginSection": 1388, "offsetInEndSection": 1669, "text": "0 days of life, respectively.CONCLUSION: In the present study, palliative multiagent chemotherapy in poor performance status patients with non-molecularly selected colorectal cancer tended to impact tumor symptoms control; however, there is no benefit in OS and a considerable risk", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37336705"}, {"offsetInBeginSection": 0, "offsetInEndSection": 577, "text": "INTRODUCTION: Cetuximab-based chemotherapy showed a statistically significantly higher response rate compared with chemotherapy such as FOLFOX. Therefore, FOLFOX plus cetuximab is suspected to be the best regimen to alleviate tumor-related symptoms with a high response rate.CASE REPORT: Here we present the results of 8 consecutive patients with metastatic colorectal cancer with poor performance status and/or severe complications who were treated with first-line FOLFOX with cetuximab. Six of 8 patients achieved an apparent clinical benefit, including radiological response", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21347194"}, {"offsetInBeginSection": 222, "offsetInEndSection": 522, "text": ") patients. Following progression beyond third- or fourth-line therapy, some patients are unsuitable for further chemotherapy because of poor performance status or patient choice. However, a significant number of patients are still candidates for further therapy despite limited standard options bein", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33068283"}, {"offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "BACKGROUND: The management of metastatic colorectal cancer patients with a poor performance status (PS) continues to be a clinical dilemma, with the potential activity and safety of treating this population remaining poorly", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32919889"}, {"offsetInBeginSection": 149, "offsetInEndSection": 973, "text": "rd therapy. However, few data have been available for patients with pretreated mCRC who are intolerant of intensive therapy (vulnerable).METHODS: We performed a multicenter retrospective study (WJOG14520G; TWILIGHT) of FTD/TPI plus bevacizumab for vulnerable patients with pretreated mCRC. Eligibility criteria included previous chemotherapy (although patients treated with all key cytotoxic agents, a fluoropyrimidine, oxaliplatin, and irinotecan, were excluded) and intolerance of full-dose combination therapy with oxaliplatin or irinotecan at the start of FTD/TPI plus bevacizumab.RESULTS: The median age of 93 evaluable patients was 79 years (range, 21-90). Intolerance of intensive therapy was attributable to an older age in 60 (65%) patients, serious concomitant disease in 24 (26%) patients, and a poor performance ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37950903"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1677, "text": "BACKGROUND: Although chemotherapy is standard for patients with mCRC and ECOG PS of 0/1, the real benefit for patients with ECOG PS > 2 remains uncertain, because they are generally excluded from clinical trials. Our objectives were to compare the survival and safety of ECOG PS 3/4 patients who were administered chemotherapy with those who received BSC only.PATIENTS AND METHODS: We retrospectively analyzed all consecutive mCRC patients who started first-line chemotherapy at our institution in a 4-year period. A multivariable Cox regression model was used to adjust for prognostic factors and logistic regression, to identify predictive factors of Grade 3/4 toxicity.RESULTS: From June 2008 to June 2012, 240 consecutive patients were included: 100 (41.7%) had an ECOG PS of 0/1, 75 (31.3%) ECOG PS of 2, and 65 (27%) ECOG PS of 3/4. Median survival for patients treated with chemotherapy was 18.4 months for patients with ECOG PS of 0/1, 10.8 months for those with ECOG PS of 2, and 6.8 months for patients with ECOG PS of 3/4. Among those with ECOG PS of 3/4, chemotherapy use led to a nonsignificant survival gain (median, 6.8 vs. 2.3 months for BSC; P = .13). Factors significantly associated with worse survival in an adjusted analysis were right-sided tumors (hazard ratio [HR], 2.97; P = .005) and ECOG PS status (ECOG PS 2 vs. 0/1; HR, 1.67; P = .025, and ECOG PS 3/4 vs. 0/1; HR, 2.67; P < .0001). The rate of Grade \u2265 3 toxicities during the first cycle did not differ significantly across ECOG groups; likely because 40% of ECOG PS 3/4 patients received upfront dose-reduced therapy. The rates of treatment-related hospitalization were similar across all ECOG gr", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25442812"}, {"offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "INTRODUCTION: Chemotherapy is difficult to administer in patients with poor performance status (PS), advanced metastatic lesion, and unresectable", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31060020"}, {"offsetInBeginSection": 406, "offsetInEndSection": 608, "text": "We performed a systematic review of the treatment outcomes of patients with metastatic colorectal cancer and poor performance status, defined as Eastern Cooperative Oncology Group performance status \u22652.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30281700"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "The effects of palliative chemotherapy in metastatic colorectal cancer patients with an ECOG performance status of 3 and 4.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25442812"}, {"offsetInBeginSection": 1602, "offsetInEndSection": 1834, "text": " rates of treatment-related hospitalization were similar across all ECOG groups. All deaths were disease-associated.CONCLUSION: Our retrospective study suggests that chemotherapy might benefit selected mCRC patients with poor PS. Wi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25442812"}, {"offsetInBeginSection": 993, "offsetInEndSection": 1127, "text": "months for patients with ECOG PS of 3/4. Among those with ECOG PS of 3/4, chemotherapy use led to a nonsignificant survival gain (medi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25442812"}, {"offsetInBeginSection": 1344, "offsetInEndSection": 1697, "text": "In conclusion, weekly CPT-11 at 100 mg/m(2) for four consecutive weeks followed by a 2-wk rest period showed antitumor efficacy and may be safely administered to heavily pretreated patients with advanced colorectal cancer and a poor performance status. Weekly CPT-11 monotherapy may be considered as a therapeutic option for this population of patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15456953"}]}
+{"question_id": "663027bb187cba990d000033", "question": "How does Pamrevlumab work?", "answer": "Pamrevlumab (FG-3019) is a fully human monoclonal antibody that binds to connective tissue growth factor (CTGF) and can be used for non-ambulatory patients with Duchenne Muscular Dystrophy.", "relevant_passage_ids": ["37248912"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Pamrevlumab, a Fully Human Monoclonal Antibody Targeting Connective Tissue Growth Factor, for Non-Ambulatory Patients with Duchenne Muscular Dystrophy.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37248912"}, {"offsetInBeginSection": 227, "offsetInEndSection": 338, "text": " Pamrevlumab (FG-3019), a fully human monoclonal antibody that binds to connective tissue growth factor (CTGF),", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37248912"}]}
+{"question_id": "662fbec6187cba990d00000f", "question": "What are the clinical indication for Transarterial Chemoembolization (TACE) in liver metastasis for colorectal cancer?", "answer": "Transarterial Chemoembolization (TACE) in liver metastasis for colorectal cancer is well-tolerated and effective in patients with unresectable chemotherapy refefractory (larger intermediate (3-5 cm), when conventional therapies fail, or metastases recurrence occurs..", "relevant_passage_ids": ["35326651", "34318754", "32468211", "23960002", "33758639", "26088872", "38041083", "32960329", "24510986", "30190956", "16944163", "35463654", "32111770", "32620520", "28915408", "25444473", "28373752", "18219891", "24451734", "29887263", "19886993"], "type": "factoid", "snippets": [{"offsetInBeginSection": 395, "offsetInEndSection": 551, "text": "vascular- and image-based treatments offered by interventional radiologists have emerged when conventional therapies fail, or metastases recurrence occurs. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35326651"}, {"offsetInBeginSection": 157, "offsetInEndSection": 262, "text": "local control rates and overall survival are relatively worse with larger, intermediate (3-5 cm) lesions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34318754"}, {"offsetInBeginSection": 1459, "offsetInEndSection": 1549, "text": "TACE is well tolerated and effective in patients with unresectable chemotherapy refractory", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32468211"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1624, "text": "PURPOSE: Transarterial chemoembolization (TACE) is currently recommended for unresectable intrahepatic tumours with no vascular invasion or metastasis to other organs. It is based on drug-eluting microspheres pre-loaded with chemotherapeutics, which are injected selectively into vessels supplying the tumour, to embolize them inducing ischaemia, and elute the drug, to induce tumour response. We present our initial experience with novel irinotecan- loaded Embocure Plus microspheres in patients with metastatic colorectal cancer tumours in the liver, and their effect on HCT-116 cell cultures in vitro.MATERIAL AND METHODS: Three consecutive male patients (median age 62 [50-76] years) with liver metastatic colorectal cancer tumours were selected. All patients had a pre-procedure contrast-enhanced computed tomography, confirming multiple metastatic liver tumours (mean tumour diameter = 42 mm; range: 14-77 mm) and periprocedural dyna-CT scans for rapid treatment results assessment. In vitro: Human colon HCT116 cancer cell line was cultured, irinotecan loaded Embocure Plus microspheres were added. Cultures were assessed after 24 hours and 72 hours of incubation in normoxia or hypoxia.RESULTS: All embolizations were technically successful, and no complications were observed. Stabilization of the targeted metastatic liver tumours in all patients was noted. In vitro: Significant decrease of the growth of HTC 116 cell lines were observed in controls compared to cells treated with Embocure Plus loaded with irinotecan in normoxia and hypoxia after 48 and 72 hours. We observed a tendency for less inhibited cell p", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33758639"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1080, "text": "BACKGROUND: About 70-80% of patients with colorectal liver metastases appear as ineligible for a curative treatment approach. Transarterial chemoembolisation (TACE) using irinotecan-eluting beads has emerged as a promising treatment option in cases with irresectable liver metastases. Despite being in clinical practice for years, little is known about the treatment characteristics and outcomes when used as per routine hospital practice.METHODS: Patients with hepatic metastases from colorectal cancer origin, admitted to contributing centres to receive TACE with drug-eluting LifePearl\u00ae Microspheres loaded with irinotecan, as part of their standard care, will be consecutively added to the registry. Data will be collected until the end of study, loss to follow-up or death. Primary endpoint is the characterisation of the treatment usage at the selected sites in Europe. Secondary endpoints include outcome parameters, safety and toxicity, as well as quality of life.CONCLUSION AND AIMS: This multicentre, international, prospective observational study conducted in European ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32620520"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1421, "text": "PURPOSE: The purpose of this study was to evaluate the therapeutic efficacy and safety of transarterial chemoembolization (TACE) in the treatment of patients with unresectable colorectal cancer liver metastases (CRCLM) who had failed systemic chemotherapy. In addition, the role of TACE in the treatment of CRCLM is also worth discussing.METHODS: This single-center retrospective study evaluated the consecutive medical records of patients with CRCLM treated with TACE from June 2014 to June 2018, who had failed at least two lines of prior chemotherapy. Therapeutic response, overall survival (OS), progression-free survival (PFS), and complications were recorded.RESULTS: Fifty-three eligible patients were included in our study. The objective tumor radiologic regression and disease control rates were 52.8% and 79.2%, respectively. Median OS and PFS were 15 months (95% confidence interval [CI] 13.1 months, 16.9 months) and 6 months (95% CI 4.7 months, 7.3 months), respectively. Multivariate analysis found that synchronous metastatic disease, presence of extrahepatic metastasis, and Child-Pugh score B were independent prognostic factor for OS and PFS. Two patients (3.8%) had severe complications. The results of subgroup analysis showed that synchronous liver metastasis and extrahepatic metastasis had an effect on the prognosis of patients, while the primary tumor sites (rectum, left, and right colon) had no", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32468211"}, {"offsetInBeginSection": 0, "offsetInEndSection": 483, "text": "In this article, we review two liver-directed therapies that are currently used for the palliative treatment of primary and secondary hepatic malignancies, transcatheter arterial chemoembolization (TACE), including a new type of TACE with drug-eluting beads, and radioembolization. Important developments and administration techniques for all therapies are discussed, as well as their integration into the current routine clinical care for management of metastatic colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30190956"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1765, "text": "Colorectal cancer (CRC) is one of the most common tumor entities worldwide and a common cause of cancer-associated death. Colorectal cancer liver metastases (CRLM) thereby constitute a severe life-limiting factor. The therapy of CRLM presents a major challenge and surgical resection as well as systemic chemotherapy remain the first-line treatment options. Over the years several locoregional, vascular- and image-based treatments offered by interventional radiologists have emerged when conventional therapies fail, or metastases recurrence occurs. Among such options is the conventional/traditional transarterial chemoembolization (cTACE) by local injection of a combination of chemotherapeutic- and embolic-agents. A similar treatment is the more recent irinotecan-loaded drug-eluting beads TACE (DEBIRI-TACE), which are administered using the same approach. Numerous studies have shown that these different types of chemoembolization can be applied in different clinical settings safely. Furthermore, such treatments can also be combined with other local or systemic therapies. Unfortunately, due to the incoherent patient populations of studies investigating TACE in CRLM, critics state that the definite evidence supporting positive patient outcomes is still lacking. In the following article we review studies on conventional and DEBIRI-TACE. Although highly dependent on the clinical setting, prior therapies and generally the study population, cTACE and DEBIRI-TACE show comparable results. We present the most representative studies on the different chemoembolization procedures and compare the results. Although there is compelling evidence for both approaches, further studies are necessary to determine which patients profit most from these therapies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35326651"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1055, "text": "We aimed to investigate the efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) in the treatment of colorectal cancer liver metastasis. A total of 120 patients with colorectal cancer liver metastasis were divided into the TACE group (receiving TACE treatment, n\u2009=\u200960) and the DEB-TACE group (receiving DEB-TACE treatment, n\u2009=\u200960). At 1 month after treatment, the objective response rate (ORR) in the TACE group and DEB-TACE group were 65.0% (39/60) and 78.3% (47/60), respectively, and the disease control rate (DCR) was 78.3% (47/60) and 85.0% (51/60), respectively. Three months later, the ORRs in TACE and DEB-TACE groups were 63.3% (38/60) and 75.0% (45/60), and the DCRs were 76.7% (46/60) and 81.7% (49/60). We showed that the 1-year overall survival (OS) in TACE and DEB-TACE groups were 100% (60/60) and 88.3% (53/60), respectively, and the 2-year OS were 78.3% (47/60) and 61.7% (37/60). Further analysis indicated that the OS in the DEB-TACE group was significantly longer than that in the TACE group (P\u2009=\u20090.045).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35463654"}, {"offsetInBeginSection": 0, "offsetInEndSection": 555, "text": "BACKGROUND: Transarterial liver-directed therapies are currently not recommended as a standard treatment for colorectal liver metastases. Transarterial chemoembolization (TACE), however, is increasingly used for patients with liver-dominant colorectal metastases after failure of surgery or systemic chemotherapy. The limited available data potentially reveals TACE as a valuable option for pre- and post-operative downsizing, minimizing time-to-surgery, and prolongation of overall survival after surgery in patients with colorectal liver only metastases", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26088872"}, {"offsetInBeginSection": 137, "offsetInEndSection": 312, "text": " Transarterial chemoembolization (TACE), however, is increasingly used for patients with liver-dominant colorectal metastases after failure of surgery or systemic chemotherapy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26088872"}, {"offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Transarterial chemoembolization (TACE) for colorectal liver metastases--current status and critical review.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26088872"}, {"offsetInBeginSection": 0, "offsetInEndSection": 312, "text": "BACKGROUND: Transarterial liver-directed therapies are currently not recommended as a standard treatment for colorectal liver metastases. Transarterial chemoembolization (TACE), however, is increasingly used for patients with liver-dominant colorectal metastases after failure of surgery or systemic chemotherapy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26088872"}, {"offsetInBeginSection": 0, "offsetInEndSection": 362, "text": "We aimed to investigate the efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) in the treatment of colorectal cancer liver metastasis. A total of 120 patients with colorectal cancer liver metastasis were divided into the TACE group (receiving TACE treatment, n\u2009=\u200960) and the DEB-TACE group (receiving DEB-TACE treatment, n\u2009=\u200960).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35463654"}, {"offsetInBeginSection": 137, "offsetInEndSection": 555, "text": " Transarterial chemoembolization (TACE), however, is increasingly used for patients with liver-dominant colorectal metastases after failure of surgery or systemic chemotherapy. The limited available data potentially reveals TACE as a valuable option for pre- and post-operative downsizing, minimizing time-to-surgery, and prolongation of overall survival after surgery in patients with colorectal liver only metastases", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26088872"}, {"offsetInBeginSection": 137, "offsetInEndSection": 686, "text": " Transarterial chemoembolization (TACE), however, is increasingly used for patients with liver-dominant colorectal metastases after failure of surgery or systemic chemotherapy. The limited available data potentially reveals TACE as a valuable option for pre- and post-operative downsizing, minimizing time-to-surgery, and prolongation of overall survival after surgery in patients with colorectal liver only metastases.PURPOSE: In this overview, the current status of TACE for the treatment of liver-dominant colorectal liver metastases is presented", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26088872"}, {"offsetInBeginSection": 0, "offsetInEndSection": 599, "text": "We aimed to investigate the efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) in the treatment of colorectal cancer liver metastasis. A total of 120 patients with colorectal cancer liver metastasis were divided into the TACE group (receiving TACE treatment, n\u2009=\u200960) and the DEB-TACE group (receiving DEB-TACE treatment, n\u2009=\u200960). At 1 month after treatment, the objective response rate (ORR) in the TACE group and DEB-TACE group were 65.0% (39/60) and 78.3% (47/60), respectively, and the disease control rate (DCR) was 78.3% (47/60) and 85.0% (51/60), respectively.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35463654"}, {"offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "PURPOSE: Transarterial chemoembolization (TACE) is currently recommended for unresectable intrahepatic tumours with no vascular invasion or metastasis to other organs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33758639"}, {"offsetInBeginSection": 1207, "offsetInEndSection": 1556, "text": "The results of subgroup analysis showed that synchronous liver metastasis and extrahepatic metastasis had an effect on the prognosis of patients, while the primary tumor sites (rectum, left, and right colon) had no effect on the prognosis.CONCLUSIONS: TACE is well tolerated and effective in patients with unresectable chemotherapy refractory CRCLM.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32468211"}, {"offsetInBeginSection": 560, "offsetInEndSection": 658, "text": "This treatment approach has symptomatic, palliative, adjuvant and potentially curative objectives.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16944163"}, {"offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "PURPOSE: The purpose of this study was to evaluate the therapeutic efficacy and safety of transarterial chemoembolization (TACE) in the treatment of patients with unresectable colorectal cancer liver metastases (CRCLM) who had failed systemic chem", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32468211"}, {"offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "OBJECTIVE: To investigate the prognostic factors in chemorefractory colorectal cancer liver metastasis (CRCLM) patients treated by transarterial chemoembolization (TACE) and sustained hepatic arterial infusion chemother", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28373752"}, {"offsetInBeginSection": 938, "offsetInEndSection": 1032, "text": "This TACE can be a feasible therapy for colorectal liver metastases as the first-line therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18219891"}, {"offsetInBeginSection": 1057, "offsetInEndSection": 1331, "text": "Additionally, the concept of TACE for liver-dominant metastatic disease with a focus on new embolization technologies is outlined.CONCLUSIONS: There is encouraging data with regard to technical success, safety, and oncologic efficacy of TACE for colorectal liver metastases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26088872"}, {"offsetInBeginSection": 0, "offsetInEndSection": 658, "text": "Liver metastasis is one of the main problems encountered in colorectal cancer management as the liver is the most common metastatic site. Several treatment options are available, among which transarterial chemotherapy has proved effective in achieving some local tumour control, improving the quality of life through symptomatic control as well as survival time. The present paper is intended to provide an overview of the techniques, indications and results of regional chemotherapy, which comprises transarterial chemoembolization (TACE) and chemoperfusion. This treatment approach has symptomatic, palliative, adjuvant and potentially curative objectives.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16944163"}, {"offsetInBeginSection": 0, "offsetInEndSection": 351, "text": "Interventional radiologists (IRs) have an expanding role in the treatment of liver metastases from colorectal cancer. Increasing data on the ability to treat liver metastases with locoregional therapies has solidified this position. Ablative approaches, such as radiofrequency ablation and microwave ablation, have shown durable eradication of tumors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24451734"}, {"offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "PURPOSE: Transarterial chemoembolization (TACE) is currently recommended for unresectable intrahepatic tumours with no vascular invasion or metastasis to othe", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33758639"}, {"offsetInBeginSection": 114, "offsetInEndSection": 272, "text": "t approach. Transarterial chemoembolisation (TACE) using irinotecan-eluting beads has emerged as a promising treatment option in cases with irresectable liver", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32620520"}, {"offsetInBeginSection": 0, "offsetInEndSection": 559, "text": "Liver metastasis is one of the main problems encountered in colorectal cancer management as the liver is the most common metastatic site. Several treatment options are available, among which transarterial chemotherapy has proved effective in achieving some local tumour control, improving the quality of life through symptomatic control as well as survival time. The present paper is intended to provide an overview of the techniques, indications and results of regional chemotherapy, which comprises transarterial chemoembolization (TACE) and chemoperfusion.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16944163"}, {"offsetInBeginSection": 0, "offsetInEndSection": 603, "text": "PURPOSE: Transarterial chemoembolization (TACE) is currently recommended for unresectable intrahepatic tumours with no vascular invasion or metastasis to other organs. It is based on drug-eluting microspheres pre-loaded with chemotherapeutics, which are injected selectively into vessels supplying the tumour, to embolize them inducing ischaemia, and elute the drug, to induce tumour response. We present our initial experience with novel irinotecan- loaded Embocure Plus microspheres in patients with metastatic colorectal cancer tumours in the liver, and their effect on HCT-116 cell cultures in vitro", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33758639"}, {"offsetInBeginSection": 155, "offsetInEndSection": 376, "text": "ic therapy. Intra-arterial therapies (IAT) including conventional transarterial chemoembolization (cTACE), drug eluting beads (DEB-TACE) and yttrium-90 radioembolization (Y-90) are indicated to prolong survival and pallia", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29887263"}, {"offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "BACKGROUND: Transarterial liver-directed therapies are currently not recommended as a standard treatment for colorectal liver metastases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26088872"}]}
+{"question_id": "663014c8187cba990d000020", "question": "What is Alzheimer's disease?", "answer": "Alzheimer's disease is a neurodegenerative disorder characterized by amyloid beta plaque and neurofibrillary tangles.", "relevant_passage_ids": ["37488880", "37264659"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Alzheimer's disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer's disease. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37488880"}, {"offsetInBeginSection": 9, "offsetInEndSection": 122, "text": "Amyloid beta plaque and neurofibrillary tangles are considered the two main hallmarks of Alzheimer's disease (AD)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37264659"}]}
+{"question_id": "662fbfc4187cba990d000010", "question": "Is short-course radiation therapy a cost-effective therapy in the neoadjuvant treatment of locally advanced rectal cancer?", "answer": "Short-course radiation therapy (SCRT) - Total Neoadjuvant Therapy (TNT) followed by Total Mesorectal Excision (TME) incurs lowest cost and improved QALYs compared with conventional long-course chemoradiotherapy (LCCRT) followed by TME and adjuvant therapy.", "relevant_passage_ids": ["35103791", "30964794", "30977859", "36072238", "35462008", "31683174", "37226566", "31234886", "34925591", "34955376", "24021342"], "type": "yesno", "snippets": [{"offsetInBeginSection": 2105, "offsetInEndSection": 2242, "text": "SCRT-TNT followed by TME incurs lower cost and improved QALYs compared with conventional LCCRT followed by TME and adjuvant chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35103791"}, {"offsetInBeginSection": 1217, "offsetInEndSection": 2130, "text": "inoperineal resection (APR) were simultaneously varied. The analysis was repeated for patients with distal rectal tumors. Analysis was conducted from January to October 2018.Exposures: Short-course radiotherapy and long-course chemoradiotherapy.Main Outcomes and Measures: Incremental cost-effectiveness ratios.Results: Short-course radiotherapy was the cost-effective strategy compared with long-course chemoradiotherapy (incremental cost-effectiveness ratio, $133\u202f495 per quality-adjusted life-year). Two-way sensitivity analysis revealed that the cost-effective approach for a given patient depended on the utilities for the NED-LAR and NED-APR states. Assuming that a greater proportion of patients with locally advanced distal tumors undergoing long-course chemoradiotherapy (39%) would proceed to LAR compared with those treated with short-course radiotherapy (19%), long-course chemoradiotherapy was the co", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30977859"}, {"offsetInBeginSection": 0, "offsetInEndSection": 2115, "text": "Importance: Short-course radiotherapy and total neoadjuvant therapy (SCRT-TNT) followed by total mesorectal excision (TME) has emerged as a new treatment paradigm for patients with locally advanced rectal adenocarcinoma. However, the economic implication of this treatment strategy has not been compared with that of conventional long-course chemoradiotherapy (LCCRT) followed by TME with adjuvant chemotherapy.Objective: To perform a cost-effectiveness analysis of SCRT-TNT vs LCCRT in conjunction with TME for patients with locally advanced rectal cancer.Design, Setting, and Participants: A decision analytical model with a 5-year time horizon was constructed for patients with biopsy-proven, newly diagnosed, primary locally advanced rectal adenocarcinoma treated with SCRT-TNT or LCCRT. Markov modeling was used to model disease progression and patient survival after treatment in 3-month cycles. Data on probabilities and utilities were extracted from the literature. Costs were evaluated from the Medicare payer's perspective in 2020 US dollars. Sensitivity analyses were performed for key variables. Data were collected from October 3, 2020, to January 20, 2021, and analyzed from November 15, 2020, to April 25, 2021.Exposures: Two treatment strategies, SCRT-TNT vs LCCRT with adjuvant chemotherapy, were compared.Main Outcomes and Measures: Cost-effectiveness was evaluated using the incremental cost-effectiveness ratio and net monetary benefits. Effectiveness was defined as quality-adjusted life-years (QALYs). Both costs and QALYs were discounted at 3% annually. Willingness-to-pay threshold was set at $50\u202f000/QALY.Results: During the 5-year horizon, the total cost was $41\u202f355 and QALYs were 2.21 for SCRT-TNT; for LCCRT, the total cost was $54\u202f827 and QALYs were 2.12, resulting in a negative incremental cost-effectiveness ratio (-$141\u202f256.77). The net monetary benefit was $69\u202f300 for SCRT-TNT and $51\u202f060 for LCCRT. Sensitivity analyses using willingness to pay at $100\u202f000/QALY and $150\u202f000/QALY demonstrated the same conclusion.Conclusions and Relevance: These findings suggest that SCRT-TNT f", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35103791"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1507, "text": "PURPOSE: Long-course chemoradiotherapy (LCRT) has been widely recommended in a majority of rectal cancer patients. Recently, encouraging data on short-course radiotherapy (SCRT) for rectal cancer has emerged. In this study, we aimed to compare these two methods in terms of short-term outcomes and cost analysis under the Korean medical insurance system.MATERIALS AND METHODS: Sixty-two patients with high-risk rectal cancer, who underwent either SCRT or LCRT followed by total mesorectal excision (TME), were classified into two groups. Twenty-seven patients received 5 Gy\u00d75 with two cycles of XELOX (capecitabine 1000 mg/m\u00b2 and oxaliplatin 130 mg/m\u00b2 every 3 weeks) followed by TME (SCRT group). Thirty-five patients received capecitabine-based LCRT followed by TME (LCRT group). Short-term outcomes and cost estimation were assessed between the two groups.RESULTS: Pathological complete response was achieved in 18.5% and 5.7% of patients in the SCRT and LCRT groups, respectively (p=0.223). The 2-year recurrence-free survival rate did not show significant difference between the two groups (SCRT vs. LCRT: 91.9% vs. 76.2%, p=0.394). The average total cost per patient for SCRT was 18% lower for inpatient treatment (SCRT vs. LCRT: $18787 vs. $22203, p<0.001) and 40% lower for outpatient treatment (SCRT vs. LCRT: $11955 vs. $19641, p<0.001) compared to LCRT. SCRT was shown to be the dominant treatment option with fewer recurrences and fewer complications at a lower cost.CONCLUSION: SCRT was well-tol", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37226566"}, {"offsetInBeginSection": 0, "offsetInEndSection": 882, "text": "Neoadjuvant treatment has become the standard of care for locally advanced rectal cancer for many years. Several neoadjuvant therapeutic options are currently used, the most common being conventionally fractionated radiotherapy (or long-course radiotherapy) administered concomitantly with chemotherapy and hypofractionated radiotherapy (or short-course radiotherapy). This meta-analysis will give a better overview of the results of several studies that compare long-course radio-chemotherapy with short-course radiotherapy, emphasizing on the severe acute and late toxicities and the postoperative results of the analyzed studies. After identification, analysis and verification of eligibility criteria, eight studies were included in the meta-analysis. The methodological quality of the selected studies was assessed using the classic Oxford quality grading system (Jadad scale).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34925591"}, {"offsetInBeginSection": 0, "offsetInEndSection": 2032, "text": "BACKGROUND: Definitive surgery with total mesorectal excision is the mainstay of treatment for locally advanced rectal cancer. Multimodality therapy improves long-term survival. Current standards advise neoadjuvant chemoradiation followed by radical surgery and adjuvant chemotherapy. Nationally, compliance with adjuvant chemotherapy is only 32%. New research evaluates the effectiveness of total neoadjuvant therapy: complete chemotherapy and chemoradiation before surgery.OBJECTIVE: The aim of this study is to determine the favored treatment for locally advanced rectal cancer by comparing the cost-effectiveness of total neoadjuvant therapy and the current standard of care.DESIGN: Decision analytical modeling using long-term costs and 5-year disease-free survival was performed to determine the cost-effectiveness after total neoadjuvant therapy and the current standard of care. Sensitivity analysis was used to investigate the effect of uncertainty in model parameters.SETTINGS: Centers for Medicare & Medicaid Services billing data perspective was adopted and outcomes modeled according to local and national databases and literature consensus.PATIENTS: Adult patients with stage II or III rectal cancer were selected.MAIN OUTCOME MEASURES: Cost-effectiveness in disease-free life-years, incremental cost-effectiveness ratio, and net monetary benefit were determined over a 5-year posttreatment period. The favored strategy was determined based on cost-effectiveness and sensitivity analyses.RESULTS: Cost-effectiveness for total neoadjuvant therapy was 40,708 $/life-year, and, for conventional therapy, cost-effectiveness was 44,248 $/life-year. Sensitivity analysis showed that, for an estimated total neoadjuvant therapy completion rate of 90%, total neoadjuvant therapy would remain the dominant strategy for any adjuvant chemotherapy completion rate of less than 93%.LIMITATIONS: The samples used to calculate completion rates are small, and survival probabilities are based on existing literature, local database va", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30964794"}, {"offsetInBeginSection": 0, "offsetInEndSection": 857, "text": "Total mesorectal excision is the cornerstone of treatment for rectal cancer. Multiple randomised trials have shown a reduction in local recurrence rates with the addition of preoperative radiotherapy, either as a 1-week hypofractionated short-course (SCRT) or a conventionally fractionated long-course (LCRT) schedule with concurrent chemotherapy. There is also increasing interest in the addition of neoadjuvant chemotherapy to radiotherapy with the aim of improving disease-free survival. The relative use of SCRT and LCRT varies considerably across the world. This is reflected in, and is probably driven in part by, disparity between international guideline recommendations. In addition, different approaches to treatment may exist both between and within countries, with variation related to patient, disease and treatment centre and financial factors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34955376"}, {"offsetInBeginSection": 1936, "offsetInEndSection": 2242, "text": "Sensitivity analyses using willingness to pay at $100\u202f000/QALY and $150\u202f000/QALY demonstrated the same conclusion.Conclusions and Relevance: These findings suggest that SCRT-TNT followed by TME incurs lower cost and improved QALYs compared with conventional LCCRT followed by TME and adjuvant chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35103791"}, {"offsetInBeginSection": 1863, "offsetInEndSection": 1935, "text": "The net monetary benefit was $69\u202f300 for SCRT-TNT and $51\u202f060 for LCCRT.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35103791"}, {"offsetInBeginSection": 1577, "offsetInEndSection": 1862, "text": "Willingness-to-pay threshold was set at $50\u202f000/QALY.Results: During the 5-year horizon, the total cost was $41\u202f355 and QALYs were 2.21 for SCRT-TNT; for LCCRT, the total cost was $54\u202f827 and QALYs were 2.12, resulting in a negative incremental cost-effectiveness ratio (-$141\u202f256.77).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35103791"}, {"offsetInBeginSection": 1873, "offsetInEndSection": 2409, "text": "Assuming that a greater proportion of patients with locally advanced distal tumors undergoing long-course chemoradiotherapy (39%) would proceed to LAR compared with those treated with short-course radiotherapy (19%), long-course chemoradiotherapy was the cost-effective approach (incremental cost-effectiveness ratio, $61\u202f123 per quality-adjusted life-year).Conclusions and Relevance: Short-course radiotherapy was the cost-effective strategy compared with long-course chemoradiotherapy for patients with locally advanced rectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30977859"}, {"offsetInBeginSection": 0, "offsetInEndSection": 899, "text": "Background and Objectives: Conventional long-course radiotherapy (LCRT) and a new paradigm of short-course radiotherapy with total neoadjuvant therapy (SCRT-TNT) are used in locally advanced rectal cancer (RC). There are few economic assessment reports available on TNT that focus on cost analysis in a country with limited funding for healthcare systems. The objective of this study was to perform a cost analysis comparing SCRT-TNT versus LCRT.Materials and Methods: In 2020-2021, a prospective registry was created to document RC patients who received neoadjuvant therapy and the costs of cancer treatments, transportation and the time patients and family members spent in the hospital. This registry outlined the direct and indirect costs of LCRT versus SCRT-TNT.Results: LCRT and SCRT-TNT regimens have direct costs that range from S/.5,993.30 to S/.27,928.36 and from S/.3,409.81 to S/.18,159.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36072238"}, {"offsetInBeginSection": 1950, "offsetInEndSection": 2115, "text": "alyses using willingness to pay at $100\u202f000/QALY and $150\u202f000/QALY demonstrated the same conclusion.Conclusions and Relevance: These findings suggest that SCRT-TNT f", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35103791"}, {"offsetInBeginSection": 688, "offsetInEndSection": 935, "text": "SCPRT is highly cost-effective with high compliance rates, hence is gaining traction in Europe and East Asia, partly because of inherent flexibility in timing and the ability to add neoadjuvant systemic chemotherapy as there is a delay to surgery.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31683174"}, {"offsetInBeginSection": 1825, "offsetInEndSection": 2022, "text": " SCRT compared with LCCRT below the WTP.CONCLUSION: Compared with LCCRT, SCRT plus chemotherapy is a more cost-effective strategy for locally advanced resectable RC in the DFS state as well as in t", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31234886"}]}
+{"question_id": "66301f5a187cba990d000028", "question": "Are there any episignatures for Duchenne Muscular Dystrophy?", "answer": "Yes, there have been identified episignatures for Duchenne Muscular Dystrophy.", "relevant_passage_ids": ["36572586"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "The discovery of the DNA methylation episignature for Duchenne muscular dystrophy.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36572586"}, {"offsetInBeginSection": 1174, "offsetInEndSection": 1297, "text": " we developed a new DMD episignature biomarker and provided novel insights into the molecular pathogenesis of this disorder", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36572586"}, {"offsetInBeginSection": 987, "offsetInEndSection": 1140, "text": "We identified a unique episignature for DMD that whose specificity was confirmed in relation other neurodevelopmental disorders with known episignatures.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36572586"}, {"offsetInBeginSection": 1141, "offsetInEndSection": 1387, "text": "By modeling the DMD episignature, we developed a new DMD episignature biomarker and provided novel insights into the molecular pathogenesis of this disorder, which have the potential to advance more effective, personalized approaches to DMD care.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36572586"}, {"offsetInBeginSection": 744, "offsetInEndSection": 1387, "text": "To further investigate DMD pathophysiology, we assessed the genome-wide DNA methylation profiles of peripheral blood from 36 patients with DMD using the combination of Illumina Infinium Methylation EPIC bead chip array and EpiSign technology. We identified a unique episignature for DMD that whose specificity was confirmed in relation other neurodevelopmental disorders with known episignatures. By modeling the DMD episignature, we developed a new DMD episignature biomarker and provided novel insights into the molecular pathogenesis of this disorder, which have the potential to advance more effective, personalized approaches to DMD care.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36572586"}, {"offsetInBeginSection": 744, "offsetInEndSection": 1140, "text": "To further investigate DMD pathophysiology, we assessed the genome-wide DNA methylation profiles of peripheral blood from 36 patients with DMD using the combination of Illumina Infinium Methylation EPIC bead chip array and EpiSign technology. We identified a unique episignature for DMD that whose specificity was confirmed in relation other neurodevelopmental disorders with known episignatures.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36572586"}]}
+{"question_id": "6621506cb9f8b89d7e000007", "question": "What are the minimum molecular determinations necessary for the initial treatment of advanced colorectal cancer in clinical practice?", "answer": "Evidence supports mutational testing for EGFR signaling pathway genes (KRAS, NRAS and BRAF mutations) and the convenience of determining the amplification of human epidermal growth factor receptor 2 (HER2), the expression of proteins in the DNA repair pathway and the study of NTRK fusions are also evaluated.", "relevant_passage_ids": ["28185757", "32418154", "35780916", "31231562", "29589315", "34448902", "36670267", "32648137", "36931147", "33994743", "31933925", "31553708", "36990254", "35837115", "32273401", "23878352", "36902296", "19190129", "37863556", "29788743", "36603179", "25605843", "28165299", "36149298", "35434030"], "type": "list", "snippets": [{"offsetInBeginSection": 775, "offsetInEndSection": 1003, "text": "Evidence supports mutational testing for EGFR signaling pathway genes, since they\u00a0provide clinically actionable information as negative predictors of benefit to anti-EGFR monoclonal antibody therapies for targeted therapy of CRC", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28185757"}, {"offsetInBeginSection": 389, "offsetInEndSection": 692, "text": "Recently published information on the essential determination of KRAS, NRAS and BRAF mutations and the convenience of determining the amplification of human epidermal growth factor receptor 2 (HER2), the expression of proteins in the DNA repair pathway and the study of NTRK fusions are also evaluated. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32418154"}, {"offsetInBeginSection": 0, "offsetInEndSection": 900, "text": "Colorectal cancers are the third most common cancers in the world. Management of both primary and metastatic colorectal cancers has evolved over the last couple of decades. Extensive research in molecular oncology has helped us understand and identify these complex intricacies in colorectal cancer biology and disease progression. These advances coupled with improved knowledge on various mutations have helped develop targeted chemotherapeutics and has allowed planning an effective treatment regimen in this era of immunotherapy with precision. The diverse chemotherapeutic and biological agents at our disposal can make decision making a very complex process. Molecular profile, including CIN, RAS, BRAF mutations, microsatellite instability, ctDNA, and consensus molecular subtypes, are some of the important factors which are to be considered while planning an individualized treatment regimen.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33994743"}, {"offsetInBeginSection": 0, "offsetInEndSection": 389, "text": "OBJECTIVE: CpG island methylation phenotype (CIMP) and microsatellite instability (MSI) are two different molecular mechanisms in colorectal cancer (CRC). Proto-oncogene KRAS, mutations in NRAS and BRAF play an important role in the formation of colorectal cancer. The correlation between the molecular typing of CIMP and MSI and the genes of KRAS, NRAS and BRAF was explored in this study", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31933925"}, {"offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "BACKGROUND AND OBJECTIVES: KRAS, NRAS, BRAF mutations and microsatellite instability (MSI) can be associated with Colorectal Cancer (CRC) development", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36990254"}, {"offsetInBeginSection": 0, "offsetInEndSection": 492, "text": "BACKGROUND AND OBJECTIVES: KRAS, NRAS, BRAF mutations and microsatellite instability (MSI) can be associated with Colorectal Cancer (CRC) development.MATERIAL AND METHODS: We evaluated 828 medical records of CRC patients from a school hospital from January/2016 to December/2020. Variables such as age, gender, ethnicity, literacy level, smoking, alcoholism, primary anatomical site, tumor staging, presence of BRAFV600E, KRAS, NRAS mutations and MSI , survival and metastasis were identified", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36990254"}, {"offsetInBeginSection": 446, "offsetInEndSection": 611, "text": "Multiple assays, including immunohistochemistry, microsatellite instability testing, MLH1 promoter methylation, and next-generation sequencing, are typically needed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37863556"}, {"offsetInBeginSection": 143, "offsetInEndSection": 349, "text": "Before systemic treatment initiation, determination of tumour genomic status for KRAS and NRAS, BRAFV600E mutations, ERBB2, and microsatellite instability and/or mismatch repair (MMR) status is recommended.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36670267"}, {"offsetInBeginSection": 976, "offsetInEndSection": 1225, "text": "To guide appropriate clinical management and treatment decisions for mCRC patients, tumour tissue analysis for DNA mismatch repair/microsatellite status and, at a minimum, KRAS, NRAS, and BRAF mutational status is mandatory at the time of diagnosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36931147"}, {"offsetInBeginSection": 522, "offsetInEndSection": 669, "text": "The treatment of the remaining vast majority mCRC patients is still based upon only two molecular determinants: the RAS and BRAF mutational status.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35780916"}, {"offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "PURPOSE: The College of American Pathologists (CAP) has developed a guideline on testing for mismatch repair (MMR) and microsatellite instability (MSI) for patients considered for immune checkpoint inhibitor therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36603179"}, {"offsetInBeginSection": 1468, "offsetInEndSection": 1703, "text": "LFIRI; patients with RAS tumor mutations did not. Molecular testing of tumors for all activating RAS mutations is essential before considering anti-epidermal growth factor receptor therapy, thereby allowing the further tailoring of cet", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25605843"}, {"offsetInBeginSection": 0, "offsetInEndSection": 930, "text": "Colorectal cancer (CRC) is still a\u00a0very common disease and one of the best characterized malignancies on a\u00a0molecular level. Interdisciplinary and multimodal treatment strategies should be preferred. In addition to surgical resection in localized stages as well as metastasectomy for oligometastatic advanced stages, neoadjuvant chemoradiotherapy for localized rectal cancer and cytostatic treatment, targeted treatment approaches should also be considered. This overview presents established and novel prognostic and predictive molecular markers of (metastasized) CRC and describes these as targeted therapy options. The determination of high microsatellite instability (MSI-H) has a\u00a0therapeutic influence when planning adjuvant therapy and also now in the treatment of metastatic CRC. Furthermore, circulating tumor DNA represents a\u00a0promising marker with respect to a\u00a0recurrence in early as well as in advanced stages of disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34448902"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1167, "text": "Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Although CRC has been comprehensively characterized at the molecular level, the tumor heterogeneity hinders the identification of reliable diagnostic, prognostic and predictive biomarkers. Molecular stratification of CRC is based on prevalent gene mutations and transcription profiles but its significance for clinical practice remains obscure. Indeed, activating mutations in the genes KRAS, NRAS and BRAF are the only predictive biomarkers for anti-EGFR antibody therapy routinely tested the clinic for advanced stages of CRC. Gene expression signatures are important for clarifying the molecular mechanisms of CRC development and progression, but only two such tests for predicting recurrence risk are commercially available. The aim of our study was to propose a diagnostic approach based on mutation and gene expression analysis that can be routinely applied in the clinic for defining the most appropriate treatment strategy for each patient. We used qPCR to determine the presence of KRAS mutations and measure the transcription levels of a panel of 26 genes in 24 CRC patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29788743"}, {"offsetInBeginSection": 0, "offsetInEndSection": 822, "text": "The revolution of precision medicine has produced unprecedented seismic shifts in the treatment paradigm of advanced cancers. Among the major killers, colorectal cancer (CRC) is far behind the others. In fact, the great successes obtained in breast, NSCLC, melanoma, and genitourinary tract tumors have been observed only in fewer than 5 % metastatic colorectal cancer (mCRC): those with the mismatch repair deficiency (dMMR), a well-known predictive factor for to the outstanding efficacy of checkpoint inhibitors (CPI). The treatment of the remaining vast majority mCRC patients is still based upon only two molecular determinants: the RAS and BRAF mutational status. New promising biomarkers include HER2, tumor mutational burden (TMB) for its possible implications on CPI efficacy, and the extremely rare NTRK fusions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35780916"}]}
+{"question_id": "66301c47187cba990d000025", "question": "What are the most common issues that need to be addressed in adults with Duchenne Muscular Dystrophy?", "answer": "Adults living with DMD need to address the following health-related issues: management of emergencies and safety of pharmacological treatments for psychiatric symptoms, chronic pain management, as well as an increasing caregivers burden.", "relevant_passage_ids": ["37724986", "32846887", "37688475", "35656606"], "type": "list", "snippets": [{"offsetInBeginSection": 1753, "offsetInEndSection": 2008, "text": "The analysis of adults living with DMD reveals several new health-related issues, such as the management of emergencies and safety of pharmacological treatments for psychiatric symptoms, chronic pain management, as well as an increasing caregivers burden.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37724986"}, {"offsetInBeginSection": 19, "offsetInEndSection": 121, "text": "Nutritional management of adults with Duchenne muscular dystrophy (DMD) is an important clinical issue", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37688475"}, {"offsetInBeginSection": 513, "offsetInEndSection": 687, "text": "Adolescents and adults with DMD have highly complex healthcare needs associated with long-term steroid usage, orthopedic, ventilation, cardiac, and gastrointestinal problems.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32846887"}]}
+{"question_id": "6621510eb9f8b89d7e000008", "question": "What histological features are described in colorectal tumors with BRAF mutation?", "answer": "The characteristic morphological features of tumors with BRAF mutation (infiltrating lymphocytes, poor grade, mucinous) remained after stratification according to microsatellite instability and methylator phenotypes.", "relevant_passage_ids": ["16403224", "17143472", "29052598", "26681025", "31162857", "25710585", "25929517", "30592501", "27914130", "24915895", "22314188", "31455041", "37792760", "32193591", "33145020", "28611337", "37240418", "32047231", "22522845", "24355196", "24925223", "30618001"], "type": "list", "snippets": [{"offsetInBeginSection": 876, "offsetInEndSection": 1092, "text": "The characteristic morphological features of tumors with BRAF mutation (infiltrating lymphocytes, poor grade, mucinous) remained after stratification according to microsatellite instability and methylator phenotypes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16403224"}, {"offsetInBeginSection": 451, "offsetInEndSection": 598, "text": "\u2022Moderately differentiated adenocarcinoma was the most frequent histological type, with 18.8% showing KRAS mutation and 11.9% showing BRAF mutation", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37792760"}, {"offsetInBeginSection": 254, "offsetInEndSection": 1507, "text": "ocarcinoma. Considering that dynamic, we aimed to determine how v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E and Kirsten rat sarcoma (KRAS) mutations relate to the location, histopathology, and degree of tumor differentiation in CRC.METHODS: With a cross-sectional design involving an observational analytical approach, we determined the relationship of BRAF V600E and KRAS mutations to the location, histopathology, and degree of tumor differentiation in CRC.RESULT: The sample contained 43 patients with CRC aged 21-80 years, with an average age of 56.0\u00a0\u00b1\u00a011.2 years, 46.5% of whom were male and 53.5% female, for a male-to-female ratio of 1.0-1.15. Most tumors were located in the right colon (n\u00a0=\u00a018, 41.9%), followed by the rectum (n\u00a0=\u00a014, 32.6%) and left colon (n\u00a0=\u00a018, 25.6%). Non-mucinous adenocarcinoma was more prevalent than mucinous adenocarcinoma, with 22 (51.2%) and 21 (48.8%) patients, respectively. Nineteen tumors were poorly differentiated (44.2%), 15 were moderately differentiated (34.9%), and nine were well-differentiated (20.9%). BRAF V600E mutations totaled six (14%), whereas non-BRAF V600E mutations totaled 37 (86.0%). BRAF V600E mutations significantly related to tumor location, degree of differentiation, an", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33145020"}, {"offsetInBeginSection": 0, "offsetInEndSection": 950, "text": "BRAF V600E and KRAS mutations that occur in colorectal cancer (CRC) define a subpopulation of patients with an inferior prognosis. Recently, the first BRAF V600E-targeting therapy has been approved and novel agents targeting KRAS G12C are being evaluated in CRC. A better understanding of the clinical characteristics of the populations defined by those mutations is needed. We created a retrospective database that collects clinical characteristics of patients with metastatic CRC evaluated for RAS and BRAF mutations in a single laboratory. A total of 7604 patients tested between October 2017 and December 2019 were included in the analysis. The prevalence of BRAF V600E was 6.77%. Female sex, primary in the right colon, high-grade, mucinous, signet cell, partially neuroendocrine histology, perineural and vascular invasion, and surgical tissue sample were factors associated with increased mutation rates. The prevalence of KRAS G12C was 3.11%.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37240418"}, {"offsetInBeginSection": 525, "offsetInEndSection": 1093, "text": "hey were 5-10-fold more frequent in tumors with infiltrating lymphocytes, location in the proximal colon, poor histological grade and mucinous appearance (P < 0.002 for each). Tumors with BRAF mutation were also 10-fold more likely to show microsatellite instability and frequent DNA methylation (P < 0.0001) compared to tumors without this mutation. The characteristic morphological features of tumors with BRAF mutation (infiltrating lymphocytes, poor grade, mucinous) remained after stratification according to microsatellite instability and methylator phenotypes. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16403224"}, {"offsetInBeginSection": 305, "offsetInEndSection": 699, "text": " The aim of the present study was to evaluate the clinical, pathological and molecular phenotype of colorectal tumors with BRAF mutations.RESULTS: Mutations in BRAF were identified in 8% (23/275) of colorectal cancers. They were 5-10-fold more frequent in tumors with infiltrating lymphocytes, location in the proximal colon, poor histological grade and mucinous appearance (P < 0.002 for each)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16403224"}, {"offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Tumour infiltrating lymphocyte status is superior to histological grade, DNA mismatch repair and BRAF mutation for prognosis of colorectal adenocarcinomas with mucinous differentiation.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32047231"}, {"offsetInBeginSection": 445, "offsetInEndSection": 701, "text": "SULTS: Mutations in BRAF were identified in 8% (23/275) of colorectal cancers. They were 5-10-fold more frequent in tumors with infiltrating lymphocytes, location in the proximal colon, poor histological grade and mucinous appearance (P < 0.002 for each). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16403224"}, {"offsetInBeginSection": 445, "offsetInEndSection": 876, "text": "SULTS: Mutations in BRAF were identified in 8% (23/275) of colorectal cancers. They were 5-10-fold more frequent in tumors with infiltrating lymphocytes, location in the proximal colon, poor histological grade and mucinous appearance (P < 0.002 for each). Tumors with BRAF mutation were also 10-fold more likely to show microsatellite instability and frequent DNA methylation (P < 0.0001) compared to tumors without this mutation. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16403224"}, {"offsetInBeginSection": 525, "offsetInEndSection": 876, "text": "hey were 5-10-fold more frequent in tumors with infiltrating lymphocytes, location in the proximal colon, poor histological grade and mucinous appearance (P < 0.002 for each). Tumors with BRAF mutation were also 10-fold more likely to show microsatellite instability and frequent DNA methylation (P < 0.0001) compared to tumors without this mutation. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16403224"}, {"offsetInBeginSection": 702, "offsetInEndSection": 1093, "text": "umors with BRAF mutation were also 10-fold more likely to show microsatellite instability and frequent DNA methylation (P < 0.0001) compared to tumors without this mutation. The characteristic morphological features of tumors with BRAF mutation (infiltrating lymphocytes, poor grade, mucinous) remained after stratification according to microsatellite instability and methylator phenotypes. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16403224"}, {"offsetInBeginSection": 524, "offsetInEndSection": 700, "text": "They were 5-10-fold more frequent in tumors with infiltrating lymphocytes, location in the proximal colon, poor histological grade and mucinous appearance (P < 0.002 for each).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16403224"}, {"offsetInBeginSection": 2612, "offsetInEndSection": 2956, "text": "Our results demonstrate that BRAF-mutated proximal colon adenocarcinomas with proficient DNA mismatch repair have a dismal prognosis with an aggressive clinical course and often display mucinous differentiation, focal signet ring histology, and other adverse histologic features such as lymphatic and perineural invasion and high tumor budding.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22314188"}, {"offsetInBeginSection": 960, "offsetInEndSection": 1250, "text": "ases and among pTNM stages. Whereas, BRAF-mutated carcinomas more frequently demonstrated histologic features such as proximal location (60.9% vs 20.9%, p\u2009=\u20090.001), low-grade histology (43.5% vs 18.0%, p\u2009=\u20090.005), mucinous differentiation (69.6% vs 25.9%, p\u2009=\u20090.001) and deficient MMR (dMMR", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25929517"}, {"offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "BRAF-mutated, microsatellite-stable adenocarcinoma of the proximal colon: an aggressive adenocarcinoma with poor survival, mucinous differentiation, and adverse morphologic features.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22314188"}, {"offsetInBeginSection": 1306, "offsetInEndSection": 1500, "text": "BRAF-mutated adenocarcinomas frequently contained areas with mucinous histology (P=0.0002) and signet ring histology (P=0.03), compared with KRAS-mutated and KRAS/BRAF wild-type adenocarcinomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22314188"}, {"offsetInBeginSection": 929, "offsetInEndSection": 1305, "text": "Compared with BRAF wild-type adenocarcinomas, BRAF-mutated adenocarcinomas more frequently demonstrated adverse histologic features such as lymphatic invasion (16/20, 80% vs. 75/161, 47%; P=0.008), mean number of lymph node metastases (4.5 vs. 2.2; P=0.01), perineural invasion (8/20, 40% vs. 13/161, 8%; P=0.0004), and high tumor budding (16/20, 80% vs. 83/161, 52%; P=0.02).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22314188"}, {"offsetInBeginSection": 329, "offsetInEndSection": 848, "text": "The mutation is found in 5 to 15% of colorectal carcinomas and is less common in Asian populations. BRAF mutations are linked with older age, female gender, cigarette smoking and are more common in the right (proximal) portion of the large intestine. BRAF mutations are associated with carcinomas of high histological grade and advanced cancer stages. Often BRAF mutated carcinomas demonstrate adverse histological features such as lymphovascular invasion, perineural invasion, tumour budding and lymph node metastases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30592501"}, {"offsetInBeginSection": 1148, "offsetInEndSection": 1240, "text": "BRAF mutations, which were strongly associated with poorly differentiated tumors (P < 0.005)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26681025"}, {"offsetInBeginSection": 294, "offsetInEndSection": 1205, "text": "t mutation. The aim of the present study was to evaluate the clinical, pathological and molecular phenotype of colorectal tumors with BRAF mutations.RESULTS: Mutations in BRAF were identified in 8% (23/275) of colorectal cancers. They were 5-10-fold more frequent in tumors with infiltrating lymphocytes, location in the proximal colon, poor histological grade and mucinous appearance (P < 0.002 for each). Tumors with BRAF mutation were also 10-fold more likely to show microsatellite instability and frequent DNA methylation (P < 0.0001) compared to tumors without this mutation. The characteristic morphological features of tumors with BRAF mutation (infiltrating lymphocytes, poor grade, mucinous) remained after stratification according to microsatellite instability and methylator phenotypes. Mutations in BRAF were mutually exclusive with mutations in KRAS but showed no clear association with the presen", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16403224"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1666, "text": "In colorectal cancer, KRAS (exons 2, 3, and 4) and NRAS (exons 2, 3, and 4) mutations are associated with resistance to antiepidermal growth factor receptor monoclonal antibodies, and BRAF mutation is a molecular marker of poor prognosis. KRAS exon 2 and BRAF-mutated colorectal cancers have well-known distinct clinicopathological characteristics. Comparison of tumors with different RAS status (exons 2, 3, and 4 of KRAS and NRAS) based on their clinicopathological characteristics has never been established. All colorectal cancer patients with RAS and BRAF testing from 2011 to 2015 were included in this observational retrospective study. Patient and tumor characteristics were collected and correlation with RAS and BRAF status was evaluated. A total of 1735 patients with colorectal cancer were included. RAS-mutated colorectal cancers (n=1002), compared with RAS wild-type colorectal cancers (n=733), were significantly associated with male gender, classical adenocarcinoma subtype, well/moderately differentiated tumors, and microsatellite stable phenotype. KRAS codon 13-mutated colorectal cancers (n=171), compared with RAS wild-type colorectal cancers, more frequently presented classical adenocarcinoma subtype and microsatellite stable phenotype. In comparison with other RAS mutations, KRAS exon 3-mutated colorectal cancers (n=23) were associated with mucinous/rare histological subtypes and, most likely to located in the rectum. KRAS exon 4-mutated colorectal cancers (n=33) were more frequently associated with mucinous/rare histological subtypes. There was no significant association between NRAS mutation (n=37) and clinicopathological features.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29052598"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1241, "text": "KRAS and BRAF mutations are well-recognized molecular alterations during colorectal carcinogenesis, but there is little agreement on their effect on tumor characteristics. Therefore, we aimed to evaluate the distribution of the most common KRAS and BRAF mutations in Greek patients with colorectal cancer and their possible associations with clinical histopathological parameters. In this study, 322 and 188 colorectal carcinomas were used for the mutation analysis of KRAS (exon 2) and BRAF (exon 15) genes, respectively. The mutational status of both genes was evaluated by polymerase chain reaction and sequencing analysis. Although the overall frequency of KRAS mutations (36.6%) seemed to be similar to those reported for other populations, the rate of point mutations at codon 13 was significantly lower (12%) in Greek patients with colorectal cancer and associated with male gender (P < 0.05). Tumors with G>T codon 12 transversions and G>C transitions showed more frequent lymph node metastasis (P < 0.05, P < 0.005, respectively). The rate of KRAS mutations gradually decreased with increasing histological grade (P < 0.05), as opposed to BRAF mutations, which were strongly associated with poorly differentiated tumors (P < 0.005).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26681025"}, {"offsetInBeginSection": 60, "offsetInEndSection": 959, "text": "ncer (CRC). The aim of our study was to evaluate the pathological and molecular features of specific KRAS mutated colorectal carcinomas. KRAS and BRAF (V600E) mutation tests were performed in 762 primary tumors from a consecutive cohort study of Chinese CRC patients.METHODS: DNA mismatch repair (MMR) status was determined by immunohistochemistry (IHC) staining. Assessment of KRAS and BRAF V600E mutational status was performed using a multiplex allele-specific PCR-based assay.RESULTS: Mutations of KRAS (34.8%) and BRAF (V600E) (3.1%) were nearly mutually exclusive. Both KRAS- and BRAF- mutated tumors were more likely to be located at proximal colon than wild-type (WT) carcinomas. KRAS-mutated carcinomas were more frequently observed in female patients (47.5% vs 37.1%, p\u2009=\u20090.005) and mucinous differentiation (34.7% vs 24.8%, p\u2009=\u20090.004), but have no difference between lymph node (LN) metas", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25929517"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1342, "text": "KRAS/BRAF mutation testing and mismatch repair (MMR) protein immunohistochemistry have an established role in routine diagnostic evaluation of colorectal carcinoma (CRC). However, since the exact impact of these molecular characteristics on tumor morphology and behavior is still subject to research, the aim of our study was to examine associations between molecular and morphologic features that had not been analyzed in this combination before. KRAS (codons 12, 13, and 61) and BRAF (codon 600) mutation status and MMR protein expression were analyzed in a consecutive series of 117 CRC samples using DNA pyrosequencing and immunohistochemistry. Tumor cell budding, infiltration pattern, and peritumoral lymphocytic (PTL) reaction was assessed applying established criteria. Molecular and morphological findings were correlated applying chi-square and Fisher's exact test. We found KRAS or BRAF mutations in 40 and 8 % of samples, while loss of MMR protein expression was observed in 11 %. Tumor budding was significantly associated with infiltrative growth, absence of PTLs, and blood and lymph vessel infiltration. Neither KRAS nor BRAF mutations were associated with a certain growth pattern or budding intensity of CRC, but loss of MMR protein expression was found in context with BRAF mutation, expanding growth, and presence of PTLs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24915895"}, {"offsetInBeginSection": 681, "offsetInEndSection": 848, "text": "Often BRAF mutated carcinomas demonstrate adverse histological features such as lymphovascular invasion, perineural invasion, tumour budding and lymph node metastases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30592501"}, {"offsetInBeginSection": 1029, "offsetInEndSection": 1209, "text": "an those with wild-type BRAF (p\u2009=\u20090.001). BRAF-mutant tumors were predominant in right-sided colon (p\u2009=\u20090.001) with higher numbers of polypoid- or mass-like morphology (p\u2009=\u20090.019) ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32193591"}, {"offsetInBeginSection": 1508, "offsetInEndSection": 1671, "text": " histopathology (p\u00a0< .01).CONCLUSION: A significant relationship exists between BRAF V600E mutations in the stool of patients with CRC and location, histopathology", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33145020"}, {"offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Mutational analysis of the BRAF gene in colorectal mucinous carcinoma in association with histological configuration.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17143472"}, {"offsetInBeginSection": 702, "offsetInEndSection": 1226, "text": "umors with BRAF mutation were also 10-fold more likely to show microsatellite instability and frequent DNA methylation (P < 0.0001) compared to tumors without this mutation. The characteristic morphological features of tumors with BRAF mutation (infiltrating lymphocytes, poor grade, mucinous) remained after stratification according to microsatellite instability and methylator phenotypes. Mutations in BRAF were mutually exclusive with mutations in KRAS but showed no clear association with the presence of TP53 mutation.C", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16403224"}, {"offsetInBeginSection": 1208, "offsetInEndSection": 1426, "text": "Moreover, morphologic features significantly associated with BRAF mutation were: serrated adenocarcinoma subtype, adenocarcinomas with a mucinous component, high histologic grade, pushing margins, stromal inflammation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25710585"}, {"offsetInBeginSection": 557, "offsetInEndSection": 790, "text": "Loss of staining was found in 110 (5.9%) of 1876 CRCs and was strongly associated with older age, right sided location, large size, BRAF V600E mutation, MMR deficiency, high histological grade and medullary morphology, (all P < .01).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24925223"}, {"offsetInBeginSection": 645, "offsetInEndSection": 911, "text": "The prevalence of BRAF V600E was 6.77%. Female sex, primary in the right colon, high-grade, mucinous, signet cell, partially neuroendocrine histology, perineural and vascular invasion, and surgical tissue sample were factors associated with increased mutation rates.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37240418"}]}
+{"question_id": "662e44e9187cba990d00000b", "question": "Is vaccination against all arboviruses indicated for pregnant women?", "answer": "No, not all arboviral vaccines are indicated for pregnant women.", "relevant_passage_ids": ["37517630"], "type": "yesno", "snippets": [{"offsetInBeginSection": 287, "offsetInEndSection": 718, "text": "Several arboviral vaccines have been licensed for many years and can be used to prevent infection in travelers, namely Japanese encephalitis, yellow fever, and tick-borne encephalitis vaccines. Recommendations on use of these vaccines in pregnancy vary. Other arboviral vaccines have been licensed but are not indicated for use in pregnant travelers (e.g., dengue vaccines) or are in development (e.g., chikungunya, Zika vaccines).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37517630"}]}
+{"question_id": "662fc4b1187cba990d000016", "question": "What are the mechanisms of action of regorafenib on tumor cells?", "answer": "Regorafenib, an oral small-molecule multi kinase inhibitor, is able to block Vascular Endothelial Growth Factor Receptors (VEGFR-1, 2, and 3), Platelet-Derived Growth Factor Receptors (PDGF), Fibroblast Growth Factor (FGF) receptor 1, Raf, TIE-2, and the kinases KIT, RET, and BRAF).  Furthermore, regorafenib has the important effect of enhancing anti-tumor immunity via macrophage modulation.", "relevant_passage_ids": ["31715423", "26419617", "24347491", "24763611", "28489887", "31163381", "29535278", "31551425", "28954993", "37559050", "32457362", "35502476", "20208561", "36720853", "24309512", "22286758", "21170960", "24756792", "26865419", "32024199", "34864311"], "type": "list", "snippets": [{"offsetInBeginSection": 223, "offsetInEndSection": 237, "text": "RAF1 inhibitor", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31715423"}, {"offsetInBeginSection": 580, "offsetInEndSection": 621, "text": "dual blockade of VEGF receptors and TIE2 ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31715423"}, {"offsetInBeginSection": 809, "offsetInEndSection": 838, "text": "FGF, PIGF, and PDGF signaling", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31715423"}, {"offsetInBeginSection": 1019, "offsetInEndSection": 1041, "text": "macrophage modulation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31715423"}, {"offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "Regorafenib, an oral small-molecule multi kinase inhibitor, is able to block Vascular Endothelial Growth Factor Receptors (VEGFR-1, 2, and 3), Platelet-Derived Growth Factor Receptors (PDGF), Fibroblast Growth Factor (FGF) receptor 1, Raf, TIE-2, and the kinases KIT, RET, and BRAF.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26419617"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1087, "text": "Regorafenib is a sorafenib-derived chemotherapy drug belonging to the multikinase inhibitor family. This agent effectively targets a wide range of tyrosine kinases involved in cancer biology, such as those implicated in oncogenesis, angiogenesis, and tumor microenvironment control. The beneficial effects of regorafenib in clinical trials of patients who suffer from advanced hepatocellular carcinoma (HCC), colorectal cancer (CRC) or gastrointestinal stromal tumors (GISTs) refractory to standard treatments led to regorafenib monotherapy approval as a second-line treatment for advanced HCC and as a third-line treatment for advanced CRC and GISTs. Multiple in vitro and in vivo studies have been performed over the last decade to reveal the molecular mechanisms of the favorable actions exerted by regorafenib in patients. Given the hypothetical loss of sensitivity to regorafenib in tumor cells, preclinical research is also searching for novel therapeutic approaches consisting of co-administration of this drug plus other agents as a strategy to improve regorafenib effectiveness.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31551425"}, {"offsetInBeginSection": 0, "offsetInEndSection": 931, "text": "Regorafenib is a multi-targeting kinase inhibitor approved for the treatment of metastatic colorectal cancer patients in refractory to standard chemotherapy. Similarly to sorafenib, this agent was originally developed as a RAF1 inhibitor. However, the kinase inhibitory profile is distinct from sorafenib. A broad-spectrum of kinase inhibition induces wide-range drug sensitivity, irrespective of mutation status of major oncogenes. This agent's main therapeutic effects are anti-angiogenesis and the remodeling of tumor microenvironment through several mechanisms of action. The dual blockade of VEGF receptors and TIE2 can lead to both additive anti-angiogenesis effects and the suggestive unique regulation of vessel stability. Additionally, it inhibits molecular escape pathways to VEGF inhibition (e.g., FGF, PIGF, and PDGF signaling), enabling its continuous antiangiogenic effect even in tumors resistant to VEGF inhibitors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31715423"}, {"offsetInBeginSection": 394, "offsetInEndSection": 1242, "text": "In addition to endothelial cells, cancer cells express the three receptors, suggesting that the antiangiogenic inhibitors affect tumor cells. In fact, we previously demonstrated that regorafenib directly acted on human colorectal cancer cells and accelerated their apoptosis resistance and migration capability. Thus, we here elucidated how regorafenib induced the malignant phenotypes in colorectal cancer cells. To identify the responsible receptor among the regorafenib-targeting proangiogenic receptors, we examined the effects of a potent selective inhibitor for VEGF-R, FGF-R or PDGF-R on apoptosis resistance and migration capability. We clarified that blockade of VEGF-R, but not FGF-R and PDGF-R, induced the malignant phenotypes. We confirmed that blocking of VEGF ligands derived from colorectal cancer cells also induced the phenotypes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28954993"}, {"offsetInBeginSection": 394, "offsetInEndSection": 807, "text": "In addition to endothelial cells, cancer cells express the three receptors, suggesting that the antiangiogenic inhibitors affect tumor cells. In fact, we previously demonstrated that regorafenib directly acted on human colorectal cancer cells and accelerated their apoptosis resistance and migration capability. Thus, we here elucidated how regorafenib induced the malignant phenotypes in colorectal cancer cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28954993"}, {"offsetInBeginSection": 394, "offsetInEndSection": 705, "text": "In addition to endothelial cells, cancer cells express the three receptors, suggesting that the antiangiogenic inhibitors affect tumor cells. In fact, we previously demonstrated that regorafenib directly acted on human colorectal cancer cells and accelerated their apoptosis resistance and migration capability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28954993"}, {"offsetInBeginSection": 271, "offsetInEndSection": 705, "text": "Thus, the antiangiogenic agents, such as regorafenib, simultaneously target those receptors on vascular endothelial cells. In addition to endothelial cells, cancer cells express the three receptors, suggesting that the antiangiogenic inhibitors affect tumor cells. In fact, we previously demonstrated that regorafenib directly acted on human colorectal cancer cells and accelerated their apoptosis resistance and migration capability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28954993"}, {"offsetInBeginSection": 271, "offsetInEndSection": 535, "text": "Thus, the antiangiogenic agents, such as regorafenib, simultaneously target those receptors on vascular endothelial cells. In addition to endothelial cells, cancer cells express the three receptors, suggesting that the antiangiogenic inhibitors affect tumor cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28954993"}, {"offsetInBeginSection": 536, "offsetInEndSection": 1035, "text": "In fact, we previously demonstrated that regorafenib directly acted on human colorectal cancer cells and accelerated their apoptosis resistance and migration capability. Thus, we here elucidated how regorafenib induced the malignant phenotypes in colorectal cancer cells. To identify the responsible receptor among the regorafenib-targeting proangiogenic receptors, we examined the effects of a potent selective inhibitor for VEGF-R, FGF-R or PDGF-R on apoptosis resistance and migration capability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28954993"}, {"offsetInBeginSection": 0, "offsetInEndSection": 393, "text": "Recently, inhibition of tumor angiogenesis has become an important anti-cancer therapy. Tumor angiogenesis is regulated by multiple signaling pathways, including VEGF and VEGF receptor (VEGF-R), FGF and FGF receptor (FGF-R), and PDGF and PDGF receptor (PDGF-R) pathways. Thus, the antiangiogenic agents, such as regorafenib, simultaneously target those receptors on vascular endothelial cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28954993"}, {"offsetInBeginSection": 706, "offsetInEndSection": 1035, "text": "Thus, we here elucidated how regorafenib induced the malignant phenotypes in colorectal cancer cells. To identify the responsible receptor among the regorafenib-targeting proangiogenic receptors, we examined the effects of a potent selective inhibitor for VEGF-R, FGF-R or PDGF-R on apoptosis resistance and migration capability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28954993"}, {"offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "PURPOSE: Regorafenib, a multikinase inhibitor targeting the Ras/Raf/MEK/ERK pathway, has recently been approved for the treatment of metastatic colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24763611"}, {"offsetInBeginSection": 0, "offsetInEndSection": 945, "text": "Sorafenib (Nexavar) is a multi-kinase inhibitor that was developed as an inhibitor of RAF-1, in the ERK1/2 pathway, but which was subsequently shown to inhibit class III tyrosine kinase receptors. (1) More recently regorafenib (Stivarga) has been developed, which is a further fluorinated version of sorafenib with greater bioavailability and similar inhibitory properties against RAF-1/class III RTKs. (2) Some of the anti-tumor effects of sorafenib have been ascribed to anti-angiogenic actions of this agent on endothelial associated kinases such as VEGFR2. Other effects of sorafenib clearly have to be due to its effects on the inherent biology of the tumor cells themselves. For example, through various mechanisms sorafenib has been shown in the laboratory and the clinic to suppress expression of the protective protein MCL-1. (3) Sorafenib has also been linked to inhibition of STAT3, NF\u03baB, and activation of the death receptor CD95. (4", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24309512"}, {"offsetInBeginSection": 133, "offsetInEndSection": 1832, "text": "Inhibition of this pathway can effectively suppress tumor cell growth. For example, sorafenib, a multi-kinase inhibitor targeting c-Raf and other oncogenic kinases, has been used clinically for treating advanced liver and kidney tumors, and also has shown efficacy against other malignancies. However, how inhibition of oncogenic signaling by sorafenib and other drugs suppresses tumor cell growth remains unclear. In this study, we found that sorafenib kills cancer cells by activating PUMA (p53-upregulated modulator of apoptosis), a p53 target and a BH3-only Bcl-2 family protein. Sorafenib treatment induces PUMA in a variety of cancer cells irrespective of their p53 status. Surprisingly, the induction of PUMA by sorafenib is mediated by I\u03baB-independent activation of nuclear factor (NF)-\u03baB, which directly binds to the PUMA promoter to activate its transcription. NF-\u03baB activation by sorafenib requires glycogen synthase kinase 3\u03b2 activation, subsequent to ERK inhibition. Deficiency in PUMA abrogates sorafenib-induced apoptosis and caspase activation, and renders sorafenib resistance in colony formation and xenograft tumor assays. Furthermore, the chemosensitization effect of sorafenib is dependent on PUMA, and involves concurrent PUMA induction through different pathways. BH3 mimetics potentiate the anti-cancer effects of sorafenib, and restore sorafenib sensitivity in resistant cells. Together, these results demonstrate a key role of PUMA-dependent apoptosis in therapeutic inhibition of Ras/Raf/MEK/ERK signaling. They provide a rationale for manipulating the apoptotic machinery to improve sensitivity and overcome resistance to the therapies that target oncogenic kinase signal", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22286758"}, {"offsetInBeginSection": 403, "offsetInEndSection": 560, "text": "(2) Some of the anti-tumor effects of sorafenib have been ascribed to anti-angiogenic actions of this agent on endothelial associated kinases such as VEGFR2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24309512"}, {"offsetInBeginSection": 835, "offsetInEndSection": 942, "text": "(3) Sorafenib has also been linked to inhibition of STAT3, NF\u03baB, and activation of the death receptor CD95.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24309512"}, {"offsetInBeginSection": 0, "offsetInEndSection": 378, "text": "PURPOSE: Regorafenib, a multikinase inhibitor targeting the Ras/Raf/MEK/ERK pathway, has recently been approved for the treatment of metastatic colorectal cancer. However, the mechanisms of action of regorafenib in colorectal cancer cells have been unclear. We investigated how regorafenib suppresses colorectal cancer cell growth and potentiates effects of other chemotherapeut", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24763611"}, {"offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Regorafenib (BAY 73-4506, Stivarga\u00ae) is an oral diphenylurea multikinase inhibitor that targets angiogenic (VEGFR1-3, TIE2), stromal (PDGFR-\u03b2, FGFR), and oncogenic receptor tyrosine kinases (KIT, RET, and RAF", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24756792"}, {"offsetInBeginSection": 1036, "offsetInEndSection": 1133, "text": "We clarified that blockade of VEGF-R, but not FGF-R and PDGF-R, induced the malignant phenotypes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28954993"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1658, "text": "Regorafenib, a novel multikinase inhibitor, has recently demonstrated overall survival benefits in metastatic colorectal cancer (CRC) patients. Our study aimed to gain further insight into the molecular mechanisms of regorafenib and to assess its potential in combination therapy. Regorafenib was tested alone and in combination with irinotecan in patient-derived (PD) CRC models and a murine CRC liver metastasis model. Mechanism of action was investigated using in vitro functional assays, immunohistochemistry and correlation with CRC-related oncogenes. Regorafenib demonstrated significant inhibition of growth-factor-mediated vascular endothelial growth factor receptor (VEGFR) 2 and VEGFR3 autophosphorylation, and intracellular VEGFR3 signaling in human umbilical vascular endothelial cells (HuVECs) and lymphatic endothelial cells (LECs), and also blocked migration of LECs. Furthermore, regorafenib inhibited proliferation in 19 of 25 human CRC cell lines and markedly slowed tumor growth in five of seven PD xenograft models. Combination of regorafenib with irinotecan significantly delayed tumor growth after extended treatment in four xenograft models. Reduced CD31 staining indicates that the antiangiogenic effects of regorafenib contribute to its antitumor activity. Finally, regorafenib significantly delayed disease progression in a murine CRC liver metastasis model by inhibiting the growth of established liver metastases and preventing the formation of new metastases in other organs. In addition, our results suggest that regorafenib displays antimetastatic activity, which may contribute to its efficacy in patients with metastatic CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24347491"}, {"offsetInBeginSection": 436, "offsetInEndSection": 875, "text": ". A novel oral multikinase inhibitor regorafenib inhibits receptor tyrosine kinases expressed on stromal cells (vascular endothelial growth factor receptor 1-3, TIE2, PDGFR-\u03b2, and fibroblast growth factors) and tumor cells (c-KIT, RET, and BRAF). These molecules are involved in tumor growth, angiogenesis, lymphangiogenesis, and stromal activation. Therefore, we examined whether regorafenib impaired the tumor-promoting effect of CAFs/MS", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26865419"}, {"offsetInBeginSection": 0, "offsetInEndSection": 818, "text": "PURPOSE: Regorafenib, a multikinase inhibitor targeting the Ras/Raf/MEK/ERK pathway, has recently been approved for the treatment of metastatic colorectal cancer. However, the mechanisms of action of regorafenib in colorectal cancer cells have been unclear. We investigated how regorafenib suppresses colorectal cancer cell growth and potentiates effects of other chemotherapeutic drugs.EXPERIMENTAL DESIGN: We determined whether and how regorafenib induces the expression of PUMA, a p53 target and a critical mediator of apoptosis in colorectal cancer cells. We also investigated whether PUMA is necessary for the killing and chemosensitization effects of regorafenib in colorectal cancer cells. Furthermore, xenograft tumors were used to test if PUMA mediates the in vivo antitumor, antiangiogenic, and chemosensitiz", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24763611"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1137, "text": "Sorafenib (Nexavar) is a multi-kinase inhibitor that was developed as an inhibitor of RAF-1, in the ERK1/2 pathway, but which was subsequently shown to inhibit class III tyrosine kinase receptors. (1) More recently regorafenib (Stivarga) has been developed, which is a further fluorinated version of sorafenib with greater bioavailability and similar inhibitory properties against RAF-1/class III RTKs. (2) Some of the anti-tumor effects of sorafenib have been ascribed to anti-angiogenic actions of this agent on endothelial associated kinases such as VEGFR2. Other effects of sorafenib clearly have to be due to its effects on the inherent biology of the tumor cells themselves. For example, through various mechanisms sorafenib has been shown in the laboratory and the clinic to suppress expression of the protective protein MCL-1. (3) Sorafenib has also been linked to inhibition of STAT3, NF\u03baB, and activation of the death receptor CD95. (4) Sorafenib is routinely dosed daily (400 mg BID) and 7 d after the start of dosing has a Cmax of ~21 \u03bcM with a nadir at 12 h of ~10 \u03bcM, and is a highly protein bound based on in vitro assays.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24309512"}, {"offsetInBeginSection": 728, "offsetInEndSection": 843, "text": "REGO treatment promotes Bim expression via the FOXO3a nuclear localization pathway following PI3K/AKT inactivation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36720853"}]}
+{"question_id": "661d5fe1eac11fad33000024", "question": "What are the types of Polycystic Kidney Disease?", "answer": "There are two types of Polycystic Kidney Disease (PKD): autosomal recesive PKD (ARPKD) and autosomal dominant PKD (ADPKD).", "relevant_passage_ids": ["24584572", "8296686", "25753522", "32475690", "34882278", "30523303", "23095811", "37823335", "37780053", "29623269", "35664268", "33125856", "36807559", "28952822", "33474686", "34177435", "33786104", "34290017", "28455745", "24011172", "34032358"], "type": "list", "snippets": [{"offsetInBeginSection": 274, "offsetInEndSection": 431, "text": "While the recessive form of PKD (ARPKD) virtually always presents in childhood, early onset can, in some instances, also occur in the dominant form (ADPKD). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24584572"}, {"offsetInBeginSection": 393, "offsetInEndSection": 494, "text": "Mutations in the genes which encode PKD1 and PKD2 lead to autosomal polycystic kidney disease (ADPKD)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37823335"}, {"offsetInBeginSection": 720, "offsetInEndSection": 800, "text": "Genetic analysis confirmed autosomal recessive polycystic kidney disease (ARPKD)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37780053"}, {"offsetInBeginSection": 122, "offsetInEndSection": 591, "text": "Autosomal-dominant polycystic kidney disease (ADPKD) is by far the most common renal cystic disease. However, there are various cystic kidney diseases, the onset of which occurs at different times in life and depends on the type of the disease and the causative genes involved. When genetic kidney diseases are discussed in the adult setting this view is usually limited on autosomal-dominant kidney disease, the most frequent genetic disorder causing adult onset ESRD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29623269"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1021, "text": "Polycystic kidneys disease refers to cyst(s) formation in kidneys with severe consequences of end stage renal disease thus have higher mortality. It is a common genetic disease occurring either as autosomal dominant polycystic kidney (ADPKD) or autosomal recessive polycystic kidney disease (ARPKD) with prevalence rates of 1/1000 and 1/40,000 respectively. Dominant forms presenting in later (>30) while recessive in earlier ages (infancy) and affecting both sexes and almost all race. The patient experiences many renal as well as extra-renal manifestations with marked hypertension and cyst formation in other organs predominantly in liver. Due to genetic basis, positive family history is considered as major risk factor. Ultrasonography remains the main stay of diagnosis along with family history, by indicating increased renal size and architectural modifications. Initially disease remains asymptomatic, later on symptomatic treatment is suggested with surgical interventions like cyst decortications or drainage.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33125856"}, {"offsetInBeginSection": 0, "offsetInEndSection": 758, "text": "INTRODUCTION: Polycystic kidney disease (PKD) is clinically and genetically heterogeneous and constitutes the most common heritable kidney disease. Most patients are affected by the autosomal dominant form (ADPKD) which generally is an adult-onset multisystem disorder. By contrast, the rarer recessive form ARPKD usually already manifests perinatally or in childhood. In some patients, however, ADPKD and ARPKD can phenotypically overlap with early manifestation in ADPKD and only late onset in ARPKD. Progressive fibrocystic renal changes are often accompanied by severe hepatobiliary changes or other extrarenal abnormalities. Areas covered: A reduced dosage of disease proteins disturbs cell homeostasis and explains a more severe clinical course in some", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28952822"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1052, "text": "Background: Polycystic kidney diseases (PKD) are an important cause of chronic kidney disease (CKD). Autosomal dominant polycystic kidney disease (ADPKD) due to PKD1 or PKD2 mutations is the most common form, but other genes can be responsible for ADPKD and its phenocopies. Among them, a form of atypical ADPKD caused by DNAJB11 mutations (DNAJB11-PKD) has been recently described.Methods: We retrospectively recruited a cohort of 27 patients from six different families sharing common ancestries and harboring the same DNAJB11 mutation (c.100C>T, p.Arg34*) and we compared it with a cohort of 42 typical ADPKD patients.Results: DNAJB11-PKD patients show small/normal-sized kidneys, with significantly smaller cysts and a slower progression to end-stage kidney disease (ESKD) than ADPKD patients. In the DNAJB11-PKD cohort, the cystic phenotype could not be detected by ultrasound in about half of the patients, but all cases with available computed tomography/magnetic resonance scans displayed cysts. Clinically, DNAJB11-PKD patients displayed prote", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35664268"}, {"offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are characterized by bilateral cystic kidney disease leading to progressive kidney function decline. These diseases also have distinct liver manifestations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33474686"}, {"offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are characterized by bilateral cystic kidney disease leading to progressive kidney function decline.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33474686"}, {"offsetInBeginSection": 0, "offsetInEndSection": 379, "text": "Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are characterized by bilateral cystic kidney disease leading to progressive kidney function decline. These diseases also have distinct liver manifestations. The range of clinical presentation and severity of both ADPKD and ARPKD is much wider than was once recognized.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33474686"}, {"offsetInBeginSection": 79, "offsetInEndSection": 171, "text": "The two main types of PKD are autosomal recessive and autosomal dominant PKD (ARPKD, ADPKD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34882278"}, {"offsetInBeginSection": 544, "offsetInEndSection": 1002, "text": "The basis of the clinical variability in both forms of PKD is not well understood and there are also limited prediction markers for disease progression for daily clinical life or surrogate endpoints for clinical trials in ARPKD or early ADPKD.As targeted therapeutic approaches to slow disease progression in PKD are emerging, it is becoming more important to reliably identify patients at risk for rapid progression as they might benefit from early therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34882278"}, {"offsetInBeginSection": 221, "offsetInEndSection": 323, "text": "The two major types of PKD show autosomal dominant (ADPKD) or autosomal recessive inheritance (ARPKD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23095811"}, {"offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Polycystic kidney disease (PKD), comprising autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD), is characterized by incessant cyst formation in the kidney and liver.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32475690"}, {"offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Autosomal dominant polycystic kidney disease (ADPKD) is the most common congenital kidney disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33786104"}, {"offsetInBeginSection": 200, "offsetInEndSection": 350, "text": "In humans, there are two types of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25753522"}, {"offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "Autosomal recessive polycystic kidney disease (RPKD) (also called infantile polycystic kidney disease) and autosomal dominant polycystic kidney disease (DPKD) (or adult form) are the two main types of genetic polycystic kidney diseases (PKD) encountered in children and infants.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8296686"}, {"offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Polycystic kidney disease (PKD) is a condition typified by multiple renal cysts and renal enlargement. Classification is usually determined by mode of inheritance-autosomal dominant PKD (ADPKD) or autosomal recessive PKD (ARPKD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34290017"}, {"offsetInBeginSection": 0, "offsetInEndSection": 415, "text": "Polycystic kidney disease (PKD) is a life-threatening condition resulting in end-stage renal disease. Two major forms of PKD are defined according to the inheritance pattern. Autosomal dominant PKD (ADPKD) is characterized by renal cysts, where nearly half of the patients suffers from renal failure in the 7th decade of life. Autosomal recessive PKD (ARPKD) is a rarer and more severe form presenting in childhood.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34177435"}, {"offsetInBeginSection": 114, "offsetInEndSection": 258, "text": "The two classic forms of PKD are autosomal recessive polycystic kidney disease (ARPKD) and autosomal dominant polycystic kidney disease (ADPKD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28455745"}, {"offsetInBeginSection": 0, "offsetInEndSection": 654, "text": "Polycystic kidney disease (PKD) is a hereditary disorder with abnormal cellular proliferation, fluid accumulation in numerous cysts, remodeling of extracellular matrix, inflammation, and fibrosis in the kidney and liver. The two major types of PKD show autosomal dominant (ADPKD) or autosomal recessive inheritance (ARPKD). ADPKD is one of the most common genetic diseases, with an incidence of 1:500-1,000. Approximately 50% of patients with ADPKD develop end-stage renal disease (ESRD) by the age of 60. On the other hand, ARPKD is relatively rare, with an incidence of approximately 1:20,000-40,000. ARPKD is diagnosed early in life, often prenatally.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23095811"}, {"offsetInBeginSection": 0, "offsetInEndSection": 503, "text": "Polycystic kidney disease (PKD) is a cystic genetic disorder of the kidneys which is typically associated with cystic bile duct dilatation in the liver in humans, and domestic and laboratory animals. In humans, there are two types of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD). ADPKD is caused by mutations in PKD1 or PKD2 gene while ARPKD is caused by mutation or loss of the PKHD1 (polycystic kidney and hepatic disease 1) gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25753522"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1307, "text": "Polycystic kidney disease (PKD), comprising autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD), is characterized by incessant cyst formation in the kidney and liver. ADPKD and ARPKD represent the leading genetic causes of renal disease in adults and children, respectively. ADPKD is caused by mutations in PKD1 encoding polycystin1 (PC1) and PKD2 encoding polycystin 2 (PC2). PC1/2 are multi-pass transmembrane proteins that form a complex localized in the primary cilium. Predominant ARPKD cases are caused by mutations in polycystic kidney and hepatic disease 1 (PKHD1) gene that encodes the Fibrocystin/Polyductin (FPC) protein, whereas a small subset of cases are caused by mutations in DAZ interacting zinc finger protein 1 like (DZIP1L) gene. FPC is a type I transmembrane protein, localizing to the cilium and basal body, in addition to other compartments, and DZIP1L encodes a transition zone/basal body protein. Apparently, PC1/2 and FPC are signaling molecules, while the mechanism that cilia employ to govern renal tubule morphology and prevent cyst formation is unclear. Nonetheless, recent genetic and biochemical studies offer a glimpse of putative physiological malfunctions and the pathomechanisms underlying both disease entities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32475690"}, {"offsetInBeginSection": 0, "offsetInEndSection": 350, "text": "Polycystic kidney disease (PKD) is a cystic genetic disorder of the kidneys which is typically associated with cystic bile duct dilatation in the liver in humans, and domestic and laboratory animals. In humans, there are two types of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25753522"}, {"offsetInBeginSection": 200, "offsetInEndSection": 503, "text": "In humans, there are two types of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD). ADPKD is caused by mutations in PKD1 or PKD2 gene while ARPKD is caused by mutation or loss of the PKHD1 (polycystic kidney and hepatic disease 1) gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25753522"}, {"offsetInBeginSection": 93, "offsetInEndSection": 291, "text": "Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are cilia-related disorders and the two main forms of monogenic cystic kidney diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30523303"}, {"offsetInBeginSection": 93, "offsetInEndSection": 493, "text": "Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are cilia-related disorders and the two main forms of monogenic cystic kidney diseases. ADPKD is a common disease that mostly presents in adults, whereas ARPKD is a rarer and often more severe form of polycystic kidney disease (PKD) that usually presents perinatally or in early childhood.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30523303"}, {"offsetInBeginSection": 93, "offsetInEndSection": 661, "text": "Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are cilia-related disorders and the two main forms of monogenic cystic kidney diseases. ADPKD is a common disease that mostly presents in adults, whereas ARPKD is a rarer and often more severe form of polycystic kidney disease (PKD) that usually presents perinatally or in early childhood. Cell biological and clinical research approaches have expanded our knowledge of the pathogenesis of ADPKD and ARPKD and revealed some mechanistic overlap between them.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30523303"}, {"offsetInBeginSection": 200, "offsetInEndSection": 692, "text": "In humans, there are two types of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD). ADPKD is caused by mutations in PKD1 or PKD2 gene while ARPKD is caused by mutation or loss of the PKHD1 (polycystic kidney and hepatic disease 1) gene. Here we report a morphologically confirmed case of spontaneous PKD in a Sprague-Dawley rat in which anatomic pathology examination revealed numerous cystic changes in the kidney and liver.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25753522"}, {"offsetInBeginSection": 0, "offsetInEndSection": 493, "text": "Cystic kidneys are common causes of end-stage renal disease, both in children and in adults. Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are cilia-related disorders and the two main forms of monogenic cystic kidney diseases. ADPKD is a common disease that mostly presents in adults, whereas ARPKD is a rarer and often more severe form of polycystic kidney disease (PKD) that usually presents perinatally or in early childhood.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30523303"}, {"offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Polycystic kidney disease (PKD) encompasses a group of genetic disorders that are common causes of renal failure. The two classic forms of PKD are autosomal recessive polycystic kidney disease (ARPKD) and autosomal dominant polycystic kidney disease (ADPKD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28455745"}, {"offsetInBeginSection": 103, "offsetInEndSection": 229, "text": "Classification is usually determined by mode of inheritance-autosomal dominant PKD (ADPKD) or autosomal recessive PKD (ARPKD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34290017"}, {"offsetInBeginSection": 102, "offsetInEndSection": 415, "text": "Two major forms of PKD are defined according to the inheritance pattern. Autosomal dominant PKD (ADPKD) is characterized by renal cysts, where nearly half of the patients suffers from renal failure in the 7th decade of life. Autosomal recessive PKD (ARPKD) is a rarer and more severe form presenting in childhood.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34177435"}, {"offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "BACKGROUND: Polycystic kidney diseases (PKD) are a group of monogenic disorders that are inherited dominantly (autosomal dominant PKD; ADPKD) or recessively, including, autosomal recessive ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24011172"}, {"offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "Polycystic kidney disease (PKD) is known to occur in three main forms, namely autosomal dominant PKD (ADPKD), autosomal recessive PKD (ARPKD) and syndromic PKD (SPKD), based on the clinical manifestations and genetic causes, which are diagnosable from the embryo stage to the later stages of life.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34032358"}, {"offsetInBeginSection": 0, "offsetInEndSection": 323, "text": "Polycystic kidney disease (PKD) is a hereditary disorder with abnormal cellular proliferation, fluid accumulation in numerous cysts, remodeling of extracellular matrix, inflammation, and fibrosis in the kidney and liver. The two major types of PKD show autosomal dominant (ADPKD) or autosomal recessive inheritance (ARPKD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23095811"}]}
+{"question_id": "66214f52b9f8b89d7e000005", "question": "Is tumor expression of Topoisomerase I a biomarker of response to irinotecan in colorectal cancer patients therapy?", "answer": "Patients with resected CRC expressing Topo I seem to benefit from irinotecan-containing adjuvant chemotherapy.", "relevant_passage_ids": ["19775480", "22108516", "15160997", "24966994", "15197779", "21874414", "28077117", "24256029", "19436196", "26542057", "33731288", "32326511", "32764831", "29261002", "37176164", "28880238", "36678550", "33790151", "28870917", "31196001", "16184927", "11177741", "38016427"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1475, "offsetInEndSection": 1585, "text": "Patients with resected CRC expressing Topo I seem to benefit from irinotecan-containing adjuvant chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19775480"}, {"offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Topoisomerase I copy number alterations as biomarker for irinotecan efficacy in metastatic colorectal cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28077117"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1481, "text": "Topoisomerase 1 (TOPO-1) and carboxylesterase 2 (CES-2) are found to play crucial roles in the pathogenesis of various cancers. The prognostic role of TOPO-1 and CES-2 in patients with metastatic colorectal cancer (mCRC) who underwent irinotecan chemotherapy was largely unknown. In the current study, we assessed the expression of TOPO-1 and CES-2 in mCRC and analyzed its potential relevance to irinotecan based therapy. A total of 98 patients with mCRC were included in this study. The expression of TOPO-1 and CES-2 in mCRC tissues was evaluated by immunohistochemistry. For TOPO-1, 46 patients showed high expression and 52 patients showed low expression. For CES-2, 53 patients showed high expression and 45 patients showed low expression. The correlation between TOPO-1 or CES-2 expression and clinicopathological characteristics of mCRC patients was analyzed. Neither TOPO-1 nor CES-2 had significant correlation with age, gender, tumor site, tumor grade and metastatic sites in mCRC patients. However, high expression of CES-2 but not TOP-1 was positively correlated with better curative effect. Kaplan-Meier and log-rank test were applied to assess the correlation between progression-free survival (PFS)/overall survival (OS) and TOPO-1 or CES-2 expression in mCRC patients. High expression of TOPO-1 and CES-2 are correlated with longer PFS and OS. In summary, our findings suggest that TOPO-1 and CES-2 may play important roles irinotecan sensitivity in mCRC patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29261002"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1479, "text": "Colorectal cancer is one of the most common malignancies, and the topoisomerase inhibitor irinotecan (CPT-11)-based chemotherapeutic regimen is currently the first-line treatment with impressive therapeutic efficacy. However, irinotecan has several clinically significant side effects, including diarrhea, which limit its clinical utility and efficacy in many patients. In an effort to discover better and improved pharmacotherapy against colorectal cancer, we synthesized a novel topoisomerase inhibitor, PCC0208037, examined its anti-tumor efficacy and related molecular mechanisms, and characterized its toxicity and pharmacokinetic profiles. PCC0208037 suppressed colorectal cancer cell (CRC) proliferation and increased cell cycle arrest, which may be related to its effects on up-regulating DNA damage response (DDR)-related molecules and apoptosis-related proteins. PCC0208037 demonstrated robust anti-tumor activity in vivo in a colorectal cancer cell xenograft model, which was comparable to or slightly better than CPT-11. In a preliminary toxicology study, PCC0208037 demonstrated much weaker tissue damage to colorectal tissue than CPT-11, and its impacts on food intake and body weight loss were more transient and recovered faster than CPT-11 in mice. This could be partially explained by the pharmacokinetic findings, which showed that PCC0208037 and its active metabolite, SN-38, were more accumulated in tumor tissue than in the intestine, as compared to CPT-11.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36678550"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1837, "text": "Biomarker-guided treatment for patients with colon cancer is needed. We tested ABCG2 and topoisomerase 1 (TOP1) mRNA expression as predictive biomarkers for irinotecan benefit in the PETACC-3 patient cohort. The present study included 580 patients with mRNA expression data from Stage III colon cancer samples from the PETACC-3 study, which randomized the patients to Fluorouracil/leucovorin (5FUL) +/- irinotecan. The primary end-points were recurrence free survival (RFS) and overall survival (OS). Patients were divided into one group with high ABCG2 expression (above median) and low TOP-1 expression (below 75 percentile) (\"resistant\") (n = 216) and another group including all other combinations of these two genes (\"sensitive\") (n = 364). The rationale for the cut-offs were based on the distribution of expression levels in the PETACC-3 Stage II set of patients, where ABCG2 was unimodal and TOP1 was bimodal with a high expression level mode in the top quarter of the patients. Cox proportional hazards regression was used to estimate the hazard ratios and the association between variables and end-points and log-rank tests to assess the statistical significance of differences in survival between groups. Kaplan-Meier estimates of the survival functions were used for visualization and estimation of survival rates at specific time points. Significant differences were found for both RFS (Hazard ratio (HR): 0.63 (0.44-0.92); p = 0.016) and OS (HR: 0.60 (0.39-0.93); p = 0.02) between the two biomarker groups when the patients received FOLFIRI (5FUL+irinotecan). Considering only the Microsatellite Stable (MSS) and Microsatellite Instability-Low (MSI-L) patients (n = 470), the differences were even more pronounced. In contrast, no significant differences were observed between the groups when patients received 5FUL alone.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32326511"}, {"offsetInBeginSection": 0, "offsetInEndSection": 759, "text": "AIM: The aim of this study was to investigate heat shock protein 90 (HSP90) and topoisomerase I (Topo I) expression and the association between both proteins and clinicopathological parameters of colorectal cancer (CRC), in order to describe their role in tumor biology regarding to Kirsten Ras (KRAS) - positive/negative cases.MATERIALS AND METHODS: Expression of HSP90 and Topo I, and KRAS gene mutations were estimated in primary CRCs.RESULTS: HSP90/Topo I immunophenotype correlated with gender, Duke staging, tumor grade and lymph node metastasis (p<0.01). Positive correlation was found between KRAS mutation and HSP90 expression (p=0.02). HSP90, Topo I expression, and co-expression of HSP90/Topo I correlated with unfavorable parameters of CRCs in res", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28870917"}, {"offsetInBeginSection": 59, "offsetInEndSection": 1253, "text": "re limited. New therapies preferable with predictive biomarkers are needed. The aim of these trials was to investigate if gene copy number of the topoisomerase 1 gene was predictive of response to the topoisomerase inhibitor irinotecan.METHODS: Two open-label, single-arm phase II studies including HER2 positive and negative patients were conducted. Patients were eligible for inclusion if the primary tumor or a metastatic lesion had increased expression of the topoisomerase 1 gene defined as a TOP1 gene copy number of \u22654 or a TOP1/CEN20 ratio of \u22652. Patients were treated with irinotecan +/- trastuzumab weekly for 4\u2009weeks following 2\u2009weeks break, until progression or unacceptable toxicities. Evaluation scans were performed every 6\u2009weeks. Primary endpoint was clinical benefit rate defined as the fraction of patients with stable disease for \u22654\u2009months.RESULTS: The pre-planned number of 18 patients in each trial was not reached, thus no formal statistical analysis could be performed. Nine patients with HER2 negative disease and three patients with HER2 positive disease were included. Three patients obtained a partial remission and two patients had SD.CONCLUSIONS: The trials did not", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31196001"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1659, "text": "PURPOSE: The camptothecin (CPT) analogs topotecan and irinotecan specifically target topoisomerase I (topoI) and are used to treat colorectal, gastric, and pancreatic cancer. Response rate for this class of drug varies from 10% to 30%, and there is no predictive biomarker for patient stratification by response. On the basis of our understanding of CPT drug resistance mechanisms, we developed an immunohistochemistry-based predictive test, P-topoI-Dx, to stratify the patient population into those who did and did not experience a response.PATIENTS AND METHODS: The retrospective validation studies included a training set (n\u00a0= 79) and a validation cohort (n\u00a0= 27) of gastric cancer (GC) patients, and 8 cohorts of colorectal cancer (CRC) patient tissue (n\u00a0= 176). Progression-free survival for 6 months was considered a positive response to CPT-based therapy. Formalin-fixed, paraffin-embedded slides were immunohistochemically stained with anti-phospho-specific topoI-Serine10 (topoI-pS10), quantitated, and analyzed statistically.RESULTS: We determined a threshold of 35% positive staining to offer optimal test characteristics in GC. The GC (n\u00a0= 79) training set demonstrated 76.6% (95% confidence interval, 64-86) sensitivity; 68.8% (41-88) specificity; positive predictive value (PPV) 92.5% (81-98); and negative predictive value (NPV) 42.3% (24-62). The GC validation set (n\u00a0= 27) demonstrated 82.4% (56-95) sensitivity and 70.0% (35-92) specificity. Estimated PPV and NPV were 82.4% (56-95) and 70.0% (35-92) respectively. In the CRC validation set (n\u00a0= 176), the 40% threshold demonstrated 87.5% (78-94) sensitivity; 70.0% (59-79) specificity; PPV ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33731288"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1297, "text": "BACKGROUND: Though irinotecan is commonly used for treating advanced gastric cancer, there is no predictive biomarker to date. We have studied the resistant mechanism for irinotecan and found that phosphorylation of serine 10 residue of topoisomerase \u2160(topo \u2160)is an important step for irinotecan resistance. We have developed an immunohistochemical staining-based biomarker; topo \u2160-pS10, for predicting irinotecan efficacy.PURPOSE: The purpose of this study is to test the accuracy of topo \u2160-pS10 immunohistochemical staining in gastric cancer clinical samples.METHODS: In this study we performed 2 sets of tests. In the training set, we stained 79 gastric cancer clinical samples which efficacy of irinotecan was measured by succinate dehydrogenase inhibition(SDI)test. In the validation set, we used 27 gastric cancer clinical samples which irinotecan was used and the efficacy was known.RESULTS: Training set: From the ROC curve the cut-off point was set at 35% positive nuclei. Sixty three cases were positive with topo \u2160-pS10 in the nuclei. With the result of irinotecan SDI, the sensitivity was 76.6% and the positive predictive value was 92.5%. This result showed that topo \u2160-pS10 positive case does not respond to irinotecan. Validation set: In this set, the sensitivity was 82.4% and the ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33790151"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1376, "text": "BACKGROUND: One of the main chemotherapeutic drugs used on a routine basis in patients with metastatic colorectal cancer ((m)CRC) is the topoisomerase-1 inhibitor, irinotecan. However, its usefulness is limited by the pre-existing or inevitable development of resistance. The ATP-binding cassette (ABC) transporter ABCG2/breast cancer resistance protein (BRCP) through its function in xenobiotic clearance might play an important role in irinotecan resistance. With a goal to evaluate the clinical significance of ABCG2 measurements, we here review the current literature on ABCG2 in relation to irinotecan treatment in CRC patients.RESULTS: Few studies have evaluated the association between ABCG2 gene or protein expression and prognosis in CRC patients. Discordant results were reported. The discrepancies might be explained by the use of different criteria for interpretation of results in the immunohistochemistry studies. Only one large study evaluated the ABCG2 protein expression and efficacy of irinotecan in mCRC (CAIRO study, n = 566). This study failed to demonstrate any correlation between ABCG2 protein expression in the primary tumor and response to irinotecan-based treatment. We recently raised questions on how to evaluate ABCG2 immunoreactivity patterns, and the results in the CAIRO study might be influenced by using a different scoring protocol than the", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28880238"}, {"offsetInBeginSection": 251, "offsetInEndSection": 804, "text": "Topoisomerase activity is particularly increased in rapidly dividing cells, such as cancer cells. Topoisomerase inhibitors have been an effective chemotherapeutic option for the treatment of several cancers. In addition, combination cancer therapy with topoisomerase inhibitors may increase therapeutic efficacy and decrease resistance or side effects. Topoisomerase inhibitors are currently being used worldwide, including in the United States, and clinical trials on the combination of topoisomerase inhibitors with other drugs are currently underway.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37176164"}, {"offsetInBeginSection": 0, "offsetInEndSection": 561, "text": "OBJECTIVE: DNA topoisomerase I is a putative biomarker of irinotecan efficacy with clinical associations previously demonstrated at the protein level. The purpose of the present study was to perform the first clinical investigation of the association between the DNA topoisomerase I gene (TOP1) copy number and objective response following irinotecan treatment in patients with metastatic colorectal cancer.MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tumor samples from 78 patients, who received irinotecan monotherapy in second line, were included", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24256029"}, {"offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Assessment of the topoisomerase I gene copy number as a predictive biomarker of objective response to irinotecan in metastatic colorectal cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24256029"}, {"offsetInBeginSection": 150, "offsetInEndSection": 561, "text": " The purpose of the present study was to perform the first clinical investigation of the association between the DNA topoisomerase I gene (TOP1) copy number and objective response following irinotecan treatment in patients with metastatic colorectal cancer.MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tumor samples from 78 patients, who received irinotecan monotherapy in second line, were included", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24256029"}, {"offsetInBeginSection": 150, "offsetInEndSection": 406, "text": " The purpose of the present study was to perform the first clinical investigation of the association between the DNA topoisomerase I gene (TOP1) copy number and objective response following irinotecan treatment in patients with metastatic colorectal cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24256029"}, {"offsetInBeginSection": 150, "offsetInEndSection": 775, "text": " The purpose of the present study was to perform the first clinical investigation of the association between the DNA topoisomerase I gene (TOP1) copy number and objective response following irinotecan treatment in patients with metastatic colorectal cancer.MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tumor samples from 78 patients, who received irinotecan monotherapy in second line, were included. TOP1 was assessed by fluorescence in situ hybridization using a technically validated dual-probe combination that hybridizes to TOP1, located at 20q12-q13.1, and to the centromere region of chromosome 20 (CEN-20)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24256029"}, {"offsetInBeginSection": 0, "offsetInEndSection": 406, "text": "OBJECTIVE: DNA topoisomerase I is a putative biomarker of irinotecan efficacy with clinical associations previously demonstrated at the protein level. The purpose of the present study was to perform the first clinical investigation of the association between the DNA topoisomerase I gene (TOP1) copy number and objective response following irinotecan treatment in patients with metastatic colorectal cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24256029"}, {"offsetInBeginSection": 0, "offsetInEndSection": 422, "text": "Topoisomerase 1 (TOPO-1) and carboxylesterase 2 (CES-2) are found to play crucial roles in the pathogenesis of various cancers. The prognostic role of TOPO-1 and CES-2 in patients with metastatic colorectal cancer (mCRC) who underwent irinotecan chemotherapy was largely unknown. In the current study, we assessed the expression of TOPO-1 and CES-2 in mCRC and analyzed its potential relevance to irinotecan based therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29261002"}, {"offsetInBeginSection": 128, "offsetInEndSection": 484, "text": "The prognostic role of TOPO-1 and CES-2 in patients with metastatic colorectal cancer (mCRC) who underwent irinotecan chemotherapy was largely unknown. In the current study, we assessed the expression of TOPO-1 and CES-2 in mCRC and analyzed its potential relevance to irinotecan based therapy. A total of 98 patients with mCRC were included in this study.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29261002"}, {"offsetInBeginSection": 128, "offsetInEndSection": 422, "text": "The prognostic role of TOPO-1 and CES-2 in patients with metastatic colorectal cancer (mCRC) who underwent irinotecan chemotherapy was largely unknown. In the current study, we assessed the expression of TOPO-1 and CES-2 in mCRC and analyzed its potential relevance to irinotecan based therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29261002"}, {"offsetInBeginSection": 634, "offsetInEndSection": 771, "text": "This article reviews the possibility of assessing Topo I protein expression in tumors as a biological marker for CPT-11 treatment in CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21874414"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Topoisomerase I expression in tumors as a biological marker for CPT-11 chemosensitivity in patients with colorectal cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21874414"}, {"offsetInBeginSection": 989, "offsetInEndSection": 1324, "text": "In addition, the efficacy of CPT-11 did not correlate with combinations subdivided according to the expression levels of topo- I mRNA and TS mRNA.CONCLUSIONS: Determination of topo- I mRNA levels of primary colorectal cancer may not be useful for predicting the efficacy of CPT-11 treatment alone or in combination with TS mRNA levels.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16184927"}, {"offsetInBeginSection": 1287, "offsetInEndSection": 1715, "text": "In relation to the applied cutoff values, nonsignificant associations with objective response were identified for the TOP1 signal count (OR: 2.41; p = 0.23) and for the TOP1/CEN-20 ratio (OR: 2.05; p = 0.30).CONCLUSIONS: Despite limitations of the study the positive associations between TOP1 and objective response suggest that further analysis in larger tumor material, preferably in a randomized setting, is highly warranted.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24256029"}, {"offsetInBeginSection": 320, "offsetInEndSection": 588, "text": "The aim of the present study has been to verify the predictive value of immunohistochemical topoisomerase-I (Topo-I) and TS primary tumour expression in a consecutive series of 62 advanced colorectal cancer patients that received a first line 5-FU/CPT-11 chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15197779"}, {"offsetInBeginSection": 123, "offsetInEndSection": 283, "text": "are needed. The aim of these trials was to investigate if gene copy number of the topoisomerase 1 gene was predictive of response to the topoisomerase inhibitor", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31196001"}, {"offsetInBeginSection": 1251, "offsetInEndSection": 1464, "text": "ot include the planned number of patients. No association between gene copy number of the topoisomerase 1 gene and response to irinotecan could be proved, however a clinical benefit was found in 5/12 patients and ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31196001"}, {"offsetInBeginSection": 152, "offsetInEndSection": 788, "text": "Irinotecan is a camptothecin derivative requiting carboxylesterase activation to SN-38, which interacts with its target enzyme, topoisomerase I.MATERIALS AND METHODS: In 9 surgical or biopsy samples of colorectal tumours and corresponding normal tissue, kept in a tumour bank, we evaluated topoisomerase I expression and activity, respectively by Western blotting and DNA relaxation assay, carboxylesterase activity using two different substrates and p53 status by immunohistochenistry.RESULTS: Topoisomerase I expression and activity were significantly correlated, as were the two types of determinations for carboxylesterase activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15160997"}, {"offsetInBeginSection": 151, "offsetInEndSection": 562, "text": "The purpose of the present study was to perform the first clinical investigation of the association between the DNA topoisomerase I gene (TOP1) copy number and objective response following irinotecan treatment in patients with metastatic colorectal cancer.MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tumor samples from 78 patients, who received irinotecan monotherapy in second line, were included.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24256029"}, {"offsetInBeginSection": 361, "offsetInEndSection": 525, "text": "arious topoisomerase I inhibitors have been evaluated in solid tumors, and irinotecan and topotecan have been approved for the treatment of epithelial malignancies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38016427"}, {"offsetInBeginSection": 112, "offsetInEndSection": 308, "text": "tal cancer. We examined the copy numbers (CN) of topoisomerase I (TOP1) as well as the ratios of TOP1/CEN-20 and TOP1/CEN-2 as biomarkers for irinotecan efficacy in patients with metastatic colore", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28077117"}, {"offsetInBeginSection": 1069, "offsetInEndSection": 1200, "text": "rboxylesterase activity and p53 staining.CONCLUSION: Topoisomerase I expression appeared as the parameter most likely to predict re", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15160997"}, {"offsetInBeginSection": 777, "offsetInEndSection": 1121, "text": "In univariate logistic regression models, the TOP1 signal count per cell and the TOP1/CEN-20 ratio were associated with objective response, which was evaluated according to RECIST v.1.1.RESULTS: Gain of TOP1 was identified in 52.6% and 37.2% using the following cutoff values: TOP1 signal count per cell \u22653.6 and TOP1/CEN-20 \u22651.5, respectively.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24256029"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1454, "text": "OBJECTIVE: DNA topoisomerase I is a putative biomarker of irinotecan efficacy with clinical associations previously demonstrated at the protein level. The purpose of the present study was to perform the first clinical investigation of the association between the DNA topoisomerase I gene (TOP1) copy number and objective response following irinotecan treatment in patients with metastatic colorectal cancer.MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tumor samples from 78 patients, who received irinotecan monotherapy in second line, were included. TOP1 was assessed by fluorescence in situ hybridization using a technically validated dual-probe combination that hybridizes to TOP1, located at 20q12-q13.1, and to the centromere region of chromosome 20 (CEN-20). In univariate logistic regression models, the TOP1 signal count per cell and the TOP1/CEN-20 ratio were associated with objective response, which was evaluated according to RECIST v.1.1.RESULTS: Gain of TOP1 was identified in 52.6% and 37.2% using the following cutoff values: TOP1 signal count per cell \u22653.6 and TOP1/CEN-20 \u22651.5, respectively. A borderline significant association (Odds ratio (OR): 1.62; p = 0.07) between a stepwise increase in the TOP1 signal count and objective response was demonstrated. In relation to the applied cutoff values, nonsignificant associations with objective response were identified for the TOP1 signal count (OR: 2.41; p = 0.23) and for th", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24256029"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1529, "text": "While several studies have reported that thymidylate synthase (TS) tumour expression can be a reliable predictive marker of clinical response to 5-Fluorouracil (5-FU) for advanced colorectal cancer patients, only a few studies that searched for predictive factors of irinotecan (CPT-11) clinical response are available. The aim of the present study has been to verify the predictive value of immunohistochemical topoisomerase-I (Topo-I) and TS primary tumour expression in a consecutive series of 62 advanced colorectal cancer patients that received a first line 5-FU/CPT-11 chemotherapy. TS and Topo-I immunostaining was observed in 76% and 43% of tumours, respectively, resulting in a significant relationship within each tumour (r=0.365, p<0.004). Patients with different TS tumour expression showed a similar percentage of Objective Clinical Response, OR (40% vs. 28% of OR in low and high TS-expressing tumours, respectively, p=ns); also, patients with different Topo-I tumour expression did not show a different probability of OR (39% vs. 29% of OR in high and low Topo-I expressing tumours, respectively; p=ns). The tumour expression of these 2 biomarkers also did not impact on time to progression and overall survival of patients. Furthermore, the combined analysis of TS and Topo-I tumour status did not permit to individualize subgroups of patients with different probability of OR. With multivariate analysis, only patient Performance Status significantly impacted on OS (Hazard ratio 4.87; p=0.02) of these patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15197779"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1068, "text": "BACKGROUND: We have examined, in this study, the feasibility of determining cellular factors contributing to irinotecan activity in colorectal cancers. Irinotecan is a camptothecin derivative requiting carboxylesterase activation to SN-38, which interacts with its target enzyme, topoisomerase I.MATERIALS AND METHODS: In 9 surgical or biopsy samples of colorectal tumours and corresponding normal tissue, kept in a tumour bank, we evaluated topoisomerase I expression and activity, respectively by Western blotting and DNA relaxation assay, carboxylesterase activity using two different substrates and p53 status by immunohistochenistry.RESULTS: Topoisomerase I expression and activity were significantly correlated, as were the two types of determinations for carboxylesterase activity. Topoisomerase I was significantly more active in tumours than in corresponding normal tissue. The three samples presenting the highest topoisomerase I expression and activity originated from the patients who responded to irinotecan treatment. No such features were apparent for c", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15160997"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1042, "text": "Irinotecan is a topoisomerase I inhibitor approved worldwide as a first- and second-line chemotherapy for advanced or recurrent colorectal cancer (CRC). Although irinotecan showed significant survival advantage for patients, a relatively low response rate and severe adverse effects demonstrated the urgent need for biomarkers searching to select the suitable patients who can benefit from irinotecan-based therapy and avoid the adverse effects. In present work, the irinotecan response (IC50 doses) of 20 CRC cell lines were correlated with the basal expression profiles investigated by RNA-seq to figure out genes responsible for irinotecan sensitivity/resistance. Genes negatively or positively correlated to irinotecan sensitivity were given after biocomputation, and 7 (CDC20, CTNNAL1, FZD7, CITED2, ABR, ARHGEF7, and RNMT) of them were validated in two CRC cell lines by quantitative real-time PCR, several of these 7 genes has been proposed to promote cancer cells proliferation and hence may confer CRC cells resistance to irinotecan.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24966994"}, {"offsetInBeginSection": 112, "offsetInEndSection": 1824, "text": "tal cancer. We examined the copy numbers (CN) of topoisomerase I (TOP1) as well as the ratios of TOP1/CEN-20 and TOP1/CEN-2 as biomarkers for irinotecan efficacy in patients with metastatic colorectal cancer.METHODS: From a national cohort, we identified 163 patients treated every third week with irinotecan 350\u00a0mg/m2 as second-line therapy. Among these 108 were eligible for analyses and thus entered the study. Primary tumors samples were collected and tissue microarray (TMA) blocks were produced. FISH analysis was performed using two probe-mixes: TOP1/CEN-20 and TOP1/CEN-2. Only samples harboring all three signals (TOP1, CEN-20 and CEN-2) using FISH were included in the analyses.RESULTS: In the TOP1/CEN-20 probe-mix the median TOP1- and CEN-20 CN were 4.46 (range: 1.5-9.5) and 2.00 (range: 0.55-4.55), respectively. The median TOP1- and CEN-2 CN in the TOP1/CEN-2 probe-mix, were 4.57 (range: 1.82-10.43) and 1.98 (range: 1.22-6.14), respectively. The median TOP1/CEN-20 ratio and TOP1/CEN-2 ratio were 1.25 (range: 0.92-2.90) and 2.05 (range: 1.00-6.00), respectively. None of the markers TOP1 CN, TOP1/CEN-20-ratio or TOP1/CEN-2-ratio were associated with progression free survival, overall survival or baseline characteristics. Yet, we observed a borderline association for a stepwise increase of the TOP1 CN in relation to objective response as hazard ratio were 1.35 (95% CI 0.96-1.90; p\u2009=\u20090.081).CONCLUSIONS: We verified a borderline significant association between increasing TOP1 CN and objective response as previously reported. Applying the probes representing CEN-20 and CEN-2, in order to investigate the ratios of TOP1/CEN-20 and TOP1/CEN-2 provided no further information in search of a ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28077117"}, {"offsetInBeginSection": 0, "offsetInEndSection": 861, "text": "Irinotecan specifically targets topoisomerase I (topoI), and is used to treat various solid tumors, but only 13-32% of patients respond to the therapy. Now, it is understood that the rapid rate of topoI degradation in response to irinotecan causes irinotecan resistance. We have published that the deregulated DNA-PKcs kinase cascade ensures rapid degradation of topoI and is at the core of the drug resistance mechanism of topoI inhibitors, including irinotecan. We also identified CTD small phosphatase 1 (CTDSP1) (a nuclear phosphatase) as a primary upstream regulator of DNA-PKcs in response to topoI inhibitors. Previous reports showed that rabeprazole, a proton pump inhibitor (PPI) inhibits CTDSP1 activity. The purpose of this study was to confirm the effects of rabeprazole on CTDSP1 activity and its impact on irinotecan-based therapy in colon cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32764831"}, {"offsetInBeginSection": 0, "offsetInEndSection": 451, "text": "The topoisomerase I (Top 1) poison irinotecan is an important component of the modern treatment of colorectal cancer. By stabilising Top 1-DNA complexes, irinotecan generates Top 1-linked DNA single-strand breaks that can evolve into double-strand breaks and ultimately cause cell death. However, cancer cells may overcome cell killing by releasing the stalled topoisomerase from DNA termini, thereby reducing the efficacy of Top 1 poisons in clinics.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22108516"}, {"offsetInBeginSection": 0, "offsetInEndSection": 633, "text": "Irinotecan (CPT-11) is used as a first- and second-line chemotherapy for advanced or recurrent colorectal cancer (CRC). However, only 20%-30% of patients show an objective response to CPT-11 and the drug has severe toxicities, such as delayed-onset diarrhea, neutropenia, nausea, and vomiting. It is important to select patients who will demonstrate sensitivity to CPT-11 treatment to avoid unnecessary drug toxicities and to introduce anticancer treatment benefits to CRC patients. DNA topoisomerase I (Topo I) is essential for vital cellular processes such as DNA replication, transcription, translation, recombination, and repair.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21874414"}, {"offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Colorectal cancer is one of the most common malignancies, and the topoisomerase inhibitor irinotecan (CPT-11)-based chemotherapeutic regimen is currently the first-line treatment with impressive therapeutic efficacy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36678550"}, {"offsetInBeginSection": 69, "offsetInEndSection": 207, "text": "We tested ABCG2 and topoisomerase 1 (TOP1) mRNA expression as predictive biomarkers for irinotecan benefit in the PETACC-3 patient cohort.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32326511"}, {"offsetInBeginSection": 0, "offsetInEndSection": 323, "text": "AIM: The aim of this study was to investigate heat shock protein 90 (HSP90) and topoisomerase I (Topo I) expression and the association between both proteins and clinicopathological parameters of colorectal cancer (CRC), in order to describe their role in tumor biology regarding to Kirsten Ras (KRAS) - positive/negative c", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28870917"}, {"offsetInBeginSection": 805, "offsetInEndSection": 1184, "text": "The primary objective of this review was to comprehensively analyze the current clinical landscape concerning the combined application of irinotecan, an extensively investigated type I topoisomerase inhibitor for colorectal cancer, and doxorubicin, an extensively researched type II topoisomerase inhibitor for breast cancer, while presenting a novel approach for cancer therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37176164"}, {"offsetInBeginSection": 554, "offsetInEndSection": 700, "text": "Preliminary data suggest that gene expression levels of topoisomerase I, p21, bcl-2, and ICE may be predictive of response to therapy with CPT-11.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11177741"}, {"offsetInBeginSection": 1331, "offsetInEndSection": 1574, "text": "Our data suggest that Topo I expression in rectal tumour mucosa might serve as a predictor of response to the neoadjuvant irinotecan-based chemoradiation, and hence might be a factor contributing to the development of individualized treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19436196"}, {"offsetInBeginSection": 744, "offsetInEndSection": 930, "text": "egion of chromosome 20 (CEN-20). In univariate logistic regression models, the TOP1 signal count per cell and the TOP1/CEN-20 ratio were associated with objective response, which was eva", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24256029"}]}
+{"question_id": "662f401b187cba990d00000e", "question": "Is Vitamin D deficiency associated with sepsis mortality?", "answer": "Yes, vitamin D deficiency is associated with mortality in sepsis patients.", "relevant_passage_ids": ["36265656"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1504, "offsetInEndSection": 1619, "text": "Vitamin D deficiency was prevalent in patients with septic shock visiting the ED and was associated with mortality.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36265656"}]}
+{"question_id": "66214b9cb9f8b89d7e000001", "question": "Which countries have a higher incidence of colorectal cancer?", "answer": "Taiwan (province of China; 62\u00b70 [48\u00b79-80\u00b70] per 100\u2009000), Monaco (60\u00b77 [48\u00b75-73\u00b76] per 100\u2009000), and Andorra (56\u00b76 [42\u00b78-71\u00b79] per 100\u2009000) had the highest age-standardised incidence rates, while Greenland (31\u00b74 [26\u00b70-37\u00b71] per 100\u2009000), Brunei (30\u00b73 [26\u00b76-34\u00b71] per 100\u2009000), and Hungary (28\u00b76 [23\u00b76-34\u00b70] per 100\u2009000) had the highest age-standardised mortality rates.", "relevant_passage_ids": ["35397795", "28283123", "28281292", "33618551", "31648977", "27268615", "26830034", "37323313", "34238851", "31105047", "33538338", "32088300", "31113868", "32173775", "33707923", "28948490", "12064704", "25145363", "2308724", "26476758", "2278112", "37874806", "34853651", "2483912", "2991145", "19897840", "25572676", "27678325", "37985710", "28337105", "10772412", "10234894", "30536395", "34048685", "34422402", "36604116", "27067591", "28378448"], "type": "list", "snippets": [{"offsetInBeginSection": 1620, "offsetInEndSection": 1989, "text": "Taiwan (province of China; 62\u00b70 [48\u00b79-80\u00b70] per 100\u2009000), Monaco (60\u00b77 [48\u00b75-73\u00b76] per 100\u2009000), and Andorra (56\u00b76 [42\u00b78-71\u00b79] per 100\u2009000) had the highest age-standardised incidence rates, while Greenland (31\u00b74 [26\u00b70-37\u00b71] per 100\u2009000), Brunei (30\u00b73 [26\u00b76-34\u00b71] per 100\u2009000), and Hungary (28\u00b76 [23\u00b76-34\u00b70] per 100\u2009000) had the highest age-standardised mortality rates.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35397795"}, {"offsetInBeginSection": 659, "offsetInEndSection": 2965, "text": "point regression analysis.RESULTS: From 2007 to 2016, 2006 to 2015, or 2005 to 2014, depending on the availability of the data, the incidence of colon cancer increased in 10 of 36 countries analyzed (all in Asia or Europe); India had the greatest increase, followed by Poland. All 10 of these countries have medium to high Human Development Index (HDI) scores. Six countries had a decrease in colon cancer incidence; these countries had the highest HDI scores; the United States had the greatest decrease, followed by Israel. Seven countries (including all countries from Northern America) had a decrease in incidence among persons older than 50 years. Eight countries had an increase in colon cancer incidence among persons younger than 50 years, including the United Kingdom and India. Countries with a decreased or stable incidence among persons 50 years or older but a significant increase in persons younger than 50 years, included Germany, Australia, the United States, Sweden, Canada, and the United Kingdom. Only Italy had a decrease in CRC incidence among persons younger than 50 years. Among women, 12 of 36 countries (all from Asia and Europe) had an increase in colon cancer incidence and 7 countries had a decrease; India had the greatest increase followed by Slovenia. Five of 36 countries had an increase in incidence of rectal cancer and 8 countries had a decrease; Ecuador and Thailand had the greatest increases in incidence. The incidence of rectal cancer among persons younger than 50 years increased significantly in Finland, Australia, Canada, the United States, and The Netherlands. Four countries had an increase in the incidence of rectal cancer in women; Ecuador had the greatest increase followed by Thailand. The incidence of rectal cancer in women decreased in 8 countries. Among women younger than 50 years, rectal cancer incidence increased, despite a decrease in women older than 50 years, in Costa Rica, Slovenia, Japan, Slovakia, Canada, and the United States there was an increase in incidence, although their elder population had a stable or decreased incidence. Twenty-four countries reported a reduction in CRC mortality, including North America, Oceania, and most European countries. Nevertheless, some countries from Asia, Latin America, and Southern Europe had sign", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32088300"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1290, "text": "BACKGROUND: The overall incidence of colorectal cancer is decreasing in many high-income countries, yet analyses in the USA and other high-income countries such as Australia, Canada, and Norway have suggested increasing incidences among adults younger than 50 years. We aimed to examine longitudinal and generational changes in the incidence of colon and rectal cancer in seven high-income countries.METHODS: We obtained data for the incidence of colon and rectal cancer from 21 population-based cancer registries in Australia, Canada, Denmark, Norway, New Zealand, Ireland, and the UK for the earliest available year until 2014. We used age-period-cohort modelling to assess trends in incidence by age group, period, and birth cohort. We stratified cases by tumour subsite according to the 10th edition of the International Classification of Diseases. Age-standardised incidences were calculated on the basis of the world standard population.FINDINGS: An overall decline or stabilisation in the incidence of colon and rectal cancer was noted in all studied countries. In the most recent 10-year period for which data were available, however, significant increases were noted in the incidence of colon cancer in people younger than 50 years in Denmark (by 3\u00b71%), New Zealand (2\u00b79%), Austral", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31105047"}, {"offsetInBeginSection": 1591, "offsetInEndSection": 2491, "text": "\u2009000 from 1990 through 2019. Taiwan (province of China; 62\u00b70 [48\u00b79-80\u00b70] per 100\u2009000), Monaco (60\u00b77 [48\u00b75-73\u00b76] per 100\u2009000), and Andorra (56\u00b76 [42\u00b78-71\u00b79] per 100\u2009000) had the highest age-standardised incidence rates, while Greenland (31\u00b74 [26\u00b70-37\u00b71] per 100\u2009000), Brunei (30\u00b73 [26\u00b76-34\u00b71] per 100\u2009000), and Hungary (28\u00b76 [23\u00b76-34\u00b70] per 100\u2009000) had the highest age-standardised mortality rates. From 1990 through 2019, a substantial rise in incidence rates was observed in younger adults (age <50 years), particularly in high Socio-demographic Index (SDI) countries. Globally, a diet low in milk (15\u00b76%), smoking (13\u00b73%), a diet low in calcium (12\u00b79%), and alcohol use (9\u00b79%) were the main contributors to colorectal cancer DALYs in 2019.INTERPRETATION: The increase in incidence rates in people younger than 50 years requires vigilance from researchers, clinicians, and policy makers and a possi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35397795"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1272, "text": "BACKGROUND: Colorectal cancer incidence among young adults in the United States is on the rise, but whether this phenomenon is present in other parts of the world is not well documented. This study aims to explore the temporal change of incidence rates for colorectal cancer in various countries across the globe.METHODS: We extracted colorectal cancer incidence and population data from 1988 to 2007 based on data from the International Agency for Research on Cancer and compared incidence between age groups. Twelve representative jurisdictions from five continents were selected. Young-onset colorectal cancer cases were defined as those ages <50 years. Joinpoint regression was used to measure the trends of colorectal cancer incidence and to estimate the annual percent change (APC).RESULTS: The APC for those ages <50 years was noted to be increasing at a faster rate as compared with those ages \u226550 years in many regions, including Australia (+1.10% vs. -0.35%), Brazil (+9.20% vs. +5.72%), Canada (+2.60% vs. -0.91%), China-Hong Kong (+1.82% vs. -0.10%), China-Shanghai (+1.13% vs. -2.68%), Japan (+2.63% vs. +0.90%), the United Kingdom (+3.33% vs. +0.77%), and the United States (+1.98% vs. -2.88%). These trends were largely driven by rectal cancer, except in Br", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31113868"}, {"offsetInBeginSection": 443, "offsetInEndSection": 876, "text": " incidence rate.RESULTS: Globally, the incidence of late-onset CRC was heterogeneous and remained increasing in most countries. The highest incidence of late-onset colon and rectal cancer was both found in males in Slovakia (156.5/100,000 and 121.5/100,000, respectively). The most pronounced increases were mostly observed in developing countries, such as Brazil (colon cancer: EAPC\u2009=\u20095.87, 95% CI 3.18, 8.63; rectal cancer: EAPC\u2009=\u2009", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32173775"}, {"offsetInBeginSection": 0, "offsetInEndSection": 702, "text": "OBJECTIVE: To summarize the colorectal cancer (CRC) burden and trend in the world, and compare the difference of CRC burden between other countries and China.METHODS: Incidence and mortality data were extracted from the GLOBOCAN2018 and Cancer Incidence in Five Continents. Age-specific incidence trend was conducted by Joinpoint analysis and average annual percent changes were calculated.RESULTS: About 1.85 million new cases and 0.88 million deaths were expected in 2018 worldwide, including 0.52 million (28.20%) new cases and 0.25 million (28.11%) deaths in China. Hungary had the highest age-standardized incidence and mortality rates in the world, while for China, the incidence and mortality ra", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33707923"}, {"offsetInBeginSection": 1259, "offsetInEndSection": 2544, "text": "13\u00b75) between 1990 and 2017. Globally, colorectal cancer accounted for 896\u2008000 (876\u2008300-915\u2008700) deaths in 2017, with an age-standardised death rate of 11\u00b75 (11\u00b73-11\u00b78) per 100\u2008000 person-years, which decreased between 1990 and 2017 (-13\u00b75% [-18\u00b74 to -10\u00b70]). Colorectal cancer was also responsible for 19\u00b70 million (18\u00b75-19\u00b75) DALYs globally in 2017, with an age-standardised rate of 235\u00b77 (229\u00b77-242\u00b70) DALYs per 100\u2008000 person-years, which decreased between 1990 and 2017 (-14\u00b75% [-20\u00b74 to -10\u00b73]). Slovakia, the Netherlands, and New Zealand had the highest age-standardised incidence rates in 2017. Greenland, Hungary, and Slovakia had the highest age-standardised death rates in 2017. Numbers of incident cases and deaths were higher among males than females up to the ages of 80-84 years, with the highest rates observed in the oldest age group (\u226595 years) for both sexes in 2017. There was a non-linear association between the Socio-demographic Index and the Healthcare Access and Quality Index and age-standardised DALY rates. In 2017, the three largest contributors to DALYs at the global level, for both sexes, were diet low in calcium (20\u00b75% [12\u00b79-28\u00b79]), alcohol use (15\u00b72% [12\u00b71-18\u00b73]), and diet low in milk (14\u00b73% [5\u00b71-24\u00b78]).INTERPRETATION: There is substantial global v", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31648977"}, {"offsetInBeginSection": 862, "offsetInEndSection": 1360, "text": "her cancer mortality was seen for most common sites; the greatest excesses were for colorectal cancer in both men and women. Cancer incidence in New Zealand women was 3.3% higher, and incidence in men was 4.7% lower, than in Australia over this period; thus the higher cancer deaths in New Zealand are not due simply to higher incidence. Over this time period, cancer mortality has fallen substantially in both countries; in New Zealand, it fell from 1990 to 2007 by 20% in women and 24% in men.CON", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25145363"}, {"offsetInBeginSection": 862, "offsetInEndSection": 1202, "text": "her cancer mortality was seen for most common sites; the greatest excesses were for colorectal cancer in both men and women. Cancer incidence in New Zealand women was 3.3% higher, and incidence in men was 4.7% lower, than in Australia over this period; thus the higher cancer deaths in New Zealand are not due simply to higher incidence. Ov", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25145363"}, {"offsetInBeginSection": 796, "offsetInEndSection": 1202, "text": "re was no significant change over time in these differentials. Higher cancer mortality was seen for most common sites; the greatest excesses were for colorectal cancer in both men and women. Cancer incidence in New Zealand women was 3.3% higher, and incidence in men was 4.7% lower, than in Australia over this period; thus the higher cancer deaths in New Zealand are not due simply to higher incidence. Ov", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25145363"}, {"offsetInBeginSection": 715, "offsetInEndSection": 1040, "text": " largest differences related to breast cancer and lung cancer in women, and colorectal cancer in both sexes. The overall incidence of cancer was higher in New Zealand, but mortality/incidence ratios were also higher for many sites--suggesting that survival after treatment has been poorer in New Zealand than in Australia.CON", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12064704"}, {"offsetInBeginSection": 426, "offsetInEndSection": 708, "text": "Although overall cancer rates were similar in men born in New Zealand to those in the Australian born men, the New Zealanders had a significantly higher risk of colorectal (SIR = 124) and testicular cancer (SIR = 227), cancers which are more common in New Zealand than in Australia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2308724"}, {"offsetInBeginSection": 579, "offsetInEndSection": 1040, "text": "Australian rates had applied, there would have been 215 fewer cancer deaths per year in New Zealand males, and 616 fewer in females. The largest differences related to breast cancer and lung cancer in women, and colorectal cancer in both sexes. The overall incidence of cancer was higher in New Zealand, but mortality/incidence ratios were also higher for many sites--suggesting that survival after treatment has been poorer in New Zealand than in Australia.CON", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12064704"}, {"offsetInBeginSection": 715, "offsetInEndSection": 1124, "text": " largest differences related to breast cancer and lung cancer in women, and colorectal cancer in both sexes. The overall incidence of cancer was higher in New Zealand, but mortality/incidence ratios were also higher for many sites--suggesting that survival after treatment has been poorer in New Zealand than in Australia.CONCLUSIONS: Considerable scope exists for reducing cancer mortality in New Zealand. Fo", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12064704"}, {"offsetInBeginSection": 206, "offsetInEndSection": 708, "text": "Indirectly age-standardised incidence ratios (SIR) showed that New Zealand born women living in NSW had higher rates of cancer at all sites combined (SIR = 112) and a significant excess of colorectal cancer (SIR = 126). Although overall cancer rates were similar in men born in New Zealand to those in the Australian born men, the New Zealanders had a significantly higher risk of colorectal (SIR = 124) and testicular cancer (SIR = 227), cancers which are more common in New Zealand than in Australia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2308724"}, {"offsetInBeginSection": 426, "offsetInEndSection": 897, "text": "Although overall cancer rates were similar in men born in New Zealand to those in the Australian born men, the New Zealanders had a significantly higher risk of colorectal (SIR = 124) and testicular cancer (SIR = 227), cancers which are more common in New Zealand than in Australia. While the SIRs for lung cancer in men and melanoma of skin in both sexes were low, no cancer was significantly less common in New Zealand born residents of NSW than in the Australian born.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2308724"}, {"offsetInBeginSection": 206, "offsetInEndSection": 425, "text": "Indirectly age-standardised incidence ratios (SIR) showed that New Zealand born women living in NSW had higher rates of cancer at all sites combined (SIR = 112) and a significant excess of colorectal cancer (SIR = 126).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2308724"}, {"offsetInBeginSection": 0, "offsetInEndSection": 481, "text": "OBJECTIVES: The aim of this study is to describe the colorectal cancer trend in the Slovakia between 2002 and 2019.BACKGROUND: In 2020, the Slovakia ranked second among the 10 countries with the highest incidence of colorectal cancer and the highest number of deaths from colorectal cancer (hereafter also referred to as CRC).METHODS: To describe the situation of CRC, indicators of incidence and mortality rates stratified by age and sex for the available time period were chosen.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37874806"}, {"offsetInBeginSection": 1104, "offsetInEndSection": 1233, "text": "egarding the prevalence of CRC. The prevalence of CRC was 0.72% in Saudi Arabia and 0.78% in the United Arab Emirate, while in Eg", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34853651"}, {"offsetInBeginSection": 1661, "offsetInEndSection": 1857, "text": "for both sexes in Saudi Arabia. In 2016, the CIRs in Saudi Arabia were 3.6 and 2.1 in females for colon cancer and rectal cancer, respectively, while in males, it was 3.3 and 2.8 for colon cancer ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34853651"}, {"offsetInBeginSection": 0, "offsetInEndSection": 353, "text": "OPINION STATEMENT: Colorectal cancer (CRC) is the third most common cancer worldwide. CRC has been thought to be less common in Asia compared to Western countries. However, the incidence rates of CRC in Asia are high and there is an increasing trend in the Asian population. Furthermore, colorectal cancer accounts for the greatest number of all inciden", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28948490"}, {"offsetInBeginSection": 746, "offsetInEndSection": 871, "text": "These results indicate that Northern Ireland has the highest underlying incidence of colorectal cancer in the United Kingdom.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2278112"}, {"offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "BACKGROUND: The overall incidence of colorectal cancer is decreasing in many high-income countries, yet analyses in the USA and other high-income countries such as Australia, Canada, and Norway have suggested increasing incidences among adults younger th", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31105047"}, {"offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "RATIONALE AND OBJECTIVE: The colorectal cancer (CRC) burden is increasing in Central and South American due to an ongoing transition towards higher lev", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27678325"}, {"offsetInBeginSection": 1651, "offsetInEndSection": 1720, "text": "Therefore, the burden of colorectal cancer is significant in Lebanon.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33618551"}, {"offsetInBeginSection": 229, "offsetInEndSection": 442, "text": "This study aims to investigate the incidence and trends of colorectal cancer in Lebanon, a country in the Middle East and North Africa region, and to compare these rates to those in regional and western countries.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33618551"}, {"offsetInBeginSection": 181, "offsetInEndSection": 365, "text": "High rates are characteristic of highly developed countries in North America, northern and western Europe. The lowest rates are found in Asia, Africa and most Latin American countries.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2483912"}, {"offsetInBeginSection": 470, "offsetInEndSection": 617, "text": "For rectal cancer, Louisiana incidence rates approximate the national rates for all but African-American males, whose rate was significantly lower.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10234894"}, {"offsetInBeginSection": 67, "offsetInEndSection": 255, "text": " cancer worldwide. CRC has been thought to be less common in Asia compared to Western countries. However, the incidence rates of CRC in Asia are high and there is an increasing trend in th", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28948490"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1175, "text": "RATIONALE AND OBJECTIVE: The colorectal cancer (CRC) burden is increasing in Central and South American due to an ongoing transition towards higher levels of human development. We describe the burden of CRC in the region and review the current status of disease control.METHODS: We obtained regional- and national-level incidence data from 48 population-based cancer registries in 13 countries, as well as cancer deaths from the WHO mortality database for 18 countries. We estimated world population age-standardized incidence (ASR) and mortality (ASMR) rates per 100,000 person-years for 2003-2007 and the estimated annual percentage change for 1997-2008.RESULTS: The CRC rate in males was 1-2 times higher than that in females. In 2003-2007, the highest ASRs were seen in Uruguayan, Brazilian and Argentinean males (25.2-34.2) and Uruguayan and Brazilian females (21.5-24.7), while El Salvador had the lowest ASR in both sexes (males: 1.5, females: 1.3). ASMRs were<10 for both sexes, except in Uruguay, Cuba and Argentina (10.0-17.7 and 11.3-12.0). CRC incidence is increasing in Chilean males. Most countries have national screening guidelines. Uruguay and Argentina have", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27678325"}, {"offsetInBeginSection": 2966, "offsetInEndSection": 3183, "text": "ficant increases in CRC mortality.CONCLUSIONS: In an analysis of incidence and mortality databases from 39 countries, we found that the incidence of colon and rectal cancers has continued to increase in countries with", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32088300"}, {"offsetInBeginSection": 877, "offsetInEndSection": 1044, "text": ".68; 95% CI 2.78, 6.62). The highest incidence of early-onset colon and rectal cancer was found in females in Switzerland (4.2/100,000) and in males in South Korea (4.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32173775"}, {"offsetInBeginSection": 1933, "offsetInEndSection": 2596, "text": "versely, colorectal cancer incidence increased in most countries where no large-scale screening programmes were available (eg, Bulgaria, Estonia, Norway, and Ukraine), with AAPCs ranging from 0\u00b73% (95% CI 0\u00b71 to 0\u00b75) to 1\u00b79% (1\u00b72 to 2\u00b76) in men and from 0\u00b76% (0\u00b74 to 0\u00b78) to 1\u00b71% (0\u00b78 to 1\u00b74) in women. The largest decreases in colorectal cancer mortality were seen in countries with long-standing screening programmes.INTERPRETATION: We observed divergent trends in colorectal cancer incidence, mortality, and stage distribution across European countries, which appear to be largely explained by different levels of colorectal cancer screening implementation.FUN", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34048685"}, {"offsetInBeginSection": 811, "offsetInEndSection": 1287, "text": "Among the 29 countries investigated, colorectal cancer incidence was observed to decrease after reaching the very high human development threshold for 12 countries; decreases were also observed in a further five countries, but the age-standardized incidence rates remained higher than that observed at the threshold. Such declines or stabilizations are likely due to colorectal cancer screening in some populations, as well as varying levels of exposure to protective factors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28281292"}, {"offsetInBeginSection": 1738, "offsetInEndSection": 2355, "text": "re high screening coverage and uptake were rapidly achieved (ie, Denmark, the Netherlands, and Slovenia), age-standardised incidence rates initially increased but then subsequently decreased. Conversely, colorectal cancer incidence increased in most countries where no large-scale screening programmes were available (eg, Bulgaria, Estonia, Norway, and Ukraine), with AAPCs ranging from 0\u00b73% (95% CI 0\u00b71 to 0\u00b75) to 1\u00b79% (1\u00b72 to 2\u00b76) in men and from 0\u00b76% (0\u00b74 to 0\u00b78) to 1\u00b71% (0\u00b78 to 1\u00b74) in women. The largest decreases in colorectal cancer mortality were seen in countries with long-standing screening programmes.INT", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34048685"}, {"offsetInBeginSection": 1738, "offsetInEndSection": 2238, "text": "re high screening coverage and uptake were rapidly achieved (ie, Denmark, the Netherlands, and Slovenia), age-standardised incidence rates initially increased but then subsequently decreased. Conversely, colorectal cancer incidence increased in most countries where no large-scale screening programmes were available (eg, Bulgaria, Estonia, Norway, and Ukraine), with AAPCs ranging from 0\u00b73% (95% CI 0\u00b71 to 0\u00b75) to 1\u00b79% (1\u00b72 to 2\u00b76) in men and from 0\u00b76% (0\u00b74 to 0\u00b78) to 1\u00b71% (0\u00b78 to 1\u00b74) in women. Th", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34048685"}, {"offsetInBeginSection": 0, "offsetInEndSection": 442, "text": "Global trends in the incidence and mortality rates of colorectal cancer show a steady increase with significant predilection to western developed countries, possibly linking it to westernized lifestyles among other risk factors. This study aims to investigate the incidence and trends of colorectal cancer in Lebanon, a country in the Middle East and North Africa region, and to compare these rates to those in regional and western countries.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33618551"}, {"offsetInBeginSection": 1028, "offsetInEndSection": 1379, "text": "INGS: In countries with long-standing programmes of screening colonoscopy and faecal tests (ie, Austria, the Czech Republic, and Germany), colorectal cancer incidence decreased substantially over time, with AAPCs ranging from -2\u00b75% (95% CI -2\u00b78 to -2\u00b72) to -1\u00b76% (-2\u00b70 to -1\u00b72) in men and from -2\u00b74% (-2\u00b77 to -2\u00b71) to -1\u00b73% (-1\u00b77 to -0\u00b79) in women. In", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34048685"}, {"offsetInBeginSection": 1585, "offsetInEndSection": 2238, "text": "Cs for these countries ranged from -0\u00b72% (95% CI -1\u00b74 to 1\u00b70) to 1\u00b75% (1\u00b71 to 1\u00b78) in men and from -0\u00b75% (-1\u00b77 to 0\u00b76) to 1\u00b72% (0\u00b78 to 1\u00b75) in women. Where high screening coverage and uptake were rapidly achieved (ie, Denmark, the Netherlands, and Slovenia), age-standardised incidence rates initially increased but then subsequently decreased. Conversely, colorectal cancer incidence increased in most countries where no large-scale screening programmes were available (eg, Bulgaria, Estonia, Norway, and Ukraine), with AAPCs ranging from 0\u00b73% (95% CI 0\u00b71 to 0\u00b75) to 1\u00b79% (1\u00b72 to 2\u00b76) in men and from 0\u00b76% (0\u00b74 to 0\u00b78) to 1\u00b71% (0\u00b78 to 1\u00b74) in women. Th", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34048685"}, {"offsetInBeginSection": 0, "offsetInEndSection": 628, "text": "BACKGROUND: The overall incidence of colorectal cancer is decreasing in many high-income countries, yet analyses in the USA and other high-income countries such as Australia, Canada, and Norway have suggested increasing incidences among adults younger than 50 years. We aimed to examine longitudinal and generational changes in the incidence of colon and rectal cancer in seven high-income countries.METHODS: We obtained data for the incidence of colon and rectal cancer from 21 population-based cancer registries in Australia, Canada, Denmark, Norway, New Zealand, Ireland, and the UK for the earliest available year until 2014", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31105047"}, {"offsetInBeginSection": 991, "offsetInEndSection": 1254, "text": "Examination of time trends during the last decades reveals a sharp increase in incidence of colorectal cancer in Japan and in eastern and southern Europe. On the other hand, incidence rates show some stagnation in North America and western Europe in recent years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10772412"}, {"offsetInBeginSection": 518, "offsetInEndSection": 655, "text": "CRC has a wide global distribution in incidence and mortality with majority of cases occurring in countries with a high or very high HDI.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34422402"}, {"offsetInBeginSection": 419, "offsetInEndSection": 570, "text": "The highest rates were observed in Western countries, especially in North America, Australasia and, to a lesser extent, in northern and western Europe.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10772412"}, {"offsetInBeginSection": 293, "offsetInEndSection": 423, "text": "Colorectal cancer is common in most countries of North America and Europe, is rare in Asia and is particularly uncommon in Africa.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2991145"}, {"offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "BACKGROUND: New Zealand has among the highest rates of colorectal cancer in the world and is an unscreened", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28378448"}]}
+{"question_id": "66302978187cba990d000034", "question": "What are the primary and secondary endpoints of Pamrevlumab?", "answer": "The primary endpoint was change from baseline in percent predicted forced vital capacity (ppFVC). Secondary endpoints included other pulmonary function tests, upper limb function and strength assessments, and changes in upper arm fat and fibrosis scores on magnetic resonance imaging.", "relevant_passage_ids": ["37248912", "31575509", "33054319"], "type": "list", "snippets": [{"offsetInBeginSection": 662, "offsetInEndSection": 761, "text": " The primary endpoint was change from baseline in percent predicted forced vital capacity (ppFVC). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37248912"}, {"offsetInBeginSection": 790, "offsetInEndSection": 947, "text": "other pulmonary function tests, upper limb function and strength assessments, and changes in upper arm fat and fibrosis scores on magnetic resonance imaging.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37248912"}, {"offsetInBeginSection": 409, "offsetInEndSection": 948, "text": "THODS: MISSION (Study 079; NCT02606136) was an open-label, Phase II, single-arm trial of pamrevlumab in 21 non-ambulatory patients with DMD (aged\u226512 years, receiving corticosteroids) who received 35-mg/kg intravenous infusions every 2 weeks for 2 years. The primary endpoint was change from baseline in percent predicted forced vital capacity (ppFVC). Secondary endpoints included other pulmonary function tests, upper limb function and strength assessments, and changes in upper arm fat and fibrosis scores on magnetic resonance imaging.R", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37248912"}, {"offsetInBeginSection": 227, "offsetInEndSection": 759, "text": " Pamrevlumab (FG-3019), a fully human monoclonal antibody that binds to connective tissue growth factor (CTGF), is in Phase III development for treatment of DMD and other diseases.METHODS: MISSION (Study 079; NCT02606136) was an open-label, Phase II, single-arm trial of pamrevlumab in 21 non-ambulatory patients with DMD (aged\u226512 years, receiving corticosteroids) who received 35-mg/kg intravenous infusions every 2 weeks for 2 years. The primary endpoint was change from baseline in percent predicted forced vital capacity (ppFVC)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37248912"}, {"offsetInBeginSection": 761, "offsetInEndSection": 993, "text": "Secondary endpoints included other pulmonary function tests, upper limb function and strength assessments, and changes in upper arm fat and fibrosis scores on magnetic resonance imaging.RESULTS: Fifteen patients completed the trial.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37248912"}, {"offsetInBeginSection": 663, "offsetInEndSection": 760, "text": "The primary endpoint was change from baseline in percent predicted forced vital capacity (ppFVC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37248912"}, {"offsetInBeginSection": 642, "offsetInEndSection": 926, "text": "2 weeks for 2 years. The primary endpoint was change from baseline in percent predicted forced vital capacity (ppFVC). Secondary endpoints included other pulmonary function tests, upper limb function and strength assessments, and changes in upper arm fat and fibrosis scores on magnet", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37248912"}, {"offsetInBeginSection": 216, "offsetInEndSection": 1365, "text": "ose tissue. Pamrevlumab (FG-3019), a fully human monoclonal antibody that binds to connective tissue growth factor (CTGF), is in Phase III development for treatment of DMD and other diseases.METHODS: MISSION (Study 079; NCT02606136) was an open-label, Phase II, single-arm trial of pamrevlumab in 21 non-ambulatory patients with DMD (aged\u226512 years, receiving corticosteroids) who received 35-mg/kg intravenous infusions every 2 weeks for 2 years. The primary endpoint was change from baseline in percent predicted forced vital capacity (ppFVC). Secondary endpoints included other pulmonary function tests, upper limb function and strength assessments, and changes in upper arm fat and fibrosis scores on magnetic resonance imaging.RESULTS: Fifteen patients completed the trial. Annual change from baseline (SE) in ppFVC was -4.2 (0.7) (95% CI -5.5, -2.8). Rate of decline in ppFVC in pamrevlumab-treated patients was slower than observed in historical published trials of non-ambulatory patients. MISSION participants experienced slower-than-anticipated muscle function declines compared with natural history and historical published trials of non-a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37248912"}, {"offsetInBeginSection": 664, "offsetInEndSection": 994, "text": "he primary endpoint was change from baseline in percent predicted forced vital capacity (ppFVC). Secondary endpoints included other pulmonary function tests, upper limb function and strength assessments, and changes in upper arm fat and fibrosis scores on magnetic resonance imaging.RESULTS: Fifteen patients completed the trial. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37248912"}, {"offsetInBeginSection": 664, "offsetInEndSection": 948, "text": "he primary endpoint was change from baseline in percent predicted forced vital capacity (ppFVC). Secondary endpoints included other pulmonary function tests, upper limb function and strength assessments, and changes in upper arm fat and fibrosis scores on magnetic resonance imaging.R", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37248912"}, {"offsetInBeginSection": 762, "offsetInEndSection": 1072, "text": "econdary endpoints included other pulmonary function tests, upper limb function and strength assessments, and changes in upper arm fat and fibrosis scores on magnetic resonance imaging.RESULTS: Fifteen patients completed the trial. Annual change from baseline (SE) in ppFVC was -4.2 (0.7) (95% CI -5.5, -2.8). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37248912"}, {"offsetInBeginSection": 762, "offsetInEndSection": 994, "text": "econdary endpoints included other pulmonary function tests, upper limb function and strength assessments, and changes in upper arm fat and fibrosis scores on magnetic resonance imaging.RESULTS: Fifteen patients completed the trial. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37248912"}, {"offsetInBeginSection": 762, "offsetInEndSection": 948, "text": "econdary endpoints included other pulmonary function tests, upper limb function and strength assessments, and changes in upper arm fat and fibrosis scores on magnetic resonance imaging.R", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37248912"}]}
+{"question_id": "66099ac8fdcbea915f00001f", "question": "What are the mechanisms of secondary resistance to anti-EGFR monoclonal antibodies in colorectal cancer treatment?", "answer": "Genetic alterations of genes in the EGFR-RAS-RAF-MEK signaling pathway and of receptor tyrosine kinases are mechanisms of acquired resistance to anti-EGFR antibodies.  The escape from anti-EGFR blockade appears to converge on the (re)activation of MEK-ERK or AKT as revealed in preclinical studies", "relevant_passage_ids": ["24913799", "22722830", "26416732", "29045518", "26372697", "24122793", "34271981", "24553387", "26869800", "28752777", "20222160", "27605871", "25293556", "38071748", "33801379", "36131281", "36063655", "32718285", "30623369", "19223544", "37948593", "34663410", "30081606", "32474402", "37791069", "31370270", "36351210", "30968289", "24666267", "23281932", "24758538", "32394048", "32665850", "36419886", "27777877", "24558511", "28507280", "28382467", "27341591", "24653627", "36717006", "25993166", "19663767", "22586650", "32229076", "17438669", "26657506", "25628445", "24054705"], "type": "list", "snippets": [{"offsetInBeginSection": 658, "offsetInEndSection": 882, "text": ". Molecular profiling of clinical specimens confirmed that genetic alterations of genes in the EGFR-RAS-RAF-MEK signaling pathway and of receptor tyrosine kinases are mechanisms of acquired resistance to anti-EGFR antibodies", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24913799"}, {"offsetInBeginSection": 554, "offsetInEndSection": 727, "text": "molecular alterations (in most instances point mutations) of KRAS are causally associated with the onset of acquired resistance to anti-EGFR treatment in colorectal cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722830"}, {"offsetInBeginSection": 1395, "offsetInEndSection": 1608, "text": "KRAS mutations as frequent drivers of acquired resistance to cetuximab in colorectal cancers, indicate that the emergence of KRAS mutant clones can be detected non-invasively months before radiographic progression", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722830"}, {"offsetInBeginSection": 884, "offsetInEndSection": 1013, "text": "The escape from anti-EGFR blockade appears to converge on the (re)activation of MEK-ERK or AKT as revealed in preclinical studies", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24913799"}, {"offsetInBeginSection": 95, "offsetInEndSection": 314, "text": "Since RAS mutations (RAS-mut) play a major role in resistance to antiepidermal growth factor receptor inhibitors (EGFR) monoclonal antibodies (Mabs), serial monitoring of RAS-mut with LB may be useful to guide treatment", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38071748"}, {"offsetInBeginSection": 0, "offsetInEndSection": 547, "text": "In the evolving molecular landscape of metastatic colorectal cancer, optimizing available tools to select patients to receive anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies is a modern challenge of colorectal oncologists. Several molecular biomarkers have been investigated in recent years as potential predictors of resistance to anti-EGFR agents in preclinical and clinical retrospective series. Nevertheless, none of them have been implemented in clinical practice due to the lack of a formal prospective demonstration.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30081606"}, {"offsetInBeginSection": 0, "offsetInEndSection": 953, "text": "The development of monoclonal antibodies (mAbs) cetuximab and panitumumab, which target the transmembrane protein epidermal growth factor receptor (EGFR), mark a major step forward in the treatment of metastatic colorectal cancer (mCRC). However, this therapeutic progress proved to be effective only in a very restricted subset of patients. Although several mechanisms of resistance, both primary and acquired, have been identified, the only established predictive tumour biomarker for the treatment of mCRC patients is the RAS mutational status. RAS activating mutations predict a lack of response to these therapies while low levels of primary resistance characterize RAS wild type (WT) patients (only about 15%). However, even WT patients that initially respond to anti-EGFR therapy, eventually undergo tumour progression. In this context, there is still more to be done in the search for effective predictive markers with therapeutic applicability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30623369"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1770, "text": "PURPOSE: Acquired resistance to anti-epidermal growth factor receptor (EGFR) inhibitor (EGFRi) therapy in colorectal cancer (CRC) has previously been explained by the model of acquiring new mutations in KRAS/NRAS/EGFR, among other MAPK-pathway members. However, this was primarily on the basis of single-agent EGFRi trials and little is known about the resistance mechanisms of EGFRi combined with effective cytotoxic chemotherapy in previously untreated patients.METHODS: We analyzed paired plasma samples from patients with RAS/BRAF/EGFR wild-type metastatic CRC enrolled in three large randomized trials evaluating EGFRi in the first line in combination with chemotherapy and as a single agent in third line. The mutational signature of the alterations acquired with therapy was evaluated. CRC cell lines with resistance to cetuximab, infusional fluorouracil, leucovorin, and oxaliplatin, and SN38 were developed, and transcriptional changes profiled.RESULTS: Patients whose tumors were treated with and responded to EGFRi alone were more likely to develop acquired mutations (46%) compared with those treated in combination with cytotoxic chemotherapy (9%). Furthermore, contrary to the generally accepted hypothesis of the clonal evolution of acquired resistance, we demonstrate that baseline resistant subclonal mutations rarely expanded to become clonal at progression, and most remained subclonal or disappeared. Consistent with this clinical finding, preclinical models with acquired resistance to either cetuximab or chemotherapy were cross-resistant to the alternate agents, with transcriptomic profiles consistent with epithelial-to-mesenchymal transition. By contrast, commonly acquired resistance alterations in the MAPK pathway do not affect sensitivity t", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36351210"}, {"offsetInBeginSection": 0, "offsetInEndSection": 881, "text": ": Targeting the epidermal growth factor receptor (EGFR) either alone or in combination with chemotherapy in patients with RAS wild type metastatic colorectal cancer (mCRC) has revolutionized the treatment of CRC, but with less results than initially envisaged. In recent years, the discovery of multiple pathways leading to the escape from anti-EGFR therapy has revealed an enormous complexity and heterogeneity of human CRC due to the intrinsic genomic instability and immune/cancer cell interaction. Therefore, understanding the mechanistic basis of acquired resistance to targeted therapies represents a major challenge to improve the clinical outcomes of patients with CRC. The latest findings strongly suggest that complex molecular alterations coupled with changes of the immune tumor microenvironment may substantially contribute to the clinical efficacy of EGFR antagonist.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31370270"}, {"offsetInBeginSection": 0, "offsetInEndSection": 586, "text": "The epidermal growth factor receptor (EGFR) and RAS/RAF signaling pathway plays pivotal roles in tumor progression via proliferation, survival, invasion, and immune evasion. Two anti-EGFR monoclonal antibodies, cetuximab and panitumumab, have become essential components in the treatment of patients with metastatic colorectal cancer (mCRC). Treatment with these anti-EGFR antibodies has shown definite benefits when administered in all treatment lines and is strongly recommended as the preferred regimen to prolong survival, especially when administered in the first- and third-lines.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30968289"}, {"offsetInBeginSection": 0, "offsetInEndSection": 518, "text": "The monoclonal antibodies (moAb) panitumumab and cetuximab target the epidermal growth factor receptor (EGFR) and have proven valuable for the treatment of metastatic colorectal cancer (mCRC). EGFR-mediated signaling involves two main intracellular cascades: on one side KRAS activates BRAF, which in turn triggers the mitogen-activated protein kinases. On the other, membrane localization of the lipid kinase PIK3CA counteracts PTEN and promotes AKT1 phosphorylation, thereby activating a parallel intracellular axis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19223544"}, {"offsetInBeginSection": 819, "offsetInEndSection": 1168, "text": "Mutations in oncogene Kirsten-RAS (KRAS) are frequently associated with resistance to anti-EGFR therapy. However, a significant number of KRAS wild-type (WT) tumors fail to obtain disease control with anti-EGFR agents. Therefore, additional biomarkers of response/resistance to these drugs such as BRAF, NRAS, PIK3CA and PTEN have been investigated.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24758538"}, {"offsetInBeginSection": 669, "offsetInEndSection": 1326, "text": "Accumulating evidence suggests that patients with mutations in EGFR downstream signaling pathways including KRAS, BRAF, PIK3CA and PTEN could be intrinsically resistant to EGFR blockade. Recent whole genome studies also suggest that dynamic alterations in signaling pathways downstream of EGFR leads to distinct oncogenic signatures and subclones which might have some impact on emerging resistance in KRAS wild-type patients. While anti-EGFR monoclonal antibodies have a clear potential in the management of a subset of patients with metastatic CRC, further studies are warranted to uncover exact mechanisms related to acquired resistance to EGFR blockade.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27777877"}, {"offsetInBeginSection": 557, "offsetInEndSection": 1043, "text": "Existing studies have demonstrated that among colorectal cancer patients with wild-type KRAS, harboring mutations of BRAF, PIK3CA, NRAS, or PTEN-null may demonstrate resistance to anti-EGFR-targeted therapy, and biomarkers detection can provide better-personalized treatment for mCRC patients. How to identify and reverse the secondary resistance to anti-EGFR monoclonal antibody therapy is also another great challenge to improve the anti-EGFR efficacy in wild-type KRAS mCRC patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26869800"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1722, "text": "A main limitation of therapies that selectively target kinase signalling pathways is the emergence of secondary drug resistance. Cetuximab, a monoclonal antibody that binds the extracellular domain of epidermal growth factor receptor (EGFR), is effective in a subset of KRAS wild-type metastatic colorectal cancers. After an initial response, secondary resistance invariably ensues, thereby limiting the clinical benefit of this drug. The molecular bases of secondary resistance to cetuximab in colorectal cancer are poorly understood. Here we show that molecular alterations (in most instances point mutations) of KRAS are causally associated with the onset of acquired resistance to anti-EGFR treatment in colorectal cancers. Expression of mutant KRAS under the control of its endogenous gene promoter was sufficient to confer cetuximab resistance, but resistant cells remained sensitive to combinatorial inhibition of EGFR and mitogen-activated protein-kinase kinase (MEK). Analysis of metastases from patients who developed resistance to cetuximab or panitumumab showed the emergence of KRAS amplification in one sample and acquisition of secondary KRAS mutations in 60% (6 out of 10) of the cases. KRAS mutant alleles were detectable in the blood of cetuximab-treated patients as early as 10 months before radiographic documentation of disease progression. In summary, the results identify KRAS mutations as frequent drivers of acquired resistance to cetuximab in colorectal cancers, indicate that the emergence of KRAS mutant clones can be detected non-invasively months before radiographic progression and suggest early initiation of a MEK inhibitor as a rational strategy for delaying or reversing drug resistance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722830"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1683, "text": "Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR), cetuximab and panitumumab, are a mainstay of metastatic colorectal cancer (mCRC) treatment. However, a significant number of patients suffer from primary or acquired resistance. RAS mutations are negative predictors of clinical efficacy of anti-EGFR antibodies in patients with mCRC. Oncogenic RAS activates the MAPK and PI3K/AKT pathways, which are considered the main effectors of resistance. However, the relative impact of these pathways in RAS-mutant CRC is less defined. A better mechanistic understanding of RAS-mediated resistance may guide development of rational intervention strategies. To this end we developed cancer models for functional dissection of resistance to anti-EGFR therapy in vitro and in vivo. To selectively activate MAPK- or AKT-signaling we expressed conditionally activatable RAF-1 and AKT in cancer cells. We found that either pathway independently protected sensitive cancer models against anti-EGFR antibody treatment in vitro and in vivo. RAF-1- and AKT-mediated resistance was associated with increased expression of anti-apoptotic BCL-2 proteins. Biomarkers of MAPK and PI3K/AKT pathway activation correlated with inferior outcome in a cohort of mCRC patients receiving cetuximab-based therapy. Dual pharmacologic inhibition of PI3K and MEK successfully sensitized primary resistant CRC models to anti-EGFR therapy. In conclusion, combined targeting of MAPK and PI3K/AKT signaling, but not single pathways, may be required to enhance the efficacy of anti-EGFR antibody therapy in patients with RAS-mutated CRC as well as in RAS wild type tumors with clinical resistance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28507280"}, {"offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "BACKGROUND: The development of secondary resistance (SR) in metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (anti-EGFR) antibodies is not fully understood at the mole", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34271981"}, {"offsetInBeginSection": 0, "offsetInEndSection": 386, "text": "Background: We aim to identify the prevalence and the role of the MAP2K1 K57N mutation in predicting resistance to anti-EGFR agents in metastatic colorectal cancer (mCRC) patients.Methods: We retrospectively reviewed tumor-based next generation sequencing (NGS) results from mCRC patients screened for enrollment in the GO40872/STARTRK-2 clinical trial between July 2019 and March 2021.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36419886"}, {"offsetInBeginSection": 767, "offsetInEndSection": 1075, "text": "Nongenetic mechanisms, including compensatory activation of receptor tyrosine kinases HER3 and MET, together with high expression of the ligands amphiregulin, transforming growth factor alpha heregulin, and hepatocyte growth factor in the tumor microenvironment also are thought to be involved in resistance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25993166"}, {"offsetInBeginSection": 572, "offsetInEndSection": 881, "text": "Further, positive predictive markers that are currently being evaluated include an increase in EGFR gene copy number and additional data suggest that other EGFR downstream pathways such as the PI3K/PTEN/AKT/mTOR and JAK/STAT pathways are also important when considering mechanisms of EGFR antibody resistance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19663767"}, {"offsetInBeginSection": 289, "offsetInEndSection": 473, "text": "The clinical efficacy of EGFR targeted antibodies is limited by the development of acquired (secondary) resistance, which typically occurs within 3-12 months from the start of therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24913799"}, {"offsetInBeginSection": 0, "offsetInEndSection": 556, "text": "Colorectal cancers (CRCs) that are sensitive to the anti-epidermal growth factor receptor (EGFR) antibodies cetuximab or panitumumab almost always develop resistance within several months of initiating therapy. We report the emergence of polyclonal KRAS, NRAS, and BRAF mutations in CRC cells with acquired resistance to EGFR blockade. Regardless of the genetic alterations, resistant cells consistently displayed mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinase (ERK) activation, which persisted after EGFR blockade.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24553387"}, {"offsetInBeginSection": 107, "offsetInEndSection": 1725, "text": "In late-stage colorectal cancer, the most commonly used targeted therapies are the monoclonal antibodies cetuximab and panitumumab, which prevent epidermal growth factor receptor (EGFR) activation. Recent studies have identified alterations in KRAS and other genes as likely mechanisms of primary and secondary resistance to anti-EGFR antibody therapy. Despite these efforts, additional mechanisms of resistance to EGFR blockade are thought to be present in colorectal cancer and little is known about determinants of sensitivity to this therapy. To examine the effect of somatic genetic changes in colorectal cancer on response to anti-EGFR antibody therapy, here we perform complete exome sequence and copy number analyses of 129 patient-derived tumour grafts and targeted genomic analyses of 55 patient tumours, all of which were KRAS wild-type. We analysed the response of tumours to anti-EGFR antibody blockade in tumour graft models and in clinical settings and functionally linked therapeutic responses to mutational data. In addition to previously identified genes, we detected mutations in ERBB2, EGFR, FGFR1, PDGFRA, and MAP2K1 as potential mechanisms of primary resistance to this therapy. Novel alterations in the ectodomain of EGFR were identified in patients with acquired resistance to EGFR blockade. Amplifications and sequence changes in the tyrosine kinase receptor adaptor gene IRS2 were identified in tumours with increased sensitivity to anti-EGFR therapy. Therapeutic resistance to EGFR blockade could be overcome in tumour graft models through combinatorial therapies targeting actionable genes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26416732"}, {"offsetInBeginSection": 129, "offsetInEndSection": 1361, "text": "Cetuximab, a monoclonal antibody that binds the extracellular domain of epidermal growth factor receptor (EGFR), is effective in a subset of KRAS wild-type metastatic colorectal cancers. After an initial response, secondary resistance invariably ensues, thereby limiting the clinical benefit of this drug. The molecular bases of secondary resistance to cetuximab in colorectal cancer are poorly understood. Here we show that molecular alterations (in most instances point mutations) of KRAS are causally associated with the onset of acquired resistance to anti-EGFR treatment in colorectal cancers. Expression of mutant KRAS under the control of its endogenous gene promoter was sufficient to confer cetuximab resistance, but resistant cells remained sensitive to combinatorial inhibition of EGFR and mitogen-activated protein-kinase kinase (MEK). Analysis of metastases from patients who developed resistance to cetuximab or panitumumab showed the emergence of KRAS amplification in one sample and acquisition of secondary KRAS mutations in 60% (6 out of 10) of the cases. KRAS mutant alleles were detectable in the blood of cetuximab-treated patients as early as 10 months before radiographic documentation of disease progression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722830"}, {"offsetInBeginSection": 0, "offsetInEndSection": 844, "text": "Anti-epidermal-growth-factor-receptor (EGFR) monoclonal antibodies (mAbs) are of great significance for RAS and BRAF wild-type metastatic colorectal cancer (mCRC) patients. However, the generation of primary and secondary resistance to anti-EGFR mAbs has become an important factor restricting its efficacy. Recent studies have revealed that non-coding RNAs (ncRNAs), especially long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are implicated in anti-EGFR antibodies resistance, affecting the sensitivity of CRC cells to Cetuximab and Panitumumab. This paper briefly reviewed the research advance of the expression, signaling network and functional mechanism of ncRNAs related to anti-EGFR mAbs resistance in CRC, as well as their relationship with clinical prognosis and the possibility of therapeutic targets.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36131281"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1428, "text": "Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR), cetuximab and panitumumab, are a mainstay of metastatic colorectal cancer (mCRC) treatment. However, a significant number of patients suffer from primary or acquired resistance. RAS mutations are negative predictors of clinical efficacy of anti-EGFR antibodies in patients with mCRC. Oncogenic RAS activates the MAPK and PI3K/AKT pathways, which are considered the main effectors of resistance. However, the relative impact of these pathways in RAS-mutant CRC is less defined. A better mechanistic understanding of RAS-mediated resistance may guide development of rational intervention strategies. To this end we developed cancer models for functional dissection of resistance to anti-EGFR therapy in vitro and in vivo. To selectively activate MAPK- or AKT-signaling we expressed conditionally activatable RAF-1 and AKT in cancer cells. We found that either pathway independently protected sensitive cancer models against anti-EGFR antibody treatment in vitro and in vivo. RAF-1- and AKT-mediated resistance was associated with increased expression of anti-apoptotic BCL-2 proteins. Biomarkers of MAPK and PI3K/AKT pathway activation correlated with inferior outcome in a cohort of mCRC patients receiving cetuximab-based therapy. Dual pharmacologic inhibition of PI3K and MEK successfully sensitized primary resistant CRC models to anti-EGFR therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28507280"}, {"offsetInBeginSection": 94, "offsetInEndSection": 748, "text": "Metastatic colorectal cancer (mCRC) patients have a poor prognosis despite improved treatments and more prolonged median survival. Monoclonal antibodies like cetuximab and panitumumab target the epidermal growth factor receptor (EGFR). They play an essential role in the treatment of metastatic colorectal cancer (mCRC) due to their efficacy in multiple phase III clinical trials across multiple treatment lines. It was discovered that anti-EGFR moAbs were only effective for a small number of patients. Mutations in KRAS and NRAS have been identified as biomarkers of drug resistance. New molecular predictors and prognostic markers are used clinically.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36717006"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1089, "text": "The monoclonal antibodies (moAb) panitumumab and cetuximab target the epidermal growth factor receptor (EGFR) and have proven valuable for the treatment of metastatic colorectal cancer (mCRC). EGFR-mediated signaling involves two main intracellular cascades: on one side KRAS activates BRAF, which in turn triggers the mitogen-activated protein kinases. On the other, membrane localization of the lipid kinase PIK3CA counteracts PTEN and promotes AKT1 phosphorylation, thereby activating a parallel intracellular axis. Constitutive activation of KRAS bypasses the corresponding signaling cascade and, accordingly, patients with mCRC bearing KRAS mutations are clinically resistant to therapy with panitumumab or cetuximab. We hypothesized that mutations activating PIK3CA could also preclude responsiveness to EGFR-targeted moAbs through a similar mechanism. Here, we present the mutational analysis of PIK3CA and KRAS and evaluation of the PTEN protein status in a cohort of 110 patients with mCRC treated with anti-EGFR moAbs. We observed 15 (13.6%) PIK3CA and 32 (29.0%) KRAS mutations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19223544"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1732, "text": "BACKGROUND: Refining the selection of metastatic colorectal cancer patients candidates for anti-epidermal growth factor receptor (EGFR) monoclonal antibodies beyond RAS and BRAF testing is a challenge of precision oncology. Several uncommon genomic mechanisms of primary resistance, leading to activation of tyrosine kinase receptors other than EGFR or downstream signalling pathways, have been suggested by preclinical and retrospective studies.PATIENTS AND METHODS: We conducted this multicentre, prospective, case-control study to demonstrate the negative predictive impact of a panel of rare genomic alterations [PRESSING (PRimary rESiStance IN RAS and BRAF wild-type metastatic colorectal cancer patients treated with anti-eGfr monoclonal antibodies) panel], including HER2/MET amplifications, ALK/ROS1/NTRK1-3/RET fusions and PIK3CA mutations. Hypothesizing a prevalence of candidate alterations of 15% and 0% in resistant and sensitive RAS and BRAF wild-type patients, respectively, with two-sided \u03b1 and \u03b2 errors of 0.05 and 0.20, 47 patients per group were needed.RESULTS: Forty-seven patients per group were included. PRESSING panel alterations were significantly more frequent in resistant (24 out of 47, 51.1%) than in sensitive (1 out of 47, 2.1%) patients (P\u2009<\u20090.001) and in right- (12 out of 29, 41.4%) than left-sided (13 out of 65, 20.0%) tumours (P\u2009=\u20090.03). The predictive accuracy of PRESSING panel and sidedness was 75.3% and 70.2%, respectively. Among hyper-selected patients, right-sidedness was still associated with resistance (P\u2009=\u20090.002). The predictive accuracy of the combined evaluation of PRESSING panel and sidedness was 80.4%. As a secondary analysis, 8 (17.0%) resistant and 0 sensitive patients showe", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29045518"}, {"offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "PURPOSE: Acquired resistance to anti-epidermal growth factor receptor (EGFR) inhibitor (EGFRi) therapy in colorectal cancer (CRC) has previously been explained by the model of acquiring new mutations in KRAS/NRAS/EGFR, among other MAPK-pathway", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36351210"}, {"offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "In the evolving molecular landscape of metastatic colorectal cancer, optimizing available tools to select patients to receive anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies is a modern challenge of colorectal oncologists.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30081606"}, {"offsetInBeginSection": 1263, "offsetInEndSection": 1499, "text": "In this review, we focus on the mechanisms of resistance to anti-EGFR monoclonal antibodies (anti-EGFR mAbs) and discuss diverse approaches to reverse resistance to this therapy in hopes of identifying more mCRC treatment possibilities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34663410"}, {"offsetInBeginSection": 0, "offsetInEndSection": 478, "text": "INTRODUCTION: A number of anti-EGFR monoclonal antibodies (mAbs) have been recently developed for the treatment of refractory metastatic colorectal cancer (mCRC). These mAbs, blocking ligand/receptor interactions, exert their biological activity via multiple mechanisms, including inhibition of cell cycle progression, potentiation of cell apoptosis, inhibition of angiogenesis, tumor cell invasion and metastasis and, potentially, induction of immunological effector mechanisms", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23281932"}, {"offsetInBeginSection": 0, "offsetInEndSection": 534, "text": "BACKGROUND: Anti-EGFR monoclonal antibodies (mAbs) have become a relevant solution for the treatment of patients with metastatic colorectal cancer. Current anti-EGFR monoclonal antibodies face a series of problems, including resistance and non-durable response, and RAS and BRAF mutations serve as exclusion criteria for treatment with anti-EGFR mAbs. Advances in molecular tumor profiling and information on subsequent pathways responsible for disease progression and drug resistance helped develop a new generation of anti-EGFR mAbs", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32718285"}, {"offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34663410"}, {"offsetInBeginSection": 223, "offsetInEndSection": 848, "text": " Several uncommon genomic mechanisms of primary resistance, leading to activation of tyrosine kinase receptors other than EGFR or downstream signalling pathways, have been suggested by preclinical and retrospective studies.PATIENTS AND METHODS: We conducted this multicentre, prospective, case-control study to demonstrate the negative predictive impact of a panel of rare genomic alterations [PRESSING (PRimary rESiStance IN RAS and BRAF wild-type metastatic colorectal cancer patients treated with anti-eGfr monoclonal antibodies) panel], including HER2/MET amplifications, ALK/ROS1/NTRK1-3/RET fusions and PIK3CA mutations", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29045518"}, {"offsetInBeginSection": 511, "offsetInEndSection": 727, "text": "Multiple genetic alterations driving resistance to anti-EGFR monoclonal antibodies have been described, with significant overlap in primary and acquired resistance mechanisms, in line with a clonal selection process.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27341591"}, {"offsetInBeginSection": 669, "offsetInEndSection": 855, "text": "Accumulating evidence suggests that patients with mutations in EGFR downstream signaling pathways including KRAS, BRAF, PIK3CA and PTEN could be intrinsically resistant to EGFR blockade.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27777877"}, {"offsetInBeginSection": 742, "offsetInEndSection": 870, "text": "Genomic alterations, such as mutations in KRAS, NRAS, and BRAF, often bypass the EGFR receptor, promoting resistance to therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37948593"}, {"offsetInBeginSection": 1539, "offsetInEndSection": 1747, "text": "In this chapter we will review main molecular biomarkers of de novo (primary) and acquired (secondary) resistance to EGFR-targeted monoclonal antibodies in metastatic CRC and discuss therapeutic implications.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28382467"}, {"offsetInBeginSection": 834, "offsetInEndSection": 1029, "text": "At present, the majority of patients display resistance due to alterations in genes related to the EGFR signalling pathway that eventually circumvent EGFR inhibition and allow cancer progression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36063655"}, {"offsetInBeginSection": 0, "offsetInEndSection": 368, "text": "Epidermal growth factor receptor (EGFR) is one of the anticancer drug targets for certain malignancies, including nonsmall cell lung cancer (NSCLC), colorectal cancer (CRC), and head and neck squamous cell carcinoma. However, the grave issue of drug resistance through diverse mechanisms persists, including secondary EGFR-mutation and its downstream RAS/RAF mutation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33801379"}, {"offsetInBeginSection": 1681, "offsetInEndSection": 1956, "text": "horter PFS in patients receiving anti-EGFR treatment. Multiple simultaneous mutations in KRAS and EGFR in the ctDNA and the decline in allele frequency after discontinuation of anti-EGFR therapy in a subset of patients suggest that several resistance mechanisms can co-exist ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25628445"}, {"offsetInBeginSection": 1645, "offsetInEndSection": 1789, "text": "s directed at EGFR may offer further improvements. However, resistance mechanisms suggest that combination therapies or multitargeted agents wil", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24054705"}]}
+{"question_id": "661d19d5eac11fad33000007", "question": "Can the neonatal Pediatric Sepsis Biomarker Risk Model (nPERSEVERE) accurately predict mortality in neonatal sepsis?", "answer": "Yes, nPERSEVERE can accurately predict mortality in neonatal sepsis.", "relevant_passage_ids": ["36513805"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1043, "offsetInEndSection": 1147, "text": "IL-8 and nPERSEVERE demonstrated good prognostic performance in a small cohort of neonates with sepsis. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36513805"}, {"offsetInBeginSection": 614, "offsetInEndSection": 826, "text": "Amongst PERSEVERE II biomarkers, IL-8 showed good prognostic performance for mortality prediction with a cutoff of 300\u2009pg/mL (sensitivity 100%, specificity 65%, negative predictive value 100%, AUC 0.87, p 0.0003)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36513805"}, {"offsetInBeginSection": 828, "offsetInEndSection": 1029, "text": "We derived a new decision tree that is neonate specific (nPERSEVERE) with improved performance compared to IL-8 (sensitivity 100%, specificity 86%, negative predictive value 100%, AUC 0.95, p\u2009<\u20090.0001)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36513805"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1366, "text": "BACKGROUND: Prognostic biomarker research neonatal sepsis is lacking. We assessed the utility of a validated pediatric prognostic tool called PERSEVERE II that uses decision tree methodology to predict mortality at discharge in neonates who experienced sepsis.METHODS: Prospective study in a dual-center cohort of neonates with sepsis admitted between June 2020 and December 2021. Biomarker analysis was done on serum samples obtained at the time of evaluation for the event.RESULTS: In a cohort of 59 neonates with a mortality rate of 15.3%, PERSEVERE II was 67% sensitive and 59% specific for mortality, p 0.27. Amongst PERSEVERE II biomarkers, IL-8 showed good prognostic performance for mortality prediction with a cutoff of 300\u2009pg/mL (sensitivity 100%, specificity 65%, negative predictive value 100%, AUC 0.87, p 0.0003). We derived a new decision tree that is neonate specific (nPERSEVERE) with improved performance compared to IL-8 (sensitivity 100%, specificity 86%, negative predictive value 100%, AUC 0.95, p\u2009<\u20090.0001).CONCLUSIONS: IL-8 and nPERSEVERE demonstrated good prognostic performance in a small cohort of neonates with sepsis. Moving toward precision medicine in sepsis, our study proposes an important tool for clinical trial prognostic enrichment that needs to be validated in larger studies.IMPACT: Prognostic and predictive biomarker research", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36513805"}, {"offsetInBeginSection": 828, "offsetInEndSection": 1146, "text": "We derived a new decision tree that is neonate specific (nPERSEVERE) with improved performance compared to IL-8 (sensitivity 100%, specificity 86%, negative predictive value 100%, AUC 0.95, p\u2009<\u20090.0001).CONCLUSIONS: IL-8 and nPERSEVERE demonstrated good prognostic performance in a small cohort of neonates with sepsis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36513805"}]}
+{"question_id": "662fc0bc187cba990d000011", "question": "Can calcium dietary supplementation reduce the risk of colorectal cancer?", "answer": "Calcium intake had protective effect against tumor of the colon.  A decreased risk of colorectal cancer by calcium intake is observed in all sub-sites in men and women.", "relevant_passage_ids": ["26675033", "16481636", "19116875", "15240785", "7752258", "12708719", "18254022", "16034903", "14974021", "8515888", "12467133", "10668490", "33369946", "8045031", "37621239", "36701139", "36650676", "36566517", "36432621", "33951958", "15570055", "10511318", "34708323", "32854492", "36315018", "30545821", "28677025", "31826765", "31784301", "15668485", "21866684", "1775941", "15098858", "8653938", "15531687", "9839734", "1544142", "12917206", "24623471", "27466215", "18843026"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1450, "offsetInEndSection": 1832, "text": " Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16481636"}, {"offsetInBeginSection": 805, "offsetInEndSection": 1023, "text": " High calcium intake had a greater protective effect against tumors of the distal colon and rectal cancer vs. proximal colon. The risk reduction associated with calcium was similar for dietary and supplemental sources.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19116875"}, {"offsetInBeginSection": 1421, "offsetInEndSection": 1701, "text": "calcium consumption was inversely related to colorectal cancer risk in Korean population where national average calcium intake level is relatively lower than Western countries. A decreased risk of colorectal cancer by calcium intake was observed in all sub-sites in men and women.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26675033"}, {"offsetInBeginSection": 545, "offsetInEndSection": 714, "text": "Calcium intake has also been found to have a beneficial role in reducing the incidence and improving survival rates of colorectal cancer in several observational studies", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37621239"}, {"offsetInBeginSection": 128, "offsetInEndSection": 267, "text": "However, whether these isoforms modify the effects of vitamin D3 and/or calcium supplementation on colorectal adenoma recurrence is unclear", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36701139"}, {"offsetInBeginSection": 2481, "offsetInEndSection": 2649, "text": "Concerning cancer, vitamin D deficiency is associated with increased incidence of and mortality from several types of cancer, such as colorectal, lung and breast cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36566517"}, {"offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Vitamin D and Calcium as Key Potential Factors Related to Colorectal Cancer Prevention and Treatment: A Systematic Review.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36432621"}, {"offsetInBeginSection": 1016, "offsetInEndSection": 2006, "text": ": 0.86, 95% CI: 0.81-0.91). The CRC incidence was decreased by circulating 25(OH)D (RR: 0.67, 95% CI: 0.59-0.77), vitamin D intake (RR: 0.85, 95% CI: 0.78-0.93) and calcium intake (RR: 0.75, 95% CI: 0.70-0.79). High-level circulating 25(OH)D triggered better overall survival (HR: 0.67, 95% CI: 0.57-0.79) and CRC-specific survival (HR: 0.63, 95% CI: 0.53-0.74). Stratified analyses showed that vitamin D and calcium significantly suppressed colorectal tumour incidence among women. Left-sided CRC risk was reversely related to circulating 25(OH)D (RR: 0.60, 95% CI: 0.41-0.88) and vitamin D intake (RR: 0.73, 95% CI: 0.57-0.93). Circulating 25(OH)D decreased colorectal adenoma (RR: 0.63, 95% CI: 0.48-0.82) and CRC (RR: 0.69, 95% CI: 0.56-0.86) risk in populations with higher calcium intake. European and American populations benefited more from vitamin D intake against colorectal tumour. A significant dose-response relationship was observed between intake of vitamin D or calcium and ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31784301"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1398, "text": "PURPOSE: Although evidence suggests an inverse association between calcium intake and colorectal cancer incidence, the influence of calcium on survival after colorectal cancer diagnosis remains unclear.Experimental Design: We prospectively assessed the association of postdiagnostic calcium intake with colorectal cancer-specific and overall mortality among 1,660 nonmetastatic colorectal cancer patients within the Nurses' Health Study and the Health Professionals Follow-up Study. Patients completed a validated food frequency questionnaire between 6 months and 4 years after diagnosis and were followed up for death. Multivariable hazard ratios (HRs) and 95% confidence intervals (95% CI) were calculated using Cox proportional hazards regression.RESULTS: Comparing the highest with the lowest quartile intake of postdiagnostic total calcium, the multivariable HRs were 0.56 (95% CI, 0.32-0.96; P trend = 0.04) for colorectal cancer-specific mortality and 0.80 (95% CI, 0.59-1.09; P trend = 0.11) for all-cause mortality. Postdiagnostic supplemental calcium intake was also inversely associated with colorectal cancer-specific mortality (HR, 0.67; 95% CI, 0.42-1.06; P trend = 0.047) and all-cause mortality (HR, 0.71; 95% CI, 0.54-0.94; P trend = 0.008), although these inverse associations were primarily observed in women. In addition, calcium from diet or dairy sources was associated with l", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30545821"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1204, "text": "Colorectal cancer (CRC) is currently considered one of the most common and lethal types of tumors. Nutrition is of notorious relevance, given its influence in CRC prevention and treatment. This systematic review aimed to revise and update the state of knowledge regarding the potential role of vitamin D and calcium as key factors involved in the prevention and treatment of CRC. A literature search was performed in PubMed and Web of Science. A total of eight studies were finally included in the present review. Vitamin D showed a protective role by promoting transcriptomic changes associated with antitumor effects. However, no significant effects of vitamin D were noted in the relapse-free survival of patients at 5 years. On the other hand, previous scientific evidence demonstrated that calcium regulates the expression of colonic proteins that decrease cell proliferation and increase cell differentiation. Nevertheless, an increased risk of associated serrated adenomas was found in response to calcium and calcium + vitamin D supplementation. Moreover, supplementation with both nutrients showed positive changes on relevant CRC biomarkers including TGF\u03b1, TGF\u03b21, APC, \u03b2-catenin and E-cadherin.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36432621"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1483, "text": "PURPOSE: Dietary calcium intake has been suggested to be protective against the development of colorectal cancer. The mean dietary calcium intake of Koreans is 490 mg/day, which is far below the recommended calcium intake of 700-800 mg/day. In this study, we explored the relationship between dietary calcium intake and colorectal cancer development in Koreans with relatively low calcium intake compared with individuals in Western countries.MATERIALS AND METHODS: The Health Examinees Study, a large-scale genomic community-based prospective cohort study, was designed to identify the general characteristics of major chronic diseases in Koreans. A total of 119,501 participants aged 40-69 years recruited between 2004 and 2013 were included in this analysis. The calcium intake level was categorized using the Dietary Reference Intakes for Koreans (KDRIs). The Cox proportional hazards regression model was used to estimate the hazard ratio (HR) and the corresponding 95% confidence intervals (CIs) for colorectal cancer risk, adjusting for potential confounders.RESULTS: In the multivariable-adjusted model, compared with the group that consumed less than the recommended amount of calcium, the group that consumed more than the recommended intake of calcium showed a significant reduction in the risk of colorectal cancer in women. (HR, 0.54; 95% CI, 0.31 to 0.95). Among men, however, no significant association was observed between dietary calcium intake and colorectal cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32854492"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1106, "text": "OBJECTIVES: Previous studies showed that high calcium intake may be associated with the reduced colorectal cancer (CRC) risk, but results were inconclusive. In this study, we evaluated whether calcium intake from diet and supplements, as well as the calcium levels itself, were associated with the CRC risk in middle-aged and older individuals. Also, we evaluated whether these associations were modified by genetic variation of calcium homeostasis.DESIGN: This study was embedded in the Rotterdam study, a prospective cohort study among adults aged 55\u2009years and older without CRC at baseline, from the Ommoord district of Rotterdam, The Netherlands (N\u2009=\u200910\u2009941). Effect modification by a predefined polygenetic risk score (PRS) from seven loci known to be associated with calcium concentrations, was evaluated.RESULTS: The incidence rate of CRC in the study population was 2.9 per 1000 person-years. Relative to the recommended dietary calcium intake, only higher than the recommended dietary calcium intake (\u22651485 mg/day) was associated with a reduced risk of CRC [hazard ratio (HR), 0.66; 95% confidence", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33369946"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1346, "text": "The effects of dietary vitamin D, Ca and dairy products intakes on colorectal cancer risk remain controversial. The present study investigated the association between these dietary intakes and the risk of colorectal cancer in Guangdong, China. From July 2010 to December 2018, 2380 patients with colorectal cancer and 2389 sex- and age-matched controls were recruited. Dietary intake data were collected through face-to-face interviews using a validated FFQ. Unconditional multivariable logistic regression models were used to calculate the OR and 95 % CI after adjusting for various confounders. Higher dietary vitamin D and Ca intakes were associated with 43 and 52 % reductions in colorectal cancer risk, with OR of 0\u00b757 (95 % CI 0\u00b746, 0\u00b770) and 0\u00b748 (95 % CI 0\u00b739, 0\u00b761), respectively, for the highest quartile (v. the lowest quartile) intakes. A statistically significant inverse association was observed between total dairy product intake and colorectal cancer risk, with an adjusted OR of 0\u00b732 (95 % CI 0\u00b727, 0\u00b739) for the highest v. the lowest tertile. Subjects who drank milk had a 48 % lower risk of colorectal cancer than those who did not (OR 0\u00b752, 95 % CI 0\u00b745, 0\u00b759). The inverse associations of dietary vitamin D, Ca, total dairy products and milk intakes with the risk of colorectal cancer were independent of sex and cancer site.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31826765"}, {"offsetInBeginSection": 0, "offsetInEndSection": 812, "text": "BACKGROUND: Although colorectal cancer (CRC) incidence is declining among adults aged \u226565\u2009years, CRC incidence in younger adults has been rising. The protective role of calcium in colorectal carcinogenesis has been well established, but evidence is lacking on whether the association varies by age at diagnosis. We investigated the association between total calcium intake and risk of overall CRC and CRC before age 55\u2009years.METHODS: In the Nurses' Health Study II (1991-2015), 94\u200a205 women aged 25-42\u2009years at baseline were included in the analysis. Diet was assessed every 4\u2009years through validated food frequency questionnaires. Multivariable-adjusted hazard ratios (HRs) and 95% CIs for CRC were estimated using the Cox proportional hazards model.RESULTS: We documented 349 incident CRC cases during 2\u200a202\u200a60", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36315018"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1005, "text": "PURPOSE: The aim of this study is to analyze the current evidence about the relationships between calcium/vitamin D and CRC based on case-control studies according to sex, tumor location and continental region to complement the information obtained in meta-analyses of other designs.METHODS: The articles were located in three databases (PUBMED, EMBASE and SCOPUS), they should be written in English language, with a case and control design and published between 1 January 1970 and 31 October 2019.RESULTS: There were 37 selected studies, 32 for intake of calcium, that involved 24,353 CRC cases and 30,650 controls, and 23 for that of VIT D, with a total of 19,076 cases and 36.746 controls included. For dietary calcium intake, the overall OR was 0.94 (95% CI 0.92-0.97), suggesting a reducing effect with a 6% decrease in CRC risk for every 300\u00a0mg of calcium ingested daily. Regarding vitamin D intake a global OR of 0.96 (95% CI 0.93-0.98) was observed, what means a 4% decrease in the risk of CRC per", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34708323"}, {"offsetInBeginSection": 0, "offsetInEndSection": 725, "text": "BACKGROUND: Concerning the chemopreventive potential of calcium against colorectal neoplasms, strong evidence from initial randomized controlled trials (RCTs) of colorectal adenoma has not been confirmed from the most recent large RCT. To explain the conflicting results, a new hypothesis was proposed that the benefit of calcium may be confined to lean individuals.METHODS: To test this hypothesis, we examined heterogeneity of the associations of calcium intake with adenoma and CRC, using data from the most recent meta-analyses of observational studies and conducting subgroup analysis by average body mass index (BMI) of study population.RESULTS: An inverse association of calcium intake with adenoma and CRC did not var", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28677025"}, {"offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14974021"}, {"offsetInBeginSection": 2144, "offsetInEndSection": 2929, "text": "A statistically significant reduction in cytolytic activity was determined during calcium supplementation (from 57% +/- 41% to 32% +/- 30%; P < .05), whereas in the placebo group, it did not change (from 42% +/- 41% to 36% +/- 27%; P > .10).CONCLUSIONS: Oral calcium supplementation was shown to cause only a minor nonstatistically significant reduction of epithelial cell proliferation in the rectum, compared with placebo, and to have no effect on the same parameter in the sigmoid and descending colon in first-degree relatives of hereditary nonpolyposis colorectal cancer patients.IMPLICATION: These results cast doubt on the value of calcium supplementation in the prevention of colorectal cancer, especially in individuals already consuming an adequate amount of dietary calcium.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7752258"}, {"offsetInBeginSection": 286, "offsetInEndSection": 948, "text": "Intervention studies with colorectal cancer as an endpoint are difficult to perform owing to the large number of patients and the long follow-up required; studies using the appearance of colorectal adenomatous polyps as a surrogate endpoint are therefore considered in reviewing the existing evidence.OBJECTIVES: This systematic review aims to assess the effect of supplementary dietary calcium on the incidence of colorectal cancer and the incidence or recurrence of adenomatous polyps.SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, the Cochrane Colorectal Cancer Group specialised register, MEDLINE, Cancerlit, and Embase, to April 2002.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14974021"}, {"offsetInBeginSection": 1388, "offsetInEndSection": 1471, "text": "In sum, our data suggest that high calcium intake may lower colorectal cancer risk.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12467133"}, {"offsetInBeginSection": 1383, "offsetInEndSection": 1646, "text": "These data indicate that a difference of < 400 to > 800 mg of calcium per day was associated with an approximately 25% reduction in risk of colorectal cancer, and this reduction in risk occurred regardless of the source of the calcium (i.e., diet or supplements).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15668485"}, {"offsetInBeginSection": 545, "offsetInEndSection": 715, "text": "Calcium intake has also been found to have a beneficial role in reducing the incidence and improving survival rates of colorectal cancer in several observational studies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37621239"}, {"offsetInBeginSection": 1097, "offsetInEndSection": 1334, "text": "Higher consumption of milk/dairy products reduces the risk of colon cancer, and high calcium intake reduces the risk of CRC. Low vitamin D intake in the study populations may limit the ability to detect a protective effect if one exists.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19116875"}, {"offsetInBeginSection": 1498, "offsetInEndSection": 1720, "text": "In conclusion, a high calcium intake and the use of calcium supplements may be protective against colorectal neoplasia, although a greater sample may be required to observe significant associations in a multivariate model.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21866684"}, {"offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Experimental and observational findings suggest that calcium intake may protect against colorectal neoplasia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10668490"}, {"offsetInBeginSection": 0, "offsetInEndSection": 798, "text": "Diet is a major determinant of colon cancer risk. Calcium may protect against colon cancer, presumably by binding cytotoxic bile acids and fatty acids. Numerous studies support this proposition. In subjects at risk for colon cancer oral calcium supplementation has been shown to reduce rectal epithelial proliferation rate, thereby supposedly decreasing cancer risk. In contrast to the original hypothesis that phosphate counteracts the effect of calcium, evidence has now been provided that phosphate is crucial for the intraluminal binding of bile acids in complexes of calcium, phosphate, and bile acids. Supplemental calcium has been shown to reduce the cytotoxic potential of fecal water, which is probably attributable to the profound effect of calcium on bile acid and fatty acid metabolism.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1775941"}, {"offsetInBeginSection": 0, "offsetInEndSection": 564, "text": "There is convincing laboratory evidence that calcium reduces the risk of colorectal cancer, but previous epidemiologic studies have reported somewhat inconsistent results. A recent large prospective study confirms that higher calcium intake is associated with a modestly reduced risk of distal colorectal cancer. There was little additional risk reduction associated with consumers of more than 700 mg calcium/day. This study also suggests that certain subgroups, such as males, smokers, and people who consume low levels of vitamin D, may be at differential risk.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15098858"}, {"offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Although laboratory data and a few adenoma prevention trials suggest that calcium supplementation may reduce the risk of colorectal neoplasia, the results of observational studies of calcium intake and colorectal cancer risk are contradictory.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12467133"}, {"offsetInBeginSection": 1359, "offsetInEndSection": 1594, "text": "There were no significant treatment interactions with baseline characteristics.CONCLUSIONS: Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16481636"}, {"offsetInBeginSection": 822, "offsetInEndSection": 1061, "text": "Women with the highest calcium intake (median 914 mg/day) had a reduced risk of colorectal cancer (rate ratio = 0.72, 95% confidence interval = 0.056-0.93, P for trend = 0.02) compared with women with the lowest intake (median 486 mg/day).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12467133"}, {"offsetInBeginSection": 1018, "offsetInEndSection": 1262, "text": "Our results suggest that natural sources of calcium such as dairy products and foods may have more effective role than supplementary calcium in terms of reducing the risk of incidence and recurrence of colorectal adenomas and advanced adenomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33951958"}, {"offsetInBeginSection": 1162, "offsetInEndSection": 1441, "text": "CI: 0.76, 1.02; P for trend = 0.04). The protective association between total calcium and colorectal adenoma was largely due to calcium supplement use, with a 27% decrease in adenoma risk for participants taking >1200 mg/d than for nonusers of supplements (odds ratio: 0.73; 95% ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15531687"}, {"offsetInBeginSection": 2439, "offsetInEndSection": 2729, "text": "oma, a reduction was found (OR 0.74, CI 0.58,0.95) when the results from both trials were combined.REVIEWER'S CONCLUSIONS: Although the evidence from two RCTs suggests that calcium supplementation might contribute to a moderate degree to the prevention of colorectal adenomatous polyps, thi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14974021"}, {"offsetInBeginSection": 2439, "offsetInEndSection": 2729, "text": "oma, a reduction was found (OR 0.74, CI 0.58,0.95) when the results from both trials were combined.AUTHORS' CONCLUSIONS: Although the evidence from two RCTs suggests that calcium supplementation might contribute to a moderate degree to the prevention of colorectal adenomatous polyps, this ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16034903"}, {"offsetInBeginSection": 2439, "offsetInEndSection": 2729, "text": "oma, a reduction was found (OR 0.74, CI 0.58,0.95) when the results from both trials were combined.AUTHORS' CONCLUSIONS: Although the evidence from two RCTs suggests that calcium supplementation might contribute to a moderate degree to the prevention of colorectal adenomatous polyps, this ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18254022"}, {"offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "OBJECTIVES: Previous studies showed that high calcium intake may be associated with the reduced colorectal cancer (CRC) risk, but results were i", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33369946"}, {"offsetInBeginSection": 748, "offsetInEndSection": 822, "text": "There was a lower risk of recurrent adenomas in subjects assigned calcium.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10668490"}, {"offsetInBeginSection": 523, "offsetInEndSection": 872, "text": "e odds ratios (OR).RESULTS: Higher levels of calcium intake were associated with reduced colon and rectal cancer risk. The following adjusted OR and 95% confidence intervals (CI) were observed, comparing the fifth quintile (based on control intake) with the first: colon cancer: OR = 0.6, 95% CI: 0.4-1.0, P-trend: 0.03; rectal cancer: OR = 0.6, 95%", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9839734"}, {"offsetInBeginSection": 1474, "offsetInEndSection": 1742, "text": "In epidemiological studies, several investigators reported inverse correlations between levels of dietary calcium intake and the incidence of colon cancer. Extrapolation of the data have suggested a protective effect of total calcium intakes above 1500 to 1800 mg/day.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1544142"}, {"offsetInBeginSection": 0, "offsetInEndSection": 382, "text": "Dietary supplements of calcium, vitamins A, C, and E, carotenoids, and omega-3 fatty acids can reduce the yield of experimental cancers in animals and reverse the pattern of abnormal epithelial proliferation in animals and humans. Epidemiological studies indicate that diets containing high amounts of these agents convey a protective effect against the development of colon cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8653938"}, {"offsetInBeginSection": 806, "offsetInEndSection": 930, "text": "High calcium intake had a greater protective effect against tumors of the distal colon and rectal cancer vs. proximal colon.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19116875"}, {"offsetInBeginSection": 931, "offsetInEndSection": 1023, "text": "The risk reduction associated with calcium was similar for dietary and supplemental sources.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19116875"}, {"offsetInBeginSection": 1097, "offsetInEndSection": 1221, "text": "Higher consumption of milk/dairy products reduces the risk of colon cancer, and high calcium intake reduces the risk of CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19116875"}, {"offsetInBeginSection": 1150, "offsetInEndSection": 1488, "text": "In whites, high beta-carotene, vitamin C, and calcium intakes were associated with 40-60% reductions in colon cancer risk when contrasting highest to lowest quartiles in both energy-adjusted and non-energy-adjusted models, e.g., OR = 0.4 (95% confidence interval, 0.3-0.6) for the highest quartile of calcium in the energy-adjusted model.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12917206"}, {"offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "BACKGROUND: Several dietary factors have been considered to be involved in the increasing incidence of colorectal cancer in industrialised countries. Experimental and epidemiological evidence has been suggestive but not conclusive for a protective role for high dietary cal", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16034903"}, {"offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "Dietary factors are major determinants of colorectal cancer risk. Especially a diet high in fat and low in fiber is recognized to be a risk factor. Dietary calcium has been suggested to be protective against colorectal cancer through the binding of intraluminal fatty acids and bile acids.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8045031"}, {"offsetInBeginSection": 1518, "offsetInEndSection": 1668, "text": "Because of the apparent synergistic effect of vitamin D and calcium, cosupplementation of both nutrients in cancer prevention programs may be advised.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15570055"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1387, "text": "Although laboratory data and a few adenoma prevention trials suggest that calcium supplementation may reduce the risk of colorectal neoplasia, the results of observational studies of calcium intake and colorectal cancer risk are contradictory. However, few studies have examined the association among women or effects in specific colon subsites. Women with colorectal cancer diagnosed through 31 December 2000 were identified by linkage to regional cancer registries. During an average 11.3 yr of follow-up of 61,463 women, we observed 572 incident cases of colorectal cancer. Using data obtained from a 67-item food frequency questionnaire and Cox proportional hazards models to estimate rate ratios and 95% confidence intervals, we found an inverse association between dietary calcium intake and colorectal cancer risk. Women with the highest calcium intake (median 914 mg/day) had a reduced risk of colorectal cancer (rate ratio = 0.72, 95% confidence interval = 0.056-0.93, P for trend = 0.02) compared with women with the lowest intake (median 486 mg/day). Furthermore, our results suggest that the inverse association may be strongest in relation to distal cancers and among older women. The association with dairy products was less clear, suggesting that calcium intake per se is more important than specific calcium sources. Vitamin D intake was not clearly associated with risk.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12467133"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1161, "text": "BACKGROUND: Calcium can reduce the risk of colorectal tumors by binding secondary bile and fatty acids, which leads to antiproliferative effects in the bowel, or by acting directly on the colonic epithelium, which affects differentiation and apoptosis.OBJECTIVE: We investigated calcium intake and risk of colon adenoma to evaluate the association of calcium intake with early stages of colorectal tumor development.DESIGN: We compared the supplemental and dietary calcium intakes of 3696 participants with histologically verified adenoma of the distal colon (ie, descending colon, sigmoid colon, or rectum) with the calcium intakes of 34 817 sigmoidoscopy-negative control participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Calcium intake was assessed at study entry with a 137-item food-frequency questionnaire and additional questions on the amount and duration of calcium supplement use.RESULTS: After adjustment for known risk factors, adenoma risk was lower by 12% for participants in the highest quintile of total calcium intake (>1767 mg/d) than for participants in the lowest quintile (<731 mg/d) (odds ratio: 0.88; 95%", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15531687"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1382, "text": "We investigated the association between calcium intake and colorectal cancer in a prospective cohort of 45,354 women without a history of colorectal cancer who successfully completed a 62-item National Cancer Institute/Block food-frequency questionnaire. Women were followed for an average of 8.5 years, during which time 482 subjects developed colorectal cancer. We used Cox proportional hazards models, with age as the underlying time metric, to estimate risk of colorectal cancer. Cut points between quintiles of energy-adjusted dietary calcium were 412, 529, 656, and 831 mg/day. We created categories for calcium from supplements as follows: 0 mg/day (n = 25,441), 0 to 400 mg/day (n = 9,452), 401 to 800 mg/day (n = 4,176), and >800 mg/day (n =6,285). Risk ratios and confidence intervals (95% CI) for increasing quintiles of dietary calcium relative to the lowest quintile were 0.79 (0.60-1.04), 0.77 (0.59-1.02), 0.78 (0.60-1.03), and 0.74 (0.56-0.98), P(trend) = 0.05. For increasing categories of calcium from supplements, the risk ratios (and 95% CI) relative to no supplement use were 1.08 (0.87-1.34), 0.96 (0.70-1.32), and 0.76 (0.56-1.02), P(trend) = 0.09. Simultaneously high consumption of calcium from diet and calcium from supplements resulted in even further risk reduction, RR = 0.54 (95% CI, 0.37-0.79) compared with low consumption of both sources of calcium.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15668485"}, {"offsetInBeginSection": 576, "offsetInEndSection": 2438, "text": "g evidence.OBJECTIVES: This systematic review aims to assess the effect of supplementary dietary calcium on the incidence of colorectal cancer and the incidence or recurrence of adenomatous polyps.SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, the Cochrane Colorectal Cancer Group specialised register, MEDLINE, Cancerlit , and Embase, to July 2007. The reference lists of identified studies were inspected for further studies, and the review literature was scrutinized.SELECTION CRITERIA: Randomised controlled trials of the effects of dietary calcium on the development of colonic cancer and adenomatous polyps in humans are reviewed. Studies of healthy adults and studies of adults at higher risk of colon cancer due to family history, previous adenomatous polyps, or inflammatory bowel disease were considered; data from subjects with familial polyposis coli are excluded. The primary outcomes were the occurrence of colon cancer, and occurrence or recurrence of any new adenomas of the colon. Secondary outcomes were any adverse event that required discontinuation of calcium supplementation, and drop-outs before the end of the study.DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data, assessed trial quality and resolved discrepancies by consensus. The outcomes were reported as odds ratios (OR) with 95% confidence intervals (CI). The data were combined with the fixed effects model.MAIN RESULTS: Two studies with 1346 subjects met the inclusion criteria. Both trials were well designed, double - blind, placebo controlled trials, included participants with previous adenomas. The doses of supplementary elemental calcium used were 1200 mg daily for a mean duration of 4 years, and 2000 mg/day for three years. The rates of loss to follow -up were 14 % and 11%. For the development of recurrent colorectal ade", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18254022"}, {"offsetInBeginSection": 576, "offsetInEndSection": 2438, "text": "g evidence.OBJECTIVES: This systematic review aims to assess the effect of supplementary dietary calcium on the incidence of colorectal cancer and the incidence or recurrence of adenomatous polyps.SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, the Cochrane Colorectal Cancer Group specialised register, MEDLINE, Cancerlit, and Embase, to April 2002. The reference lists of identified studies were inspected for further studies, and the review literature was scrutinized.SELECTION CRITERIA: Randomised controlled trials of the effects of dietary calcium on the development of colonic cancer and adenomatous polyps in humans are reviewed. Studies of healthy adults and studies of adults at higher risk of colon cancer due to family history, previous adenomatous polyps, or inflammatory bowel disease were considered; data from subjects with familial polyposis coli are excluded. The primary outcomes were the occurrence of colon cancer, and occurrence or recurrence of any new adenomas of the colon. Secondary outcomes were any adverse event that required discontinuation of calcium supplementation, and drop-outs before the end of the study.DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data, assessed trial quality and resolved discrepancies by consensus. The outcomes were reported as odds ratios (OR) with 95% confidence intervals (CI). The data were combined with the fixed effects model.MAIN RESULTS: Two studies with 1346 subjects met the inclusion criteria. Both trials were well designed, double - blind, placebo controlled trials, included participants with previous adenomas. The doses of supplementary elemental calcium used were 1200 mg daily for a mean duration of 4 years, and 2000 mg/day for three years. The rates of loss to follow -up were 14 % and 11%. For the development of recurrent colorectal ade", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14974021"}, {"offsetInBeginSection": 576, "offsetInEndSection": 2438, "text": "g evidence.OBJECTIVES: This systematic review aims to assess the effect of supplementary dietary calcium on the incidence of colorectal cancer and the incidence or recurrence of adenomatous polyps.SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, the Cochrane Colorectal Cancer Group specialised register, MEDLINE, Cancerlit, and Embase, to April 2002. The reference lists of identified studies were inspected for further studies, and the review literature was scrutinized.SELECTION CRITERIA: Randomised controlled trials of the effects of dietary calcium on the development of colonic cancer and adenomatous polyps in humans are reviewed. Studies of healthy adults and studies of adults at higher risk of colon cancer due to family history, previous adenomatous polyps, or inflammatory bowel disease were considered; data from subjects with familial polyposis coli are excluded. The primary outcomes were the occurrence of colon cancer, and occurrence or recurrence of any new adenomas of the colon. Secondary outcomes were any adverse event that required discontinuation of calcium supplementation, and drop-outs before the end of the study.DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data, assessed trial quality and resolved discrepancies by consensus. The outcomes were reported as odds ratios (OR) with 95% confidence intervals (CI). The data were combined with the fixed effects model.MAIN RESULTS: Two studies with 1346 subjects met the inclusion criteria. Both trials were well designed, double - blind, placebo controlled trials, included participants with previous adenomas. The doses of supplementary elemental calcium used were 1200 mg daily for a mean duration of 4 years, and 2000 mg/day for three years. The rates of loss to follow -up were 14 % and 11%. For the development of recurrent colorectal ade", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16034903"}, {"offsetInBeginSection": 375, "offsetInEndSection": 2681, "text": "ion occurs. Oral calcium supplementation has been proposed as a dietary intervention for individuals at high risk of colorectal cancer because of its ability to reduce rectal epithelial cell proliferation through the binding of fatty and bile acids. Placebo-controlled studies, however, have yielded varying results.PURPOSE: We conducted a randomized, double-blinded, placebo-controlled trial to test oral calcium supplementation in patients at high risk of developing hereditary nonpolyposis colorectal cancer.METHODS: Thirty subjects at risk for this cancer, with an increased epithelial cell proliferation along the colon and rectum, were randomly assigned to either a placebo group (n = 15) or a treatment group (n = 15). They received either oral calcium carbonate (CaCO3) supplements (1.5 g) or placebo (cellulose and starch) three times a day during a 12-week period. Colonic biopsy specimens (rectal, sigmoidal, and descending) were obtained prior to and after the intervention trial, during endoscopy, for determination of labeling index (LI) of whole crypts and crypt compartments by 5-bromo-2'-deoxyuridine incorporation and immunohistochemistry. Proportional bile acid compositions in duodenal bile and cytolytic activity of fecal water were also determined. All P values represent two-tailed tests of statistical significance.RESULTS: Statistically significant reductions, comparing before with after intervention, in rectal whole-crypt LI after receiving either calcium supplements (from 10.9% +/- 5.2% [mean +/- SD] to 6.2% +/- 1.5%; P < .02) or placebo (from 11.7% +/- 4.7% to 8.2% +/- 3.1%; P < .05) were observed. In the three bowel segments, no statistically significant differences were observed between the supplemental calcium and placebo groups. A statistically significant reduction in cytolytic activity was determined during calcium supplementation (from 57% +/- 41% to 32% +/- 30%; P < .05), whereas in the placebo group, it did not change (from 42% +/- 41% to 36% +/- 27%; P > .10).CONCLUSIONS: Oral calcium supplementation was shown to cause only a minor nonstatistically significant reduction of epithelial cell proliferation in the rectum, compared with placebo, and to have no effect on the same parameter in the sigmoid and descending colon in first-degree relatives of her", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7752258"}, {"offsetInBeginSection": 66, "offsetInEndSection": 672, "text": "Especially a diet high in fat and low in fiber is recognized to be a risk factor. Dietary calcium has been suggested to be protective against colorectal cancer through the binding of intraluminal fatty acids and bile acids. Because of their cell-damaging properties these substances may stimulate colorectal epithelial cell proliferation and so promote colorectal cancer development. In this article data from in vitro, animal and human studies on the intraluminal effects of calcium, on its effects on colorectal epithelium and on the association between calcium intake and colorectal cancer are reviewed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8045031"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1167, "text": "BACKGROUND: Studies in animals have suggested that calcium may reduce the risk of colorectal cancer. However, results from epidemiologic studies of intake of calcium or dairy foods and colorectal cancer risk have been inconclusive.METHODS: We pooled the primary data from 10 cohort studies in five countries that assessed usual dietary intake by using a validated food frequency questionnaire at baseline. For most studies, follow-up was extended beyond that in the original publication. The studies included 534 536 individuals, among whom 4992 incident cases of colorectal cancer were diagnosed between 6 and 16 years of follow-up. Pooled multivariable relative risks for categories of milk intake and quintiles of calcium intake and 95% confidence intervals (CIs) were calculated. All statistical tests were two-sided.RESULTS: Milk intake was related to a reduced risk of colorectal cancer. Compared with the lowest category of intake (<70 g/day), relative risks of colorectal cancer for increasing categories (70-174, 175-249, and > or =250 g/day) of milk intake were 0.94 (95% CI = 0.86 to 1.02), 0.88 (95% CI = 0.81 to 0.96), and 0.85 (95% CI = 0.78 to 0.94), r", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15240785"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "PURPOSE: Dietary calcium intake has been suggested to be protective against the development of colorecta", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32854492"}, {"offsetInBeginSection": 2007, "offsetInEndSection": 2191, "text": "olorectal tumour incidence.CONCLUSIONS: Vitamin D and calcium play additively chemopreventive roles in colorectal adenoma incidence, malignant transformation and progression, especiall", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31784301"}, {"offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "The effects of dietary vitamin D, Ca and dairy products intakes on colorectal cancer risk remain controversial.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31826765"}, {"offsetInBeginSection": 813, "offsetInEndSection": 883, "text": " person-years of follow-up. Higher total calcium intake was associated", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36315018"}, {"offsetInBeginSection": 1006, "offsetInEndSection": 1096, "text": "100\u00a0IU/day of vitamin D.CONCLUSION: Higher dietary intakes of calcium and vitamin D are as", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34708323"}, {"offsetInBeginSection": 1205, "offsetInEndSection": 1500, "text": "In conclusion, vitamin D supplementation seems to have a protective effect in the prevention and treatment of CRC, while calcium intake showed contradictory effects as a prevention or treatment tool; therefore, further studies are necessary to well understand its relevance in patients with CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36432621"}, {"offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "BACKGROUND: Concerning the chemopreventive potential of calcium against colorectal neoplasms, strong evidence from initial randomized controlled trials (RCTs) of colorectal adenoma has not been confirmed from the most recen", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28677025"}, {"offsetInBeginSection": 149, "offsetInEndSection": 772, "text": " Experimental and epidemiological evidence has been suggestive but not conclusive for a protective role for high dietary calcium intake. Intervention studies with colorectal cancer as an endpoint are difficult to perform owing to the large number of patients and the long follow-up required; studies using the appearance of colorectal adenomatous polyps as a surrogate endpoint are therefore considered in reviewing the existing evidence.OBJECTIVES: This systematic review aims to assess the effect of supplementary dietary calcium on the incidence of colorectal cancer and the incidence or recurrence of adenomatous polyps", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14974021"}, {"offsetInBeginSection": 149, "offsetInEndSection": 772, "text": " Experimental and epidemiological evidence has been suggestive but not conclusive for a protective role for high dietary calcium intake. Intervention studies with colorectal cancer as an endpoint are difficult to perform owing to the large number of patients and the long follow-up required; studies using the appearance of colorectal adenomatous polyps as a surrogate endpoint are therefore considered in reviewing the existing evidence.OBJECTIVES: This systematic review aims to assess the effect of supplementary dietary calcium on the incidence of colorectal cancer and the incidence or recurrence of adenomatous polyps", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16034903"}, {"offsetInBeginSection": 1367, "offsetInEndSection": 1558, "text": "ctum in both men and women.CONCLUSION: In conclusion, calcium consumption was inversely related to colorectal cancer risk in Korean population where national average calcium intake level is r", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26675033"}, {"offsetInBeginSection": 2291, "offsetInEndSection": 2438, "text": "ion of 4 years, and 2000 mg/day for three years. The rates of loss to follow -up were 14 % and 11%. For the development of recurrent colorectal ade", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14974021"}, {"offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Mechanistic and epidemiologic studies provide considerable evidence for a protective association between calcium intake and incident colorectal cancer (CRC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24623471"}, {"offsetInBeginSection": 1460, "offsetInEndSection": 1575, "text": "In conclusion, both dietary and supplementary calcium intake may continue to decrease CRC risk beyond 1,000 mg/day.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24623471"}, {"offsetInBeginSection": 571, "offsetInEndSection": 743, "text": "Total calcium intake (\u22651,400 vs. <600 mg/d) was associated with a statistically significant lower risk of colon cancer (multivariable relative risk: 0.78, 95%CI: 0.65-0.95)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27466215"}, {"offsetInBeginSection": 1388, "offsetInEndSection": 1506, "text": ". Higher calcium intake was associated with a lower risk of developing colon cancer, especially for distal colon cance", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27466215"}, {"offsetInBeginSection": 406, "offsetInEndSection": 532, "text": "It is also unclear whether the decrease in the index correlates with a decrease in occurrence or recurrence of colonic tumors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8515888"}, {"offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Several recent studies have examined the hypothesis that calcium supplementation (1.2-2.0 g/day) protects against colon cancer in persons at high risk.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8515888"}, {"offsetInBeginSection": 288, "offsetInEndSection": 405, "text": "Although in most studies the labeling index tended to decrease during supplementation, the results were inconsistent.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8515888"}, {"offsetInBeginSection": 533, "offsetInEndSection": 647, "text": "Use of calcium prophylaxis for persons at risk for colon cancer should be reserved for controlled clinical trials.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8515888"}, {"offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Does dietary calcium supplementation reduce the risk of colon cancer?", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8515888"}, {"offsetInBeginSection": 1016, "offsetInEndSection": 1198, "text": ": 0.86, 95% CI: 0.81-0.91). The CRC incidence was decreased by circulating 25(OH)D (RR: 0.67, 95% CI: 0.59-0.77), vitamin D intake (RR: 0.85, 95% CI: 0.78-0.93) and calcium intake (R", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31784301"}, {"offsetInBeginSection": 1881, "offsetInEndSection": 2006, "text": " against colorectal tumour. A significant dose-response relationship was observed between intake of vitamin D or calcium and ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31784301"}, {"offsetInBeginSection": 564, "offsetInEndSection": 859, "text": "In a multivariate analysis adjusting for potential confounding variables, calcium intake was significantly, inversely associated with colorectal cancer risk (P for trend=0.01); the odds ratio for the highest versus lowest quintile of calcium intake was 0.64 (95% confidence interval, 0.45-0.93).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18843026"}, {"offsetInBeginSection": 1394, "offsetInEndSection": 1514, "text": "These results add to support for a joint action of calcium and vitamin D in the prevention of colorectal carcinogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18843026"}, {"offsetInBeginSection": 1637, "offsetInEndSection": 1816, "text": "These combined data suggest that administration of supplemental calcium or low-fat dairy foods may have a significant effect upon colonic polyp and perhaps colon cancer incidence.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10511318"}, {"offsetInBeginSection": 1323, "offsetInEndSection": 1414, "text": "t related to overall risk.CONCLUSIONS: Our results support the hypothesis that calcium mode", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12708719"}]}
+{"question_id": "66300ee7187cba990d00001c", "question": "What is the prevalence of intellectual developmental disorders in Duchenne Muscular Dystrophy?", "answer": "The prevalence of intellectual developmental disorders in Duchenne Muscular Dystrophy is 22%.", "relevant_passage_ids": ["36440509"], "type": "factoid", "snippets": [{"offsetInBeginSection": 1369, "offsetInEndSection": 1517, "text": "The global prevalence of intellectual developmental disorder (IDD) was 8% in Becker muscular dystrophy and 22% in Duchenne muscular dystrophy (DMD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36440509"}]}
+{"question_id": "660999bffdcbea915f00001b", "question": "Is treatment with acetyl salicylic acid indicated to prevent colorectal adenomas?", "answer": "Daily use of aspirin is associated with a significant reduction in the incidence of colorectal adenomas in patients with previous colorectal cancer.", "relevant_passage_ids": ["12621132", "21307305", "8625297", "2380401", "26404953", "36556972", "14640056", "19055515", "19211452", "33682036", "36075073", "33594505", "35905195", "29137605", "35400827", "34911904", "34836419", "21435744", "11895877", "37173923", "38064111", "22122763", "16548099", "36084548", "17111262", "12795046", "15726503", "10213222", "24133627", "12946035", "19148797", "8791132", "28143522", "8693304", "32887653", "14757613", "10874542", "17339622", "15054679", "22084361", "20496537"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1767, "offsetInEndSection": 1915, "text": "Daily use of aspirin is associated with a significant reduction in the incidence of colorectal adenomas in patients with previous colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12621132"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1362, "text": "Background and Objectives: Aberrant crypt foci (ACF) are one of the earliest putative preneoplastic and, in some cases, neoplastic lesions in human colons. Many studies have confirmed the reduction of ACFs and colorectal adenomas after treatment with acetylsalicylic acid (ASA) commonly referred to as ASA; however, the minimum effective dose of ASA and the duration of use has not been fully elucidated. The objective of our study was to assess the significance of low dose ASA (75-mg internally once daily) to study the chemopreventive effect of ASA in ACF and adenomas development in patients taking this drug for a minimum period of 10 years. Materials and Methods: Colonoscopy, combined with rectal mucosa staining with 0.25% methylene blue, was performed on 131 patients. The number of rectal ACF in the colon was divided into three groups: ACF < 5; ACF 5\u221210; and ACF > 10. Patients were divided into two groups: the \u201cWith ASA\u201d group (the study group subjects taking ASA 75-mg daily for 10 years); and \u201cWithout ASA\u201d group (control group subjects not taking ASA chronically). The incidence of different types of rectal ACF and colorectal polyps in both groups of subjects was analysed and ascertained. Results: Normal ACF was found in 12.3% in the study group vs. 87.7% control group, hyperplastic 22.4% vs. 77.6%, dysplastic 25% vs. 75%, mixed 0% vs. 100%.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36556972"}, {"offsetInBeginSection": 0, "offsetInEndSection": 2008, "text": "BACKGROUND: Beneficial effects of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) against recurrent colorectal adenomas have been documented in systematic reviews; however, the results have not been conclusive. Uncertainty remains about the appropriate dose of aspirin for adenoma prevention. The persistence of the protective effect of NSAIDs against recurrent adenomas after treatment cessation is yet to be established.METHODS: Our objective was to update and systematically evaluate the evidence for aspirin and other NSAIDs on the incidence of recurrent colorectal adenomas taking into consideration the risks of random error and to appraise the quality of evidence using GRADE (The Grading of Recommendations, Assessment, Development and Evaluation) approach. Retrieved trials were evaluated using Cochrane risk of bias instrument. Meta-analytic estimates were calculated with random-effects model and random errors were evaluated with trial sequential analysis (TSA).RESULTS: In patients with a previous history of colorectal cancer or adenomas, low-dose aspirin (80-160\u00a0mg/day) compared to placebo taken for 2 to 4\u00a0years reduces the risk of recurrent colorectal adenomas (relative risk (RR), 0.80 [95% CI (confidence interval), 0.70-0.92]). TSA indicated a firm evidence for this beneficial effect. The evidence indicated moderate GRADE quality. Low-dose aspirin also reduces the recurrence of advanced adenomas (RR, 0.66 [95% CI, 0.44-0.99]); however, TSA indicated lack of firm evidence for a beneficial effect. High-dose aspirin (300-325\u00a0mg/day) did not statistically reduce the recurrent adenomas (RR, 0.90 [95% CI, 0.68-1.18]). Cyclooxygenase-2 (COX-2) inhibitors (e.g. celecoxib 400\u00a0mg/day) were associated with a significant decrease in the recurrence of both adenomas (RR, 0.66 [95% CI, 0.59-0.72]) and advanced adenomas (RR, 0.45 [95% CI, 0.33-0.57]); however, this association did not persist and there was a trend of an increased risk of recurrent adenomas observed 2", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29137605"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1219, "text": "As colon cancer is one of the most common cancers in the world, practical prevention strategies for colon cancer are needed. Recently, treatment with aspirin and/or 5-aminosalicylic acid-related agents was reported to reduce the number of intestinal polyps in patients with familial adenomatous polyposis. To evaluate the mechanism of aspirin and 5-aminosalicylic acid for suppressing the colon polyp growth, single and combined effects of 5-aminosalicylic acid and sodium salicylate (metabolite of aspirin) were tested in the two human colon cancer cells with different cyclooxygenase-2 expression levels and intestinal polyp-derived cells from familial adenomatous polyposis model mouse. The combination induced cell-cycle arrest at the G1 phase along with inhibition of cell growth and colony-forming ability in these cells. The combination reduced cyclin D1 via proteasomal degradation and activated retinoblastoma protein. The combination inhibited the colony-forming ability of mouse colonic mucosa cells by about 50% and the colony-forming ability of mouse intestinal polyp-derived cells by about 90%. The expression level of cyclin D1 in colon mucosa cells was lower than that in intestinal polyp-derived cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35400827"}, {"offsetInBeginSection": 77, "offsetInEndSection": 908, "text": "rldwide. Aspirin, due to its antineoplastic effects, has been suggested to have chemopreventive effects on colorectal cancer based on recent trials. We conducted this systematic review and meta-analysis to provide an updated evidence about the long-term efficacy of daily aspirin use in the prevention of colorectal cancer.METHODS: We searched Medline/PubMed, Ovid, Web of Science, and Cochrane Library. We included randomized controlled trials (RCTs) that compared the efficacy of daily aspirin use to placebo in healthy individuals at the time of study entry. The desired outcomes of this review were the incidence of advanced lesions (i.e., adenomas with villous component, adenomas \u22651\u00a0cm in diameter, adenomas with high-grade dysplasia, and/or invasive cancer) and colorectal adenomas.RESULTS: A total of 15 articles representi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33682036"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1157, "text": "Salicylic acid (SA) has observationally been shown to decrease colorectal cancer (CRC) risk. Aspirin (acetylsalicylic acid, that rapidly deacetylates to SA) is an effective primary and secondary chemopreventive agent. Through a Mendelian randomization (MR) approach, we aimed to address whether levels of SA affected CRC risk, stratifying by aspirin use. A two-sample MR analysis was performed using GWAS summary statistics of SA (INTERVAL and EPIC-Norfolk, N = 14,149) and CRC (CCFR, CORECT, GECCO and UK Biobank, 55,168 cases and 65,160 controls). The DACHS study (4410 cases and 3441 controls) was used for replication and stratification of aspirin-use. SNPs proxying SA were selected via three methods: (1) functional SNPs that influence the activity of aspirin-metabolising enzymes; (2) pathway SNPs present in enzymes' coding regions; and (3) genome-wide significant SNPs. We found no association between functional SNPs and SA levels. The pathway and genome-wide SNPs showed no association between SA and CRC risk (OR: 1.03, 95% CI: 0.84-1.27 and OR: 1.08, 95% CI: 0.86-1.34, respectively). Results remained unchanged upon aspirin use stratification.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34836419"}, {"offsetInBeginSection": 494, "offsetInEndSection": 636, "text": "These data support the use of acetylsalicylic acid (AAS) or aspirin, a COX-2 inhibitor, as an effective agent in colorectal cancer prevention.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21435744"}, {"offsetInBeginSection": 0, "offsetInEndSection": 688, "text": "BACKGROUND: The results of Aspirin prevention of colorectal adenomas in patients with familial adenomatous polyposis (FAP) are controversial.METHODS: We conducted a biomarker-based clinical study in eight FAP patients treated with enteric-coated low-dose Aspirin (100 mg daily for three months) to explore whether the drug targets mainly platelet cyclooxygenase (COX)-1 or affects extraplatelet cellular sources expressing COX-isozymes and/or off-target effects in colorectal adenomas.RESULTS: In FAP patients, low-dose Aspirin-acetylated platelet COX-1 at Serine529 (>70%) was associated with an almost complete inhibition of platelet thromboxane (TX) B2 generation ex vivo (serum TXB2).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37173923"}, {"offsetInBeginSection": 1303, "offsetInEndSection": 1587, "text": "Aspirin was not found to have an effect on the risk of advanced lesions or adenomas beyond 5\u00a0years (hazard ratio (HR)\u2009=\u20090.82, P\u2009=\u20090.07 and HR\u2009=\u20090.99, P\u2009=\u20090.82, respectively).CONCLUSION: Overall, aspirin (particularly high dose) only reduced the risk of advanced lesions up to 5\u00a0years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33682036"}, {"offsetInBeginSection": 947, "offsetInEndSection": 1159, "text": "To date, although there is compelling evidence that the use of aspirin protects against adenoma and colorectal cancer, the optimal dose and duration of aspirin required to obtain this effect remain to be defined.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21435744"}, {"offsetInBeginSection": 776, "offsetInEndSection": 946, "text": "However, randomized controlled trials of aspirin report discrepant results, although there is an decrease in the relative risk of adenoma recurrence of approximately 17%.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21435744"}, {"offsetInBeginSection": 1191, "offsetInEndSection": 1353, "text": "The 81-mg daily aspirin dose suppressed PGE(2) levels to an equivalent extent as did the 650-mg dose and supports the use of this dose for chemoprevention trials.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11895877"}, {"offsetInBeginSection": 1588, "offsetInEndSection": 1811, "text": "However, the overall interaction was not significant.CONCLUSIONS: In a prospective study, the combination of calcitriol, aspirin, and calcium carbonate did not prevent recurrence of colorectal adenomas over a 3-year period.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26404953"}, {"offsetInBeginSection": 78, "offsetInEndSection": 262, "text": "Long-term observational retrospective studies on nurses and health professionals demonstrated that regular aspirin users had a significantly lower incidence of colorectal cancer (RCT).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38064111"}, {"offsetInBeginSection": 263, "offsetInEndSection": 421, "text": "Prospective studies on patients with a high risk of developing colorectal polyps/cancer confirmed that aspirin use significantly lowered colorectal dysplasia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38064111"}, {"offsetInBeginSection": 967, "offsetInEndSection": 1189, "text": "% CI 0.84-1.12; P = 0.66; I2 = 34%), aspirin use was found to be associated with reduced recurrence of colorectal adenomas (RR 0.83; 95% CI 0.72-0.95; P = 0.006; I2 = 63%) and reduced mortality of CRC (RR 0.79; 95% CI 0.64", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33594505"}, {"offsetInBeginSection": 342, "offsetInEndSection": 580, "text": "Several epidemiological studies, four randomized controlled trials (RCTs) of colorectal polyp recurrence, and RCTs in patients with hereditary colorectal cancer syndromes, have shown that aspirin reduces incidence of colorectal neoplasia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22122763"}, {"offsetInBeginSection": 1945, "offsetInEndSection": 2165, "text": "We found no statistically significant effect modification for any of the baseline factors studied.CONCLUSION: Aspirin is effective for the prevention of colorectal adenomas in individuals with a history of these lesions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19211452"}, {"offsetInBeginSection": 637, "offsetInEndSection": 775, "text": "Several cohort and case control studies have shown that regular use of aspirin reduces the risk of colorectal cancer by approximately 50%.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21435744"}, {"offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "BACKGROUND & AIMS: Chemopreventive strategies might be used to reduce the recurrence of colorectal adenomas and the incidence of", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26404953"}, {"offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "BACKGROUND: Intake of aspirin is associated with reduction in risk of colorectal adenoma an", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21307305"}, {"offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Acetylsalicylic acid was recently shown to inhibit the development of colorectal adenomas in subjects with a moderately increased risk for colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14640056"}, {"offsetInBeginSection": 1579, "offsetInEndSection": 1873, "text": "In conclusion, lipid metabolism and liver function were correlated with the suppressive effect of aspirin on the recurrence of colorectal adenoma.PREVENTION RELEVANCE: Aspirin has been shown to prevent the onset of colorectal adenoma and cancer, and its effect modifications have been analyzed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36075073"}, {"offsetInBeginSection": 687, "offsetInEndSection": 844, "text": "In particular, the investigators demonstrate that participants who consumed more than one standard aspirin tablet per day had the greatest reduction in risk.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12946035"}, {"offsetInBeginSection": 642, "offsetInEndSection": 837, "text": "The clinical guideline for the use of aspirin, NSAIDs, and COX-2 inhibitors for primary prevention of colorectal cancer that was prepared for the U.S Preventive Services Task Force is introduced.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19148797"}, {"offsetInBeginSection": 740, "offsetInEndSection": 913, "text": "(4) Aspirin and sulindac were tested for the prevention of polyps in patients with familial adenomatous polyposis, with uncertain results and weak evidence of effectiveness.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16548099"}, {"offsetInBeginSection": 129, "offsetInEndSection": 343, "text": "colorectal cancer. We performed a randomized, double-blind, placebo-controlled trial to determine whether a combination of acetylsalicylic acid (aspirin), calcitriol, and calcium carbonate could prevent colorectal ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26404953"}, {"offsetInBeginSection": 977, "offsetInEndSection": 1242, "text": "ial analysis (TSA).RESULTS: In patients with a previous history of colorectal cancer or adenomas, low-dose aspirin (80-160\u00a0mg/day) compared to placebo taken for 2 to 4\u00a0years reduces the risk of recurrent colorectal adenomas (relative risk (RR), 0.80 [95% CI (confid", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29137605"}, {"offsetInBeginSection": 0, "offsetInEndSection": 504, "text": "Chemoprevention refers to the use of specific natural or synthetic chemical agents to reverse, suppress, or prevent the progression to invasive cancer. The ideal chemopreventive agent is safe and nontoxic over the long term. It should be easy to take and demonstrated to be effective in randomized trials in humans. Aspirin and NSAIDs meet many of the criteria for an ideal agent. The literature on aspirin and NSAIDs makes it clear that these agents can prevent colorectal cancer and precursor adenomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8791132"}, {"offsetInBeginSection": 0, "offsetInEndSection": 563, "text": "BACKGROUND: Although aspirin is recommended for the prevention of colorectal cancer, the specific individuals for whom the benefits outweigh the risks are not clearly defined. Moreover, the precise mechanisms by which aspirin reduces the risk of cancer are unclear. We recently launched the ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED) trial to address these uncertainties.METHODS/DESIGN: ASPIRED is a prospective, double-blind, multidose, placebo-controlled, biomarker clinical trial of aspirin use in individuals previously diagnos", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28143522"}, {"offsetInBeginSection": 818, "offsetInEndSection": 1010, "text": "Recent epidemiologic surveys also suggest that individuals who regularly take NSAIDs, particularly acetylsalicylic acid, have about a 50% decrease in colorectal cancer incidence and mortality.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8693304"}, {"offsetInBeginSection": 139, "offsetInEndSection": 1517, "text": "Colorectal carcinogenesis is a multistep process characterized by molecular and cellular alterations that result in an identifiable precursor lesion, ie, the adenomatous polyp. The transition from normal mucosa to adenoma and its subsequent progression to carcinoma are protracted events that offer opportunities for preventive interventions. Suppression or reversal of the carcinogenic process in the colorectum with nonpharmacologic or pharmacologic agents, ie, chemoprevention, is an area of considerable research interest and activity. Interest in this field derives from multiple epidemiologic studies showing that regular and continued use of nonsteroidal anti-inflammatory drugs (NSAIDs), predominantly aspirin, is associated with significant reductions in both colorectal adenoma and carcinoma incidence. NSAIDs were first shown to be effective in patients with familial adenomatous polyposis (FAP). Subsequent randomized trials in FAP demonstrated that sulindac and the selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, can significantly regress existing adenomas, and resulted in Food and Drug Administration (FDA) approval of celecoxib for adjunctive management of these patients. Based on the aforementioned data, aspirin and coxibs have been or are currently being evaluated for the prevention of sporadic adenoma recurrence in high-risk patient populations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15726503"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1606, "text": "BACKGROUND & AIMS: Chemopreventive strategies might be used to reduce the recurrence of colorectal adenomas and the incidence of colorectal cancer. We performed a randomized, double-blind, placebo-controlled trial to determine whether a combination of acetylsalicylic acid (aspirin), calcitriol, and calcium carbonate could prevent colorectal adenoma recurrence.METHODS: We included 1107 patients with 1 or more sporadic adenoma(s) removed from the colon or rectum at centers in Europe, Russia, or the United States, from 2004 through 2010. Inclusion criteria were 1 adenoma greater than 1 cm in diameter, more than 1 adenoma of any size, or an adenoma of any size and first-degree relatives with colorectal cancer. Subjects were assigned randomly to groups given 0.5 \u03bcg calcitriol, 75 mg acetylsalicylic acid, and 1250 mg calcium carbonate (n\u00a0= 209), or placebo (n\u00a0= 218), each day for 3 years. The primary outcome was adenoma recurrence assessed by colonoscopy after 3 years. Secondary outcomes were the proportion of patients with advanced adenomas, the total number of colorectal adenomas, and adenoma size and features.RESULTS: The trial was stopped in October 2010 because of futility. In this analysis, we found no differences between groups in the rate of recurrence (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.61-1.48), adverse effects, or secondary outcomes. Subgroup analyses indicated that the treatment effects may be influenced by smoking status (nonsmokers OR, 0.65; 95% CI, 0.26-1.22 vs current smokers OR, 1.70; 95% CI, 0.70-4.09; P value interaction < .05). However, the overa", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26404953"}, {"offsetInBeginSection": 0, "offsetInEndSection": 636, "text": "Colorectal adenomas are precursors of most colorectal cancers and are consequently a surrogate endpoint for assessing the efficacy of chemopreventive agents. Cyclooxygenase-2 (COX-2) levels have been found to be increased in a significant number of colorectal carcinomas and adenomas. COX-2 overexpression is linked to carcinogenesis due to increased production of prostaglandins, which seem to play an important role in angiogenesis, cell proliferation and migration, as well as in apoptosis. These data support the use of acetylsalicylic acid (AAS) or aspirin, a COX-2 inhibitor, as an effective agent in colorectal cancer prevention.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21435744"}, {"offsetInBeginSection": 326, "offsetInEndSection": 921, "text": "en studied.METHODS: We measured serum salicylate levels in participants in a randomized controlled trial with calcium supplementation for the prevention of colorectal adenomas. Generalized linear models were used to assess the association between serum levels and adenoma risk during the follow-up period of the trial.RESULTS: We did not find an association with recurrence of adenomas or advanced adenomas with serum salicylate levels at year 1 among nonusers of aspirin. There was no effect modification of the chemopreventive effect of calcium supplementation in reducing risk of recurrent ad", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21307305"}, {"offsetInBeginSection": 0, "offsetInEndSection": 3946, "text": "There is evidence that aspirin--and apparently other NSAIDs--may be protective agents against cancer in the gastrointestinal tract. These effects are particularly well documented in the colon and rectum. Even considered in isolation, the observational data regarding colorectal neoplasia are quite strong, and the reality of a protective effect is buttressed by clinical trial data showing that aspirin prevents sporadic adenomas. Furthermore, the NSAIDs sulindac celecoxib have actually led to the regression of existing colorectal polyps in patients with FAP. Clearly, NSAIDs have the potential to suppress carcinogenesis in the large bowel. Observational data suggesting inverse associations of NSAIDs with cancers of the stomach and esophagus have emerged from several case-control studies and a few cohort analyses. In some studies the findings display features often associated with causal relationships, for example decreasing risks with increasing doses or duration of use. Nonetheless, the data currently do not support a secure conclusion that NSAIDs protect against these malignancies. The relevant data are not nearly as extensive as those for the colorectum, and case-control investigation of these upper gastrointestinal sites may be particularly delicate. It is conceivable that early symptoms of cancer (or of pre-invasive lesions) may have discouraged NSAID use in the cancer patients, creating the appearance of a protective association of the drugs with the risk of these malignancies. More extensive observational data particularly from cohort studies would be desirable to confirm the existing findings and clarify the doses and durations of use required for an effect. Clinical trial investigation might also be practical for pre-neoplastic endpoints, or--in carefully selected populations--perhaps with cancer as the focus. There are only relatively limited data available regarding the effect of NSAIDs on cancer of the pancreas. However, the studies that have investigated this malignancy have reported indications that NSAIDs may have a protective effect. The effects of NSAIDs on cancers outside the gastrointestinal tract are not clear. Some investigations suggest that NSAID use, particularly aspirin, is inversely associated with risk of cancers of the breast or ovary, but several well-done studies have not seen these associations, and the observations could have been due to bias or confounding. Findings regarding prostate cancer are similarly conflicting. The urinary tract is one organ system in which several studies have reported an increased cancer risk in association with NSAID use. Nonetheless, the effects remain unclear. There is only limited available information regarding carcinoma of the bladder, and no firm conclusions can be drawn at this point. More extensive data have been generated regarding the effect of NSAIDs--largely salicylates--on renal cell carcinoma or cancer or the renal pelvis and ureter. Although some studies have reported increased risks, there are also findings suggesting no association. It is particularly difficult for observational studies to ascertain with confidence the true effects of aspirin because of the suspected relationship of these cancers with use of phenacetin and perhaps acetaminophen. Further data--particularly from careful and large cohort studies--would be important to clarify these issues. As a body of research, the findings discussed here from epidemiological studies and clinical trials have begun to clarify the effect of NSAIDs on carcinogenesis in various organs in humans. There is clear potential for protective effects at several anatomic sites. Even for the colorectum, however, it is probably premature to now begin to use these drugs widely for cancer prevention. To reach that point, a weighing of the risks and benefits of the drugs needs to be made, together with a judgement regarding the benefits of alternative means of prevention.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12795046"}, {"offsetInBeginSection": 332, "offsetInEndSection": 612, "text": "Also, in a randomized clinical trial in Lynch syndrome reported that aspirin was shown to reduce the colorectal cancer with long-term tracking; and in a randomized trial in familial adenomatous polyposis, reported that aspirin was shown to reduce the increase of colorectal polyp.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34911904"}, {"offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "BACKGROUND: Randomized, double-blind, placebo-controlled trials have established that regular aspirin use reduces the risk for recurrent colorec", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14757613"}, {"offsetInBeginSection": 785, "offsetInEndSection": 969, "text": "Compared with non-users, long-term users (1 year and more) of nonaspirin NSAIDs had a 40% decreased risk of colorectal adenoma (relative risk = 0.6; 95% confidence interval = 0.4-0.9).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10874542"}, {"offsetInBeginSection": 1126, "offsetInEndSection": 1368, "text": "The risk of developing colorectal adenoma was reduced in long-term users of aspirin at doses of 300 mg daily (relative risk = 0.6; 95% confidence interval = 0.4-1.0), but reduced risk was not evident with daily doses of 75 and 150 mg aspirin.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10874542"}, {"offsetInBeginSection": 888, "offsetInEndSection": 1227, "text": " follow-up colonoscopy. We found that the relative risks of any adenoma (when compared with the placebo group) were 0.859 in the high dose of aspirin groups (95% confidence interval (CI), 0.756-0.976, P = 0.019), 0.826 in the low dose of aspirin groups (95% CI 0.706-0.965, P = 0.016) and 0.836 in the both aspirin combined groups (95% CI ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19055515"}, {"offsetInBeginSection": 1419, "offsetInEndSection": 1552, "text": "t considering the dose.CONCLUSION: This meta-analysis suggests that aspirin prevents recurrent colorectal adenomas among patients wit", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19055515"}, {"offsetInBeginSection": 2016, "offsetInEndSection": 2126, "text": "e baseline factors studied.CONCLUSION: Aspirin is effective for the prevention of colorectal adenomas in indiv", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19211452"}, {"offsetInBeginSection": 874, "offsetInEndSection": 1179, "text": ", celecoxib, or aspirin. From the combined results of three trials, significantly fewer patients in the aspirin group developed recurrent sporadic colorectal adenomas (relative risk, 0.77 (95 percent confidence interval, 0.61, 0.96), number needed to treat 12.5 (95 percent confidence interval, 7.7, 25)) ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15054679"}, {"offsetInBeginSection": 568, "offsetInEndSection": 803, "text": "A separate metaanalysis of nearly 3,000 patients with a history of colorectal adenoma or cancer in four randomized adenoma prevention trials showed that aspirin reduced the occurrence of advanced adenomas by 28% and any adenoma by 17%.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22084361"}, {"offsetInBeginSection": 313, "offsetInEndSection": 492, "text": "Aspirin is the best studied chemopreventive agent for CRC, with randomized trials demonstrating its efficacy in reducing recurrence of colorectal adenomas in higher risk patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20496537"}]}
+{"question_id": "65cfad2d1930410b13000014", "question": "Concizumab is used for which diseases?", "answer": "Concizumab is developed for hemophilia A and B.", "relevant_passage_ids": ["37341887", "35869698", "37146647", "37646676", "30137664", "28594458", "31394258", "30614620", "33570646", "33819375", "35465188", "25641556", "31444162", "30146094", "29931593", "29517971", "35290453", "35088769", "32008381", "29845491", "31676141", "34581771", "30408848", "30559263"], "type": "list", "snippets": [{"offsetInBeginSection": 226, "offsetInEndSection": 599, "text": "Concizumab is being developed by Novo Nordisk for the treatment of hemophilia A and B with and without inhibitors. In March 2023, concizumab was approved in Canada for the treatment of adolescent and adult patients (12 years of age or older) with hemophilia B who have FIX inhibitors and require routine prophylaxis to prevent or reduce the frequency of bleeding episodes. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37341887"}, {"offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "Some non-factor products that work by facilitating the coagulation pathway (emicizumab) and blocking the anticoagulant pathway (fitusiran, concizumab and marstacimab) for patients with haemophilia (H) have been developed, and clinical trials using these products are currently ongoing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35869698"}, {"offsetInBeginSection": 176, "offsetInEndSection": 299, "text": "A previous trial of concizumab (explorer4) established proof of concept in patients with hemophilia A or B with inhibitors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37646676"}, {"offsetInBeginSection": 12, "offsetInEndSection": 174, "text": "Concizumab is an anti-tissue factor pathway inhibitor monoclonal antibody designed to achieve hemostasis in all hemophilia types, with subcutaneous administration", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37646676"}, {"offsetInBeginSection": 341, "offsetInEndSection": 598, "text": "In March 2023, concizumab was approved in Canada for the treatment of adolescent and adult patients (12 years of age or older) with hemophilia B who have FIX inhibitors and require routine prophylaxis to prevent or reduce the frequency of bleeding episodes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37341887"}, {"offsetInBeginSection": 599, "offsetInEndSection": 736, "text": "This article summarizes the milestones in the development of concizumab leading to this first approval for the treatment of hemophilia B.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37341887"}, {"offsetInBeginSection": 2086, "offsetInEndSection": 2226, "text": "Conclusion explorer\u21223 data support further clinical development of concizumab for use in people with hemophilia, with or without inhibitors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30137664"}, {"offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Concizumab as a Subcutaneous Prophylactic Treatment Option for Patients with Hemophilia A or B: A Review of the Evidence and Patient's Perspectives.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35465188"}, {"offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Concizumab is a novel subcutaneous prophylactic therapy for hemophilia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33570646"}, {"offsetInBeginSection": 0, "offsetInEndSection": 340, "text": "Concizumab (Alhemo\u2122), a subcutaneously administered humanised monoclonal IgG4 antibody against tissue factor pathway inhibitor (TFPI), binds to the Kunitz-2 domain of TFPI and prevents TFPI from binding to activated Factor X. Concizumab is being developed by Novo Nordisk for the treatment of hemophilia A and B with and without inhibitors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37341887"}, {"offsetInBeginSection": 220, "offsetInEndSection": 446, "text": "Prophylaxis with subcutaneous long-acting non-factor products that improve in vivo thrombin generation is now under intensive investigation (concizumab, fitusiran) or successfully employed (emicizumab) in haemophilia patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31676141"}, {"offsetInBeginSection": 375, "offsetInEndSection": 585, "text": "Concizumab is a monoclonal antibody (mAb) against tissue factor pathway inhibitor (TFPI), currently in clinical development as a subcutaneous prophylactic therapy for hemophilia\u00a0A/B with and without inhibitors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30614620"}, {"offsetInBeginSection": 148, "offsetInEndSection": 656, "text": "A monoclonal antibody (concizumab) targeting tissue factor pathway inhibitor (TFPI) that can be administered subcutaneously (s.c.) has the potential to alter current concepts of prophylaxis in hemophilia.OBJECTIVES: To evaluate the safety and describe the pharmacokinetics and pharmacodynamics of single-dose concizumab in healthy volunteers and patients with hemophilia A or B.METHODS: In this first human dose, phase 1, multicenter, randomized, double-blind, placebo-controlled trial escalating single i.v.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25641556"}, {"offsetInBeginSection": 0, "offsetInEndSection": 599, "text": "Concizumab (Alhemo\u2122), a subcutaneously administered humanised monoclonal IgG4 antibody against tissue factor pathway inhibitor (TFPI), binds to the Kunitz-2 domain of TFPI and prevents TFPI from binding to activated Factor X. Concizumab is being developed by Novo Nordisk for the treatment of hemophilia A and B with and without inhibitors. In March 2023, concizumab was approved in Canada for the treatment of adolescent and adult patients (12 years of age or older) with hemophilia B who have FIX inhibitors and require routine prophylaxis to prevent or reduce the frequency of bleeding episodes. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37341887"}, {"offsetInBeginSection": 0, "offsetInEndSection": 739, "text": "Concizumab is a novel subcutaneous prophylactic therapy for hemophilia. It is a hemostatic rebalancing agent that binds to the Kunitz-2 domain of tissue factor pathway inhibitor (TFPI), one of the molecules that contributes to downregulation of coagulation thereby preventing TFPI from binding to and blocking the factor Xa (FXa) active site. When the TFPI inhibitory activity is decreased, sufficient FXa is produced by the FVIIa-tissue factor complex to achieve hemostasis. On the basis of this mechanism of action, concizumab is expected to be equally effective in hemophilia A and B, regardless of inhibitor status. Moreover, the concizumab mechanism of action does not interfere with the regulation of coagulation downstream of TFPI. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33570646"}, {"offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "BACKGROUND: Concizumab is an anti-tissue factor pathway inhibitor monoclonal antibody designed to achieve hemostasis in all hemophilia types, with subcutaneous admi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37646676"}, {"offsetInBeginSection": 0, "offsetInEndSection": 564, "text": "Concizumab is a monoclonal, humanized IgG4 antibody specific for the Kunitz-2 domain of Tissue Factor Pathway Inhibitor (TFPI). Preclinical studies in vitro or on animal models and in vivo have demonstrated the ability of concizumab to restore thrombin generation, promoting the establishment of a procoagulant action; all these results were subsequently confirmed in the studies of EXPLORER program. Concizumab may represent a new opportunity for the treatment of persons with hemophilia, so there is much anticipation for the results of the ongoing trials still.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35465188"}, {"offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Concizumab is a humanized monoclonal antibody in clinical investigation directed against membrane-bound and soluble tissue factor pathway inhibitor (mTFPI and sTFPI) for treatment of hemophilia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31394258"}, {"offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "BACKGROUND: The anti-tissue factor plasma inhibitor monoclonal antibody concizumab is under clinical investigation for subcutaneous prophylaxis of hemophilia A/B (HA/HB) with or without", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33819375"}, {"offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Correction to: Inhibition of Tissue Factor Pathway Inhibitor (TFPI) as a Treatment for Haemophilia: Rationale with Focus on Concizumab.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29931593"}, {"offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Concizumab is a novel subcutaneous prophylactic therapy for hemophilia. It is a hemostatic rebalancing agent", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33570646"}, {"offsetInBeginSection": 300, "offsetInEndSection": 419, "text": "development of concizumab in people with hemophilia. SUMMARY: Background Concizumab is a humanized mAb targeting tissue", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30137664"}]}
+{"question_id": "65f7736fc4010b4d78000024", "question": "What type of extracolonic tumors does the PMS2 germline mutation cause?", "answer": "Heterozygous PMS2 mutation carriers were at small increased risk for colorectal and endometrial cancer but not for any other Lynch syndrome-associated cancer.", "relevant_passage_ids": ["30161022", "25856668", "15256438", "19132747", "27435373", "29758216", "34357101", "18273873", "22714864", "15077197", "26110232", "18602922", "31056861", "17258725", "31860975"], "type": "factoid", "snippets": [{"offsetInBeginSection": 1516, "offsetInEndSection": 1675, "text": "Heterozygous PMS2 mutation carriers were at small increased risk for colorectal and endometrial cancer but not for any other Lynch syndrome-associated cancer. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30161022"}, {"offsetInBeginSection": 454, "offsetInEndSection": 569, "text": "PMS2 mutation carriers had more extracolonic cancers although these differences were not statistically significant.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22714864"}, {"offsetInBeginSection": 247, "offsetInEndSection": 553, "text": "pectrum. However, the age-specific cumulative risk (penetrance) of these cancers is still poorly defined for PMS2-associated Lynch syndrome. Using a large data set from a worldwide collaboration, our aim was to determine accurate penetrance measures of cancers for carriers of heterozygous pathogenic PMS2 ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30161022"}, {"offsetInBeginSection": 45, "offsetInEndSection": 158, "text": "PMS2 have been shown to cause Lynch syndrome. The penetrance of the cancer and tumor spectrum has been repeatedly", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25856668"}]}
+{"question_id": "65f7080fc4010b4d78000019", "question": "Do stroke patients have a lower risk of Obstructive Sleep Apnea?", "answer": "Obstructive sleep apnea (OSA) is a common sleep disorder characterized by repetitive cessation or reduction in airflow during sleep and stroke patients have a higher risk of OSA.", "relevant_passage_ids": ["37443640", "36889030", "31231783", "20075361", "18927265", "26731604", "23914326", "37849347", "22215237", "19122572", "17324369", "23666861", "24395523", "16299668", "19275628", "33204196", "12800780", "32755811", "29060173", "30680373", "37388591"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Sleep-Disordered Breathing and Prognosis after Ischemic Stroke: It Is Not Apnea-Hypopnea Index That Matters.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37443640"}, {"offsetInBeginSection": 11, "offsetInEndSection": 147, "text": " Sleep-disordered breathing (SDB) is highly prevalent after stroke and is considered to be a risk factor for poor post-stroke outcomes. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37443640"}, {"offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Post-stroke sleep disturbance and recurrent cardiovascular and cerebrovascular events: A systematic review and meta-analysis.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36889030"}, {"offsetInBeginSection": 204, "offsetInEndSection": 339, "text": "The relationship between sleep and stroke is complex: sleep disturbances are likely both a contributor to, and consequence of, stroke. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36889030"}, {"offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "BACKGROUND AND PURPOSE: Obstructive sleep apnea (OSA) is seldom considered in the diagnostic investigation in the poststroke period although it is a stroke risk factor and has adverse prognostic implications after stroke.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20075361"}, {"offsetInBeginSection": 455, "offsetInEndSection": 628, "text": "Following stroke, patients have a high prevalence of OSA, which diminishes the potential for rehabilitation, increases the risk of secondary stroke, and heightens mortality.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17324369"}, {"offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "More of the half of the stroke patients have sleep-disordered breathing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16299668"}, {"offsetInBeginSection": 120, "offsetInEndSection": 287, "text": "Obstructive sleep apnea, a form of sleep-disordered breathing, is associated with multiple major stroke risk factors but is also an independent risk factor for stroke.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23914326"}, {"offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "The majority of stroke patients have clinically significant obstructive sleep apnea (OSA).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24395523"}, {"offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Obstructive sleep apnea (OSA) has been considered as one of the risk factors for ischemic stroke, but the impact of OSA on wake-up stroke (WUS) is not well studied. We aimed to determine the relationship between OSA and WUS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22215237"}, {"offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Obstructive Sleep Apnea (OSA) is a prevalent disease that has emerged as a new cerebrovascular disease (CVD) risk factor, which is independent of its association to hypertension, age and other known conditions that increase CVD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19275628"}, {"offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Obstructive sleep apnea (OSA) has been found to be an independent risk factor for stroke in large epidemiological studies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23666861"}, {"offsetInBeginSection": 27, "offsetInEndSection": 181, "text": "Obstructive sleep apnea (OSA) is prevalent after stroke and associated with recurrent stroke, prolonged hospitalization, and decreased functional recovery", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37849347"}, {"offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "The majority of stroke patients have clinically significant obstructive sleep apnea (OSA). Also, recent evidence demonstrates that OSA serves as an independent risk factor for stroke.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24395523"}, {"offsetInBeginSection": 0, "offsetInEndSection": 622, "text": "Obstructive sleep-disordered breathing (SDB), which includes primary snoring through to obstructive sleep apnea syndrome (OSAS), may cause compromise of respiratory gas exchange during sleep, related to transient upper airway narrowing disrupting ventilation, and causing oxyhemoglobin desaturation and poor sleep quality. SDB is common in chronic disorders and has significant implications for health. With prevalence rates globally increasing, this condition is causing a substantial burden on health care costs. Certain populations, including people with sickle cell disease (SCD), exhibit a greater prevalence of OSAS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33204196"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1548, "text": "Obstructive sleep apnea (OSA) has been considered as one of the risk factors for ischemic stroke, but the impact of OSA on wake-up stroke (WUS) is not well studied. We aimed to determine the relationship between OSA and WUS. We prospectively recruited 71 patients with mild to moderate ischemic stroke during hospitalization. Patients were classified into WUS and non-WUS. A full-night sleep respiratory study was performed between 3 and 14 days after stroke onset. Demographic data, sleep respiratory data, heart rate variability, stroke risk factors, stroke classification and sleep-related scales were recorded. We compared the differences in the variables between the two groups and determined the independent variables associated with WUS. Of the 71 patients, 26 (36.6%) had WUS. The patients with WUS had a significantly higher apnea-hypopnea index (23.1 \u00b1 19.4 vs. 12.5 \u00b1 11.9, p = 0.016), obstructive apnea index (7.8 \u00b1 9.7 vs. 3.0 \u00b1 4.0, p = 0.021) and lower mean blood oxygen saturation (95.1 \u00b1 1.5 vs. 95.8 \u00b1 1.3, p = 0.046) than the non-WUS patients. There were no significant differences in demographic data, stroke risk factors, sleep-related scales or heart rate variability. Logistic regression revealed that severe sleep-disordered breathing (apnea-hypopnea index \u226530) was the only independent variable associated with WUS (OR 6.065, 95% CI 1.451-25.350; p = 0.014). We conclude that in patients with mild to moderate ischemic stroke, OSA is the only risk factor associated with WUS, which cannot be distinguished clinically from n", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22215237"}, {"offsetInBeginSection": 0, "offsetInEndSection": 319, "text": "Sleep-related breathing disorders are strongly associated with increased risk of stroke independent of known risk factors. The direction of causation favors sleep-disordered breathing leading to stroke rather than the other way around, although definitive proof of this awaits the results of prospective cohort studies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12800780"}, {"offsetInBeginSection": 962, "offsetInEndSection": 1397, "text": "Based on a meta-analysis of the cohort studies, treatment with CPAP was associated with a lower incidence of stroke and cardiac events with relative risks of 0.27 [0.14-0.53], and 0.54 [0.38-0.75], respectively, although this could not be reproduced in the RCT and the studies using administrative data.CONCLUSIONS: Treating with CPAP in patients with OSA might decrease the risk of stroke, although there is some conflicting evidence.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26731604"}, {"offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "BACKGROUND AND PURPOSE: Obstructive sleep apnea (OSA) has been shown to increase the risk of stroke.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26731604"}, {"offsetInBeginSection": 673, "offsetInEndSection": 872, "text": "CPAP) treatment in these patients. Observational studies have shown an increased risk of ischemic stroke in patients with untreated OSA when compared with patients treated with CPAP; however, results", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31231783"}, {"offsetInBeginSection": 487, "offsetInEndSection": 710, "text": "The relationship between sleep-disordered breathing and stroke risk factors is complex, and likely part of the risk for cerebrovascular events is because of higher cardiovascular risk factors in patients with increased RDI.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12800780"}, {"offsetInBeginSection": 1353, "offsetInEndSection": 1585, "text": "poor functional prognosis.CONCLUSIONS: Severe OSA is an independent risk factor for a poor functional prognosis in patients with acute ischemic stroke, and quantitative EEG during sleep showed a significant slow wave enhancement, su", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36516602"}, {"offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Obstructive sleep apnea (OSA) has been considered as one of the risk factors for ischemic stroke,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22215237"}, {"offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Obstructive sleep apnea (OSA) increases the risk of stroke independent of known vascular and metabolic risk", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18927265"}, {"offsetInBeginSection": 18, "offsetInEndSection": 157, "text": "apnea (OSA) is a common disorder and the major sleep-related risk factor for cerebrovascular disease. There is a dose-response relationship", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17324369"}, {"offsetInBeginSection": 0, "offsetInEndSection": 406, "text": "Obstructive Sleep Apnea (OSA) is a sleep disorder with a high prevalence in the general population. It is a risk factor for many cardiovascular diseases, and an independent risk factor for cerebrovascular diseases such as stroke. After an apnea episode, both arterial blood pressure and cerebral blood flow velocity change in function of the apnea duration (AD). We hypothesized that the relative excursion", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29060173"}, {"offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "Obstructive Sleep Apnea (OSA) is a common co-morbid condition in stroke patients. It represents a very important risk factor for stroke in addition to the other established ones such as hypertension, cardiovascular disease (CVD), hyperlipidemia, atrial fibrillation (AF), type 2 diabetes mellitus (T2DM), stress, smoking, and heavy drinking.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30680373"}, {"offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Obstructive sleep apnea (OSA), prevalent in patients with stroke, increases the risks of cardiovascular events and stroke.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32755811"}, {"offsetInBeginSection": 138, "offsetInEndSection": 248, "text": "OSA is an independent risk factor for acute ischemic stroke (AIS) and a contributor to other key risk factors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37388591"}, {"offsetInBeginSection": 370, "offsetInEndSection": 679, "text": "Obstructive sleep apnea (OSA), one of the most common and serious sleep disturbances, manifests itself in almost 50% of all stroke patients. Sleep apnea patients who experience a stroke may be at a greater impairment in their rehabilitation potential and have increased risk of secondary stroke and mortality.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19122572"}]}
+{"question_id": "65f859b2c4010b4d78000050", "question": "Should all babies diagnosed with spina bifida be operated within the first week of life?", "answer": "No, not all babies diagnosed with spina bifida should be operated on within the first week of life. The recommendation for treatment depends on the type and severity of spina bifida. Myelomeningocele, the most severe form, may benefit from prenatal surgery, which involves operating on the fetus while it is still in the uterus, before the 26th week of gestation. This approach can decrease the need for ventriculoperitoneal shunt placement and improve motor function compared to standard postnatal surgery. , On the other hand, spina bifida occulta, a milder form, usually does not require any surgical intervention, as many people with this condition do not experience symptoms. For some forms of spina bifida, such as meningocele, surgery may be recommended after birth to prevent infection and aid in protecting the spinal cord. , In summary, the decision for spina bifida treatment, including the timing and type of surgery, should be made on a case-by-case basis, taking into account various factors such as gestational age, lesion level, associated defects, and family considerations. Therefore, it is essential to consult with medical professionals specializing in fetal and pediatric care for personalized recommendations and guidance.", "relevant_passage_ids": ["35735913", "30486637", "36964773", "37970655", "2012704", "27179533", "37975651"], "type": "yesno", "snippets": [{"offsetInBeginSection": 324, "offsetInEndSection": 475, "text": "treatment for spina bifida has made great advancements, from surgical closure of the defect after birth to the now state-of-the-art intrauterine repair", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35735913"}, {"offsetInBeginSection": 363, "offsetInEndSection": 479, "text": "Advances in fetal treatment have made minimally invasive prenatal surgery a realistic consideration for spina bifida", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30486637"}, {"offsetInBeginSection": 571, "offsetInEndSection": 770, "text": "Prenatal surgery for spina bifida via open fetal surgery with hysterotomy decreases the rate of ventriculoperitoneal shunt placement and improves motor function compared to standard postnatal surgery", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30486637"}, {"offsetInBeginSection": 1643, "offsetInEndSection": 1673, "text": "fetoscopic spina bifida repair", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30486637"}, {"offsetInBeginSection": 2124, "offsetInEndSection": 2158, "text": "prenatal treatment of spina bifida", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30486637"}, {"offsetInBeginSection": 323, "offsetInEndSection": 401, "text": "Spina bifida should be found in utero for the immediate operation after birth.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2012704"}, {"offsetInBeginSection": 230, "offsetInEndSection": 334, "text": "Babies born with spina bifida require early closure surgery, done within the first 2-3\u00a0days after birth.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36964773"}, {"offsetInBeginSection": 0, "offsetInEndSection": 555, "text": "OBJECTIVES: To determine if the lower extremity motor function of a fetus with open spina bifida deteriorates within a four-week interval between their first prenatal motor assessment at 22\u2009weeks of gestation and second presurgical evaluation in cases operated at later gestational age (26-27\u2009weeks of gestation), and to compare prenatal and postnatal motor function to the anatomical level of the lesion.METHODS: Multicenter cohort study involving cases from two centers that perform percutaneous fetoscopic repair of open spina bifida (SAFER technique).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37970655"}, {"offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "PURPOSE: Clinical guidelines recommend repair of open spina bifida (SB) prenatally or within the first days of an infant's life.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27179533"}, {"offsetInBeginSection": 1257, "offsetInEndSection": 1522, "text": "Infants born in lower level nursery care hospitals with were less likely to have timely repairs (aPR\u00a0=\u00a00.71, 95\u00a0% CI 0.52-0.98) than those born in higher level nursery care hospitals.CONCLUSIONS: Most infants with SB had surgical repair in the first 2\u00a0days of life.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27179533"}, {"offsetInBeginSection": 12, "offsetInEndSection": 219, "text": "To determine simple prenatal imaging parameters that can easily be acquired to predict the need for postnatal CSF diversion (PCD) surgery in fetuses undergoing open fetal surgery for open spina bifida (OSB).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37975651"}]}
+{"question_id": "6446884b57b1c7a31500006f", "question": "What is Oculopharyngeal Muscular Dystrophy (OPMD)?", "answer": "Oculopharyngeal muscular dystrophy (OPMD) is a rare late-onset intractable neuromuscular disease, characterized by slowly progressive ocular, facial, pharyngeal and distal limb muscle weakness.", "relevant_passage_ids": ["33805441", "35942670", "14526187", "29725764", "32842713", "34225694", "7795598", "22249111", "37634163", "25426070", "17110089", "31743248", "35025870", "16333769", "18432080", "37926637", "12619777", "12944420", "37923656", "37849345", "37519616", "3584810", "11742947", "10711989", "25860803", "9084936", "9585341", "15645184", "9601650", "16648376", "31537606", "36462961", "17296297", "5940325", "8689911", "25283883", "28575395", "30412104", "20184794", "16319127", "18577654", "16642034", "28361972", "20207626", "25831437", "30894671", "10555658", "21199860", "27980005", "28303574", "11139982", "9392018", "12945950", "28590779", "27854203", "23399899", "30860873", "19484687", "19101703", "15864313", "21602480", "36691350", "19080757", "30837270", "9296168", "34380753", "35859342", "32804098", "35112761", "23815790", "21204267", "23793615", "25816335", "21316245", "31066242", "12673802", "11001936", "17138075"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Oculopharyngeal muscular dystrophy (OPMD) is a late-onset intractable myopathy, characterized by slowly progressive ptosis, dysphagia, and proximal limb weakness.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33805441"}, {"offsetInBeginSection": 19, "offsetInEndSection": 210, "text": "Oculopharyngodistal myopathy (OPDM) is a rare adolescent or adult-onset neuromuscular disease that is characterized by progressive ocular, facial, pharyngeal and distal limb muscle weakness. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35942670"}, {"offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Oculopharyngeal muscular dystrophy (OPMD) is a rare, primarily autosomal dominant, late onset muscular dystrophy commonly presenting with ptosis, dysphagia, and subsequent weakness of proximal muscles", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37926637"}, {"offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Oculopharyngeal muscular dystrophy (OPMD) is a rare late-onset muscle disease associated with progressive dysphagia", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37923656"}, {"offsetInBeginSection": 19, "offsetInEndSection": 201, "text": "Muscle weakness, and its association with mobility limitations, has received little study in oculopharyngeal muscular dystrophy (OPMD) using quantitative and standardized assessments", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37849345"}, {"offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disorder characterized by progressive eyelid drooping, swallowing difficulties and proximal limb weakness.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17110089"}, {"offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant muscular dystrophy which presents typically after the age of 50 with progressive eyelid drooping and an increasing difficulty in swallowing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7795598"}, {"offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant late-onset neuromuscular degenerative disease characterized by ptosis, dysphagia, and proximal muscle weakness.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25283883"}, {"offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant muscular dystrophy characterized by late onset ptosis, proximal muscle weakness and swallowing difficulties.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9601650"}, {"offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant muscle disorder, usually of late onset.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16333769"}, {"offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Oculopharyngeal muscular dystrophy is a localized or restricted variety of muscular dystrophy, characterized by bilateral ptosis, myopathic facies, external ophthalmoplegia and dysphagia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/5940325"}, {"offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Oculopharyngeal muscular dystrophy (OPMD) is a late adult onset, autosomal dominant muscular dystrophy characterized by ptosis and dysphagia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9585341"}, {"offsetInBeginSection": 781, "offsetInEndSection": 930, "text": "OPMD is a unique disease sharing common pathogenic features with other polyalanine disorders, as well as with polyglutamine and dystrophic disorders.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17110089"}, {"offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Oculopharyngeal muscular dystrophy (OPMD) is a muscle disease of late onset associated with progressive ptosis of the eyelids, dysphagia, and unique tubulofilamentous intranuclear inclusions (INIs).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14526187"}, {"offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Oculopharyngeal muscular dystrophy (OPMD) is a rare genetic disorder with late-onset progressive myopathy affecting mainly head and neck striated muscles.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8689911"}, {"offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Oculopharyngeal muscular dystrophy (OPMD) is a rare, primarily autosomal dominant, late onset muscular dystrophy commonly presenting with ptosis, dysphagia, and subsequent weakness of proximal muscles.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37926637"}, {"offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant form of late-onset muscular dystrophy. Ptosis (droopy eyelids) and dysphagia (difficulty swallowing) are the most common presenting symptoms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18432080"}, {"offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "RATIONALE: Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant late-onset progressive muscle disorder typically characterized by ptosis, difficulty in swallowing, and proximal lim", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30412104"}, {"offsetInBeginSection": 0, "offsetInEndSection": 320, "text": "BACKGROUND: Oculopharyngeal muscular dystrophy (OPMD) is a rare inherited muscular disorder, clinically characterized by late-onset, slowly progressive bilateral ptosis, dysphagia, and proximal limb weakness. A short polyalanine expansion in the polyadenylate binding-protein nuclear 1 (PABPN1) gene is a commonly report", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20184794"}, {"offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "BACKGROUND: Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant late onset neuromuscular disease characterised by proximal muscle weakness, ptosis, and swallowing", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16648376"}, {"offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Oculopharyngeal muscular dystrophy (OPMD) belongs to the group of protein aggregation disorders and is caused by extensions of the N-terminal polyalanine stretch of the nuclear polyA-binding protein 1 (PABPN1).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16319127"}, {"offsetInBeginSection": 0, "offsetInEndSection": 312, "text": "BACKGROUND: Oculopharyngeal muscular dystrophy (OPMD) is a late onset hereditary myopathy of autosomal dominant transmission characterised by ptosis, dysphagia and limb weakness. The disease is caused by short heterozygous expansions of a (GCN)(10) triplet located in the first exon of the PABPN1 gene at chromos", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18577654"}, {"offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "OBJECTIVE: Oculopharyngeal muscular dystrophy (OPMD) is a rare neuromuscular disorder characterized by late-onset development of bilateral eyelid ptosis, ophthalmoparesis and dysphagia with further progression to proximal limb muscle weakness that is an under recognized condition.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31743248"}, {"offsetInBeginSection": 377, "offsetInEndSection": 1057, "text": "OPMD is caused by a short expansion of the alanine repeat (GCN trinucleotide) in the poly(adenylate)-binding protein nuclear1 (PABPN1) gene.METHODS: We performed a retrospective review of undiagnosed cases that initially presented with ptosis, diplopia, dysphagia, muscle weakness, muscular dystrophy and/or myasthenia gravis from 2000 to 2015 at two institutions in Southern California.RESULTS: Twenty-five patients were identified to have OPMD with genetic confirmation.CONCLUSIONS: Even though a rare condition, the prevalence is disproportionally frequent in certain ethnic groups and in certain regions; thus, we report our experience of OPMD patients in Southern California.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31743248"}, {"offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset syndrome characterized by progressive degeneration of particular muscles.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16642034"}, {"offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant, late-onset muscle disorder characterized by ptosis, swallowing difficulties, proximal limb weakness and nuclear aggregates in skeletal muscles.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28361972"}, {"offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Oculopharyngeal muscular dystrophy (OPMD) is a rare, primarily autosomal dominant, late onset muscular dystrophy commonly presenting with ptosis, dysphagia, and subsequent weakness of proximal muscles. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37926637"}, {"offsetInBeginSection": 0, "offsetInEndSection": 408, "text": "Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant muscle disorder, usually of late onset. OPMD is among the few triplet repeat diseases/ polyalanine (poly(A)) expansion diseases for which the function of the mutated gene is quite well established. The disease is characterised by slowly progressive bilateral ptosis, dysphagia and proximal limb weakness, appearing after the age of 40 years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16333769"}, {"offsetInBeginSection": 0, "offsetInEndSection": 506, "text": "BACKGROUND: Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant late onset neuromuscular disease characterised by proximal muscle weakness, ptosis, and swallowing difficulty. The only causative mutation described to date is a triplet repeat expansion consisting of two to seven additional base triplets in a repeat sequence in exon 1 of the polyadenine binding protein nuclear 1 (PABPN1) gene. This results in an increase in length of a polyalanine tract in the PABPN1 protein from 10 to 12-", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16648376"}, {"offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "INTRODUCTION: Oculopharyngeal muscular dystrophy (OPMD) presents with progressive ptosis, dysphagia and limb girdle weakness, and is caused by expansion of a trinucleotide tandem repeat within the gene encoding poly-(A) bind", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21602480"}, {"offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "BACKGROUND: Oculopharyngeal muscular dystrophy (OPMD) has long been characterized by a combination of bilateral ptosis and dysphagia and subsequent limb gird", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27854203"}, {"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "OBJECTIVE: Oculopharyngeal muscular dystrophy (OPMD) is a late-onset inherited neuromuscular disorder, with progressive ptosis and dysphagia as common mani", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36691350"}, {"offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant myopathy with almost benign course.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11139982"}, {"offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "It has been 10 years since the identification of the first PABPN1 gene (GCN)(n)/polyalanine mutations responsible for oculopharyngeal muscular dystrophy (OPMD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19080757"}, {"offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Oculopharyngeal muscular dystrophy (OPMD) is a late onset myopathy usually presenting in the 5th or 6th decade of life with progressive ptosis, dysphagia and proximal muscle weakness.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17296297"}, {"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Oculopharyngeal muscular dystrophy (OPMD) is a rare progressive disease characterized by bilateral ptosis and dysphagia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3584810"}, {"offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Autosomal dominant oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disease with worldwide distribution.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10711989"}, {"offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Oculopharyngeal muscular dystrophy (OPMD) is a late-onset, primarily autosomal dominant disease caused by a short GCN expansion", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30837270"}, {"offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Oculopharyngeal muscular dystrophy (OPMD) is an autosomal-dominant, adult-onset disorder defined by blepharoptosis, dysphagia, and proximal muscle weakness.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27980005"}, {"offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Oculopharyngeal muscular dystrophy (OPMD) is a muscle disease of late onset associated with progressive ptosis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14526187"}, {"offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "BACKGROUND: Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscular dystrophy characterised by slowly progressive ptosis, dysphagia, and proximal", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34225694"}, {"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscular dystrophy caused by a polyalanine expansion mutation", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21199860"}, {"offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disorder characterized by progressive eyelid drooping, swallowing difficulties and proximal limb", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17110089"}, {"offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "BACKGROUND: Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disorder characterized by progressive ptosis, dysphagia and p", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12945950"}, {"offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disorder characterized by ptosis, dysphagia and proximal limb", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20207626"}, {"offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disorder characterized by progressive eyelid drooping (ptosis), swallowing difficulties (dysphagia),", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12619777"}, {"offsetInBeginSection": 84, "offsetInEndSection": 443, "text": "currently no cures. Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant late-onset, progressive disease that generally presents in the fifth or sixth decade with dysphagia, ptosis and proximal limb weakness. OPMD is caused by the abnormal expansion of a (GCG)n trinucleotide repeat in the coding region of the poly-(A) binding protein nuclear 1", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15864313"}, {"offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "BACKGROUND: Oculopharyngeal muscular dystrophy (OPMD) has long been characterized by a combination of bilateral ptosis and dysphagia and subsequent", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27854203"}, {"offsetInBeginSection": 190, "offsetInEndSection": 539, "text": "Oculopharyngeal muscular dystrophy (OPMD) is caused by a small expansion of the polyalanine tract in the poly(A)-binding protein nuclear 1 (PABPN1). Aggregation of expanded PABPN1 into intranuclear inclusions (INIs) in skeletal muscle fibers is the pathological hallmark of OPMD. In this study what we have analyzed in muscle fibers of OPMD patients", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22249111"}, {"offsetInBeginSection": 167, "offsetInEndSection": 291, "text": "OPMD is caused by a small expansion of a short polyalanine tract in the poly (A) binding protein nuclear 1 protein (PABPN1).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17110089"}, {"offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Oculopharyngeal muscular dystrophy (OPMD) is a late-onset myopathic genetic disorder characterized by chronic progressive dysphagia and ptosis with or without proximal limb weakness.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37519616"}, {"offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscle disorder characterized by progressive dysphagia and bilateral ptosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17138075"}, {"offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disorder characterized by progressive eyelid drooping (ptosis), swallowing difficulties (dysphagia), and proximal limb weakness.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12619777"}, {"offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Oculopharyngeal muscular dystrophy (OPMD) is a muscle-specific, late-onset degenerative disorder whereby muscles of the eyes (causing ptosis), throat (leading to dysphagia), and limbs (causing proximal limb weakness) are mostly affected.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25860803"}, {"offsetInBeginSection": 13, "offsetInEndSection": 168, "text": "utations in the gene encoding poly(A)-binding protein nuclear 1 (PABPN1) result in oculopharyngeal muscular dystrophy (OPMD). This disease is of late-onset", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28303574"}, {"offsetInBeginSection": 270, "offsetInEndSection": 315, "text": "OPMD courses with muscle atrophy and weakness", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28303574"}]}
+{"question_id": "65d144731930410b13000040", "question": "What is the mechanisms of action of Dersimelagon?", "answer": "Dersimelagon is a novel orally administered selective agonist for melanocortin receptor 1 that is being investigated for the treatment of erythropoietic protoporphyria, X-linked protoporphyria, and diffuse cutaneous systemic sclerosis.", "relevant_passage_ids": ["37043653", "37060458", "37078227", "36840969", "36050717", "35665216"], "type": "summary", "snippets": [{"offsetInBeginSection": 297, "offsetInEndSection": 422, "text": "Dersimelagon is a new, orally administered, selective melanocortin 1 receptor agonist that increases levels of skin eumelanin", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37043653"}, {"offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "PURPOSE: To describe outcomes from the first-in-human study of dersimelagon, an investigational oral selective MC1R agonist, under development for the treatment of erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37060458"}, {"offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Absorption, metabolism, and excretion of [14 C]dersimelagon, an investigational oral selective melanocortin 1 receptor agonist, in preclinical species and healthy volunteers.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37078227"}, {"offsetInBeginSection": 0, "offsetInEndSection": 292, "text": "Dersimelagon (formerly MT-7117) is a novel, orally administered nonpeptide small molecule selective agonist for melanocortin 1 receptor currently being investigated for the treatment of erythropoietic protoporphyria, X-linked protoporphyria, and diffuse cutaneous systemic sclerosis (dcSSc). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37078227"}, {"offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Dersimelagon is a novel orally administered selective agonist for melanocortin receptor 1 being investigated for the treatment of erythropoietic protoporphyria, X-linked protoporphyria, and diffuse cutaneous systemic sclerosis. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36840969"}, {"offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Dersimelagon, a novel oral melanocortin 1 receptor agonist, demonstrates disease-modifying effects in preclinical models of systemic sclerosis.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36050717"}, {"offsetInBeginSection": 297, "offsetInEndSection": 719, "text": "Dersimelagon is a new, orally administered, selective melanocortin 1 receptor agonist that increases levels of skin eumelanin.METHODS: We conducted a randomized, placebo-controlled, phase 2 trial to investigate the efficacy and safety of dersimelagon with respect to the time to onset and the severity of symptoms associated with sunlight exposure in patients with erythropoietic protoporphyria or X-linked protoporphyria.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37043653"}, {"offsetInBeginSection": 0, "offsetInEndSection": 644, "text": "PURPOSE: To describe outcomes from the first-in-human study of dersimelagon, an investigational oral selective MC1R agonist, under development for the treatment of erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP).METHODS: In this double-blind, placebo-controlled phase 1 study, the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple ascending oral doses of dersimelagon in healthy participants were evaluated.RESULTS: Dersimelagon was generally well tolerated in healthy participants, with the most common TEAEs being lentigo (52.8%) and skin hyperpigmentation (50.0%) after multiple doses.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37060458"}, {"offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "Dersimelagon (formerly MT-7117) is a novel, orally administered nonpeptide small molecule selective agonist for melanocortin 1 receptor currently being investigated for the treatment of erythropoietic protoporphyria, X-linked protoporphyria, and diffuse cutaneous systemic sclerosis (dcSSc).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37078227"}, {"offsetInBeginSection": 126, "offsetInEndSection": 506, "text": "The purpose of this study is to investigate the potential of dersimelagon, a novel oral MC1R agonist, as a therapeutic agent for systemic sclerosis (SSc).METHODS: The effects of dersimelagon phosphoric acid (MT-7117) on skin fibrosis and lung inflammation were evaluated in bleomycin (BLM)-induced SSc murine models that were optimized for prophylactic and therapeutic evaluation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36050717"}, {"offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Melanogenic effect of dersimelagon (MT-7117), a novel oral melanocortin 1 receptor agonist.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35665216"}, {"offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Dersimelagon is a novel orally administered selective agonist for melanocortin receptor 1 being investigated for the treatment of erythropoietic protoporphyria, X-linked protoporphyria, and diffuse cutaneous systemic sclerosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36840969"}, {"offsetInBeginSection": 297, "offsetInEndSection": 423, "text": "Dersimelagon is a new, orally administered, selective melanocortin 1 receptor agonist that increases levels of skin eumelanin.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37043653"}, {"offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Dersimelagon is a novel orally administered selective agonist for melanocortin receptor 1 being investigated for the treatment of erythropoietic protoporphyria, X-linked protoporphyria, and diffuse cutaneous systemic sclerosis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36840969"}, {"offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "BACKGROUND: Activation of melanocortin 1 receptor (MC1R) is known to exert broad anti-inflammatory and anti-fibrotic effects. The purpose of this study is to investigate the potential of dersimelagon, a novel oral MC1R agonist, as a therapeutic agent for systemic scle", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36050717"}, {"offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Dersimelagon is a novel orally administered selective agonist for melanocortin receptor 1 being investigated for the treatment", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36840969"}, {"offsetInBeginSection": 233, "offsetInEndSection": 472, "text": "xcruciating phototoxic attacks after exposure to visible light. Dersimelagon is a new, orally administered, selective melanocortin 1 receptor agonist that increases levels of skin eumelanin.METHODS: We conducted a randomized, placebo-contr", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37043653"}, {"offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Dersimelagon (formerly MT-7117) is a novel, orally administered nonpeptide small molecule selective agonist for melanocortin", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37078227"}]}
+{"question_id": "65f7728fc4010b4d78000021", "question": "What proportion of risk is attributable to obesity in colorectal cancer women development?", "answer": "The men in the obese/obese group had a higher risk of colon cancer than women (hazard ratio\u2009=\u20091.13 [1.10-1.17] in men, and hazard ratio\u2009=\u20091.04 [1.01-1.18] in women, P\u2009=\u20090.001).", "relevant_passage_ids": ["17823417", "37264099", "32791859", "23481261", "29259258", "30326010", "12117878", "17696248", "11169969", "19207714", "22312135", "33070559", "28703702", "17855691", "20843489", "27196525", "32868317"], "type": "factoid", "snippets": [{"offsetInBeginSection": 1166, "offsetInEndSection": 1586, "text": "Colon cancer risk increased with increasing waist circumference (per 10-cm increase) in both men (RR: 1.33; 95% CI: 1.19, 1.49) and women (RR: 1.16; 95% CI: 1.09, 1.23) and with increasing waist-hip ratio (per 0.1-unit increase) in both men (RR: 1.43; 95% CI: 1.19, 1.71) and women (RR: 1.20; 95% CI: 1.08, 1.33).CONCLUSIONS: The association between obesity and colon and rectal cancer risk varies by sex and cancer site", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17823417"}, {"offsetInBeginSection": 999, "offsetInEndSection": 1177, "text": " The men in the obese/obese group had a higher risk of colon cancer than women (hazard ratio\u2009=\u20091.13 [1.10-1.17] in men, and hazard ratio\u2009=\u20091.04 [1.01-1.18] in women, P\u2009=\u20090.001). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37264099"}, {"offsetInBeginSection": 809, "offsetInEndSection": 1015, "text": "Compared with individuals with normal weight, overweight and obese young adults had a significantly higher risk of CRC (relative risks (RR):18%, 95% CI:1.08, 1.28\uff1b RR:32%, 95% CI: 1.11, 1.56, respectively).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32791859"}, {"offsetInBeginSection": 1087, "offsetInEndSection": 1210, "text": "cant from a BMI of 23.4 kg/m2 [spline analysis]) and women (HR for overweight, 1.54; 95% CI, 1.22-1.93; HR for obesity, 1.5", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28736986"}, {"offsetInBeginSection": 906, "offsetInEndSection": 1060, "text": "r association than females. Population attributable fraction for colorectal cancer by BMI \u2265 25 kg/m(2) was 3.62% (95% CI 1.91-5.30) for males and 2.62% (9", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21597097"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1558, "text": "OBJECTIVE: Excess body weight, defined by body mass index (BMI), may increase the risk of colorectal cancer. As a prerequisite to the determination of lifestyle attributable risks, we undertook a systematic review and meta-analysis of prospective observational studies to quantify colorectal cancer risk associated with increased BMI and explore for differences by gender, sub-site and study characteristics.METHOD: We searched MEDLINE and EMBASE (to December 2007), and other sources, selecting reports based on strict inclusion criteria. Random-effects meta-analyses and meta-regressions of study-specific incremental estimates were performed to determine the risk ratio (RR) and 95% confidence intervals (CIs) associated with a 5 kg/m(2) increase in BMI.RESULTS: We analysed 29 datasets from 28 articles, including 67,361 incident cases. Higher BMI was associated with colon (RR 1.24, 95% CIs: 1.20-1.28) and rectal (1.09, 1.05-1.14) cancers in men, and with colon cancer (1.09, 1.04-1.12) in women. Associations were stronger in men than in women for colon (P < 0.001) and rectal (P = 0.005) cancers. Associations were generally consistent across geographic populations. Study characteristics and adjustments accounted for only moderate variations of associations.CONCLUSION: Increasing BMI is associated with a modest increased risk of developing colon and rectal cancers, but this modest risk may translate to large attributable proportions in high-prevalence obese populations. Inter-gender differences point to potentially important mechanistic diffe", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19207714"}, {"offsetInBeginSection": 194, "offsetInEndSection": 938, "text": "The proportion of all cancers attributable to overweight has, however, never been systematically estimated. We reviewed the epidemiological literature and quantitatively summarised, by meta-analysis, the relationship between excess weight and the risk of developing cancer at the 6 sites listed above. Estimates were then combined with sex-specific estimates of the prevalence of overweight [body mass index (BMI) 25-29 kg/m(2)] and obesity (BMI > or = 30 kg/m(2)) in each country in the European Union to obtain the proportion of cancers attributable to excess weight. Overall, excess body mass accounts for 5% of all cancers in the European Union, 3% in men and 6% in women, corresponding to 27,000 male and 45,000 female cancer cases yearly.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11169969"}, {"offsetInBeginSection": 1063, "offsetInEndSection": 1206, "text": "s would be avoided by 2040. The population attributable fractions (PAF) for excess weight were much higher for males (between 13.5% and 18.2%) ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20843489"}, {"offsetInBeginSection": 635, "offsetInEndSection": 1079, "text": "Among men, when the highest and lowest fifths were compared, BMI (HR\u2009=\u20091.35, 95%CI: 1.13-1.61; Ptrend\u2009<\u20090.0001), waist circumference (HR\u2009=\u20091.66, 95%CI: 1.39-1.99; Ptrend\u2009<\u20090.0001), waist-to-hip ratio (HR\u2009=\u20091.58, 95%CI: 1.31-1.91; Ptrend\u2009<\u20090.0001), total body fat percentage (HR\u2009=\u20091.27, 95%CI: 1.06-1.53; Ptrend\u2009=\u20090.002), and trunk fat percentage (HR\u2009=\u20091.31, 95%CI: 1.09-1.58; Ptrend\u2009=\u20090.002) were associated with greater colorectal cancer risk.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29259258"}, {"offsetInBeginSection": 1632, "offsetInEndSection": 2377, "text": "Similar associations were observed among women without a family history of CRC and without lower endoscopy within the past 10 years. Both BMI at 18 years of age and weight gain since 18 years of age contributed to this observation. Compared with women with a BMI of 18.5 to 20.9 at 18 years of age, the RR of early-onset CRC was 1.32 (95% CI, 0.80-2.16) for women with a BMI of 21.0 to 22.9 and 1.63 (95% CI, 1.01-2.61) for women with a BMI of 23.0 or greater at 18 years of age (P\u2009=\u2009.66 for trend). Compared with women who had gained less than 5.0 kg or had lost weight, the RR of early-onset CRC was 1.65 (95% CI, 0.96-2.81) for women gaining 20.0 to 39.9 kg and 2.15 (95% CI, 1.01-4.55) for women gaining 40.0 kg or more (P\u2009=\u2009.007 for trend).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30326010"}, {"offsetInBeginSection": 803, "offsetInEndSection": 948, "text": " Compared to women with normal BMI, women who were obese had HRs of 1.39 (95%CI 1.12-1.74) and 1.64 (95%CI 1.24-2.16) for CRC and CC respectively", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30448606"}, {"offsetInBeginSection": 712, "offsetInEndSection": 1475, "text": " Compared with the reference group (WC 65-75), the HRs [95% confidence interval (CI)] of colorectal cancer in WC <65, 75-85, 85-95, and >95 groups were 1.01 (0.91-1.11), 1.02 (0.97-1.07), 1.09 (1.00-1.18), and 1.31 (1.12-1.52), respectively, in premenopausal women and 1.01 (0.95-1.17), 1.09 (1.07-1.12), 1.19 (1.00-1.18), and 1.30 (1.25-1.35), respectively, in postmenopausal women. Compared with the reference group (BMI 18.5-22.9), HRs (95% CI) for colorectal cancer in BMI <18.5, 23-25, 25-30, and >30 groups were 0.99 (0.87-1.14), 0.99 (0.94-1.06), 0.98 (0.92-1.04), and 1.06 (0.92-1.20), respectively, in premenopausal women. In postmenopausal women, those values were 0.99 (0.93-1.05), 1.05 (1.03-1.08), 1.11 (1.09-1.13), and 1.20 (1.16-1.25), respectively", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32868317"}]}
+{"question_id": "65f490fac4010b4d78000010", "question": "Has MDMA(ecstasy) been successfully used to treat PTSD disorder?", "answer": "Yes MDMA, a compound belonging to the family of entactogens, has been demonstrated to be useful to treat post-traumatic stress disorders.", "relevant_passage_ids": ["37611653", "37484678", "36184377", "12691208", "26579955", "35272210", "34150406", "37987270", "29524515", "36311515", "38004320", "26371762", "34465250", "34855694", "30949077", "36713926", "35915689", "35230652", "33972795", "36815187", "37404971", "36189781", "24648791", "30632995", "28741031", "28635375", "37709999", "30529341", "35700643"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 336, "text": "The application of MDMA in conjunction with psychotherapy has in recent years seen a resurgence of clinical, scientific, and public interest in the treatment of posttraumatic stress disorder (PTSD). Clinical trials have shown promising safety and efficacy, but the mechanisms underlying this treatment form remain largely unestablished.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37611653"}, {"offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "MDMA-assisted psychotherapy for PTSD: Growing evidence for memory effects mediating treatment efficacy", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37611653"}, {"offsetInBeginSection": 0, "offsetInEndSection": 381, "text": "Post-traumatic stress disorder (PTSD) is a prevalent psychiatric condition that significantly impacts daily functioning in patients but lacks adequate treatment options. 3,4-methylenedioxymethamphetamine (MDMA) as an adjunct to psychotherapy for the treatment of PTSD has been studied increasingly for the last two decades and has shown promising results through quantitative data.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37484678"}, {"offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "Psychedelics and related compounds have shown efficacy for the treatment of a variety of conditions that are prevalent among older adults, including mood disorders, the psychological distress associated with a serious medical illness, post-traumatic stress disorder (PTSD), and prolonged grief disorde", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36184377"}, {"offsetInBeginSection": 944, "offsetInEndSection": 1112, "text": "MDMA-assisted psychotherapy has emerged as an innovative approach to treating PTSD, leading to sustained reductions in symptoms and even promoting post-traumatic growth", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38004320"}, {"offsetInBeginSection": 751, "offsetInEndSection": 907, "text": "MDMA can reduce PTSD symptoms even in treatment-resistant cases by increasing certain neurohormones, i.e., dopamine, serotonin, norepinephrine, and oxytocin", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37987270"}, {"offsetInBeginSection": 159, "offsetInEndSection": 375, "text": "MDMA used as an adjunct during psychotherapy sessions has demonstrated effectiveness and acceptable safety in reducing PTSD symptoms in Phase 2 trials, with durable remission of PTSD diagnosis in 68% of participants.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29524515"}, {"offsetInBeginSection": 1437, "offsetInEndSection": 1680, "text": "These findings suggest that MDMA enhances fear memory extinction through a BDNF-dependent mechanism, and that MDMA may be a useful adjunct to exposure-based therapies for PTSD and other anxiety disorders characterized by altered fear learning.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26371762"}, {"offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "MDMA-assisted psychotherapy for treatment of PTSD has recently progressed to Phase 3 clinical trials and received Breakthrough Therapy designation by the FDA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29524515"}, {"offsetInBeginSection": 1194, "offsetInEndSection": 1464, "text": "Based on the pharmacology of MDMA and the available translational literature of memory reconsolidation, fear learning, and PTSD, this review suggests a neurobiological rationale to explain, at least in part, the large effect sizes demonstrated for MDMA in treating PTSD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29524515"}, {"offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "3,4 Methylenedioxymethamphetamine (MDMA)-assisted therapy has been recently found to be highly effective for treatment of posttraumatic stress disorder (PTSD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34465250"}, {"offsetInBeginSection": 1258, "offsetInEndSection": 1721, "text": "Finally, the amount of recovery from PTSD after MDMA-AT correlated with changes in four functional connections during autobiographical memory recall: the left amygdala-left posterior cingulate cortex (PCC), left amygdala-right PCC, left amygdala-left insula, and left isthmus cingulate-left posterior hippocampus.Discussion: Amygdala-insular functional connectivity is reliably implicated in PTSD and anxiety, and both regions are impacted by MDMA administration.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36713926"}, {"offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "MDMA-assisted psychotherapy for PTSD: Are memory reconsolidation and fear extinction underlying mechanisms?", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29524515"}, {"offsetInBeginSection": 261, "offsetInEndSection": 495, "text": ". A series of six phase-II clinical trials studying MDMA-AT for treatment-resistant PTSD\u00a0found that 54% of MDMA-AT full-dose participants no longer met the diagnosis of PTSD after two MDMA sessions, compared to 23% in the control grou", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35915689"}, {"offsetInBeginSection": 751, "offsetInEndSection": 908, "text": "MDMA can reduce PTSD symptoms even in treatment-resistant cases by increasing certain neurohormones, i.e., dopamine, serotonin, norepinephrine, and oxytocin.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37987270"}, {"offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "BACKGROUND AND OBJECTIVE: Intensive psychotherapy assisted with 3,4-methylenedioxymethamphetamine (MDMA-AT) was shown in Phase 3 clinical trials to substantially reduce post-traumatic stress disorder (PTSD) symptoms compared to p", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35230652"}, {"offsetInBeginSection": 142, "offsetInEndSection": 552, "text": "We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33972795"}, {"offsetInBeginSection": 613, "offsetInEndSection": 755, "text": "MDMA therapy for PTSD is now entering the final Phase 3 stage of drug development, with a target set for licensing by the FDA and EMA in 2021.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30949077"}, {"offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "A proposed mechanism for the MDMA-mediated extinction of traumatic memories in PTSD patients treated with MDMA-assisted therapy.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36311515"}, {"offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "INTRODUCTION: 3,4-Methylenedioxymethamphetamine (MDMA/\"ecstasy\") is an empathogen that can give rise to increased pleasure and empathy and may effectively treat post-traumatic stress disorder.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36189781"}, {"offsetInBeginSection": 187, "offsetInEndSection": 324, "text": "Most clinical MDMA research in patients to date has focused on MDMA-assisted psychotherapy to treat posttraumatic stress disorder (PTSD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30949077"}, {"offsetInBeginSection": 193, "offsetInEndSection": 403, "text": "der (PTSD). A recent Phase 3 clinical trial reported high efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for treating patients with severe PTSD compared to a therapy with placebo group (N", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36815187"}, {"offsetInBeginSection": 1255, "offsetInEndSection": 1428, "text": "3,4-Methylenedioxymethamphetamine, which activates 5-HT2A receptors, has been successful in the treatment of PTSD and has recently achieved status as a breakthrough therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30632995"}, {"offsetInBeginSection": 0, "offsetInEndSection": 374, "text": "The FDA and the Spanish Ministry of Health have concluded that the risk/benefit ratio is favorable under certain circumstances for clinical studies investigating MDMA-assisted psychotherapy. Both agencies have approved pilot studies in chronic posttraumatic stress disorder (PTSD) patients who have failed to obtain relief from at least one course of conventional treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12691208"}, {"offsetInBeginSection": 175, "offsetInEndSection": 290, "text": "nical trials, MDMA-assisted therapy (MDMA-AT) has shown marked success in the treatment of PTSD and may be promisin", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35272210"}, {"offsetInBeginSection": 142, "offsetInEndSection": 552, "text": "We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37404971"}, {"offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA) persistently improves symptoms of post-traumatic stress disorder (PTSD) when combined with psy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28741031"}, {"offsetInBeginSection": 136, "offsetInEndSection": 315, "text": "Relevantly, enduring improvements in Post-Traumatic Stress Disorder (PTSD) symptoms have been found in response to 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28635375"}, {"offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "This multi-site, randomized, double-blind, confirmatory phase 3 study evaluated the efficacy and safety of 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) versus placebo with identical therapy in participants with moderate to severe post-traumatic stress disorder (PTSD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37709999"}, {"offsetInBeginSection": 805, "offsetInEndSection": 959, "text": "o have anxiolytic effects, whereas 3,4-methylenedioxymethamphetamine (MDMA) has been used effectively to treat post-traumatic stress disorder (PTSD), with", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34855694"}, {"offsetInBeginSection": 2011, "offsetInEndSection": 2242, "text": "Finally, even though MDMA is listed as a Schedule I compound by the Drug Enforcement Agency, MDMA-assisted psychotherapy for patients with chronic, treatment-resistant posttraumatic stress disorder is currently under investigation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24648791"}, {"offsetInBeginSection": 55, "offsetInEndSection": 212, "text": "(MDMA, 'ecstasy') has been proposed to have long-term positive effects on post-traumatic stress disorder (PTSD) symptoms when combined with psychotherapy. No", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26371762"}, {"offsetInBeginSection": 726, "offsetInEndSection": 1009, "text": "has shown that MDMA, used as a catalyst in psychotherapy, is effective in treating posttraumatic stress disorder (PTSD). This review also examines the psychopharmacological basis for the efficacy of MDMA-assisted psychotherapy. Specifically, the brain regions involved with both PTSD", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26579955"}, {"offsetInBeginSection": 4, "offsetInEndSection": 416, "text": "FDA and the Spanish Ministry of Health have concluded that the risk/benefit ratio is favorable under certain circumstances for clinical studies investigating MDMA-assisted psychotherapy. Both agencies have approved pilot studies in chronic posttraumatic stress disorder (PTSD) patients who have failed to obtain relief from at least one course of conventional treatment. These studies, the only ones in the world", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12691208"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1445, "text": "Background: 3,4-methylenedioxymethamphetamine (MDMA), known recreationally as \"Molly\" or \"Ecstasy\", is a triple monoamine reuptake inhibitor. MDMA specifically acts as a weak 5-HT1 and 5-HT2 receptor agonist, targeting 5-HT2A, 5-HT2B, and 5-HT2C\u00a0receptors. Its potential use for therapeutic purposes with these pharmacological profiles remains a controversial subject. Studies have shown the potential benefits in clinical trials for post-traumatic stress disorder (PTSD). A larger amount of data has been provided for the push in support of MDMA-assisted psychotherapy in these patients.\u00a0 Objective: The aim of this article is to compute a meta-analysis and conduct a systematic review of the effects of MDMA on PTSD, discussing the potential benefits and adverse events relative to dosing and stability of treatment. Methods:\u00a0Articles were collected and analyzed for systematic review: 16 articles were included in the systematic review that met the criteria for the use of MDMA in the treatment of PTSD as well as assessing the safety and efficacy of the drug in human participants. Ten studies were used for the meta-analysis, with a cumulative sample size of 168 patients. The significance of the findings on dosing and efficacy of MDMA in healthy human participants was quantified based on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and PTSD symptom scores. Results: The disorders for which MDMA demonstrated a net positive o", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34150406"}, {"offsetInBeginSection": 1286, "offsetInEndSection": 1511, "text": "These findings are consistent with a general memory-disrupting effect of MDMA and suggest that MDMA could augment psychotherapy by modifying fear memories during reconsolidation without necessarily enhancing their extinction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30529341"}, {"offsetInBeginSection": 1551, "offsetInEndSection": 1785, "text": "These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33972795"}, {"offsetInBeginSection": 974, "offsetInEndSection": 1124, "text": "In recent human-subject studies MDMA-assisted therapy resulted in significant improvement in PTSD symptoms with a good safety and side effect profile.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35700643"}, {"offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Clinical trials have demonstrated that 3,4-methylenedioxymethamphetamine (MDMA) paired with psychotherapy is more effective at reducing symptoms of post-traumatic stress disorder (PTSD) than psychotherapy or pharmacotherapy, alone or in combination.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30529341"}]}
+{"question_id": "65f843cbc4010b4d78000042", "question": "What is a spillover event?", "answer": "A spillover event is the transmission of a pathogen from one host species to another. It involves the physical transfer of viral or other infectious particles across species boundaries, and is often the trigger for infectious disease outbreaks and emergence events. Spillover events can be influenced by factors like host ecology, environment, habitat fragmentation, biodiversity loss, livestock density, and human-animal interactions.", "relevant_passage_ids": ["37367190", "37672628", "28555073", "36379648", "29134435", "36169531", "35537080", "31401953", "31401965", "25667339", "16358422", "15540144", "32427175", "30096035", "37786724", "37007505", "35632729", "37321337", "29351657", "34864994", "34018336"], "type": "summary", "snippets": [{"offsetInBeginSection": 994, "offsetInEndSection": 1166, "text": "importance of assessing the zoonotic potential of widely distributed batborne CoV in order to monitor changes in genomic composition of viruses and prevent spillover events", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37367190"}, {"offsetInBeginSection": 12, "offsetInEndSection": 420, "text": "Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic flavivirus and the leading cause of pediatric encephalitis in the Asian Pacific region. The transmission cycle primarily involves Culex spp. mosquitoes and Ardeid birds, with domestic pigs (Sus scrofa domestica) being the source of infectious viruses for the spillover of JEV from the natural endemic transmission cycle into the human population", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37672628"}, {"offsetInBeginSection": 299, "offsetInEndSection": 471, "text": "Spillover events, which involve the physical transfer of viral particles across species, could therefore be directly promoted by conditions of host ecology and environment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29134435"}, {"offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Bats are the natural reservoir host for many pathogenic and non-pathogenic viruses, potentially spilling over to humans and domestic animals directly or via an intermediate host.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35537080"}, {"offsetInBeginSection": 438, "offsetInEndSection": 820, "text": "Here we aim to provide a synthetic explanation by arguing that domestication, horizontal gene transfer even between superkingdoms as well as gradual exchange of microbiome (microbiome succession) are essential in the whole scenario. We present a new perspective at the molecular level which can explain the observations of frequent pathogen spillover events at the ecological level.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37007505"}, {"offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "H5N1 highly pathogenic avian influenza viruses (HPAIV) emerged in wild birds in Chile in December 2022 and spilled over into poultry, marine mammals, and one human.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37786724"}, {"offsetInBeginSection": 0, "offsetInEndSection": 360, "text": "Forecasting the risk of pathogen spillover from reservoir populations of wild or domestic animals is essential for the effective deployment of interventions such as wildlife vaccination or culling. Due to the sporadic nature of spillover events and limited availability of data, developing and validating robust, spatially explicit, predictions is challenging.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33657095"}, {"offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Nipah virus is a zoonotic virus harbored by bats and lethal to humans. Bat-to-human spillovers occur every winter in Bangladesh.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29351657"}, {"offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "INTRODUCTION: The increasing incidence of pathogen transmission from animals to humans (zoonotic spillover events) has been attributed to behavioural practices and ecological and socioeconomic change.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36379648"}, {"offsetInBeginSection": 193, "offsetInEndSection": 370, "text": "In the simplest form of human exposure, spillover occurs from the enzootic cycle when humans enter zoonotic foci and/or enzootic amplification increases circulation near humans.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16358422"}, {"offsetInBeginSection": 735, "offsetInEndSection": 993, "text": "Some viruses, such as Rift Valley fever, Japanese encephalitis and Venezuelan equine encephalitis viruses (VEEV) undergo secondary amplification involving replication in livestock animals, resulting in greater levels of spillover to humans in rural settings.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16358422"}, {"offsetInBeginSection": 535, "offsetInEndSection": 699, "text": "Pathogen spillover occurs when epidemics in a host population are driven not by transmission within that population but by transmission from a reservoir population.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15540144"}, {"offsetInBeginSection": 433, "offsetInEndSection": 597, "text": "The detection of a virus in bats does not imply that spillover will occur and several biological, ecological and anthropogenic factors play a role in such an event.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32427175"}, {"offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Zoonotic spillover, which is the transmission of a pathogen from a vertebrate animal to a human, presents a global public health burden but is a poorly understood phenomenon.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28555073"}, {"offsetInBeginSection": 905, "offsetInEndSection": 1066, "text": "Further surveillance of spillover events is warranted to assess the emergence and potential onward transmission of mammalian adapted H5N1 HPAIV in South America.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37786724"}, {"offsetInBeginSection": 0, "offsetInEndSection": 437, "text": "Emerging infectious diseases have posed growing medical, social and economic threats to humanity. The biological background of pathogen spillover or host switch, however, still has to be clarified. Disease ecology finds pathogen spillovers frequently but struggles to explain at the molecular level. Contrarily, molecular biological traits of host-pathogen relationships with specific molecular binding mechanisms predict few spillovers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37007505"}, {"offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Zoonotic spillover is a phenomenon characterized by the transfer of pathogens between different animal species. Most human emerging infectious diseases originate from non-human animals, and human-related environmental disturbances are the driving forces of the emergence of new human pathogens.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36169531"}, {"offsetInBeginSection": 367, "offsetInEndSection": 554, "text": "Despite their importance, little is known about their enzootic cycles of transmission, amplifying hosts and vectors, and biotic and abiotic factors involved in spillover events to humans.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35632729"}, {"offsetInBeginSection": 107, "offsetInEndSection": 268, "text": "Molecular data suggest that spillover from other hosts may be responsible for the emergence of this infectious disease, but the scale of such studies is limited.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30096035"}, {"offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "The concept of environmental \"spillover\" of pathogens to humans is widely used in the scientific literature about emerging diseases with the idea that it is scientifically proven.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37321337"}, {"offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Zoonotic spillover is a phenomenon characterized by the transfer of pathogens between different animal species.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36169531"}, {"offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "For pathogens known to transmit across host species, strategic investment in disease control requires knowledge about where and when spillover transmission is likely.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31401965"}, {"offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Pathogen spillover between different host species is the trigger for many infectious disease outbreaks and emergence events, and ecosystem boundary areas have been suggested as spatial hotspots of spillover.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31401953"}, {"offsetInBeginSection": 281, "offsetInEndSection": 437, "text": "Investigating the processes that lead to spillover fundamentally involves interactions between animals, humans, pathogens and the environments they inhabit.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34018336"}]}
+{"question_id": "64467f8657b1c7a31500006d", "question": "How can Emery-Dreifuss Muscular Dystrophy (EDMD) be inherited?", "answer": "EDMD can be inherited in an X-linked recessive, autosomal dominant or autosomal recessive fashion.", "relevant_passage_ids": ["30506906", "28214269", "27179216", "21496632", "17567779", "10838246", "23349612", "17217858", "16550925", "12424964", "36897110", "37251241", "17013557", "22480903", "10732816", "10220866", "10080180", "10711990", "11731280", "1998333", "16585054", "37257496", "35607917", "10838245", "34026875", "9536090", "16804269", "23622360", "3203701", "8042665", "19021551", "11930270", "22555292", "10814726", "3417305", "31645980", "11470279", "11503164"], "type": "list", "snippets": [{"offsetInBeginSection": 207, "offsetInEndSection": 239, "text": "X-linked recessive EDMD patient ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30506906"}, {"offsetInBeginSection": 401, "offsetInEndSection": 713, "text": " Therefore, myoblast/fibroblast cultures from biopsy and tissue sections from a panel of nine Emery-Dreifuss muscular dystrophy patients (4 male, 5 female) including those carrying emerin and FHL1 (X-linked) and several lamin A (autosomal dominant) mutations were stained for the proteins linked to the disorder.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28214269"}, {"offsetInBeginSection": 373, "offsetInEndSection": 581, "text": "he majority of the EDMD cases described so far are of the emerinopathy (EDMD1) kind, with a recessive X-linked mode of inheritance, or else laminopathy (EDMD2), with an autosomal dominant mode of inheritance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27179216"}, {"offsetInBeginSection": 155, "offsetInEndSection": 429, "text": "EDMD is also distinctive for its association with defects of the cardiac conduction system that can result in sudden death. It can be inherited in an X-linked, autosomal dominant, or autosomal recessive fashion and is caused by mutations in proteins of the nuclear membrane.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21496632"}, {"offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "BACKGROUND: Emery-Dreifuss muscular dystrophy (EDMD2) is a rare form of muscular dystrophy that is inherited as an autosomal dominant trait.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36897110"}, {"offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Emery-Dreifuss muscular dystrophy (EDMD) is inherited in an X-linked or autosomal manner.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17217858"}, {"offsetInBeginSection": 90, "offsetInEndSection": 207, "text": "The inheritance pattern of Emery-Dreifuss muscular dystrophy (EDMD) is X linked, whereas EDMD2 is autosomal dominant.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23349612"}, {"offsetInBeginSection": 0, "offsetInEndSection": 581, "text": "Emery-Dreifuss muscular dystrophy (EDMD), a rare inherited disease, is characterized clinically by humero-peroneal muscle atrophy and weakness, multijoint contractures, spine rigidity and cardiac insufficiency with conduction defects. There are at least six types of EDMD known so far, of which five have been associated with mutations in genes encoding nuclear proteins. The majority of the EDMD cases described so far are of the emerinopathy (EDMD1) kind, with a recessive X-linked mode of inheritance, or else laminopathy (EDMD2), with an autosomal dominant mode of inheritance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27179216"}, {"offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Emery-Dreifuss muscular dystrophy (EDMD) is an inherited disorder affecting skeletal and cardiac muscles and characterized by muscular atrophy, contractures, and cardiomyopathy with conduction defects. It can be X-linked or autosomal.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22480903"}, {"offsetInBeginSection": 0, "offsetInEndSection": 503, "text": "Emery-Dreifuss muscular dystrophy is characterized by the clinical triad of early onset contractures of elbows, Achilles tendons and spine, wasting and weakness with a predominantly humero-peroneal distribution and life-threatening cardiac conduction defects and/or cardiomyopathy. Two main types of inheritance have been described: the X-linked form is caused by mutations in the STA gene on locus Xq28 and the gene for the autosomal dominant form (LMNA gene) has been localized on chromosome 1q11-q23.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11731280"}, {"offsetInBeginSection": 0, "offsetInEndSection": 359, "text": "Emery-Dreifuss muscular dystrophy (EDMD) is an inherited disorder characterized by slowly progressive skeletal muscle weakness in a humero-peroneal distribution, early contractures and prominent cardiomyopathy with conduction block. Mutations in EMD, encoding emerin, and LMNA, encoding A-type lamins, respectively, cause X-linked and autosomal dominant EDMD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17567779"}, {"offsetInBeginSection": 0, "offsetInEndSection": 577, "text": "Emery-Dreifuss muscular dystrophy (EDMD) is a muscular disorder characterized by 1) early contracture of the elbows. Achilles tendons and post-cervical muscles, 2) slowly progressive muscle wasting and weakness with a humeroperoneal distribution, and 3) life-threatening cardiomyopathy with conduction block. Most of families with EDMD show X-linked recessive inheritance with mutations in the STA gene on chromosome Xq28, which encodes a protein named emerin. A rare autosomal dominant form of EDMD (AD-EDMD) is caused by mutations in lamin A/C gene (LMNA) on chromosome 1q21.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12424964"}, {"offsetInBeginSection": 233, "offsetInEndSection": 359, "text": "Mutations in EMD, encoding emerin, and LMNA, encoding A-type lamins, respectively, cause X-linked and autosomal dominant EDMD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17567779"}, {"offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Activation of MAPK in hearts of EMD null mice: similarities between mouse models of X-linked and autosomal dominant Emery Dreifuss muscular dystro", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17567779"}, {"offsetInBeginSection": 223, "offsetInEndSection": 389, "text": "Autosomally inherited EDMD is caused by mutations in LMNA, which encodes A-type nuclear lamins, intermediate filament proteins associated with inner nuclear membrane.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17217858"}, {"offsetInBeginSection": 12, "offsetInEndSection": 139, "text": "Emery-Dreifuss muscular dystrophy (EDMD2) is a rare form of muscular dystrophy that is inherited as an autosomal dominant trait", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36897110"}, {"offsetInBeginSection": 0, "offsetInEndSection": 389, "text": "Emery-Dreifuss muscular dystrophy (EDMD) is inherited in an X-linked or autosomal manner. X-linked EDMD is caused by mutations in EMD, which encodes an integral protein of the nuclear envelope inner membrane called emerin. Autosomally inherited EDMD is caused by mutations in LMNA, which encodes A-type nuclear lamins, intermediate filament proteins associated with inner nuclear membrane.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17217858"}, {"offsetInBeginSection": 0, "offsetInEndSection": 950, "text": "Emery-Dreifuss muscular dystrophy (EDMD) is the third most common X-linked muscular dystrophy. This disorder is characterized by childhood onset of early contractures, humeroperoneal muscle atrophy, and cardiac conduction abnormalities. Weakness is slowly progressive, but there is a broad spectrum of clinical severity. Patients and carriers are at risk of sudden death. Regular cardiac evaluation is mandatory to assess the risk of cardiac arrhythmias. Unique atrial pathology is seen at autopsy. The mutated gene in EDMD is localized to the long arm of the X chromosome. Mutations in the gene lead to abolished synthesis of the gene product, emerin. Emerin is localized to the nuclear membrane of skeletal, cardiac, and smooth muscle. The term Emery-Dreifuss syndrome describes patients who have the EDMD phenotype without X-linked inheritance. There is no treatment for the underlying disease, but early placement of pacemakers may be lifesaving.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10711990"}, {"offsetInBeginSection": 0, "offsetInEndSection": 429, "text": "Emery-Dreifuss muscular dystrophy (EDMD) is a progressive muscle-wasting disorder defined by early contractures of the Achilles tendon, spine, and elbows. EDMD is also distinctive for its association with defects of the cardiac conduction system that can result in sudden death. It can be inherited in an X-linked, autosomal dominant, or autosomal recessive fashion and is caused by mutations in proteins of the nuclear membrane.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21496632"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1310, "text": "Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early contractures of elbows and Achilles tendons, slowly progressive muscle wasting and weakness, and a cardiomyopathy with conduction blocks which is life-threatening. Two modes of inheritance exist, X-linked (OMIM 310300) and autosomal dominant (EDMD-AD; OMIM 181350). EDMD-AD is clinically identical to the X-linked forms of the disease. Mutations in EMD, the gene encoding emerin, are responsible for the X-linked form. We have mapped the locus for EDMD-AD to an 8-cM interval on chromosome 1q11-q23 in a large French pedigree, and found that the EMD phenotype in four other small families was potentially linked to this locus. This region contains the lamin A/C gene (LMNA), a candidate gene encoding two proteins of the nuclear lamina, lamins A and C, produced by alternative splicing. We identified four mutations in LMNA that co-segregate with the disease phenotype in the five families: one nonsense mutation and three missense mutations. These results are the first identification of mutations in a component of the nuclear lamina as a cause of inherited muscle disorder. Together with mutations in EMD (refs 5,6), they underscore the potential importance of the nuclear envelope components in the pathogenesis of neuromuscular disorders.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10080180"}, {"offsetInBeginSection": 75, "offsetInEndSection": 253, "text": "One family presented a rare autosomal dominant variant of Emery-Dreifuss muscular dystrophy, another with X-linked recessive inheritance showed unusual intrafamilial variability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8042665"}, {"offsetInBeginSection": 372, "offsetInEndSection": 581, "text": "The majority of the EDMD cases described so far are of the emerinopathy (EDMD1) kind, with a recessive X-linked mode of inheritance, or else laminopathy (EDMD2), with an autosomal dominant mode of inheritance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27179216"}, {"offsetInBeginSection": 170, "offsetInEndSection": 302, "text": "Autosomal dominant EDMD caused by LMNA mutations is more common than the X-linked form and often more severe, with an earlier onset.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19021551"}, {"offsetInBeginSection": 575, "offsetInEndSection": 793, "text": "The most common etiology of autosomal dominant EDMD is an LMNA gene mutation; LMNA encodes the intermediate filament protein lamins A and C, which constitute the major scaffolding protein of the inner nuclear membrane.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21496632"}, {"offsetInBeginSection": 309, "offsetInEndSection": 460, "text": "Most of families with EDMD show X-linked recessive inheritance with mutations in the STA gene on chromosome Xq28, which encodes a protein named emerin.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12424964"}, {"offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Emery-Dreifuss muscular dystrophy (EDMD) is inherited in an X-linked or autosomal manner. X-linked EDMD is caused", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17217858"}, {"offsetInBeginSection": 0, "offsetInEndSection": 365, "text": "Emery-Dreifuss muscular dystrophy (EDMD) is a progressive muscle-wasting disorder defined by early contractures of the Achilles tendon, spine, and elbows. EDMD is also distinctive for its association with defects of the cardiac conduction system that can result in sudden death. It can be inherited in an X-linked, autosomal dominant, or autosomal recessive fashion", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21496632"}, {"offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Emery-Dreifuss muscular dystrophy (EDMD) is the third most common X-linked muscular dystrophy. This disorder is", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10711990"}, {"offsetInBeginSection": 235, "offsetInEndSection": 581, "text": "There are at least six types of EDMD known so far, of which five have been associated with mutations in genes encoding nuclear proteins. The majority of the EDMD cases described so far are of the emerinopathy (EDMD1) kind, with a recessive X-linked mode of inheritance, or else laminopathy (EDMD2), with an autosomal dominant mode of inheritance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27179216"}, {"offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "EDMD (Emery-Dreifuss muscular dystrophy) is caused by mutations in either the gene encoding for lamin A/C (LMNA) located at 1q21.2-q21.3 or emerin (EMD) located at Xq28. Autosomal dominant EDMD caused by LMNA mutations is more common than the X-linked form and often more severe, with an earlier onset.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19021551"}, {"offsetInBeginSection": 235, "offsetInEndSection": 612, "text": "Clinically indistinguishable X-linked and autosomal forms of EDMD have been described. Mutations in the STA gene, encoding the nuclear envelope protein emerin, are responsible for X-linked EDMD, while mutations in the LMNA gene encoding lamins A and C by alternative splicing have been found in patients with autosomal dominant, autosomal recessive, and sporadic forms of EDMD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11503164"}, {"offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "Emery-Dreifuss muscular dystrophy (EDMD) is a neuromuscular degenerative condition with an associated dilated cardiomyopathy and cardiac conduction defect. It can be inherited in either an X-linked or autosomal manner by mutations in the nuclear proteins emerin and lamin A/C, respectively. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17013557"}, {"offsetInBeginSection": 152, "offsetInEndSection": 398, "text": "Different subtypes of EDMD have been described, with the two most common forms represented by the X-linked EDMD1, caused by mutations in the EMD gene encoding emerin, and the autosomal EDMD2, due to mutations in the LMNA gene encoding lamin A/C. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37257496"}]}
+{"question_id": "65d12b451930410b13000031", "question": "Can valproate be used during pregnancy?", "answer": "No. Valproate is associated with high risk of malformations and should no be used during pregnancy.", "relevant_passage_ids": ["36433783", "36287388", "36401747", "37485793", "37294532", "36828241", "37684052", "38061552", "36381886", "18360539", "25400349", "19198722", "38062774", "35926210", "28953852", "21216127", "24161312", "27875769", "26329145", "11460259", "19892633", "3114906", "18062721"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1038, "offsetInEndSection": 1279, "text": "Compared to lamotrigine, there was an increased risk of malformations associated with valproate (n\u00a0=\u00a02,031, aRR\u00a0=\u00a02.05, 95% CI\u00a0=\u00a01.70-2.46) and topiramate (n\u00a0=\u00a0509, aRR\u00a0=\u00a01.81, 95% CI\u00a0=\u00a01.26-2.60), which increased in a dose-dependent manner.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36433783"}, {"offsetInBeginSection": 1509, "offsetInEndSection": 1860, "text": "Valproate was associated with several malformation subtypes, including nervous system, cardiac, oral clefts, clubfoot, and hypospadias, whereas lamotrigine and carbamazepine were not.INTERPRETATION: Topiramate is associated with an increased risk of MCM similar to that associated with valproate, but lower doses may mitigate the risks for both drugs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36433783"}, {"offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "INTRODUCTION: Prenatal exposure to valproate and related substances is associated with a risk of malformations and/or neurodevelopmental disorders.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36287388"}, {"offsetInBeginSection": 1647, "offsetInEndSection": 1793, "text": "Increased awareness and compliance among healthcare professionals regarding risk minimization measures could limit prenatal exposure to valproate.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36287388"}, {"offsetInBeginSection": 1792, "offsetInEndSection": 1947, "text": "CONCLUSIONS: Our proof-of-concept analysis based on GePaRD showed a strong association between intrauterine exposure to VPA and occurrence of spina bifida.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36401747"}, {"offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Proposal for reference values for the developmental effects of valproate based on human data using a benchmark dose approach.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36828241"}, {"offsetInBeginSection": 439, "offsetInEndSection": 598, "text": "Major congenital malformations (MCMs) in offsprings of mothers exposed to valproate during pregnancy have been reported in international scientific literature.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36828241"}, {"offsetInBeginSection": 739, "offsetInEndSection": 1112, "text": "Valproate, in monotherapy and polytherapy, has been associated with elevated risk of major congenital malformations and neurodevelopmental disorders in children born to mothers who took it. Topiramate and phenobarbital are also associated with elevated risks of congenital malformations and neurodevelopmental disorders, though the risks are lower than those of valproate. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37684052"}, {"offsetInBeginSection": 175, "offsetInEndSection": 385, "text": "Valproic acid (VPA), a widely prescribed first-line antiepileptic drug for epilepsy and various neurological conditions, has been associated with a 4-fold increase in the risk of NTDs when used during pregnancy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38062774"}, {"offsetInBeginSection": 747, "offsetInEndSection": 892, "text": "This finding suggests the need for reappraisal of the use of valproate in women who may become pregnant or are pregnant whilst the drug is taken.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18360539"}, {"offsetInBeginSection": 430, "offsetInEndSection": 499, "text": "Valproate of sodium should be avoided, if possible, during pregnancy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21216127"}, {"offsetInBeginSection": 453, "offsetInEndSection": 604, "text": "At valproate doses of 1400 mg and below per day, the mean rate of pregnancies with fetal malformations was 6.42% and did not seem to be dose-dependent.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18360539"}, {"offsetInBeginSection": 0, "offsetInEndSection": 332, "text": "Valproic acid (VPA, valproate, Depakote) is a commonly used anti-seizure medication (ASM) in the treatment of epilepsy and a variety of other neurological disorders. While VPA and other ASMs are efficacious for management of seizures, they also increase the risk for adverse pregnancy outcomes, including neural tube defects (NTDs).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35265619"}, {"offsetInBeginSection": 820, "offsetInEndSection": 1293, "text": "Sodium valproate is a known teratogen, and is discouraged in pregnancy, but what choice is open to women who rely on this medication to stabilise their mood?CONCLUSIONS: The large majority of women of childbearing age with bipolar disorder should not be prescribed sodium valproate as the risks to the unborn fetus far outweigh the benefits of the medication, as other drugs have similar if not better efficacy to stabilize the mother's mood, with lower risks to the fetus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28953852"}, {"offsetInBeginSection": 481, "offsetInEndSection": 598, "text": "The use of valproate is contraindicated during pregnancy due to teratogenicity and neurocognitive delay and deficits.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24161312"}, {"offsetInBeginSection": 764, "offsetInEndSection": 1278, "text": "Spina bifida is the only specific major congenital malformation significantly associated with exposure to Carbamazepine monotherapy Despite the small number of studies on the teratogenic effects of new antiepileptic drugs, the analysis of the literature shows that exposure of the fetus to the new antiepileptic drugs is associated with a lower risk of major congenital malformations compared to the use of older drugs.EXPERT OPINION: Where possible, Valproate should be avoided in women of childbearing potential.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26329145"}, {"offsetInBeginSection": 0, "offsetInEndSection": 443, "text": "BACKGROUND: The use of valproic acid during pregnancy has been associated with adverse fetal outcomes, including major and minor congenital malformations, intrauterine growth retardation (IUGR), hyperbilirubinemia, hepatotoxicity, transient hyperglycemia, and fetal and neonatal distress. In addition, intrauterine exposure to valproic acid has been associated with an increased risk of central nervous system abnormalities, primarily neural t", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11460259"}, {"offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "PURPOSE: Valproate is an effective wide-spectrum anti-epileptic drug that is also known to be teratogenic. Its administration in epileptic women remains contr", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27875769"}, {"offsetInBeginSection": 701, "offsetInEndSection": 812, "text": "Therefore, we strongly recommend avoidance of valproic acid and supplementation of folic acid during pregnancy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25400349"}, {"offsetInBeginSection": 810, "offsetInEndSection": 958, "text": "Therefore, we recommend that valproic acid must be avoided during pregnancy, as new generation of anticonvulsant drugs have emerged into the market.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19198722"}, {"offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "BACKGROUND: The use of valproic acid during pregnancy has been associated with adverse fetal outcomes, including major and minor congenital malformations, intrauterine growth retardation (IUGR), hyperbilirubinemia, hepatotoxicity, transient hyperglycemia, and fetal and neonat", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11460259"}, {"offsetInBeginSection": 238, "offsetInEndSection": 500, "text": "Women of childbearing age taking valproate should be warned of its teratogenicity and advised to plan pregnancies, take a higher dose of folate, discuss reducing the dose of valproate or changing the medication with their physician, and have antenatal screening.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19892633"}, {"offsetInBeginSection": 563, "offsetInEndSection": 844, "text": "It also includes the importance of awareness among middle-aged women with mental illness regarding the teratogenic effects of sodium valproate use and the relevance of discussion by physicians with patients regarding the usage of this drug despite being aware of the complications.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36381886"}, {"offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Sodium valproate is a teratogen responsible for a wide range of abnormalities, including neural tube defects.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19892633"}, {"offsetInBeginSection": 594, "offsetInEndSection": 958, "text": "Sodium valproate, a widely used anticonvulsant and mood regulator, is a well-recognized teratogen that can result in severe limb deformities, craniosynostosis, neural tube defects and neurodevelopmental retardation. Therefore, we recommend that valproic acid must be avoided during pregnancy, as new generation of anticonvulsant drugs have emerged into the market.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19198722"}, {"offsetInBeginSection": 489, "offsetInEndSection": 700, "text": "Sodium valproate, a widely used anticonvulsant and mood regulator, is a well-recognized teratogen that can result in facial dysmorphism, craniosynostosis, neural tube defects, and neurodevelopmental retardation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25400349"}, {"offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Valproic acid use during pregnancy results in an absolute risk for spina bifida of 1-2%. This increased risk is comparable to the recurrence risk for neural tube defects and warrants informed counselling and access to prenatal diagnosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3114906"}, {"offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Within several years after receiving U.S. Food and Drug Administration (FDA) approval in the late 1970s, valproate was shown to increase the risk for major congenital malformations and learning disabilities in the offspring of women who used the drug during pregnancy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35926210"}, {"offsetInBeginSection": 1034, "offsetInEndSection": 1152, "text": "The teratogenic effects of valproic acid appear to be dose dependent, with higher risks at dosage levels >1000 mg/day.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18062721"}]}
+{"question_id": "65f7725ec4010b4d78000020", "question": "Which dietary compounds are associated with colorectal cancer incidence?", "answer": "Red and red processed meat, lower intakes of dietary fiber and alcohol are associated with colorectal cancer incidence", "relevant_passage_ids": ["33591366", "34455534", "7576993", "29873077", "33596716", "21700901", "25954732", "37740374", "20400781", "12737716", "28205448", "24659930", "8381240", "17700421", "33410363", "8850441", "10422555", "23577027", "12718613"], "type": "list", "snippets": [{"offsetInBeginSection": 2093, "offsetInEndSection": 2288, "text": "This umbrella review found convincing evidence of an association between lower CRC risk and higher intakes of dietary fiber, dietary calcium, and yogurt and lower intakes of alcohol and red meat.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33591366"}, {"offsetInBeginSection": 1826, "offsetInEndSection": 2134, "text": "high red meat intake was positively\u00a0associated with risk of breast cancer, endometrial cancer,\u00a0colorectal cancer, colon cancer, rectal cancer, lung cancer, and hepatocellular carcinoma, and high processed meat intake was positively\u00a0associated with risk of breast, colorectal, colon,\u00a0rectal, and lung cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34455534"}, {"offsetInBeginSection": 2135, "offsetInEndSection": 2276, "text": "Higher risk of colorectal, colon, rectal, lung, and renal cell cancers were also observed with high total red and processed meat consumption.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34455534"}, {"offsetInBeginSection": 108, "offsetInEndSection": 326, "text": "Epidemiological studies have shown that a high fat (or meat) intake is associated positively and a high starch, fibre (non-starch polysaccharide), vegetable and fruit intake negatively with colorectal cancer incidence.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7576993"}, {"offsetInBeginSection": 156, "offsetInEndSection": 401, "text": "Consumption of high amounts of red and processed meat and low intake of fiber and multiple protective phytochemicals found in fruits, vegetables, and whole grains might be responsible for the high incidence of this neoplasm in the Western world.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24659930"}, {"offsetInBeginSection": 0, "offsetInEndSection": 2633, "text": "Although the etiology of colorectal cancer is multifactorial, experimental evidence suggests a role for dietary factors in the promotion of this disease. The complex interrelations governing energy balance and the consumption of fat, fiber, and micronutrients make it difficult to define the precise role of specific dietary factors in the etiology of colorectal neoplasms. Epidemiologic studies have demonstrated a correlation between the prevalence of colorectal cancer and per capita consumption of meat and fat. Case-control studies investigating the relation between colorectal cancer and dietary fat consumption have yielded inconsistent results. Prospective studies have failed to demonstrate a relation between fat consumption and subsequent risk for colorectal cancer. There is an inverse correlation between fiber intake and the prevalence of colorectal carcinoma. A more detailed analysis of the influence of various types of dietary fiber on the subsequent risk for colorectal cancer will provide a better understanding of this relation. Fiber derived from fruits and vegetables may provide more effective protection than cereal fibers. Correlational studies have established an association between total caloric intake and the prevalence of colorectal carcinoma. The design of future studies investigating the influence of individual dietary constituents on the risk for colorectal cancer must control for variations in energy balance as a confounding variable. Recent evidence suggests that a variety of micronutrients, including calcium, vitamin D, selenium, and vitamins A, C, and E, exert an anticarcinogenic effect. Studies designed to evaluate the influence of alcohol consumption on colorectal carcinogenesis have yielded inconclusive results. The potential influence of food preparation methods on colorectal carcinogenesis requires further evaluation. There is no conclusive evidence to support any of the hypotheses proposed to explain the role of dietary factors in colorectal carcinogenesis. Intervention trials designed to monitor intermediate markers for colorectal cancer such as increased epithelial-cell proliferation rates and the development of aberrant crypt architecture provide the opportunity for testing these hypotheses in relatively short-term studies. The results from such studies can be utilized in the design of large-scale, long-term prospective studies to evaluate the influence of dietary factors on the development of colorectal neoplasms. These trials should generate the information required to develop strategies for diet modification to reduce the incidence of colorectal carcinoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8381240"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1614, "text": "The association between diet and colorectal cancer has been studied in depth for many decades, with equivocal results. It has been hypothesized that cancers arising in the distal and proximal colon have different pathologies, and therefore different risk factors. As such, it is possible that diet-related factors might influence colorectal neoplasia differently depending on the subsite. Recent evidence indicates that women may be more likely to develop proximal cancers than men. Additionally, the link between certain dietary factors and colorectal neoplasia in women seems to vary by menopausal status. Given these observations, women may be affected differently than men by diet-related factors. The objective of this article was therefore to review the data for diet and colorectal adenomas and cancer, and then attempt to address the potential differences in the association of diet-related factors and colorectal neoplasia in men and women. For total energy intake, selenium, and fiber, it seems that there may be slightly stronger effects in men as compared with women, whereas calcium and folate seem to affect both sexes similarly. With regard to vitamin D and colorectal cancer, women may exhibit stronger associations than men. Perhaps the most evidence for a sex-specific effect is observed for obesity, where more substantial direct relationships between body size and colorectal neoplasia have been reported for men than for women. However, this observation may be influenced by the differential effects in women by menopausal status. Further research on sex-specific dietary effects is warranted.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17700421"}, {"offsetInBeginSection": 116, "offsetInEndSection": 321, "text": "Alcoholic beverages enhance the risk of cancer of the oral cavity, pharynx, larynx and oesophagus, while the relation is less well established for cancer in the stomach, pancreas, colon, rectum and breast.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10422555"}, {"offsetInBeginSection": 715, "offsetInEndSection": 928, "text": "For alcohol, there seems to be a stronger association with rectal cancer than with colon cancer, and for meat a somewhat stronger association with distal colon and rectal cancer, relative to proximal colon cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23577027"}, {"offsetInBeginSection": 443, "offsetInEndSection": 561, "text": "Further, meat consumption is associated with increased risk but this, too, is not explained solely by its fat content.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8850441"}, {"offsetInBeginSection": 1173, "offsetInEndSection": 1509, "text": "Incidences of colorectal cancer were positively associated with fat and oil intake, of both plant and animal types; a positive link was noted with animal protein but the association with plant protein consumption was inverse, as was also the case for carbohydrate and cereals; no simple association was evident with total energy intake.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12718613"}, {"offsetInBeginSection": 315, "offsetInEndSection": 602, "text": "The endogenous formation of N-nitroso compounds is a possible explanation because red and processed meat, but not white meat or fish, cause a dose-dependent increase in faecal ATNCs (apparent total N-nitroso compounds) and the formation of nitroso-compound-specific DNA adducts in humans", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17956350"}, {"offsetInBeginSection": 584, "offsetInEndSection": 921, "text": "High intakes of total lipid (ORT3 vs T1 = 4.15, 95% CI: 1.33-12.96, p for trend = 0.034), saturated fatty acid (ORT3 vs T1 = 2.96, 95% CI: 1.24-7.04, p for trend = 0.016) and monounsaturated fatty acid (ORT3 vs T1 = 3.04, 95% CI: 1.23-7.54, p for trend = 0.018) were significantly associated with increased incidence of colorectal cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25954732"}, {"offsetInBeginSection": 1721, "offsetInEndSection": 1867, "text": " eating a diet high in total lipid, saturated fatty acids and monounsaturated fatty acids is associated with higher incidence of colorectal cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25954732"}, {"offsetInBeginSection": 438, "offsetInEndSection": 937, "text": "In conjunction with obesity and physical inactivity, which induce a state of insulin resistance, certain dietary patterns that stimulate insulin secretion, including high intakes of red and processed meats, saturated and trans-fats, and highly processed carbohydrates and sugars, may increase the risk of colon cancer. There is evidence suggesting that some component of red meat may independently increase the risk of colorectal cancer, and some micronutrients may be important as protective agents", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12737716"}, {"offsetInBeginSection": 957, "offsetInEndSection": 1077, "text": ". Conversely, acidic food, reheated food, meat, spicy food, and alcohol are associated with the increment case of cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33410363"}, {"offsetInBeginSection": 751, "offsetInEndSection": 1026, "text": " Increased colorectal cancer risk regarding the lowest vs the highest intake quartile emerged for: vitamin B12 (3.41), cholesterol (3.15), total fat (2.87), saturated fat (1.98), animal protein (1.95), energy (1.85), alcohol (1.70), iron (1.49), refined carbohydrates (1.39).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15989062"}]}
+{"question_id": "65f494d7c4010b4d78000013", "question": "What is the relationship between  Electroporation (EP) and DNA vaccines?", "answer": "Electroporation (EP) is an effective way to increase the DNA vaccines immunogenicity.", "relevant_passage_ids": ["36992261", "38063059", "15110305", "19619001", "21180650", "38034030", "37860767", "17961089", "18847301", "21530212", "25535102", "18353952", "18989354", "24510831", "24510835", "22284894", "31174938", "36365078", "28646234", "29953259", "17239494", "21752954", "22644389", "22894954", "23684840", "20951666", "23085605"], "type": "factoid", "snippets": [{"offsetInBeginSection": 182, "offsetInEndSection": 260, "text": "Electroporation (EP) is an effective way to increase the immunogenicity of DNA", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38063059"}, {"offsetInBeginSection": 228, "offsetInEndSection": 378, "text": "n this study, we challenged this concept by characterizing the immunological response induced by a plasmid DNA vaccine delivered using electroporation", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36992261"}, {"offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Intradermal delivery of DNA vaccines via electroporation (ID-EP) has shown clinical promise, but the use of needle electrodes is typically required to achieve consistent results", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38034030"}, {"offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "In vivo electroporation (EP) has been shown to augment the immunogenicity of plasmid DNA vaccines, but its mechanism of action has not been fully characterized.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18353952"}, {"offsetInBeginSection": 1445, "offsetInEndSection": 1559, "text": "These data establish EP as a potent method for stimulating humoral responses induced by DNA vaccination in humans.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19619001"}, {"offsetInBeginSection": 432, "offsetInEndSection": 655, "text": "Electroporation (EP), a promising approach that dramatically enhances expression of the encoded antigen as well as the potency and immunogenicity of DNA vaccines, could facilitate clinical implementation of DNA vaccination.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17961089"}, {"offsetInBeginSection": 207, "offsetInEndSection": 347, "text": "Electroporation (EP) has emerged as an effective method for delivering DNA vaccines, significantly enhancing humoral and cellular responses.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15110305"}, {"offsetInBeginSection": 639, "offsetInEndSection": 865, "text": "DNA Electroporation may prove to be the \"missing link\" in the evolution of DNA vaccines allowing for enhanced immune responses from DNA vaccination in humans thereby resulting in protection from disease post-pathogen exposure.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24510831"}, {"offsetInBeginSection": 809, "offsetInEndSection": 919, "text": "In vivo EP has the key features of improved DNA uptake, increased antigen expression and a local inflammation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21180650"}, {"offsetInBeginSection": 256, "offsetInEndSection": 717, "text": "DNA vaccines have been proposed as a promising approach for introducing foreign antigens into the host for inducing protective immunity against infectious and cancer diseases. Nevertheless, because of their poor immunogenicity, plasmid DNA vaccination strategies need further implementations. Recent data suggest electrotransfer as a useful tool to improve DNA-based vaccination protocols, being able to stimulate both the humoral and cellular immune responses.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24510835"}, {"offsetInBeginSection": 310, "offsetInEndSection": 561, "text": "Importantly, EP dramatically enhanced the neutralizing potency of the humoral response, since antibodies induced by low DNA dose (10 \u03bcg) were able to highly neutralize DHBV and to recognize ten antigenic regions, including four neutralization epitopes", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22284894"}, {"offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "In vivo electroporation of plasmid DNA (DNA-EP) is an efficient and safe method for vaccines resulting in increased DNA uptake, enhanced protein expression and increased immune responses to the target antigen in a variety of species.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18989354"}, {"offsetInBeginSection": 232, "offsetInEndSection": 488, "text": "Herein, we report a screening system based on DNA vaccines and a micro-electroporation/electrophoresis system (MEES), which greatly improved the efficacy of DNA vaccines, elevating humoral and cellular immune responses by over 400- and 35-fold respectively", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37860767"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1010, "text": "Electroporation can improve intramuscular DNA vaccination efficacy but the exact antigen presentation mechanism remains unclear. We reported here that a similar immuno-potentiation effect was also observed by stimulating the skeletal muscles with electric pulses (EP) a few days prior to DNA inoculation (EP + n days + DNA). The application of EP by itself activated proinflammatory chemokine genes and stress genes. It also triggered an influx of inflammatory monocytes/macrophages (MPs). After DNA inoculation, the plasmids were seen taken up by these inflammatory MPs, which migrated to the draining LNs subsequently. The antibody responses results were fast and strong. Furthermore, MPs isolated from the draining LNs of EP + n days + DNA treated mice were capable of stimulating Ag specific CD4+ T cell proliferation in vitro. Based on these observations, we proposed that the local inflammation resulted from EP treatment played an important role in facilitating antigen presentation of the DNA vaccines.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17239494"}, {"offsetInBeginSection": 209, "offsetInEndSection": 642, "text": "One of the uses of EP in vivo is plasmid DNA electrotransfer to the skin for DNA vaccination. EP of tissues induces reduction of blood flow and, in combination with plasmid DNA, induction of an immune response. One of the EP protocols for plasmid DNA electrotransfer to the skin is a combination of high-voltage (HV) and low-voltage (LV) pulses. However, the effects of this pulse combination on skin-vessel blood flow are not known.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22644389"}, {"offsetInBeginSection": 0, "offsetInEndSection": 357, "text": "In vivo electroporation (EP) is used to enhance the uptake of nucleic acids and its association with DNA vaccination greatly stimulates immune responses to vaccine antigens delivered through the skin. However, the effect of EP on cutaneous cell behavior, the dynamics of immune cell recruitment and local inflammatory factors, have not been fully described.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28646234"}, {"offsetInBeginSection": 84, "offsetInEndSection": 484, "text": "Recent delivery techniques such as the gene gun and in vivo electroporation (EP)/electrotransfer (ET) have completely changed the efficiency of DNA vaccines in humans. In vivo EP exerts multiple effects that contribute to its efficiency. The two central factors are most likely the increased DNA uptake due to the transient membrane destabilization, and the local tissue damage acting as an adjuvant.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25535102"}, {"offsetInBeginSection": 0, "offsetInEndSection": 661, "text": "Non-viral in vivo administration of plasmid DNA for vaccines and immunotherapeutics has been hampered by inefficient delivery. Methods to enhance delivery such as in vivo electroporation (EP) have demonstrated effectiveness in circumventing this difficulty. However, the contact-dependent nature of EP has resulting side effects in animals and humans. Noncontact delivery methods should, in principle, overcome some of these obstacles. This report describes a helium plasma-based delivery system that enhanced humoral and cellular antigen-specific immune responses in mice against an intradermally administered HIV gp120-expressing plasmid vaccine (pJRFLgp120).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22894954"}, {"offsetInBeginSection": 0, "offsetInEndSection": 529, "text": "The immune responses elicited following delivery of DNA vaccines to the skin has previously been shown to be significantly enhanced by the addition of electroporation (EP) to the treatment protocol. Principally, EP increases the transfection of plasmid DNA (pDNA) into the resident skin cells. In addition to increasing the levels of in vivo transfection, the physical insult induced by EP is associated with activation of innate pathways which are believed to mediate an adjuvant effect, further enhancing DNA vaccine responses.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29953259"}, {"offsetInBeginSection": 262, "offsetInEndSection": 583, "text": "Electroporation (EP) is an effective way to enhance the immunogenicity of DNA vaccines, but because of the different configurations of the devices that are used for EP, it is necessary to carefully select the conditions of the procedure, including characteristics such as voltage, current strength, number of pulses, etc.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36365078"}, {"offsetInBeginSection": 188, "offsetInEndSection": 1039, "text": "Our laboratory has been evaluating DNA plasmid based Pfs25 vaccine in mice and non-human primates. Previously, we established that in vivo electroporation (EP) delivery is an effective method to improve the immunogenicity of DNA vaccine encoding Pfs25 in mice. In order to optimize the in vivo EP procedure and test for its efficacy in more clinically relevant larger animal models, we employed in vivo EP to evaluate the immune response and protective efficacy of Pfs25 encoding DNA vaccine in nonhuman primates (olive baboons, Papio anubis). The results showed that at a dose of 2.5mg DNA vaccine, antibody responses were significantly enhanced with EP as compared to without EP resulting in effective transmission blocking efficiency. Similar immunogenicity enhancing effect of EP was also observed with lower doses (0.5mg and 1mg) of DNA plasmids.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23684840"}, {"offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "The immune responses elicited following delivery of DNA vaccines to the skin has previously been shown to be significantly enhanced by the addition of electroporation (EP) to the treatment protocol.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29953259"}, {"offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "In vivo electroporation (EP) has proven to significantly increase plasmid transfection efficiency and to augment immune responses after immunization with plasmids.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21752954"}, {"offsetInBeginSection": 193, "offsetInEndSection": 404, "text": "Two main strategies to increase DNA-based vaccine potency are the employment of immuno-adjuvants such as heat shock proteins (HSPs) and a method of improving the delivery of naked plasmid DNA by electroporation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23085605"}, {"offsetInBeginSection": 294, "offsetInEndSection": 529, "text": "In addition to increasing the levels of in vivo transfection, the physical insult induced by EP is associated with activation of innate pathways which are believed to mediate an adjuvant effect, further enhancing DNA vaccine responses.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29953259"}, {"offsetInBeginSection": 88, "offsetInEndSection": 329, "text": "electroporation (EP) has been shown to generate potent and efficacious immune responses in the clinic. Needle-free jet injection has also been reported to improve DNA vaccine delivery over standard needle and syringe in clinical trials. Here", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31174938"}, {"offsetInBeginSection": 460, "offsetInEndSection": 685, "text": "Of these, EP mediated delivery has generated considerable enthusiasm and appears to have had a great impact in vaccine immunogenicity and efficacy by increasing antigen delivery upto a 1000 fold over naked DNA delivery alone.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21530212"}, {"offsetInBeginSection": 477, "offsetInEndSection": 818, "text": "One novel in vivo delivery method for plasmid vaccines is electroporation, which is the application of short pulses of electric current immediately after, and at the site of, an injection of a genetic vaccine. This method has been shown to significantly augment the transfection efficacy and the subsequent vaccine-specific immune responses.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20951666"}, {"offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Electroporation of skeletal muscle induces danger signal release and antigen-presenting cell recruitment independently of DNA vaccine administration.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18847301"}, {"offsetInBeginSection": 1, "offsetInEndSection": 177, "text": "ecruitment of antigen-presenting cells to the site of inoculation and augmentation of human immunodeficiency virus type 1 DNA vaccine immunogenicity by in vivo electroporation.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18353952"}]}
+{"question_id": "65f84d20c4010b4d7800004a", "question": "Is measles immunisation the best public health approach to reduce incidence of measles worldwide?", "answer": "Measles immunisation is considered to be the best public health approach to reduce the incidence of measles worldwide.", "relevant_passage_ids": ["36680212", "37971951", "28673424", "34953518", "34590128", "28646947", "22298303", "8034506", "21855993", "31009080", "36414136", "3811010", "31622151", "12721887", "33303011", "28966000", "26562349", "11435120", "30156949", "2867355", "26065443"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1540, "offsetInEndSection": 1713, "text": "renewing efforts to vaccinate all children with 2 MCV doses and strengthening surveillance, thereby preventing outbreaks and accelerating progress toward measles elimination", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971951"}, {"offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "Measles is a highly contagious, vaccine-preventable disease", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971951"}, {"offsetInBeginSection": 1087, "offsetInEndSection": 1170, "text": "an estimated 57 million measles deaths were averted by vaccination during 2000-2022", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971951"}, {"offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Measles is a highly contagious, but vaccine-preventable disease", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36680212"}, {"offsetInBeginSection": 108, "offsetInEndSection": 223, "text": "the administration of two doses of measles vaccines is the most effective strategy to prevent and eliminate measles", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36680212"}, {"offsetInBeginSection": 1029, "offsetInEndSection": 1205, "text": "The use of early measles vaccination at 4 months of age could be an effective strategy to prevent severe morbidity and death from both measles and RSV infections in many LMICs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34953518"}, {"offsetInBeginSection": 619, "offsetInEndSection": 795, "text": "Measles is best prevented through vaccination, and the major reductions in measles incidence and mortality have renewed interest in regional elimination and global eradication.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28673424"}, {"offsetInBeginSection": 77, "offsetInEndSection": 307, "text": "Since 2000, vaccination campaigns against measles, which is highly contagious but preventable through the measles-mumps-rubella (MMR) vaccine, have reduced both the global incidence of the disease and measles deaths by 80 percent.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31009080"}, {"offsetInBeginSection": 417, "offsetInEndSection": 557, "text": "In other parts of the world the incidence of this disease has been dramatically reduced following effective measles immunisation programmes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3811010"}, {"offsetInBeginSection": 420, "offsetInEndSection": 512, "text": "This achievement attests to the enormous importance of measles vaccination to public health.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21855993"}, {"offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "Measles is a highly contagious disease that results from infection with measles virus and is still responsible for more than 100\u2008000 deaths every year, down from more than 2 million deaths annually before the introduction and widespread use of measles vaccine.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28673424"}, {"offsetInBeginSection": 1461, "offsetInEndSection": 1586, "text": "This highly effective and well-tolerated vaccine has greatly reduced the number of measles cases and saved millions of lives.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36414136"}, {"offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Worldwide during the 1980s remarkable progress was made in controlling measles through increasing routine measles vaccination to nearly 80%.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12721887"}, {"offsetInBeginSection": 1422, "offsetInEndSection": 1590, "text": "Measles immunization has dramatically reduced measles occurrence, but improved control is necessary to prevent the estimated 1 million deaths still occurring each year.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8034506"}, {"offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "The global measles vaccination program has been extraordinarily successful in reducing measles-related disease and deaths worldwide.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34590128"}, {"offsetInBeginSection": 722, "offsetInEndSection": 946, "text": "Routine immunization with MCV has been the cornerstone for the control and prevention of measles. Two doses of MCV are 97% effective in preventing measles, qualifying MCV as one of the most effective vaccines ever developed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34590128"}, {"offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "BACKGROUND: Measles is a highly contagious and serious infection. Before the introduction of vaccination, measles caused yearly epidemics putting vulnerable children at risk of brain damage and death. Despite safe and cost-effective vaccines, measles remains a leading cause of death in childr", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33303011"}, {"offsetInBeginSection": 0, "offsetInEndSection": 497, "text": "INTRODUCTION: One of the goals of the Global Measles and Rubella Strategic Plan is the reduction in global measles mortality, with high measles vaccination coverage as one of its core components. While measles mortality has been reduced more than 79%, the disease remains a major cause of childhood vaccine preventable disease burden globally. Measles immunization requires a two-dose schedule and only countries with strong, stable immunization programs can rely on routine services to deliver th", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28966000"}, {"offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "In 2000, the United Nations General Assembly adopted the Millennium Development Goals (MDG), with MDG4 being a two-thirds reduction in child mortality by 2015, and with measles vaccination coverage being one of the three indicators of progress toward this goal.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26562349"}, {"offsetInBeginSection": 118, "offsetInEndSection": 481, "text": "In 2001, to accelerate the reduction in measles cases achieved by vaccination, the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) developed a strategy to deliver 2 doses of measles-containing vaccine (MCV) to all children through routine services and supplementary immunization activities (SIAs) and improved disease surveillance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22298303"}, {"offsetInBeginSection": 357, "offsetInEndSection": 528, "text": "Health care and community collaboration led to coverage rates of measles vaccination increasing from 80% to 95% within three months and a significant decline in incidence.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31622151"}, {"offsetInBeginSection": 241, "offsetInEndSection": 419, "text": "Remarkable progress in reducing the number of people dying from measles has been made through measles vaccination, with an estimated 164,000 deaths attributed to measles in 2008.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21855993"}, {"offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "An immunisation programme to eliminate measles, mumps, and rubella from Finland within 10 years was", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2867355"}, {"offsetInBeginSection": 220, "offsetInEndSection": 401, "text": "Measles vaccination programs have been among the greatest public health achievements reducing, eliminating endemic measles in the whole of the Americas and across much of the globe.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28646947"}, {"offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "Vaccination is one of history's most successful public health interventions. Since 2000, vaccination campaigns against measles, which is highly contagious but preventable through the measles-mumps-rubella (MMR) vaccine, have reduced both the global incidence of the disease and measles deaths by 80 percent.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31009080"}, {"offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Increased measles immunization has led to a significant decline in measles incidence and mortality.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30156949"}, {"offsetInBeginSection": 251, "offsetInEndSection": 358, "text": "The incidence of measles worldwide has decreased dramatically since the introduction of effective vaccines.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11435120"}, {"offsetInBeginSection": 820, "offsetInEndSection": 946, "text": "Two doses of MCV are 97% effective in preventing measles, qualifying MCV as one of the most effective vaccines ever developed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34590128"}, {"offsetInBeginSection": 1207, "offsetInEndSection": 1409, "text": "Because measles is one of the most contagious human diseases, maintenance of high (\u226595%) 2-dose MCV coverage is crucial for controlling the spread of measles and successfully reaching measles eliminatio", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34590128"}, {"offsetInBeginSection": 786, "offsetInEndSection": 961, "text": "Strengthening immunization programs and keeping vaccination coverage rates above 95% with a two-dose schedule will be necessary for measles control strategies in the Americas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26065443"}]}
+{"question_id": "64179034690f196b5100002b", "question": "What type of DMD can golodirsen be used for?", "answer": "Patients with a confirmed mutation of the DMD gene that is amenable to exon 53 skipping.", "relevant_passage_ids": ["32026421", "33025945", "33407808", "30171533", "36401027", "34788571", "32483212", "32139505", "32947786", "34092651"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Golodirsen (Vyondys 53\u2122), an antisense oligonucleotide of the phophorodiamidate morpholino oligomer (PMO) subclass designed to induce exon 53 skipping", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32026421"}, {"offsetInBeginSection": 251, "offsetInEndSection": 455, "text": "In December 2019, intravenous golodirsen received its first global approval in the USA for the treatment of DMD in patients with a confirmed mutation of the DMD gene that is amenable to exon 53 skipping, ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32026421"}, {"offsetInBeginSection": 332, "offsetInEndSection": 505, "text": "Two exon 53 skipping PMOs, golodirsen and viltolarsen, have received conditional approval for treating patients due to their ability to restore dystrophin protein expression", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36401027"}, {"offsetInBeginSection": 377, "offsetInEndSection": 482, "text": "Eteplirsen and golodirsen, AONs for DMD exons 51 and 53 skipping, have been recently approved by the FDA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32483212"}, {"offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "Golodirsen (Vyondys 53\u2122), an antisense oligonucleotide of the phophorodiamidate morpholino oligomer (PMO) subclass designed to induce exon 53 skipping, has been developed by Sarepta Therapeutics for the treatment of Duchenne muscular dystrophy (DMD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32026421"}, {"offsetInBeginSection": 251, "offsetInEndSection": 514, "text": "In December 2019, intravenous golodirsen received its first global approval in the USA for the treatment of DMD in patients with a confirmed mutation of the DMD gene that is amenable to exon 53 skipping, based on positive results from a phase I/II clinical trial.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32026421"}, {"offsetInBeginSection": 351, "offsetInEndSection": 649, "text": "Antisense-mediated exon skipping is most extensively studied in Duchenne muscular dystrophy (DMD) and has developed from in vitro proof-of-concept studies to clinical trials targeting various single exons such as exon 45 (casimersen), exon 53 (NS-065/NCNP-01, golodirsen), and exon 51 (eteplirsen).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30171533"}, {"offsetInBeginSection": 332, "offsetInEndSection": 506, "text": "Two exon 53 skipping PMOs, golodirsen and viltolarsen, have received conditional approval for treating patients due to their ability to restore dystrophin protein expression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36401027"}, {"offsetInBeginSection": 783, "offsetInEndSection": 901, "text": "Golodirsen is a provisionally approved PMO-based drug for approx. 8% of all DMD patients amenable to exon 53 skipping.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33025945"}, {"offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "The aim of this Phase 1/2, 2-part, multicenter trial was to report clinical safety and efficacy of long-term golodirsen treatment among ambulatory patients with exon 53 skip-amenable Duchenne muscular dystrophy (DMD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34788571"}, {"offsetInBeginSection": 0, "offsetInEndSection": 352, "text": "OBJECTIVE: To report safety, pharmacokinetics, exon 53 skipping, and dystrophin expression in golodirsen-treated patients with Duchenne muscular dystrophy (DMD) amenable to exon 53 skipping.METHODS: Part 1 was a randomized, double-blind, placebo-controlled, 12-week dose titration of once-weekly golodirsen; part 2 is an ongoing, open-label evaluation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32139505"}, {"offsetInBeginSection": 1259, "offsetInEndSection": 1982, "text": "Sarcolemmal localization of dystrophin was demonstrated by significantly increased dystrophin-positive fibers (week 48, p < 0.001) and a positive correlation (Spearman r = 0.663; p < 0.001) with dystrophin protein change from baseline, measured by Western blot and immunohistochemistry.CONCLUSION: Golodirsen was well-tolerated; muscle biopsies from golodirsen-treated patients showed increased exon 53 skipping, dystrophin production, and correct dystrophin sarcolemmal localization.CLINICALTRIALSGOV IDENTIFIER: NCT02310906.CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that golodirsen is safe and Class IV evidence that it induces exon skipping and novel dystrophin as confirmed by 3 different assays.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32139505"}, {"offsetInBeginSection": 109, "offsetInEndSection": 285, "text": "golodirsen treatment among ambulatory patients with exon 53 skip-amenable Duchenne muscular dystrophy (DMD). Part 1 was a 12-week, randomized, double-blind, placebo-controlled,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34788571"}, {"offsetInBeginSection": 207, "offsetInEndSection": 386, "text": "DMD gene. In particular, PMOs for skipping exon 44 have been developing in clinical trials, such as the drug NS-089/NCNP-02. Two exon 53 skipping PMOs, golodirsen and viltolarsen,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36401027"}, {"offsetInBeginSection": 898, "offsetInEndSection": 1078, "text": "Very recently, golodirsen and viltolarsen, for treatment of DMD patients amenable to skipping exon 53, have been approved by regulatory agencies in the USA and Japan, respectively.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34092651"}, {"offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "OBJECTIVE: To report safety, pharmacokinetics, exon 53 skipping, and dystrophin expression in golodirsen-treated patients with Duchenne muscular dystrophy (DMD) amenable to exon 5", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32139505"}, {"offsetInBeginSection": 330, "offsetInEndSection": 544, "text": "However, several new personalized therapies, including antisense oligonucleotides eteplirsen for DMD exon 51 skipping and golodirsen and viltolarsen for DMD exon 53 skipping, have been approved in the last 4 years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32947786"}]}
+{"question_id": "65d137871930410b1300003e", "question": "What are active ingredients of Trikafta?", "answer": "Trikafta includes elexacaftor/tezacaftor/ivacaftor.", "relevant_passage_ids": ["36653239", "37503734", "37222401", "36831163", "34026156", "34356748", "32853178", "34357110", "31784874", "33775603", "35021019"], "type": "list", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "The combination of CFTR modulators ivacaftor, tezacaftor and elexacaftor (Trikafta\u00ae, Kaftrio\u00ae) significantly improve outcomes, including survival in a broad range of cystic fibrosis patients. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36653239"}, {"offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "CONTEXT: Elexacaftor/Tezacaftor/Ivacaftor (ETI; Trikafta\u2122) enhances aberrant cystic fibrosis transmembrane conductance regulator (CFTR) function and may improve the insulin secretory defects associated with a deterioration in clinical outcomes in pancreatic insufficient cystic fibrosis (PI-CF).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37503734"}, {"offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "INTRODUCTION: A triple combination of CFTR modulators ELE/TEZ/IVA (elexacaftor/tezacaftor/ivacaftor, Trikafta\u2122) has been evaluated in clinical trials for people with cystic fibrosis (pwCF) and was approved to the European and US market. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37222401"}, {"offsetInBeginSection": 1128, "offsetInEndSection": 1408, "text": "The method has been validated following international (EMA) guidelines for bioanalytical method validation and has been tested on plasma samples from 62 CF patients treated with the three-drug combination IVA/TEZ/ELX, marketed as Kaftrio\u00ae or Trikafta\u00ae, in steady-state condition. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36831163"}, {"offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Trikafta, a triple-combination drug, consisting of folding correctors VX-661 (tezacaftor), VX-445 (elexacaftor) and the gating potentiator VX-770 (ivacaftor) provided unprecedented clinical benefits for patients with the most common cystic fibrosis (CF) mutation, F508del.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34357110"}, {"offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Allosteric folding correction of F508del and rare CFTR mutants by elexacaftor-tezacaftor-ivacaftor (Trikafta) combination.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32853178"}, {"offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Trikafta, the combination of elexacaftor (VX-445), tezacaftor (VX-661) and ivacaftor (VX-770), was approved for therapy of cystic fibrosis (CF) patients with at least one allele of the CFTR mutation F508del.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33775603"}, {"offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "We present a novel case of an urticaria multiforme-type drug reaction to the new cystic fibrosis medication Trikafta (elexacaftor + tezacaftor + ivacaftor).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34026156"}, {"offsetInBeginSection": 0, "offsetInEndSection": 313, "text": "The new CFTR modulator combination, elexacaftor/tezacaftor/ivacaftor (Trikafta) was approved by the FDA in October 2019 for treatment of Cystic Fibrosis in patients 6 years of age or older who have at least one F508del mutation in one allele and a minimal-function or another F508del mutation in the other allele.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34356748"}, {"offsetInBeginSection": 0, "offsetInEndSection": 356, "text": "The combination of CFTR modulators ivacaftor, tezacaftor and elexacaftor (Trikafta\u00ae, Kaftrio\u00ae) significantly improve outcomes, including survival in a broad range of cystic fibrosis patients. These drugs have complicated metabolic profiles that make the potential for drug interactions an important consideration for prescribers, care providers and patient", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36653239"}, {"offsetInBeginSection": 0, "offsetInEndSection": 891, "text": "CONTEXT: Elexacaftor/Tezacaftor/Ivacaftor (ETI; Trikafta\u2122) enhances aberrant cystic fibrosis transmembrane conductance regulator (CFTR) function and may improve the insulin secretory defects associated with a deterioration in clinical outcomes in pancreatic insufficient cystic fibrosis (PI-CF).OBJECTIVE: This longitudinal case-control study assessed changes in \u03b2-cell function and secretory capacity measures over two visits in individuals with PI-CF who were initiated on ETI after the baseline visit (2012-2018) and 1) restudied between 2019-2021 (ETI group) vs. 2) those restudied between 2015-2018 and not yet treated with CFTR modulator therapy (controls).METHODS: Nine ETI participants (mean\u2009\u00b1\u2009SD age 25\u2009\u00b1\u20095 years) and eight matched controls were followed up after median(IQR) 5(4-7) and 3(2-3) years, respectively (p\u2009<\u20090.01), with ETI initiation a median of 1 year before follow-up.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37503734"}, {"offsetInBeginSection": 0, "offsetInEndSection": 402, "text": "A fixed-dose combination tablet of the cystic fibrosis transmembrane conductance regulator (CFTR) corrector tezacaftor and the CFTR potentiator ivacaftor with the next-generation CFTR corrector elexacaftor (hereafter referred to as elexacaftor/ivacaftor/tezacaftor) [Trikafta\u2122] has been developed by Vertex Pharmaceuticals Inc. to treat patients with the most common cystic fibrosis mutation (F508del).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31784874"}, {"offsetInBeginSection": 0, "offsetInEndSection": 376, "text": "Based on its clinical benefits, Trikafta - the combination of folding correctors VX-661 (tezacaftor), VX-445 (elexacaftor), and the gating potentiator VX-770 (ivacaftor) - was FDA approved for treatment of patients with cystic fibrosis (CF) carrying deletion of phenylalanine at position 508 (F508del) of the CF transmembrane conductance regulator (CFTR) on at least 1 allele.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32853178"}, {"offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "The combination of CFTR modulators ivacaftor, tezacaftor and elexacaftor (Trikafta\u00ae, Kaftrio\u00ae) significantly improve outcomes, including survival in a broad range of cystic fibrosis patient", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36653239"}, {"offsetInBeginSection": 32, "offsetInEndSection": 169, "text": "Trikafta - the combination of folding correctors VX-661 (tezacaftor), VX-445 (elexacaftor), and the gating potentiator VX-770 (ivacaftor)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32853178"}, {"offsetInBeginSection": 261, "offsetInEndSection": 409, "text": "pyrin domain-containing protein 3) inflammasome. Objectives: To explore the effect of the CFTR modulator elexacaftor/tezacaftor/ivacaftor (Trikafta)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35021019"}]}
+{"question_id": "65f77397c4010b4d78000025", "question": "What proportion of alteration in NTRK genes are attributable to colorectal cancer?", "answer": "In common cancers, rates were consistently below 0.5%. Rare morphological subtypes, colorectal microsatellite instability, and driver mutation exclusion cancers had higher rates.", "relevant_passage_ids": ["36914665", "28174090", "36041373", "34402529", "31567189", "36077692"], "type": "factoid", "snippets": [{"offsetInBeginSection": 975, "offsetInEndSection": 1154, "text": " In common cancers, rates were consistently below 0.5%. Rare morphological subtypes, colorectal microsatellite instability, and driver mutation exclusion cancers had higher rates.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36914665"}, {"offsetInBeginSection": 1241, "offsetInEndSection": 1456, "text": "The proportion of patients with targets for genetically matched therapies differed among subtypes (salivary duct carcinoma: 82%, adenoid cystic carcinoma 28%, mucoepidermoid carcinoma 50%, acinic cell carcinoma 33%)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36077692"}, {"offsetInBeginSection": 782, "offsetInEndSection": 935, "text": "Of 15,223 patients analyzed, 38 (0.25%) had NTRK gene fusions in 11 tumor types, the most common were breast cancer, colorectal cancer (CRC), and sarcoma", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36041373"}, {"offsetInBeginSection": 945, "offsetInEndSection": 1135, "text": "TRK positivity was observed in 11 of 58 (19%) MLH1-methylated MSI-high CRCs, 4 of 23 (17%) sessile serrated lesions with dysplasia (SSLDs), and 5 of 132 (4%) sessile serrated lesions (SSLs).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34402529"}, {"offsetInBeginSection": 772, "offsetInEndSection": 1020, "text": "colorectal cancers, prevalence of the NTRK fusions is well below 5%. Selective inhibition of TRK signaling may therefore be beneficial among patients whose tumors vary in histologies, but share underlying oncogenic NTRK gene alterations. Currently,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28174090"}, {"offsetInBeginSection": 188, "offsetInEndSection": 298, "text": "Of the 7008 tumors screened for NTRK expression using a pan-Trk antibody, 16 (0.23%) had Trk immunoreactivity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31567189"}]}
+{"question_id": "65f1d234c4010b4d78000005", "question": "Please list the Janus Kinase inhibitors used to treat Inflammatory Bowel Disease(IBD)", "answer": "Several small-molecule JAK inhibitors (JAKis) including abrocitinib, baricitinib, filgotinib,  peficitinib, tofacitinib, risankizumab upadacitinib, deucavacitinib are now approved for the treatment of various immune-mediated inflammatory diseases.", "relevant_passage_ids": ["36936239", "36515243", "36913180", "37004800", "37855324", "37036140", "29938545", "26608188", "32873116", "35505771", "37226522", "37977068", "29225517", "33207299", "34089259", "31227590", "32440190", "31879750", "35018293", "34884361", "35300073", "37480322"], "type": "list", "snippets": [{"offsetInBeginSection": 1073, "offsetInEndSection": 1323, "text": "Although there are currently no approved JAK inhibitors for Crohn's disease, upadacitinib and filgotinib have shown increased remission rates in these patients. Other JAK inhibitors, including gut-selective molecules, are currently being studied IBD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36936239"}, {"offsetInBeginSection": 1, "offsetInEndSection": 151, "text": "he Clinical Response of Upadacitinib and Risankizumab Is Associated With Reduced Inflammatory Bowel Disease Anti-TNF-\u03b1 Inadequate Response Mechanisms.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36515243"}, {"offsetInBeginSection": 340, "offsetInEndSection": 533, "text": "Tofacitinib, a non-selective small molecule JAK inhibitor, and\u00a0upadacitinib and filgotinib, which are selective JAK-1 inhibitors, have been approved by the US Food and Drug Administration (FDA)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36913180"}, {"offsetInBeginSection": 237, "offsetInEndSection": 323, "text": "Tofacitinib, a pan-JAK inhibitor, has spearheaded the new JAK class for IBD treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37004800"}, {"offsetInBeginSection": 532, "offsetInEndSection": 1404, "text": " We conducted a comparative phosflow study of four JAKinibs (filgotinib, upadacitinib, tofacitinib, and deucravacitinib) to observe subtle mechanistic differences that may dictate their clinical behavior. Resected mesenteric lymph node (MLN) cells from 19 patients (9 CD, 10 UC) were analyzed by flow cytometry in the presence or absence of different cytokine stimuli and titrated JAKinibs.RESULTS: We found a higher potency of the JAK 1/3-preferential inhibitor, tofacitinib, for JAK 3-dependent cytokine signaling pathways in comparison to filgotinib, but a higher potency of the JAK 1-preferential inhibitors, filgotinib and upadacitinib, for JAK 3-independent cytokine signaling pathways. Deucravacitinib, a TYK2-preferential inhibitor, demonstrated a much narrower selectivity by inhibiting only IL-10 and IFN-\u03b2pathways, albeit more potently than the other JAKinibs .", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37855324"}, {"offsetInBeginSection": 12, "offsetInEndSection": 157, "text": "Upadacitinib, a novel and selective inhibitor of Janus kinase 1, has demonstrated promising efficacy in managing inflammatory bowel disease (IBD)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37977068"}, {"offsetInBeginSection": 250, "offsetInEndSection": 447, "text": "Tofacitinib was the first pan-Janus kinase (Jak) inhibitor approved for the treatment of IBD, targeting the 4 isoforms of cytokine-associated Jaks (Jak1, Jak2, Jak3, and tyrosine-protein kinase 2).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35505771"}, {"offsetInBeginSection": 1399, "offsetInEndSection": 1805, "text": "Tofacitinib, dosed orally, intracecally, or applied to the colonic lumen in vitro, produced dose-dependent, and maximal inhibition of oxazolone or IFN\u03b3-induced STAT1 phosphorylation in the colon.CONCLUSIONS: Localized colonic JAK inhibition, by intracecal delivery of tofacitinib, provides colonic target engagement and efficacy in a mouse colitis model at doses which do not impact splenic NK cell counts.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29225517"}, {"offsetInBeginSection": 1089, "offsetInEndSection": 1207, "text": "Tofacitinib is an oral, small molecule JAK inhibitor that is being investigated as a targeted immunomodulator for IBD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26608188"}, {"offsetInBeginSection": 801, "offsetInEndSection": 905, "text": "Tofacitinib, a pan-JAK inhibitor, has been recently approved for the treatment of moderate-to-severe UC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31227590"}, {"offsetInBeginSection": 1242, "offsetInEndSection": 1397, "text": ". Tofacitinib, a pan-JAK inhibitor, has shown good efficacy and safety in UC clinical trials and has been recently approved for the treatment of UC patient", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32440190"}, {"offsetInBeginSection": 685, "offsetInEndSection": 864, "text": "Tofacitinib is an oral pan-JAK inhibitor, primarily of JAK1 and JAK3, that was recently approved by the Food and Drug Administration (FDA) for the chronic treatment of UC in 2018.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32873116"}, {"offsetInBeginSection": 136, "offsetInEndSection": 258, "text": "The oral formulation of tofacitinib has recently been approved for the treatment of moderate-to-severe ulcerative colitis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31879750"}, {"offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "Tofacitinib is the only medicine in the class of Janus kinase (JAK) inhibitors that has been approved for use in moderate-to-severely active ulcerative colitis (UC). The potential of other JAK inhibitors to treat UC has not been fully explored.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35018293"}, {"offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Tofacitinib, the First Oral Janus Kinase Inhibitor Approved for Adult Ulcerative Colitis.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32873116"}, {"offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "INTRODUCTION: Janus Kinase inhibitors (JAKi) are a new class of oral therapies for the treatment of moderate-severe ulcerative colitis with additional potential for the treatment of moderate-severe Cr", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37226522"}, {"offsetInBeginSection": 731, "offsetInEndSection": 907, "text": "Tofacitinib, inhibiting signaling via different types of JAKs, has been already approved for ulcerative colitis, and several other small-molecule are still under investigation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34884361"}, {"offsetInBeginSection": 881, "offsetInEndSection": 1045, "text": "Tofacitinib has been shown to be therapeutically efficacious, to have a tolerable safety profile, and to be available for adult patients with moderate-to-severe UC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35300073"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1442, "text": "The inflammatory diseases ulcerative colitis and Crohn's disease constitute the two main forms of inflammatory bowel disease (IBD). They are characterized by chronic, relapsing inflammation of the gastrointestinal tract, significantly impacting on patient quality of life and often requiring prolonged treatment. Existing therapies for IBD are not effective for all patients, and an unmet need exists for additional therapies to induce and maintain remission. Here we describe the mechanism of action of the Janus kinase (JAK) inhibitor, tofacitinib, for the treatment of IBD and the effect of JAK inhibition on the chronic cycle of inflammation that is characteristic of the disease. The pathogenesis of IBD involves a dysfunctional response from the innate and adaptive immune system, resulting in overexpression of multiple inflammatory cytokines, many of which signal through JAKs. Thus JAK inhibition allows multiple cytokine signaling pathways to be targeted and is expected to modulate the innate and adaptive immune response in IBD, thereby interrupting the cycle of inflammation. Tofacitinib is an oral, small molecule JAK inhibitor that is being investigated as a targeted immunomodulator for IBD. Clinical development of tofacitinib and other JAK inhibitors is ongoing, with the aspiration of providing new treatment options for IBD that have the potential to deliver prolonged efficacy and clinically meaningful patient benefits. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26608188"}, {"offsetInBeginSection": 1284, "offsetInEndSection": 1521, "text": "Deucravacitinib, a novel, oral, selective TYK2 inhibitor, and brepocitinib and PF-06826647, TYK2 inhibitors that bind to the active site in the catalytic domain, are in development for IBD and other immune-mediated inflammatory diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34089259"}, {"offsetInBeginSection": 419, "offsetInEndSection": 596, "text": "Currently, in Japan, three Janus kinase inhibitors, namely tofacitinib, filgotinib, and upadacitinib, are available for the treatment of patients with active ulcerative colitis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37036140"}, {"offsetInBeginSection": 447, "offsetInEndSection": 675, "text": "ass of drugs.AREAS COVERED: This review describes the JAK-STAT pathway and analyzes the efficacy and safety of new small molecules such as filgotinib, upadacitinib, TD-1473, peficitinib, and Pf-06651600/Pf-06700841, showing data", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29938545"}, {"offsetInBeginSection": 1021, "offsetInEndSection": 1199, "text": "ld be preferred in first line, filgotinib, tofacitinib or ustekinumab in second line. A steroid-dependent course in both diseases requires azathioprine or vedolizumab, in second ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37480322"}, {"offsetInBeginSection": 226, "offsetInEndSection": 641, "text": "Tofacitinib is the first compound of a promising class of new small molecules approved for the treatment of IBD. This pan-Janus kinase (JAK) inhibitor (JAKi) targets the four isoforms of cytokine associated JAKs (JAK1, JAK2, JAK3 and TYK2). Next generations JAKi with marked selectivity for specific JAK isoforms or gut-restricted effect are in development, with promising results in phase I and II clinical trials.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33207299"}, {"offsetInBeginSection": 99, "offsetInEndSection": 534, "text": "Janus kinase (JAK)-signal transducers and activators of transcription pathway are strongly involved in the pathophysiology of inflammatory bowel disease. Generally, Janus kinase inhibitors are being used for the treatment of rheumatoid arthritis and other immunological diseases, with the therapeutic promising effects. Currently, in Japan, three Janus kinase inhibitors, namely tofacitinib, filgotinib, and upadacitinib, are available", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37036140"}]}
+{"question_id": "65f83281c4010b4d78000040", "question": "Are only babies and young children at risk of severe malaria in endemic areas?", "answer": "No, everybody is at risk, though the people at highest risk are young children and pregnant women.", "relevant_passage_ids": ["37365258", "35916146", "34905777", "35382261", "33465125", "15480963", "25300703", "17102547"], "type": "yesno", "snippets": [{"offsetInBeginSection": 68, "offsetInEndSection": 168, "text": "malaria in pregnancy remains a significant cause of low birth weight, stillbirth, and severe anaemia", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37365258"}, {"offsetInBeginSection": 139, "offsetInEndSection": 205, "text": "mortality rates from severe malaria (SM) remain significantly high", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35916146"}, {"offsetInBeginSection": 546, "offsetInEndSection": 571, "text": "SM in adults and children", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35916146"}, {"offsetInBeginSection": 12, "offsetInEndSection": 38, "text": "Cerebral malaria in adults", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34905777"}, {"offsetInBeginSection": 1258, "offsetInEndSection": 1306, "text": "Brain involvement is common in adults with SNCM ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34905777"}, {"offsetInBeginSection": 117, "offsetInEndSection": 214, "text": "Cerebral malaria (CM) is a rapidly progressive and severe form of Plasmodium falciparum infection", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35382261"}, {"offsetInBeginSection": 480, "offsetInEndSection": 638, "text": "CM, often associated with fatal outcomes even in treated subjects, is usually diagnosed at autopsy.Case presentation: We present the case of a 36-year-old man", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35382261"}, {"offsetInBeginSection": 639, "offsetInEndSection": 914, "text": "Acute episodes of severe malaria, repeated malaria infections leading to severe anemia, and infection during pregnancy which predisposes to low birth weight, a major risk factor for neonatal death, account for the majority of malaria-related deaths in young African children.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15480963"}, {"offsetInBeginSection": 12, "offsetInEndSection": 184, "text": "Pregnancy increases the risk of malaria and this is associated with poor health outcomes for both the mother and the infant, especially during the first or second pregnancy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25300703"}, {"offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Malaria is a potentially life-threatening disease with approximately half of the world's population at risk. Young children and pregnant women are hit hardest by the disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33465125"}, {"offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "BACKGROUND: Pregnancy increases the risk of malaria and this is associated with poor health outcomes for both the mother and the infant, especially during the first or second", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25300703"}, {"offsetInBeginSection": 62, "offsetInEndSection": 128, "text": "In India, both adults and children are affected by severe malaria.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17102547"}]}
+{"question_id": "64414bdb57b1c7a315000058", "question": "What types of glucosteroids are used for the management of Duchenne muscular dystrophy?", "answer": "The glucosteroids used for the management of Duchenne muscular dystrophy are prednisone, prednisolone and deflazacort.", "relevant_passage_ids": ["35713895", "35723111", "35073949", "33053810", "12026233", "28823869", "33104035", "8289083", "8186713", "37927274", "18334131"], "type": "list", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "Prednisone and deflazacort in Duchenne muscular dystrophy: ", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35713895"}, {"offsetInBeginSection": 652, "offsetInEndSection": 766, "text": "Prednisone and deflazacort are steroids that help to reduce muscle inflammation and are used as treatments for DMD", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35713895"}, {"offsetInBeginSection": 0, "offsetInEndSection": 354, "text": "Deflazacort and prednisone/prednisolone are the current standard of care for patients with Duchenne muscular dystrophy (DMD) based on evidence that they improve muscle strength, improve timed motor function, delay loss of ambulation, improve pulmonary function, reduce the need for scoliosis surgery, delay onset of cardiomyopathy, and increase survival.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35723111"}, {"offsetInBeginSection": 444, "offsetInEndSection": 680, "text": "This analysis considered patients from the UK NorthStar database (2003-2020) on one of five regimes: \"GC na\u00efve\", \"deflazacort daily\" (DD), \"deflazacort intermittent\" (DI), \"prednisolone daily\" (PD) and \"prednisolone intermittent\" (PI). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35073949"}, {"offsetInBeginSection": 851, "offsetInEndSection": 1202, "text": "From this review, it is clear that until a definitive treatment for Duchenne muscular dystrophy is available, the use of deflazacort and prednisone with judicious dietary control and close clinical monitoring for side effects seems the best intervention for interim preservation of function in such a common devastating disorder of young growing boys.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12026233"}, {"offsetInBeginSection": 291, "offsetInEndSection": 465, "text": "Glucocorticoid steroids, like prednisone, are known to delay loss of ambulation in patients with Duchenne muscular dystrophy but are accompanied by prominent adverse effects.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28823869"}, {"offsetInBeginSection": 588, "offsetInEndSection": 694, "text": "Corticosteroid therapy (prednisone and deflazacort) is the only effective pharmacologic treatment for DMD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18334131"}, {"offsetInBeginSection": 100, "offsetInEndSection": 272, "text": "Glucocorticoid steroids such as prednisone and deflazacort are recommended for treating Duchenne Muscular Dystrophy where their use prolongs ambulation and life expectancy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33104035"}, {"offsetInBeginSection": 1575, "offsetInEndSection": 1748, "text": ": These results helped the researchers to learn more about the differences between how well prednisone and deflazacort work in males with DMD based on their medical records.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35713895"}, {"offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Prednisone (Pred) and Deflazacort (Dfz) are commonly used glucocorticoids (GCs) for Duchenne muscular dystrophy (DMD) treatment and management.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33053810"}, {"offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "In recent years, various clinical trials have documented the benefit of glucocorticoid therapy in the palliation of Duchenne muscular dystrophy (DMD). Prednisone therapy, daily or on alternate days, has been confirmed to be of value in enhancing muscle strength and function in DMD for up to two years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8289083"}, {"offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Prednisolone has been shown to improve strength in Duchenne dystrophy, the improvement starting within 10 days of treatment and reaching a maximum by 3 months, and then plateauing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8186713"}, {"offsetInBeginSection": 188, "offsetInEndSection": 528, "text": "Glucocorticoids such as prednisone and deflazacort have powerful anti-inflammatory benefits and are the standard of care for DMD, but their long-term use can result in severe adverse side effects; thus, vamorolone was designed as a unique dissociative steroidal anti-inflammatory drug, to retain efficacy and minimise these adverse effects.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37927274"}]}
+{"question_id": "65cfd4b21930410b13000020", "question": "Cilta-cel was developed for treatment of which disease?", "answer": "Cilta-cel, a BCMA-targeting chimeric antigen receptor T-cell therapy for multiple myeloma.", "relevant_passage_ids": ["36411210", "36271807", "36269898", "37497629", "37272512", "34885106", "34840088", "35764490", "34175021", "37913909", "37716872", "37704875", "36720180", "37014590", "37750399", "35900317"], "type": "factoid", "snippets": [{"offsetInBeginSection": 1174, "offsetInEndSection": 1407, "text": " Additional indirect treatment comparisons conducted separately for ide-cel and cilta-cel have demonstrated that these CAR-T therapies hold promise for substantial clinical benefit relative to currently available treatments for RRMM.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36411210"}, {"offsetInBeginSection": 0, "offsetInEndSection": 607, "text": "OBJECTIVE: This study used the latest available data cuts from the CARTITUDE-1 and KarMMa clinical trials to update previously published matching-adjusted indirect treatment comparisons (MAICs) assessing the comparative efficacy of ciltacabtagene autoleucel (cilta-cel) versus the FDA-approved idecabtagene vicleucel (ide-cel) dose range of 300 to 450\u2009\u00d7\u2009106 CAR-positive T-cells in the treatment of patients with relapsed or refractory multiple myeloma (RRMM) who were previously treated with a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody (i.e. triple-class exposed)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36271807"}, {"offsetInBeginSection": 1645, "offsetInEndSection": 1850, "text": "CONCLUSIONS: These analyses demonstrate improved efficacy with cilta-cel versus ide-cel for all outcomes over longer follow-up and highlight its therapeutic potential in triple-class exposed RRMM patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36271807"}, {"offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "PURPOSE: CARTIFAN-1 aimed to evaluate the efficacy and safety of ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen-targeting chimeric antigen receptor T-cell therapy, in Chinese patients with relapsed/refractory multiple myeloma (RRMM).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36269898"}, {"offsetInBeginSection": 1776, "offsetInEndSection": 1978, "text": "CONCLUSION: These data demonstrate a favorable risk-benefit profile for a single infusion of cilta-cel, resulting in early, deep, and durable responses in heavily pretreated patients with RRMM in China.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36269898"}, {"offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Cilta-cel, a BCMA-targeting CAR-T therapy for heavily pretreated patients with relapsed/refractory multiple myeloma.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37497629"}, {"offsetInBeginSection": 0, "offsetInEndSection": 323, "text": "Cilta-cel, a BCMA-targeting chimeric antigen receptor T-cell therapy for multiple myeloma, was approved in USA on 28 February 2022, for patients with relapsed or refractory disease who have received \u22654 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37497629"}, {"offsetInBeginSection": 0, "offsetInEndSection": 432, "text": "Since 2021, 2 B cell maturation antigen (BCMA)-directed chimeric antigen receptor T cell (CAR-T) therapies-idecabtagene vicleucel (ide-cel), and ciltacabtagene autoleucel (cilta-cel)-have been approved by the US Food and Drug Administration (FDA) for treating relapsed or refractory multiple myeloma (RRMM) after 4 or more prior lines of therapy, including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37913909"}, {"offsetInBeginSection": 0, "offsetInEndSection": 602, "text": "BACKGROUND: In the single-arm, phase 1b/2 CARTITUDE-1 study, ciltacabtagene autoleucel (cilta-cel), an anti-B-cell maturation antigen chimeric antigen receptor T-cell (CAR-T) therapy, showed encouraging efficacy in US patients with multiple myeloma (MM) who previously received an immunomodulatory drug, proteasome inhibitor, and anti-CD38 monoclonal antibody (triple-class exposed).PATIENTS AND METHODS: A dataset of US patients refractory to an anti-CD38 monoclonal antibody (MAMMOTH) was used to identify patients who would meet eligibility for CARTITUDE-1 and received subsequent non-CAR-T therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34840088"}, {"offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "BACKGROUND: Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37272512"}, {"offsetInBeginSection": 0, "offsetInEndSection": 765, "text": "BACKGROUND: CARTITUDE-1 aimed to assess the safety and clinical activity of ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T-cell therapy with two B-cell maturation antigen-targeting single-domain antibodies, in patients with relapsed or refractory multiple myeloma with poor prognosis.METHODS: This single-arm, open-label, phase 1b/2 study done at 16 centres in the USA enrolled patients aged 18 years or older with a diagnosis of multiple myeloma and an Eastern Cooperative Oncology Group performance status score of 0 or 1, who received 3 or more previous lines of therapy or were double-refractory to a proteasome inhibitor and an immunomodulatory drug, and had received a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34175021"}, {"offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Ciltacabtagene autoleucel (cilta-cel) is a Chimeric antigen receptor T-cell therapy with the potential for long-term disease control in heavily pre-treated patients with relapsed/refractory multiple myeloma (RRMM).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34885106"}, {"offsetInBeginSection": 0, "offsetInEndSection": 410, "text": "INTRODUCTION: Ciltacabtagene autoleucel (cilta-cel), is a B-cell maturation antigen-directed, genetically modified autologous chimeric antigen receptor T-cell (CAR-T) immunotherapy. It is indicated for treatment for adult patients with relapsed or refractory multiple myeloma (RRMM) after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monocl", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37014590"}, {"offsetInBeginSection": 0, "offsetInEndSection": 557, "text": "INTRODUCTION: This study estimated the comparative efficacy of ciltacabtagene autoleucel (cilta-cel; CARTITUDE-1), a chimeric antigen receptor (CAR)-T-cell therapy, versus 3 non-CAR-T therapies (belantamab mafodotin [DREAMM-2], selinexor plus dexamethasone [STORM Part 2], and melphalan flufenamide plus dexamethasone [HORIZON]), each with distinct mechanisms of action, for the treatment of patients with relapsed or refractory multiple myeloma (RRMM) who were triple-class exposed to an immunomodulatory drug, proteasome inhibitor, and an anti-CD38 monocl", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35764490"}, {"offsetInBeginSection": 159, "offsetInEndSection": 528, "text": "Two BCMA-directed CAR T-cell products - idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) - have received US Food and Drug Administration (FDA) approval for patients with relapsed/refractory MM who underwent four or more prior lines of therapy (including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37750399"}, {"offsetInBeginSection": 0, "offsetInEndSection": 433, "text": "Since 2021, 2 B cell maturation antigen (BCMA)-directed chimeric antigen receptor T cell (CAR-T) therapies-idecabtagene vicleucel (ide-cel), and ciltacabtagene autoleucel (cilta-cel)-have been approved by the US Food and Drug Administration (FDA) for treating relapsed or refractory multiple myeloma (RRMM) after 4 or more prior lines of therapy, including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37913909"}, {"offsetInBeginSection": 118, "offsetInEndSection": 402, "text": "nancies. Ciltacabtagene autoleucel (cilta-cel), a second-generation CAR-T cell with double B cell maturation antigen (BCMA) targeting binding domains, showed an 88% overall response rate (ORR) in patients with relapsed/refractory multiple myeloma (MM), which were carried out in our i", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36720180"}, {"offsetInBeginSection": 712, "offsetInEndSection": 935, "text": "The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) has approved two BCMA-targeting CAR T cell products, idecabtagene vicleucel (Ide-cel) and ciltacabtagene autoleucel (Cilta-cel), for use in RRMM.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37704875"}, {"offsetInBeginSection": 803, "offsetInEndSection": 975, "text": "The autologous CAR-T cell therapy against BCMA (ide-cel and cilta-cel) shows the best efficacy with an overall response rate and a median progression-free survival in RRMM.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35900317"}, {"offsetInBeginSection": 132, "offsetInEndSection": 413, "text": "eptor (CAR) T cell therapies, because their engineered cells may include allogeneic T cells. Ciltacabtagene autoleucel (cilta-cel) demonstrated early, deep, durable responses and manageable safety in heavily pretreated relapsed/refractory multiple myeloma patients. We retrospectiv", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37716872"}]}
+{"question_id": "65f772d3c4010b4d78000022", "question": "Which oncogene somatic mutations are associated to in situ carcinoma evolution from colonic polyp adenomas?", "answer": "APC, BRAF, EGFR, NRAS, KRAS, PIK3CA, POLE, POLD1, SMAD4, PTEN, and TP53 are oncogene somatic mutations associated to in situ carcinoma evolution from colonic polyp adenomas.", "relevant_passage_ids": ["35173208", "8607008", "27221540", "10391560", "23565319", "29069792", "32543103", "32384323", "28325827", "21915664", "16896030", "2841597"], "type": "list", "snippets": [{"offsetInBeginSection": 835, "offsetInEndSection": 952, "text": "The APC, KRAS and TP53 mutation frequencies were slightly lower in adenoma samples than in in situ carcinoma samples.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35173208"}, {"offsetInBeginSection": 472, "offsetInEndSection": 543, "text": "APC, BRAF, EGFR, NRAS, KRAS, PIK3CA, POLE, POLD1, SMAD4, PTEN, and TP53", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35173208"}, {"offsetInBeginSection": 1120, "offsetInEndSection": 1197, "text": "APC gene 42.9-56.0-54.5%; KRAS gene 32.7-32.0-45.5%; TP53 gene 8.2-20.0-18.2%", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35173208"}, {"offsetInBeginSection": 1017, "offsetInEndSection": 1181, "text": "Sequential mutations of the APC and KRAS were judged-based on a database search-to be characteristic of the adenoma-carcinoma sequence in colorectal carcinogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32543103"}, {"offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Colorectal carcinogenesis in familial adenomatous polyposis (FAP) follows a conventional adenoma-carcinoma sequence", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32384323"}, {"offsetInBeginSection": 1238, "offsetInEndSection": 1580, "text": "Of the remaining nine neoplasms, six had a K-ras mutation in the adenomatous portion only and three had one pattern in the adenomatous portion and a different pattern in the in situ carcinoma portion.CONCLUSIONS: LOH of the APC gene is an early and persistent feature in the evolution of a benign colorectal adenoma into an in situ carcinoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10391560"}, {"offsetInBeginSection": 641, "offsetInEndSection": 880, "text": "Our study clearly demonstrates that tubulovillous and villous adenomas, as well as both the benign and malignant parts of in situ carcinomas, are statistically more likely to contain a somatic KRAS gene mutation than colorectal carcinomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23565319"}, {"offsetInBeginSection": 523, "offsetInEndSection": 640, "text": "A KRAS mutation was found in 61.9% of 134 adenomas, 67.8% of 84 in situ carcinomas, and just 31.6% of 171 carcinomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23565319"}, {"offsetInBeginSection": 283, "offsetInEndSection": 562, "text": "Activating mutations in either the BRAF (in SSAs) or the KRAS oncogene (in TSAs) have been determined as the initiating molecular alterations, followed by epigenetic methylation of CpG islands in promoter regions of genes which are implicated in cell cycle control or DNA repair.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21915664"}, {"offsetInBeginSection": 1520, "offsetInEndSection": 1655, "text": "Our data supports the multistep model of gradual accumulation of mutations, especially in the driver genes, such as APC, TP53 and KRAS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35173208"}, {"offsetInBeginSection": 299, "offsetInEndSection": 471, "text": "The adenomatous polyposis coli (APC) gene and mismatch repair genes are found to be dysfunctional early in the neoplastic process; either as inherited or somatic mutations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8607008"}, {"offsetInBeginSection": 776, "offsetInEndSection": 965, "text": "Adenomas had lower mutational rates than did colorectal cancers and showed recurrent alterations in known cancer driver genes (APC, KRAS, FBXW7, TCF7L2) and AIs in chromosomes 5, 7, and 13.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27221540"}, {"offsetInBeginSection": 375, "offsetInEndSection": 1470, "text": "mutations (V600E) in the BRAF oncogene. Both of these features are seen in sporadic colorectal carcinomas with microsatellite instability (MSI) which is potentially consistent with an origin of these cancers from precursor SSA/Ps. Dysplasia is detected in a subset of SSA/Ps with a high risk of progression to carcinoma. An uncommon serrated polyp is the traditional serrated adenoma that is typically found in the left colon, has a tubulovillous architecture, and frequently harbors mutant KRAS To date, the epidemiology of these serrated lesions is poorly understood, and limited observational data suggest a potential chemopreventive benefit of nonsteroidal anti-inflammatory drugs. The current primary strategy to reduce the risk of colorectal carcinoma from serrated polyps is to enhance their detection at colonoscopy and to ensure their complete removal. This review provides insight into the epidemiologic, clinical, histopathologic, and molecular features of serrated polyps and includes data on their endoscopic detection and chemoprevention. Cancer Prev Res; 10(5); 270-8. \u00a92017 AACR.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28325827"}, {"offsetInBeginSection": 675, "offsetInEndSection": 876, "text": "We found that ras-gene mutations occurred in 58 percent of adenomas larger than 1 cm and in 47 percent of carcinomas. However, ras mutations were found in only 9 percent of adenomas under 1 cm in size.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2841597"}, {"offsetInBeginSection": 1437, "offsetInEndSection": 1634, "text": "Individuals with a Ki-ras mutated adenoma were more likely to overexpress p53 (OR, 2.46; 95% CI, 1.36-4.46), and 94.8% of adenomas with both alterations were classified as advanced (P <or= 0.0001).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16896030"}]}
+{"question_id": "65f1eb84c4010b4d78000008", "question": "What is prurigo nodularis?", "answer": "Prurigo nodularis (PN) is a chronic neuroimmune skin disease characterized by bilaterally distributed pruritic hyperkeratotic nodules on extremities and trunk.  The lesions are very pruritic and the condition may occur in any age group.", "relevant_passage_ids": ["37506977", "37245863", "36806647", "34268319", "35083742", "32461078", "18652691", "16197418", "10972090", "24825138", "32877138", "27578077", "35502157", "30261199", "29135018", "35986886", "20946583", "17352720", "38016088", "2359730", "37811660", "37663166", "36966024", "33771530", "34289753", "36304386", "34314056", "1884861", "2227059", "34965028", "37108838", "32454098", "31561504", "19398916"], "type": "summary", "snippets": [{"offsetInBeginSection": 12, "offsetInEndSection": 173, "text": "Prurigo nodularis (PN) is a chronic neuroimmune skin disease characterized by bilaterally distributed pruritic hyperkeratotic nodules on extremities and trunk. N", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37506977"}, {"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Prurigo nodularis (PN) is an understudied inflammatory skin disease characterized by pruritic, hyperkeratotic nodules. I", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37245863"}, {"offsetInBeginSection": 12, "offsetInEndSection": 95, "text": "Prurigo nodularis (PN) is an extremely pruritic, chronic inflammatory skin disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36806647"}, {"offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "BACKGROUND: Prurigo nodularis (PN), or nodular prurigo, is a chronic, debilitating, inflammatory skin disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24825138"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Prurigo nodularis (PN) is a subtype of chronic prurigo presenting single to multiple symmetrically distributed, hyperkeratotic and intensively itching papules and nodules.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29135018"}, {"offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Prurigo nodularis is a chronic skin condition characterized by severely pruritic nodules that cause a profound negative impact on quality of life.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32461078"}, {"offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Prurigo nodularis (PN), or chronic prurigo, is a distinct disease characterized by the presence of chronic pruritus and multiple localized or generalized pruriginous lesions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35986886"}, {"offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Prurigo nodularis is a chronic dermatologic condition involving the development of multiple cutaneous nodules in the setting of intractable pruritus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30261199"}, {"offsetInBeginSection": 172, "offsetInEndSection": 302, "text": "PN evolves along with chronic pruritus in the context of diverse dermatological, systemic, neurological or psychiatric conditions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29135018"}, {"offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Prurigo nodularis is a chronic condition characterized by a papulonodular pruriginous eruption of unknown aetiology.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16197418"}, {"offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "BACKGROUND: Prurigo nodularis (PN) is a chronic inflammatory skin disease with nodular itch", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20946583"}, {"offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "INTRODUCTION: Prurigo nodularis is an unusual disorder of unknown aetiology, which is notoriously resistant to therapy, and is characterized by extremely pruritic nodules with well-defined clinical symptoms and histopatholog", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18652691"}, {"offsetInBeginSection": 12, "offsetInEndSection": 160, "text": "Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by severely itchy and often painful bumps on the arms, legs, and trunk", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37663166"}, {"offsetInBeginSection": 12, "offsetInEndSection": 143, "text": "Prurigo nodularis (PN) is a chronic inflammatory skin condition that has a significant unmet needs for effective treatment options.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36966024"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Prurigo nodularis of Hyde is an unusual disorder of unknown aetiology characterized by extremely pruritic nodules with well defined clinical and histopathological aspects.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10972090"}, {"offsetInBeginSection": 0, "offsetInEndSection": 348, "text": "Prurigo nodularis is a chronic inflammatory skin disease consisting of severely pruritic nodules that can be very debilitating for patients. The basis of this skin condition is immunological dysregulation and neural amplification, driven by T-lymphocytes, mast cells, eosinophilic granulocytes, macrophages, and cytokines mediating itchy processes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35502157"}, {"offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "BACKGROUND: Prurigo nodularis (PN), or nodular prurigo, is a chronic, debilitating, inflammatory skin disease. It can be very difficult to manage, and represents a challenge for th", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24825138"}, {"offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Prurigo nodularis is a chronic condition characterized by a papulonodular pruriginous eruption of unknown aetiology. This condition is a difficult disease to treat and causes frustration to both the patient and the treating doctor.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16197418"}, {"offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Prurigo nodularis (PN) is an understudied, chronic inflammatory skin disease that disproportionately affects African Americans and presents with intensely pruritic nodules of unknown etiology.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33771530"}, {"offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by the presence of pruritic nodules. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38016088"}, {"offsetInBeginSection": 0, "offsetInEndSection": 429, "text": "INTRODUCTION: Prurigo nodularis (PN) or chronic prurigo of nodular type (CNPG) is a subtype of chronic prurigo with severe pruritus and neuroimmune underlying pathophysiology occurring in a plethora of dermatological, systemic, neurologic, and psychiatric conditions.AREAS COVERED: We review the increasing repertoire of biologics in the treatment of CNPG focusing on those targeting interleukins 4, 13, 31, oncostatin M and IgE.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34289753"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Prurigo nodularis (PN) is a chronic skin disease that manifests with severe itchy, firm, hyperkeratotic nodules distributed on the trunk and the extremities symmetrically.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36304386"}, {"offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "Characterized by the clinical presentation of individual to multiple symmetrically distributed, hyperkeratotic, and intensely itchy papules and nodules, prurigo nodularis (PN) is a rare disease that emerges in patients with chronic pruritus due to continuous scratching over a long period of time.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27578077"}, {"offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "We report a case of prurigo nodularis of Hyde as the presenting sign of Hodgkin's disease in a 22-year-old girl.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1884861"}, {"offsetInBeginSection": 19, "offsetInEndSection": 82, "text": "Prurigo nodularis is the most severe degree of chronic prurigo.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32877138"}, {"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "INTRODUCTION: Prurigo nodularis (PN) is a chronic inflammatory skin condition that presents with pruritus and hyperkera", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37811660"}, {"offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "BACKGROUND: Prurigo nodularis (PN) is a chronic dermatologic condition manifesting as multiple papulonodular lesions occurring on the background of inten", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34965028"}, {"offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Prurigo nodularis (PN) is an understudied inflammatory skin disease characterized by pruritic, hyperkeratotic nodules.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37245863"}, {"offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Prurigo nodularis is an intensely pruritic dermatosis characterized by lichenified and excoriated papules and nodules.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17352720"}, {"offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Prurigo nodularis (PN) is a chronic condition characterized by the presence of nodular lesions accompanied by intense pruritus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37108838"}, {"offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Prurigo nodularis is an uncommon pediatric cutaneous disorder that is associated with intense pruritus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2359730"}, {"offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intensely pruritic, hyperkeratotic nodules that favor the extensor surfaces of the extremities and the trunk.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32454098"}, {"offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized oftentimes by symmetrically distributed, severely pruritic nodules.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31561504"}, {"offsetInBeginSection": 1025, "offsetInEndSection": 1282, "text": "Prurigo nodularis is a chronic condition characterized by intensely pruritic, lichenified, or excoriated papules and nodules of unknown etiology. It is assumed to represent a cutaneous reaction pattern to repeated scrubbing or scratching caused by pruritus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19398916"}, {"offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "BACKGROUND: Prurigo nodularis is a debilitating skin condition that is classified as rare by the Genetic and Rare Diseases Information Center (GARD) and the National Organization for Rare Dise", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35083742"}, {"offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Chronic prurigo is a debilitating skin disease characterized by the presence of chronic pruritus and scratching-related pruriginous lesion", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34268319"}]}
+{"question_id": "65f8447fc4010b4d78000043", "question": "What is the main cause of spillover events?", "answer": "The main cause of spillover events is the disruption of habitats of the reservoir species.", "relevant_passage_ids": ["37019573", "29466832", "37007505", "37000877", "33052311"], "type": "factoid", "snippets": [{"offsetInBeginSection": 925, "offsetInEndSection": 1161, "text": "the extent of land use for food production and the agricultural practices employed that shape four archetypal food systems, each with a distinct risk profile with respect to zoonotic spillovers and differing dimensions of sustainability", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37019573"}, {"offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Pathogen spillover from wildlife to domestic animals and humans", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29466832"}, {"offsetInBeginSection": 579, "offsetInEndSection": 651, "text": "the highest spillover risk occurs at intermediate levels of habitat loss", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29466832"}, {"offsetInBeginSection": 1169, "offsetInEndSection": 1414, "text": "We conclude that that the processes of domestication, horizontal gene transfer and microbial succession might be important mechanisms behind the many spillover events driven and accelerated by climate change, biodiversity loss and globalization.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37007505"}, {"offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Human land modification is a known driver of animal-to-human transmission of infectious agents (zoonotic spillover).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37000877"}, {"offsetInBeginSection": 239, "offsetInEndSection": 461, "text": "Spillover events are associated to varying degrees with high habitat fragmentation, biodiversity loss through land use change, high livestock densities, agricultural inputs, and wildlife hunting-all facets of food systems.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37019573"}, {"offsetInBeginSection": 149, "offsetInEndSection": 491, "text": "The emerging infections that lead to substantive epidemics or pandemics are typically zoonoses that cross species boundaries at vulnerable points of animal-human interface. The sharing of space between wildlife and humans, and their domesticated animals, has dramatically increased in recent decades and is a key driver of pathogen spillover.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33052311"}]}
+{"question_id": "644108b157b1c7a315000053", "question": "What are the most commonly used pain scales for the measurement of pain in ICU?", "answer": "The most common pain scales used to measure pain in ICU are the following: critical-care pain observation tool (CPOT) and behavioral pain scale (BPS).", "relevant_passage_ids": ["35656052", "32389396", "30834018", "28362033", "27833752", "30820228"], "type": "list", "snippets": [{"offsetInBeginSection": 99, "offsetInEndSection": 280, "text": "This study aims to compare the diagnostic value of the critical-care pain observation tool (CPOT) and the behavioral pain scale (BPS) for pain assessment among unconscious patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35656052"}, {"offsetInBeginSection": 1319, "offsetInEndSection": 1579, "text": " CPOT and BPS have acceptable discriminant validity in differentiating nonnociceptive and nociceptive procedural pain although the effect size of CPOT is larger than that of BPS. Although both instruments have low reliability, the reliability of BPS is better.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35656052"}, {"offsetInBeginSection": 11, "offsetInEndSection": 216, "text": " To determine the concordance of Zurich Observation Pain Assessment (ZOPA) with the behavioural Pain Scale (BPS) and the Critical Care Pain Observation Tool (CPOT) to detect pain in nonverbal ICU patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32389396"}, {"offsetInBeginSection": 1232, "offsetInEndSection": 1350, "text": "ZOPA is concordant with the BPS and the CPOT to indicate pain but detects pain earlier due to the low threshold value.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32389396"}, {"offsetInBeginSection": 1563, "offsetInEndSection": 1770, "text": "Based on available evidence and investigations, CPOT and BPS tools have good validity and reliability to be used in pain assessment in Nonverbal Intubated Critically Adult Patients after Open-Heart Surgery. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30834018"}, {"offsetInBeginSection": 1073, "offsetInEndSection": 1258, "text": "Current research shows that the two tools best validated for patients unable to self-report pain are the Behavioral Pain Scale (BPS) and the Critical Care Pain Observation Tool (CPOT). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28362033"}, {"offsetInBeginSection": 2040, "offsetInEndSection": 2199, "text": "In critically ill mechanically ventilated patients, both CPOT and BPS can be used for assessment of pain intensity with different sensitivity and specificity. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27833752"}, {"offsetInBeginSection": 1464, "offsetInEndSection": 1651, "text": "Critically ill patients in ICU experience a different range of pain in routine daily care. BPS and CPOT scales could be used successfully for monitoring of pain in this group of patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30820228"}]}
+{"question_id": "65d373e21930410b13000049", "question": "What medication were tested in the PEMMELA trial?", "answer": "PEMMELA was a single-arm phase 2 study that tested pembrolizumab plus lenvatinib as second-line and third-line for patients with pleural mesothelioma.", "relevant_passage_ids": ["37844598"], "type": "list", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Pembrolizumab plus lenvatinib in second-line and third-line patients with pleural mesothelioma (PEMMELA): a single-arm phase 2 study.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37844598"}]}
+{"question_id": "65f77328c4010b4d78000023", "question": "What is the pathophysiological mechanism by which the microbiota produce malignant lesions in colonic mucosa?", "answer": "Perturbations of the colonic microbiota can contribute to the initiation and progression of colorectal cancer, leading to an increase in pathogenic bacteria as Bilophila wadsworthia, as well as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, and Clostridium septicum. This can contribute to disease through increasing carcinogenic metabolite/toxin production, inducing inflammation, and activating oncogenic signaling. On the other hand, pathogenic bacteria have heightened iron acquisition mechanisms.", "relevant_passage_ids": ["32825236", "24071482", "30151274", "15727814", "27028619", "37111185", "30218667", "36572792", "36527679", "28153960", "33937029", "27295340", "24412617", "31554963", "36572998", "36704106", "35013389", "33577585", "31330830", "32398370", "31027304", "35211486", "31735976", "26727419", "3039469", "32991312", "22868282", "12820718", "30413188", "19064190", "35664967", "34063108", "35090978"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 347, "text": "Perturbations of the colonic microbiota can contribute to the initiation and progression of colorectal cancer, leading to an increase in pathogenic bacteria at the expense of protective bacteria. This can contribute to disease through increasing carcinogenic metabolite/toxin production, inducing inflammation, and activating oncogenic signaling. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32825236"}, {"offsetInBeginSection": 672, "offsetInEndSection": 807, "text": "Most pathogenic bacteria have heightened iron acquisition mechanisms and therefore tend to outcompete protective bacteria for free iron", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32825236"}, {"offsetInBeginSection": 331, "offsetInEndSection": 532, "text": "alterations in communication between the mucosal immune system and gut microbial communities have been implicated as the core defect that leads to chronic intestinal inflammation and cancer development", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24071482"}, {"offsetInBeginSection": 687, "offsetInEndSection": 894, "text": "multiple proposed pathogenic microorganisms including sulfidogenic bacteria such as Bilophila wadsworthia, as well as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, and Clostridium septicum.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30151274"}, {"offsetInBeginSection": 558, "offsetInEndSection": 830, "text": "We focus on some of the mechanisms by which the colonic microbiota drives the progression towards colorectal malignancy including generation of reactive metabolites and carcinogens, alterations in host carbohydrate expression and induction of chronic mucosal inflammation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15727814"}, {"offsetInBeginSection": 612, "offsetInEndSection": 840, "text": "This review evaluates the pathophysiology of how a diet-associated shift in gut microbiota, so-called the microbial sulfur diet, provokes injuries and inflammation to the colonic mucosa and contributes to the development of CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37111185"}, {"offsetInBeginSection": 155, "offsetInEndSection": 430, "text": "While certain members of the colonic microbiota have been shown to promote the host's health there are also numerous studies that have implicated other members of the colonic microbiota in the development of colorectal cancer, a prominent malignancy within the western world.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15727814"}, {"offsetInBeginSection": 1068, "offsetInEndSection": 1321, "text": "We believe that using probiotics or altering the gut microbiota will likely be effective tools in the fight against CRC treatment.PURPOSE: In this review, we revisited the association between gut microbiota and colorectal cancer whether cause or effect.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36572792"}, {"offsetInBeginSection": 431, "offsetInEndSection": 557, "text": "In this review we consider the evidence for the role of bacteria in colorectal cancer from molecular and animal model studies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15727814"}, {"offsetInBeginSection": 1322, "offsetInEndSection": 1568, "text": "The various factors which influence gut microbiome in patients with CRC and possible mechanism in relation with development of CRC.CONCLUSION: The clinical significance of the intestinal microbiota may aid in the prevention and management of CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36572792"}, {"offsetInBeginSection": 239, "offsetInEndSection": 379, "text": "Gut microbiota drive the development of inflammation within the colon and such inflammation is implicated in colonic neoplastic development.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27028619"}, {"offsetInBeginSection": 523, "offsetInEndSection": 611, "text": "Bacterial sulfur metabolism is recognized as a critical mechanism of EOCRC pathogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37111185"}, {"offsetInBeginSection": 308, "offsetInEndSection": 450, "text": "nting CRC. Hydrogen sulfide, produced by autochthonous sulfidogenic bacteria, triggers proinflammatory pathways and hyperproliferation, and is", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28153960"}, {"offsetInBeginSection": 824, "offsetInEndSection": 983, "text": "microbial encroachment towards the colonic epithelium may promote inflammation and oxidative stress and even translocation of species across the colonic lumen.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33937029"}, {"offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "Chronic consumption of excess ethanol increases the risk of colorectal cancer. The pathogenesis of ethanol-related colorectal cancer (ER-CRC) is thought to be partly mediated by gut microbes. Specifically, bacteria in the colon and rectum convert ethanol to acetaldehyde (AcH), which is carcinogenic.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27295340"}, {"offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Commensal gut microflora and dietary fiber protect against colonic inflammation and colon cancer through unknown targets. Butyrate, a bacterial product from fermentation of dietary fiber in the colon, has been implicated in this process.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24412617"}, {"offsetInBeginSection": 332, "offsetInEndSection": 653, "text": "Sequencing studies have revealed microbial compositional and ecological changes in patients with CRC, whereas functional studies in animal models have pinpointed the roles of several bacteria in colorectal carcinogenesis, including Fusobacterium nucleatum and certain strains of Escherichia coli and Bacteroides fragilis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31554963"}, {"offsetInBeginSection": 494, "offsetInEndSection": 657, "text": "Microbiota, IL10KO, and their combination altered 0.4%, 0.4%, and 4% of CpG island methylation, respectively. These are comparable to what is seen in colon cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36572998"}, {"offsetInBeginSection": 1174, "offsetInEndSection": 1361, "text": "Further understanding the precise mechanism(s) of the oral-gut microbial axis in PD, IBD, and colorectal cancer pathogenesis will be pivotal in diagnosis, prognosis, and future treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36527679"}, {"offsetInBeginSection": 428, "offsetInEndSection": 634, "text": "Recent studies suggest that dysbiosis of the oral microbiota can alter the microbial composition in relative abundance or diversity of the distal gut, leading to the progression of digestive carcinogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36527679"}, {"offsetInBeginSection": 1005, "offsetInEndSection": 1173, "text": "As such, oral microbiota dysbiosis involving specific bacteria, including Fusobacterium nucleatum and Porphyromonas gingivalis, can ultimately lead to gut malignancies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36527679"}, {"offsetInBeginSection": 841, "offsetInEndSection": 996, "text": "Specific members of the colonic microbiota may promote IL17A production and IL17A-producing cell functions in the colonic mucosa to promote carcinogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30218667"}, {"offsetInBeginSection": 307, "offsetInEndSection": 424, "text": "To learn about gut microbiota signatures in tissues of the colorectal polyp and normal colorectal mucosa, and faeces.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36704106"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1492, "text": "The colonic epithelium is exposed to a mixture of compounds through diet, among which some are procarcinogens, whereas others have a protective effect. Therefore, the net impact of these compounds on human health depends on the overall balance between all factors involved. Strong scientific evidence has demonstrated the relationship between nitrosamines (NA), heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PAHs), which are the major genotoxins derived from cooking and food processing, and cancer. The mechanisms of the relationship between dietary toxic xenobiotics and cancer risk are not yet well understood, but it has been suggested that differences in dietary habits affect the colonic environment by increasing or decreasing the exposure to mutagens directly and indirectly through changes in the composition and activity of the gut microbiota. Several changes in the proportions of specific microbial groups have been proposed as risk factors for the development of neoplastic lesions and the enrichment of enterotoxigenic microbial strains in stool. In addition, changes in the gut microbiota composition and activity promoted by diet may modify the faecal genotoxicity/cytotoxicity, which can be associated with a higher or lower risk of developing cancer. Therefore, the interaction between dietary components and intestinal bacteria may be a modifiable factor for the development of colorectal cancer in humans and deserves more attention in the near future.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31027304"}, {"offsetInBeginSection": 191, "offsetInEndSection": 930, "text": "Here, we report that non-pathogenic microbiota accelerate age-related methylation drift in the colon when compared with germ-free mice. DNA methylation analyses showed that microbiota and IL10KO were associated with changes in 5% and 4.1% of CpG sites, while mice with both factors had 18% alterations. Microbiota, IL10KO, and their combination altered 0.4%, 0.4%, and 4% of CpG island methylation, respectively. These are comparable to what is seen in colon cancer. Ageing changes were accelerated in the IL10KO mice with microbiota, and the affected genes were more likely to be altered in colon cancer. Thus, the microbiota affect DNA methylation of the colon in patterns reminiscent of what is observed in ageing and colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36572998"}]}
+{"question_id": "65ef83acdffffb9b6b000002", "question": "is carotenodermia caused by an excess of lycopene in the diet?", "answer": "Carotenodermia is a yellow to orange skin discoloration due to epidermal deposition of carotene.", "relevant_passage_ids": ["37916485", "3421202", "3434946", "9830271", "9525273", "7747541", "12839253", "16556283"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Carotenodermia is a yellow to orange skin discoloration due to epidermal deposition of carotene. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37916485"}, {"offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "We evaluated the relation between plasma levels of carotenoids and carotenodermia in 30 men receiving carotenoid supplementation for 42 d", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3421202"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Four cases of carotenodermia are presented, secondary to marked ingestion of carotenoid-rich vegetables.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3434946"}, {"offsetInBeginSection": 333, "offsetInEndSection": 572, "text": "This literature review revealed that in carotenodermia associated with high \u03b2-carotene intake the discoloration tends to be widespread, mainly in thick areas of the skin (e.g., the palm of the hand), and can last from 14\u2009days to 4.5\u2009years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37916485"}, {"offsetInBeginSection": 226, "offsetInEndSection": 332, "text": "Here, I review approximately 100 previous cases of carotenodermia in humans due to high \u03b2-carotene intake.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37916485"}, {"offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Carotenodermia is a yellow to orange skin discoloration due to epidermal deposition of carotene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37916485"}, {"offsetInBeginSection": 683, "offsetInEndSection": 935, "text": "These observations may be useful to investigators planning clinical trials with beta-carotene and to clinicians assessing the significance of carotenodermia in men taking beta-carotene supplements or following diets high in carotenoid-containing foods.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3421202"}, {"offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Carotenodermia may arise from excessive dietary intake of carotene containing foods.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9830271"}, {"offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Carotenodermia may arise from excessive dietary intake of carotene containing foods. We reported a 22-year-old woman", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9830271"}, {"offsetInBeginSection": 0, "offsetInEndSection": 435, "text": "We evaluated the relation between plasma levels of carotenoids and carotenodermia in 30 men receiving carotenoid supplementation for 42 d. Five subjects each were randomly assigned to one of six treatment groups: 30 mg purified beta-carotene supplement, 12 mg beta-carotene supplement, 272 g cooked carrots, 300 g cooked broccoli, 180 g tomato juice, and placebo. Definite carotenodermia was observed only in the five subjects who took", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3421202"}, {"offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "To study the effects of carotenoids on the initiation of liver carcinogenesis by aflatoxin B1 (AFB1)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9525273"}, {"offsetInBeginSection": 385, "offsetInEndSection": 568, "text": "The results of an oral loading with beta-carotene (1 mg/kg) provide indirect evidence that the girl's carotenemia is due to a probably genetic defect in the metabolism of carotenoids.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7747541"}, {"offsetInBeginSection": 0, "offsetInEndSection": 332, "text": "Carotenemia is characterized by an abnormal yellowish orange pigmentation of the skin, most prominently seen on the palms and soles. Although it is associated with several disease such as diabetes, hypothyroidism and anorexia nervosa, it is caused by excessive intake of carotene-rich food such as oranges and carrots in most cases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16556283"}, {"offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Carotenemia is a common benign pediatric condition of yellowing of the skin and elevated beta-carotene levels in the blood. The condition is usually caused by excessive beta-carotene intake but is also more rarely associated with a few serious metabolic disorders.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12839253"}, {"offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "We describe a 3-year-old girl with long-standing yellow discoloration of her skin and a 3-fold increase in the plasma carotenoid concentration compared to normal, but no history of excessive carotene intake or familial carotenemia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7747541"}]}
+{"question_id": "65f85231c4010b4d7800004d", "question": "Which are the two main active ingredients of the standard PrEP (Pre-Exposure Prophylaxis)?", "answer": "Rmtricitabine and tenofovir are the main active ingredients of the standard PrEP (Pre-Exposure Prophylaxis).", "relevant_passage_ids": ["32801927", "31430318", "33569743", "30199098", "28322067", "27651184", "31558423", "29893246", "32164425", "27391203", "22067069", "30815960", "37198721", "32272075", "28919303", "23838404", "25300863", "30272493", "37798438", "37938875", "35653585", "22158861", "32711800"], "type": "list", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Pre-exposure prophylaxis (PrEP) against HIV infection with tenofovir/emtricitabine", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32801927"}, {"offsetInBeginSection": 32, "offsetInEndSection": 55, "text": "emtricitabine/tenofovir", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31430318"}, {"offsetInBeginSection": 836, "offsetInEndSection": 1026, "text": "PrEP with daily oral tenofovir/emtricitabine combination is the recommended PrEP regimen, and TDF alone can be considered as an alternative regimen for IDUs and heterosexually active adults.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27651184"}, {"offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine was adopted by WHO as a strategy to reduce HIV incidence.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31558423"}, {"offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Tenofovir disoproxil fumarate combined with emtricitabine is a highly effective oral pre-exposure prophylaxis (PrEP) agent for preventing the acquisition of HIV.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29893246"}, {"offsetInBeginSection": 161, "offsetInEndSection": 318, "text": "A novel distribution pathway of tenofovir-disoproxil fumarate and emtricitabine PrEP was implemented, which reduced monthly PrEP costs by 16-fold in Germany.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32164425"}, {"offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "INTRODUCTION: Tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are nucleoside reverse transcriptase inhibitors approved as pre-exposure prophylaxis (PrEP) against human immunodeficienc", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27391203"}, {"offsetInBeginSection": 211, "offsetInEndSection": 487, "text": "A pivotal component in the current drug combination regimens for the treatment of AIDS as well as the ongoing PrEP trials is tenofovir disoproxil fumarate (TDF, Viread\u00ae) and its combination with emtricitabine (FTC). The combination of TDF with FTC has been marketed as Truvada", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22067069"}, {"offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "The antiretroviral combination of emtricitabine-tenofovir disoproxil fumarate (FTC/TDF) was approved by the U.S. Food and Drug Administration for use as pre-exposure prophylaxis (PrEP) in individuals at high risk for acquiring human immunodeficiency virus (HIV) in July 2012.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30815960"}, {"offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "WHO guidelines recommend daily oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) for pre-exposure prophylaxis (PrEP) of HIV in people at high risk of HIV infection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37198721"}, {"offsetInBeginSection": 0, "offsetInEndSection": 332, "text": "The US Food and Drug Administration (FDA) approved oral daily tenofovir/emtricitabine (Truvada) for pre-exposure prophylaxis of human immunodeficiency virus (HIV) infection in 2012 on the basis of two randomized controlled trials (RCTs), one in men who have sex with men (MSM) and another in HIV serodiscordant heterosexual couples.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30199098"}, {"offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "Antiretroviral pre-exposure prophylaxis (PrEP) for the prevention of HIV infection was demonstrated to be efficacious and safe earlier this decade from pivotal studies using oral emtricitabine-tenofovir disoproxil fumarate.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32272075"}, {"offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "BACKGROUND: Pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate is highly effective against acquisition of H", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28919303"}, {"offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "INTRODUCTION: Tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are nucleoside reverse transcriptase inhibitors approved as pre-exposure prophylaxis (PrEP) against human immunodeficiency virus (HIV).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27391203"}, {"offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "BACKGROUND: Antiretroviral pre-exposure prophylaxis (PrEP), with daily oral tenofovir disoproxil fumarate or tenofovir disoproxil fumarate in combination with emtricitabine, has been shown to be efficacious for HIV-1 prevention.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25300863"}, {"offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Drug safety evaluation of oral tenofovir disoproxil fumarate-emtricitabine for pre-exposure prophylaxis for human immunodeficiency virus infection.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27391203"}, {"offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Pre-exposure prophylaxis (PrEP) with tenofovir/emtricitabine (TDF/FTC) will soon be available in the Netherlands.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23838404"}, {"offsetInBeginSection": 98, "offsetInEndSection": 364, "text": "HIV pre-exposure prophylaxis (PrEP) with daily coformulated emtricitabine and tenofovir disoproxil fumarate is a promising biomedical HIV prevention modality; however, it has not yet been shown to be efficacious in the transgender population due to data limitations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30272493"}, {"offsetInBeginSection": 0, "offsetInEndSection": 334, "text": "Pre-exposure prophylaxis (PrEP) with tenofovir (TFV) disoproxil fumarate and emtricitabine administered orally daily is effective in preventing human immunodeficiency virus (HIV) acquisition in both men and women with sufficient adherence; however, the adherence-efficacy relationship in cisgender women has not been well established.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37798438"}, {"offsetInBeginSection": 105, "offsetInEndSection": 341, "text": "Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) is currently the only medication recommended for pre-exposure prophylaxis (PrEP) by the Centers for Disease Control and Prevention (CDC) in people at high risk for HIV acquisition.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28322067"}, {"offsetInBeginSection": 212, "offsetInEndSection": 309, "text": "Two PrEP medications are currently approved: emtricitabine/tenofovir disoproxil fumarate (Truvada", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33569743"}, {"offsetInBeginSection": 20, "offsetInEndSection": 189, "text": "d event-driven HIV pre-exposure prophylaxis (PrEP) with oral tenofovir-emtricitabine is highly effective to prevent HIV in men who have sex with men (MSM). PrEP care gen", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37938875"}, {"offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Background: Daily pre-exposure prophylaxis (PrEP) regimen of tenofovir/emtricitabine", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35653585"}, {"offsetInBeginSection": 363, "offsetInEndSection": 497, "text": "Here, we evaluated two drugs that are preferentially used for PrEP: tenofovir (TFV) disoproxil fumarate (TDF) and emtricitabine (FTC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22158861"}, {"offsetInBeginSection": 172, "offsetInEndSection": 751, "text": "Here, we report primary results from a blinded phase 3 study evaluating the efficacy and safety of pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir alafenamide versus emtricitabine and tenofovir disoproxil fumarate for HIV prevention.METHODS: This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in regions of Europe and North America, where there is a high incidence of HIV or prevalence of people living with HIV, or both.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32711800"}, {"offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Penetration of tenofovir and emtricitabine in mucosal tissues: implications for prevention of HIV-1 transmission.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22158861"}]}
+{"question_id": "6451007857b1c7a315000093", "question": "What is the cause of Leigh syndrome?", "answer": "Leigh syndrome may result from several defects of mitochondrial enzyme complexes, including pyruvate dehydrogenase complex, and respiratory chain complexes I, II, III, IV, V.", "relevant_passage_ids": ["18651330", "8338207", "10443880", "36237717", "35217561", "19470250", "18805359", "17582259", "25681084", "20202874", "19714555", "29512743", "10360771", "15824269", "25807530", "33097395", "31334367", "21982779", "27344648", "26657515", "17106447", "36795052", "15214016", "12943968", "34849584", "23034978", "14729820", "8250532", "11317352", "21617257", "11955926", "7715756", "36813320", "34933094", "3125426", "32478789", "12134275", "19046652", "16023078", "20819849", "16773507", "18176892", "9063742", "33894360", "17336115", "25419155", "8411720", "2792954", "32351444", "26506407", "20472868", "24731534", "34045482", "19780766", "29228836", "28351484", "12661941"], "type": "factoid", "snippets": [{"offsetInBeginSection": 281, "offsetInEndSection": 443, "text": "It may result from several defects of mitochondrial enzyme complexes, including pyruvate dehydrogenase complex, and respiratory chain complexes I, II, III, IV, V.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18651330"}, {"offsetInBeginSection": 2788, "offsetInEndSection": 3040, "text": "Leigh syndrome may result from different enzyme defects, most notably pyruvate dehydrogenase complex deficiency, cytochrome c oxidase deficiency, complex I deficiency, and complex V deficiency associated with the recently described NARP point mutation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8338207"}, {"offsetInBeginSection": 0, "offsetInEndSection": 411, "text": "Leigh syndrome is a subacute necrotising encephalomyopathy proven by post-mortem analysis of brain tissue showing spongiform lesions with vacuolation of the neuropil followed by demyelination, gliosis and capillary proliferation caused by mutations in one of over 75 different genes, including nuclear- and mitochondrial-encoded genes, most of which are associated with mitochondrial respiratory chain function.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27344648"}, {"offsetInBeginSection": 143, "offsetInEndSection": 251, "text": "Deficiency of pyruvate dehydrogenase complex E1 alpha subunit (PDHA1) is the common cause of Leigh syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17582259"}, {"offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "Subacute necrotizing encephalomyelopathy (Leigh's syndrome) is a rare neurodegenerative disease in the adult. The precise metabolic defect is unknown, but abnormalities of a mitochondrial enzyme system related to cytochrome-c oxidase or pyruvate dehydrogenase are described.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7715756"}, {"offsetInBeginSection": 164, "offsetInEndSection": 353, "text": "Leigh syndrome is the most common clinical presentation of pediatric mitochondrial disease, typically appearing in the first few years of life, and involving severe multisystem pathologies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34933094"}, {"offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "A new patient with Leigh's syndrome (subacute necrotizing encephalomyelopathy due to pyruvate dehydrogenase complex deficiency) is presented.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3125426"}, {"offsetInBeginSection": 90, "offsetInEndSection": 288, "text": "We report a novel m.4296G>A variant in the mitochondrial tRNA isoleucine gene in a child with Leigh syndrome, mitochondrial proliferation, lactic acidosis, and abnormal respiratory chain enzymology.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21982779"}, {"offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Leigh syndrome is the most common pediatric presentation of mitochondrial disease. This neurodegenerative disorder is genetically heterogeneous, and to date pathogenic mutations in >75 genes have been identified, encoded by 2 genomes (mitochondrial and nuclear).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26506407"}, {"offsetInBeginSection": 0, "offsetInEndSection": 447, "text": "Leigh syndrome or subacute necrotizing encephalomyelopathy is a rare, rapidly progressive neurodegenerative disorder. In general, symptoms such as shortness of breath and decreased cardiac function usually occur within 1 year of life. It is a serious disease with a mortality rate of 75% in 2-3 years. The cause of Leigh syndrome is DNA mutation. Approximately 75% of patients have nuclear DNA mutations while 25% have mitochondrial DNA mutations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36237717"}, {"offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Leigh disease presenting in utero due to a novel missense mutation in the mitochondrial DNA-ND3.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20202874"}, {"offsetInBeginSection": 199, "offsetInEndSection": 410, "text": "It can be caused by more than 75 different gene mutations, of nuclear and mitochondrial origin, involving all respiratory chain complexes, with less than 25% of Leigh syndrome having mitochondrial DNA mutations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31334367"}, {"offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "The most common mitochondrial disorder in children is Leigh syndrome, which is a progressive and genetically heterogeneous neurodegenerative disorder caused by mutations in nuclear genes or mitochondrial DNA (mtDNA).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29228836"}, {"offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Leigh syndrome (LS) is a neurogenetic disorder of children caused by mutations in at least 75 genes which impair mitochondrial bioenergetics.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28351484"}]}
+{"question_id": "65d129621930410b1300002e", "question": "What is Primary Diffuse Meningeal Melanomatosis?", "answer": "Primary Diffuse Meningeal Melanomatosis is a rare variant of meningeal melanoma that causes diffusely invasive lesions of the pia mater with a tumor of melanocytic origin.", "relevant_passage_ids": ["35166475", "32004738", "31690266", "20220448", "12533338", "17330185", "36412389", "30516687", "35260265", "35060532", "30496931", "21743173", "23483049", "8852008", "28126183", "20558070"], "type": "summary", "snippets": [{"offsetInBeginSection": 158, "offsetInEndSection": 369, "text": "In case of diffusely invasive lesions of the pia mater with a tumor of melanocytic origin (without signs of extracranial metastases), the tumors are classified as primary diffuse meningeal melanomatosis (PDMM). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35166475"}, {"offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "BACKGROUND: Primary meningeal melanomatosis is a rare leptomeningeal tumor, and the diagnosis is challenging due to nonspecific clinical symptoms and radiologic findings.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32004738"}, {"offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Primary diffuse meningeal melanomatosis - a rare form of meningeal melanoma: case report.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31690266"}, {"offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "BACKGROUND: Meningeal melanomatosis is a rare type of central nervous system neoplasm (with incidence ranging between 3 and 5%) that develops in the course of malignant melanoma. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31690266"}, {"offsetInBeginSection": 0, "offsetInEndSection": 299, "text": "Primary diffuse meningeal melanomatosis can clinically mimic a wide variety of other conditions, including lymphoma, leukemia, neurosarcoidosis, metastatic carcinoma, acute disseminated encephalomyelitis, subacute meningitis, viral encephalitis, and idiopathic hypertrophic cranial pachymeningitis. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20220448"}, {"offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "We report a case of primary diffuse meningeal melanomatosis, a rare variant of primary malignant melanoma of the CNS, in a 68-year-old woman. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12533338"}, {"offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Melanoma malignum constitutes only 0.1% of central nervous system neoplasms. It can occur either as a solid tumour or as a diffuse meningeal melanomatosis. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17330185"}, {"offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Meningeal melanomatosis is an infrequent tumor originating from the melanocytes in the leptomeninges and one of the recognized primary melanocytic tumors of the central nervous system.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36412389"}, {"offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Meningeal melanomatosis is an infrequent tumor originating from the melanocytes in the leptomeninges and one of the recognized primary melanocytic tumors of the central nervous system", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36412389"}, {"offsetInBeginSection": 14, "offsetInEndSection": 137, "text": "Primary diffuse leptomeningeal melanomatosis is an extremely rare variant of primary melanoma of the central nervous system", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35260265"}, {"offsetInBeginSection": 11, "offsetInEndSection": 126, "text": "Primary diffuse leptomeningeal melanomatosis (PDLM) is a rare disease that affects melanocytes in the leptomeninges", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35060532"}, {"offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "Primary melanocytic neoplasms of the central nervous system (CNS) are rare lesions arising from melanocytes of the leptomeninges. They include diffuse leptomeningeal melanocytosis or melanomatosis, melanocytoma and primary malignant melanoma. We have reviewed the English literature regarding these lesions, which ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20558070"}, {"offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "BACKGROUND: Primary diffuse leptomeningeal melanomatosis (PDLM) is an extremely rare pathologic condition that can mimic several other neurologic disease states.METHODS: We report a rare case of PDLM without evidence of a primary focus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30496931"}, {"offsetInBeginSection": 158, "offsetInEndSection": 368, "text": "In case of diffusely invasive lesions of the pia mater with a tumor of melanocytic origin (without signs of extracranial metastases), the tumors are classified as primary diffuse meningeal melanomatosis (PDMM).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35166475"}, {"offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "INTRODUCTION: Primary diffuse leptomeningeal melanomatosis is an extremely rare variant of primary melanoma of the central nervous system.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35260265"}, {"offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "We report a case of primary diffuse meningeal melanomatosis, a rare variant of primary malignant melanoma of the CNS, in a 68-year-old woman.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12533338"}, {"offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "BACKGROUND: Primary meningeal melanomatosis is a rare leptomeningeal tumor, and the diagnosis is challenging due to nonspecific clinical symptoms and radiolog", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32004738"}, {"offsetInBeginSection": 0, "offsetInEndSection": 629, "text": "Primary diffuse meningeal melanomatosis can clinically mimic a wide variety of other conditions, including lymphoma, leukemia, neurosarcoidosis, metastatic carcinoma, acute disseminated encephalomyelitis, subacute meningitis, viral encephalitis, and idiopathic hypertrophic cranial pachymeningitis. We report on a young patient with primary diffuse meningeal melanomatosis who presented with papilledema, flaccid paraparesis, and cognitive impairment. The importance of imaging of the whole central nervous system, cerebrospinal fluid analysis, and pathohistological examination is emphasized in making the appropriate diagnosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20220448"}, {"offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Primary meningeal melanomatosis is a rare, aggressive variant of primary malignant melanoma of the central nervous system, which arises from melanocytes within the leptomeninges and carries a poor prognosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23483049"}, {"offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Primary meningeal melanomatosis is a rare, aggressive variant of primary malignant melanoma of the central nervous system, which arises from melanocytes within the leptomeninges and carries a poor prognosis. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23483049"}, {"offsetInBeginSection": 0, "offsetInEndSection": 788, "text": "Melanoma malignum constitutes only 0.1% of central nervous system neoplasms. It can occur either as a solid tumour or as a diffuse meningeal melanomatosis. A case of the latter form of central nervous system melanoma is presented in a 44-year-old man, suffering from headaches, cerebrospinal fluid protein elevation, optic disc oedema, hydrocephalus, seizures, cranial nerves and multilevel spinal root damage. Above mentioned neurological manifestations gradually increased within 18 months after onset of first symptoms of the disease (headache). The clinical course in our patient suggested diffuse leptomeningeal involvement. Despite the use of detailed diagnostic procedures, the correct diagnosis of primary diffuse meningeal melanomatosis was established at postmortem examination.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17330185"}, {"offsetInBeginSection": 0, "offsetInEndSection": 935, "text": "A case of primary leptomeningeal melanomatosis without cutaneous lesions is reported. The clinical findings for a six months period were: intracranial hypertension syndrome, progressive cranial polineuropathy and a spinal involvement in a six years old child. CT brain scan showed enlarged subarachnoid spaces without contrast enhancement. MRI brain scan evidenced furthermore a focal lesion in right talamus. MRI spinal scan was normal. Examination of CSF showed elevated protein and reduced glucose concentrations as well as mild pleocytosis. Serologies and cultures investigating viral, bacterial, mycobacterial, fungal or parasitic infections resulted negative. CSF cytologic examination failed to show malignant cells. Postmortem diagnosis after neuropathological examination was made. This is an uncommon case of primary leptomeningeal melanomatosis, presenting the difficulty of diagnosis when cutaneous lesions are not present.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8852008"}, {"offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "We report a case of primary diffuse meningeal melanomatosis, a rare variant of primary malignant melanoma of the CNS, in a 68-year-old woman. The disease mimicked intracranial hypotension syndrome and was diagnosed only at autopsy (CSF cytologic results were negative).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12533338"}, {"offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Meningeal melanomatosis is an infrequent tumor originating from the melanocytes in the leptomeninges and one of the recognized primary melanocytic tumors of the central nervous system. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36412389"}, {"offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "BACKGROUND: Meningeal melanomatosis is an extra-axial well-encapsulated malignant tumour with diffuse meningeal growth and dark coloration (due to high melanin contents), while meningeal melanocytoma is the focalized ben", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28126183"}, {"offsetInBeginSection": 85, "offsetInEndSection": 290, "text": "These lesions arise from the melanocytes located within leptomeninges and include diffuse melanocytosis and meningeal melanomatosis (seen in neurocutaneous melanosis), melanocytoma, and malignant melanoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21743173"}, {"offsetInBeginSection": 28, "offsetInEndSection": 105, "text": "diffuse meningeal melanomatosis, a rare variant of primary malignant melanoma", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12533338"}, {"offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "INTRODUCTION: Primary diffuse leptomeningeal melanomatosis is an extremely rare variant of primary melanoma of the central nervous system. It is characterized by a variety of nonspecific clinical, radiological, and histopathological features requiring differential diagnosis from a variet", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35260265"}, {"offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Primary diffuse leptomeningeal melanomatosis is a rare variant of malignant melanoma of the central nervous system, arising from melanocytes of leptomeninges.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30516687"}]}
+{"question_id": "65f77236c4010b4d7800001f", "question": "Do black race patients have worse survival in colorectal cancer?", "answer": "Yes, black patients with Stage IV colorectal cancer have worse survival if they are older age and did not receive chemotherapy. Black patients in the study population were more likely to be female, have medical comorbidities, and come from areas with lower average income and baseline education. Among patients younger than 45 years, black patients had significantly increased hazard of death compared to white patients. , It is worth noting that outcomes in colorectal cancer treatment are historically worse in Black people and residents of rural areas. The intersection of race and rurality worsens outcomes, with the poorest outcomes observed in black individuals in rural areas. Genomics also play a role, as black patients have a higher incidence of colorectal cancer and worse survival rates when compared to white people.", "relevant_passage_ids": ["29146523", "24231453", "19673013", "35176030", "10826011", "23576691", "35078631", "37859816", "34374082", "36586755", "28538169", "36636091", "38082093", "20626015", "27138583", "21997132", "23375764", "31600666", "12560428", "24440976", "26703651", "18708384", "27467183", "15983985", "10564677", "35905109", "22012028", "11076244", "24662267", "31632483", "37868544", "16601428", "21710235", "33234793", "17116545", "33141623", "18300824"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1189, "offsetInEndSection": 1356, "text": "The absolute 5-year survival difference between black and white unmatched patients with CRC was 9.2% (57.3% for black patients vs 66.5% for\u00a0white patients; P\u00a0<\u00a0.0001).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29146523"}, {"offsetInBeginSection": 1068, "offsetInEndSection": 1507, "text": "Unadjusted survival analysis found a 15% higher chance of dying for black patients compared with white patients (hazard ratio [HR] = 1.15; 95% confidence interval (CI) = 1.08 to 1.22; P < .001). Adjustment for patient, tumor, and demographic variables marginally reduced the risk of death (HR = 1.08; 95% CI = 1.01 to 1.15; P = .03). After adjustment for differences in treatment, the increased risk of death for black patients disappeared", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24231453"}, {"offsetInBeginSection": 1944, "offsetInEndSection": 2171, "text": "In an analysis of data\u00a0from the National Cancer Database, we found that insurance coverage differences accounted for approximately one half of the disparity in survival rate of black vs white patients with CRC, 18-64 years old;", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29146523"}, {"offsetInBeginSection": 1216, "offsetInEndSection": 1478, "text": "Compared to Whites, Blacks (AOR: 1.99; 95% CI: 1.64-2.41), Hispanics (AOR: 2.49; 95% CI: 1.94-3.19) and colorectal cancer patients in the other category (AOR: 1.72; 95% CI: 1.35-2.18) were more likely to receive inpatient treatment with chemotherapy/radiotherapy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38082093"}, {"offsetInBeginSection": 1625, "offsetInEndSection": 2093, "text": "Propensity-score matching identified 27,640 patients; Black race was associated with worse 5-year overall survival (67.5% vs 70.2%, P\u00a0= .003) and cancer-specific survival (79.4% vs 82.3%, P < .001).CONCLUSIONS: This US population-based analysis confirms poorer overall survival and cancer-specific survival in Black patients undergoing surgery for nonmetastatic colon cancer despite accounting for trans-sectoral factors that have been implicated in structural racism.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35078631"}, {"offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "BACKGROUND: Black patients are disproportionally impacted by colorectal cancer, both with respect to incidence and mortality.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35078631"}, {"offsetInBeginSection": 931, "offsetInEndSection": 1199, "text": "Black patients have significantly lower rates of receiving chemotherapy as compared to white patients (61.1% vs 75.37%, p\u00a0=\u00a00.0018).CONCLUSION: Patients with Stage IV colorectal cancer have worse survival if they are black, older age, and did not receive chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36586755"}, {"offsetInBeginSection": 2042, "offsetInEndSection": 2384, "text": "Decreased survival outcomes in Black patients were more pronounced for those who underwent nonstandard treatment, particularly when treating stage III disease (HR: 1.30; 95% CI: 1.19-1.42; P<0.0001).Conclusions: Nonstandard treatment in stage II and III rectal cancer is associated with worse survival compared to standard treatment regimens.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36636091"}, {"offsetInBeginSection": 235, "offsetInEndSection": 600, "text": "Our objective is to determine if Black compared to White race is associated with worse survival in colon cancer, while accounting for socioeconomic and clinical factors.METHODS: A retrospective analysis was performed of Black or White patients with nonmetastatic colon cancer in the Surveillance, Epidemiology, and End Results cancer registry between 2008 and 2016.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35078631"}, {"offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "BACKGROUND AND OBJECTIVE: African Americans have worse outcomes in colorectal can", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24440976"}, {"offsetInBeginSection": 145, "offsetInEndSection": 400, "text": "The mortality rate from CRC is highest among African Americans compared to any other racial or ethnic group. Much of the disparity in mortality is likely due to diagnosis at later stages of the disease, which could result from unequal access to screening.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26703651"}, {"offsetInBeginSection": 997, "offsetInEndSection": 1166, "text": " (6.2%) non-Chinese Asians. African-Americans had a greater proportion of metastatic stage at presentation (P < 0.0001) and decreased CRC-specific survival (P < 0.0001 f", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18708384"}, {"offsetInBeginSection": 1167, "offsetInEndSection": 1643, "text": "r colon and rectal cancer). After adjustment for age, sex, histology, site within the colon, and stage, African-Americans [colon: HR, 1.19; 95% confidence interval (95% CI), 1.14-1.25; rectum: HR, 1.27; 95% CI, 1.17-1.38] had an increased risk of death compared with Caucasians. However, after further adjustment for SES and treatment, the risk of death for African-Americans compared with Caucasians was substantially diminished (colon: HR, 1.08; 95% CI, 1.03-1.13; rectum: H", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18708384"}, {"offsetInBeginSection": 1472, "offsetInEndSection": 2018, "text": "Black patients experienced lower rates and risk of grade \u22653 fatigue (6.6% vs 13.3%; OR, 0.46; 95% CI, 0.24-0.91) but were equally likely to be treated with a dose reduction (OR, 1.09; 95% CI, 0.72-1.65).CONCLUSIONS: No difference in OS, PFS, or response to therapy was observed between Black patients and White patients in an equal treatment setting of the CALGB/SWOG 80405 randomized controlled trial.LAY SUMMARY: Despite improvements in screening and treatment, studies have demonstrated worse outcomes in Black patients with colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34374082"}, {"offsetInBeginSection": 0, "offsetInEndSection": 2089, "text": "Among all racial groups in the U.S., African Americans (AA) have the highest incidence of and mortality from colorectal cancer (CRC). Although socioeconomic factors, as the major contributors to racial disparity of CRC, have been widely investigated, there is a dearth of information germane to understanding its biological basis. To better elucidate the clinicopathologic features we extracted demographic, clinical, pathologic and molecular features of 500 consecutive cases of CRC diagnosed at our institution which has an AA-predominant patient population (75% of all patients). We compared data from our AA patients with those of white patients both from our institution and from SEER and the published literature for meaningful comparison. AA patients were more likely to be at an advanced disease stage (25.9% vs. 20.8%, p = 0.041), have low grade tumors (89.2% vs. 77.5%, p<0.001) in cecum (18.7% vs. 16.2%, p<0.001) and <60-years-old than white patients (31.8% vs. 26.3%, p = 0.015). The frequency of KRAS mutation was higher in AA patients than in white patients (56.8% vs. 20.7%, p<0.001). Amongst subtypes of KRAS tested in CRC, codon 12 mutation is more common in AA than white patients (85.2% vs. 68.9%, p = 0.020). Compared with other racial groups, we found AA patients to have worse disease-free survival (HR = 3.682, p = 0.035). Also, AA patients with CRC in distal (sigmoid and rectum) or proximal (cecum) colon have worse overall survival than those with CRC in middle colon (HR = 2.926, p = 0.014), a finding not observed in white patients. In both racial groups, advanced stage, perforation, and hypertension were independent prognostic factors for overall survival (p<0.05). Similarly, low body-mass index at presentation, mucinous adenocarcinoma, lymphovascular invasion, perineural invasion and KRAS mutations were independent factors significantly associated with poor disease-free survival. Collectively, our data provide new insights into the roles of clinicopathologic features, especially anatomic distribution, in predicting outcomes of CRC in AA population.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35905109"}, {"offsetInBeginSection": 182, "offsetInEndSection": 290, "text": "Survival from CRC in AAs is lower than in Caucasians, and the mean age of CRC development in AAs is younger.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21710235"}, {"offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "African Americans have the greatest incidence of colorectal cancer than any other racial or ethnic group. This population's survival from colorectal cancer is lower than that in the White population.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18300824"}, {"offsetInBeginSection": 12, "offsetInEndSection": 275, "text": "Black patients and underinsured patients with colorectal cancer (CRC) present with more advanced disease and experience worse outcomes. The study aim was to evaluate the interaction of health insurance status and race with treatment and survival in metastatic CRC", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35176030"}, {"offsetInBeginSection": 819, "offsetInEndSection": 991, "text": " Chemotherapy use was higher among White compared to Black patients. 3-year mortality rate was higher for Blacks and lower for Hispanics, in comparison with White patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35176030"}, {"offsetInBeginSection": 522, "offsetInEndSection": 824, "text": "In American blacks, there is evidence for a higher prevalence of right-sided colonic tumors and an earlier age of onset of colorectal cancer. In addition, blacks have the highest colon cancer incidence in the United States among ethnic groups and have poorer 5-year survival rates compared with whites.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10826011"}, {"offsetInBeginSection": 853, "offsetInEndSection": 974, "text": "among patients younger than 50 years old, NHBs experienced significantly worse OS than NHWs (HR: 2.03, 95% CI: 1.30-3.19)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23576691"}, {"offsetInBeginSection": 231, "offsetInEndSection": 475, "text": ". This study assessed whether non-Hispanic Whites (NHW) and non-Hispanic Blacks (NHB) differ in colon cancer survival in an equal-access health care system and examined whether racial differences varied by demographic and tumor characteristics.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23576691"}, {"offsetInBeginSection": 818, "offsetInEndSection": 1082, "text": "Black patients had significantly lower overall survival compared to White patients, with median overall survival of 1.9 years and 2.5 years respectively. In a multivariate analysis, Black race posed a significant hazard (HR 1.70, CI 1.01-2.90, p=0.0467) for death.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28538169"}, {"offsetInBeginSection": 1014, "offsetInEndSection": 1142, "text": ". Black patients had worse long-term survival after colorectal surgery (hazard ratio [HR], 1.21; 95% CI, 1.17 to 1.25; P < .001)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23375764"}, {"offsetInBeginSection": 2159, "offsetInEndSection": 2319, "text": " Black patients had lower five-year survival rates when compared with their White counterparts as well as increased rates of being diagnosed with this disease. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37868544"}, {"offsetInBeginSection": 972, "offsetInEndSection": 1468, "text": "Black patients had a 41% increased risk of presenting at advanced stage per IoD [risk ratio (RR) 1.41, 95% confidence intervals (CI) 1.18, 1.69] and White patients saw a 17% increase (RR 1.17, 95%CI 1.04, 1.31). Black patients were 5% less likely to undergo surgical resection (RR 0.95, 95%CI 0.90, 0.99), whereas Whites were 5% more likely (RR 1.05, 95%CI 1.03, 1.07). Black patients had 43% increased hazards of cancer-specific mortality with increasing IoD (hazard ratio (HR) 1.43, 95%CI 1.17,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33234793"}, {"offsetInBeginSection": 1261, "offsetInEndSection": 1504, "text": "The results revealed poor overall survival for AAs compared with EAs, especially for those\u00a0< 50 years of age. The greater prevalence of proximal CRC at diagnosis among younger AAs (vs. EAs) might contribute to the racial difference in survival", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28065664"}, {"offsetInBeginSection": 14, "offsetInEndSection": 142, "text": "African Americans (AAs) compared with European Americans (EAs) have poorer stage-specific survival from colorectal cancer (CRC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28065664"}]}
+{"question_id": "65f1dadac4010b4d78000007", "question": "Can Antioxidant curcumin kill tumor cells?", "answer": "Yes,  Antioxidant curcumin can kill tumor cells", "relevant_passage_ids": ["37191314", "36986483", "37333486", "37210578", "20426658", "22508043", "11795474", "34904972", "11676493", "29642292", "24495080", "24453488", "24566313", "36358950", "17069615", "21110780", "28628644", "26004342", "25349781", "32116190", "23489691", "12680238", "10456330", "37979287", "37957863", "37806480", "37587146", "37322603", "16376585", "15142674", "31717651", "27051644", "22475723", "24627632", "18347134", "27572503", "32307747", "10069393", "25360677", "28949267", "18252805", "25667441", "29752960", "37820211"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Curcumin inhibits colon cancer malignant progression and promotes T cell killing by regulating miR-206 expression", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37191314"}, {"offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Curcumin and Andrographis Exhibit Anti-Tumor Effects in Colorectal Cancer via Activation of Ferroptosis and Dual Suppression of Glutathione Peroxidase-4 and Ferroptosis Suppressor Protein-1.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36986483"}, {"offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Curcumin induces apoptosis in human hepatocellular carcinoma cells by decreasing the expression of STAT3/VEGF/HIF-1\u03b1 signaling.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37333486"}, {"offsetInBeginSection": 747, "offsetInEndSection": 886, "text": "The CUR/SeNPs present excellent antitumor efficacy, respectively, which supports the nanocomposite matrix to efficiently kill cancer cells ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34904972"}, {"offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Curcumin is known to possess various biological functions, including anti-inflammatory, antioxidative, and anti-cancer activities", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29642292"}, {"offsetInBeginSection": 426, "offsetInEndSection": 565, "text": "Drugs such as etoposide, doxorubicin, and mitoxantrone are frontline therapies for a variety of solid tumors and hematological malignancies", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24495080"}, {"offsetInBeginSection": 1270, "offsetInEndSection": 1481, "text": "In conclusion, we demonstrated for the first time that antioxidants such as trolox can potentiate cancer cell killing by curcumin, a finding which may help in the development of novel drug combination therapies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22508043"}, {"offsetInBeginSection": 1367, "offsetInEndSection": 1559, "text": "This study provided data on the potential cytotoxic activity of the combination of CUR with DSS and may provide a useful tool for the development of a therapeutic combination against melanoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36358950"}, {"offsetInBeginSection": 1226, "offsetInEndSection": 1433, "text": "The data together suggested that curcumin may inhibit cancer cells proliferation by perturbing microtubule assembly dynamics and may be used to develop efficacious curcumin analogues for cancer chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17069615"}, {"offsetInBeginSection": 573, "offsetInEndSection": 718, "text": "The combination of curcumin (10 \u03bcM) and trolox (10-50 \u03bcM) induced apoptosis of cancer cells as evidenced by PARP cleavage and caspase-3 activatio", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22508043"}, {"offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Curcumin, a natural polyphenol in the spice turmeric, has been found to exhibit anticancer activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22508043"}, {"offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "Curcumin, a phenolic antioxidant compound derived from the rhizome of the turmeric plant Curcuma longa, has proven to be a modulator of intracellular signaling pathways that control cancer cell growth, inflammation, invasion and apoptosis, revealing its anticancer potential.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24566313"}, {"offsetInBeginSection": 0, "offsetInEndSection": 430, "text": "Curcumin, the active ingredient from the spice turmeric (Curcuma longa Linn), is a potent antioxidant and anti-inflammatory agent. It has been recently demonstrated to possess discrete chemopreventive activities. However, the molecular mechanisms underlying such anticancer properties of curcumin still remain unrealized, although it has been postulated that induction of apoptosis in cancer cells might be a probable explanation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11676493"}, {"offsetInBeginSection": 0, "offsetInEndSection": 783, "text": "Curcumin, a well-known dietary pigment derived from Curcuma longa, has been shown to be a potent antiinflammatory, antioxidant, and anticarcinogenic compound. The present study was designed to investigate the cytotoxic potential of curcumin against a range of human tumor cell lines in an attempt to understand its mechanism of action, which may lead to its possible therapeutic applications. We have shown that different cancer cell lines differ in their sensitivity to curcumin. Cell lines established from malignancies like leukemia, breast, colon, hepatocellular, and ovarian carcinomas underwent apoptosis in the presence of curcumin, whereas cell lines from lung, kidney, prostate, cervix, CNS malignancies, and melanomas showed resistance to the cytotoxic effects of curcumin.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11795474"}, {"offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Curcumin is a polyphenol derived from the plant Curcuma longa that induces apoptotic cell death in malignant cancer cell lines.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21110780"}, {"offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Curcumin, an extract from the turmeric rhizome (Curcuma longa), is known to exhibit anti-inflammatory, antioxidant, chemopreventive and antitumoral activities against aggressive and recurrent cancers. Accumulative data indicate that curcumin may induce cancer cell death.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28628644"}, {"offsetInBeginSection": 227, "offsetInEndSection": 312, "text": "Curcumin, obtained from the rhizome of Curcuma longa, has potent anticancer activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26004342"}, {"offsetInBeginSection": 600, "offsetInEndSection": 753, "text": "Curcumin suppresses the growth of human malignant glioma cells via ROS-dependent prostate apoptosis response-4 (Par-4) induction and ceramide generation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25349781"}, {"offsetInBeginSection": 2044, "offsetInEndSection": 2184, "text": "These findings support further studies on the therapeutic potential of CUR in combination with standard therapies in breast cancer patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23489691"}, {"offsetInBeginSection": 721, "offsetInEndSection": 934, "text": "Furthermore, expression of the pro-apoptotic protein Bad was up-regulated and expression of the anti-apoptotic proteins Bcl-2 and Bcl-xl was down-regulated in cells that had been treated with trolox plus curcumin.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22508043"}, {"offsetInBeginSection": 573, "offsetInEndSection": 720, "text": "The combination of curcumin (10 \u03bcM) and trolox (10-50 \u03bcM) induced apoptosis of cancer cells as evidenced by PARP cleavage and caspase-3 activation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22508043"}, {"offsetInBeginSection": 101, "offsetInEndSection": 279, "text": "Although curcumin is generally considered an antioxidant, it is also able to elicit apoptosis through the generation of ROS, thereby functioning as a pro-oxidant in cancer cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22508043"}, {"offsetInBeginSection": 848, "offsetInEndSection": 1130, "text": "This review aims to discuss TRAIL and its underlying apoptotic mechanisms, the combinational treatment of Cur and TRAIL in view of their respective limitations, and the underlying apoptotic mechanisms activated by the sensitization of cancers by Cur towards TRAIL-induced apoptosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32116190"}, {"offsetInBeginSection": 1754, "offsetInEndSection": 1906, "text": "Thus dietary curcumin ameliorates radiation-induced pulmonary fibrosis and increases mouse survival while not impairing tumor cell killing by radiation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20426658"}, {"offsetInBeginSection": 136, "offsetInEndSection": 424, "text": "In this study, we tested the hypothesis that a multifunctional nanocomposite platform containing nanoparticles (NPs) with the photothermal agent IR820 and bioactive drug curcumin (Cur) would be able to prevent tumor recurrence, limit bacterial wound infections, and promote wound healing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37979287"}, {"offsetInBeginSection": 1348, "offsetInEndSection": 1445, "text": " Curcuminoids could be a promising anti-cancer agent for the treatment of human colorectal cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37957863"}, {"offsetInBeginSection": 1786, "offsetInEndSection": 1883, "text": "Furthermore, these anti-cancer effects were higher when using Niosomal (Asc\u00a0+\u00a0Cur) than Asc\u00a0+\u00a0Cur", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37806480"}, {"offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Resveratrol, curcumin, and quercetin are the secondary metabolites from medicinal food homology plants, that have been proven their potency in cancer treatment", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37587146"}, {"offsetInBeginSection": 614, "offsetInEndSection": 713, "text": "Curcumin treatment inhibited proliferation and migration of cancer cells in a dose dependent manner", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37322603"}, {"offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "Curcumin, a natural polyphenol in the spice turmeric, has been found to exhibit anticancer activity. Although curcumin is generally considered an antioxidant, it is also able to elicit apoptosis through the generation of ROS, thereby functioning as a pro-oxidant in cancer cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22508043"}, {"offsetInBeginSection": 0, "offsetInEndSection": 590, "text": "Curcumin is a polyphenol derived from the plant Curcuma longa that induces apoptotic cell death in malignant cancer cell lines. It has been shown previously that mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) plays an essential role in defense against oxidative stress by supplying NADPH for antioxidant systems. This study demonstrates that curcumin decreased the activity of IDPm, both as a purified enzyme and in cultured cells. It also shows that curcumin-induced apoptosis in the colon cancer cell line HCT116 is significantly enhanced by suppression of IDPm activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21110780"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1131, "text": "Curcumin, the active ingredient from the spice turmeric (Curcuma longa Linn), is a potent antioxidant and anti-inflammatory agent. It has been recently demonstrated to possess discrete chemopreventive activities. However, the molecular mechanisms underlying such anticancer properties of curcumin still remain unrealized, although it has been postulated that induction of apoptosis in cancer cells might be a probable explanation. In the current study, curcumin was found to decrease the Ehrlich's ascites carcinoma (EAC) cell number by the induction of apoptosis in the tumor cells as evident from flow-cytometric analysis of cell cycle phase distribution of nuclear DNA and oligonucleosomal fragmentation. Probing further into the molecular signals leading to apoptosis of EAC cells, we observed that curcumin is causing tumor cell death by the up-regulation of the proto-oncoprotein Bax, release of cytochrome c from the mitochondria, and activation of caspase-3. The status of Bcl-2 remains unchanged in EAC, which would signify that curcumin is bypassing the Bcl-2 checkpoint and overriding its protective effect on apoptosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11676493"}, {"offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Curcumin, an active ingredient from the rhizome of the plant, Curcuma longa, has antioxidant, anti-inflammatory and anti-cancer activities. It has recently been demonstrated that the chemopreventive activities of curcumin might be due to its ability to inhibit cell growth and induce apoptosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16376585"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1014, "text": "Curcumin, the active ingredient of the rhizome of Curcuma longa has anti-inflammatory, antioxidant and antiproliferative activities. Although its precise mode of action remains elusive, studies have shown that chemopreventive action of curcumin might be due to its ability to induce apoptosis in cancer cells. Curcumin was shown to be responsible for the inhibition of AK-5 tumor (a rat histiocytoma) growth by inducing apoptosis in AK-5 tumor cells via caspase activation. This study was designed to investigate the mechanism leading to the induction of apoptosis in AK-5 tumor cells. Curcumin treatment resulted in the hyperproduction of reactive oxygen species (ROS), loss of mitochondrial membrane potential (delta psi(m)) and cytochrome c release to the cytosol, with the concomitant exposure of phosphatidylserine (PS) residues on the cell surface. This study suggests redox signalling and caspase activation as the mechanisms responsible for the induction of curcumin mediated apoptosis in AK-5 tumor cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10456330"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1194, "text": "Curcumin, a phenolic compound from the rhizome of the plant Curcuma longa has anti-inflammatory, antioxidant and anti-cancer activities. Although the precise mode of action of this compound is not yet elucidated, studies have shown that chemo-preventive action of curcumin might be due to its ability to induce apoptosis and to arrest cell cycle. This study investigated the cellular and molecular changes induced by curcumin leading to the induction of apoptosis in human lung cancer cell lines-A549 and H1299. A549 is p53 proficient and H1299 is p53 null mutant. The lung cancer cells were treated with curcumin (0-160 microM) for 12-72 h. Curcumin inhibited the growth of both the cell lines in a concentration dependent manner. Growth inhibition of H1299 cell lines was both time and concentration dependent. Curcumin induced apoptosis in both the lung cancer cell lines. A decrease in expression of p53, bcl-2, and bcl-X(L) was observed after 12 h exposure of 40 microM curcumin. Bak and Caspase genes remained unchanged up to 60 microM curcumin but showed decrease in expression levels at 80-160 microM. The data also suggest a p53 independent induction of apoptosis in lung cancer cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15142674"}, {"offsetInBeginSection": 303, "offsetInEndSection": 450, "text": "Curcumin exhibits anti-inflammatory, anticarcinogenic, antiproliferative, antiangiogenic, and antioxidant properties in various cancer cell models.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22475723"}, {"offsetInBeginSection": 216, "offsetInEndSection": 702, "text": "The anticancer potential of curcumin stems from its ability to suppress proliferation of a wide variety of tumor cells, down-regulate transcription factors NF-kappa B, AP-1 and Egr-1; down-regulate the expression of COX2, LOX, NOS, MMP-9, uPA, TNF, chemokines, cell surface adhesion molecules and cyclin D1; down-regulate growth factor receptors (such as EGFR and HER2); and inhibit the activity of c-Jun N-terminal kinase, protein tyrosine kinases and protein serine/threonine kinases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12680238"}, {"offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Curcumin (diferuloylmethane) is found in large quantities in the roots of Curcuma longa. It possesses strong antioxidant and anti-inflammatory properties, and inhibits chemically-induced carcinogenesis in the skin, forestomach, colon, and liver.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24627632"}, {"offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Curcumin (diferuloylmethane), a natural polyphenol present in turmeric, possesses a wide spectrum of pharmacological properties, including antioxidant and antitumor metastatic activities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27572503"}, {"offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "BACKGROUND: Curcumin has been shown to exert pleiotropic biological effects, including anti-tumorigen", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31717651"}, {"offsetInBeginSection": 494, "offsetInEndSection": 727, "text": "Curcumin is a natural phenolic compound which shows potent anticancer activities in different tumors, alone or as an adjuvant with other antitumor drugs to prevent or inhibit the survival and cancer progression by various mechanisms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32307747"}, {"offsetInBeginSection": 1012, "offsetInEndSection": 1227, "text": "It has been demonstrated that curcumin regulates signaling pathways in cancer cells, reduces the expression of proteins related to drug resistance, and increases the performance of antitumor drugs at various levels.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32307747"}, {"offsetInBeginSection": 1228, "offsetInEndSection": 1340, "text": "Curcumin reverses multidrug resistance mechanisms and increases sensitivity of resistance cells to chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32307747"}, {"offsetInBeginSection": 137, "offsetInEndSection": 210, "text": "Curcumin inhibited AK-5 tumor growth and induced apoptosis in AK-5 cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10069393"}, {"offsetInBeginSection": 329, "offsetInEndSection": 556, "text": "Curcumin, a natural polyphenol compound found in the spice turmeric, is known for its anti-cancer properties at doses over 10 \u00b5M, and often at 50 \u00b5M, and it exerts its effects on cancer cells in part by activation of MAP kinase", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25360677"}, {"offsetInBeginSection": 1271, "offsetInEndSection": 1424, "text": "But curcumin-loaded SLN exhibited antioxidant properties, substantiating the conclusions that curcumin's effect in cancer cells is highly dose dependent.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28949267"}, {"offsetInBeginSection": 646, "offsetInEndSection": 874, "text": "The results demonstrated that MG-63 osteosarcoma cells were much more sensitive in terms of cytotoxicity to curcumin, while the healthy human osteoblasts exhibited a higher healthy viability after 24 hours of curcumin treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24453488"}, {"offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Curcumin is known to possess various biological functions, including anti-inflammatory, antioxidative, and anti-cancer activities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29642292"}, {"offsetInBeginSection": 0, "offsetInEndSection": 389, "text": "Curcumin is known to possess various biological functions, including anti-inflammatory, antioxidative, and anti-cancer activities. Natural killer (NK) cells are large lymphocytes that directly kill cancer cells. However, many aggressive cancers, including breast cancer, were reported to escape the successful killing of NK cells in a tumor microenvironment. In this study, we investigated", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29642292"}, {"offsetInBeginSection": 1796, "offsetInEndSection": 2091, "text": "Together, these results suggest a novel mechanism for curcumin-mediated radiosensitization involving increased ROS and ERK1/2 activation and suggest that curcumin application (either systemically or topically) may be an effective radiation modifying modality in the treatment of cervical cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18252805"}, {"offsetInBeginSection": 1422, "offsetInEndSection": 1548, "text": " The ability of curcumin to induce apoptosis in tumor cells and its anti-angiogenic potential will be discussed in this review", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25667441"}, {"offsetInBeginSection": 140, "offsetInEndSection": 294, "text": "It has recently been demonstrated that the chemopreventive activities of curcumin might be due to its ability to inhibit cell growth and induce apoptosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16376585"}, {"offsetInBeginSection": 1245, "offsetInEndSection": 1391, "text": "y supplementing it with curcumin. Curcumin supplementation exaggerates oxidative stress and apoptosis leading to cancer cell death by modulating p", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29752960"}, {"offsetInBeginSection": 304, "offsetInEndSection": 539, "text": "Curcumin has recently been discovered to have anti-cancer properties through its impact on numerous biological pathways involved in carcinogenesis, metastasis, tumorigenesis, cell cycle regulation, mutagenesis, and oncogene expression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37820211"}, {"offsetInBeginSection": 431, "offsetInEndSection": 707, "text": "In the current study, curcumin was found to decrease the Ehrlich's ascites carcinoma (EAC) cell number by the induction of apoptosis in the tumor cells as evident from flow-cytometric analysis of cell cycle phase distribution of nuclear DNA and oligonucleosomal fragmentation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11676493"}, {"offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Curcumin activates a ROS/KEAP1/NRF2/miR-34a/b/c cascade to suppress colorectal cancer metastasis.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37210578"}, {"offsetInBeginSection": 129, "offsetInEndSection": 444, "text": " With its low toxicity profile, curcumin (diferuloylmethane), a naturally occurring flavinoid derived from the rhizome of Curcuma longa, has great promise. In vitro and in vivo preclinical studies have shown its inhibitory anticancer, antioxidant, anti-inflammatory, antiproliferative, and proapoptotic activities. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18347134"}]}
+{"question_id": "65f85f77c4010b4d78000053", "question": "Should we treat all patients with glaucoma?", "answer": "Yes, treating all glaucoma patients is essential to prevent the progression of visual field defects.", "relevant_passage_ids": ["36564597", "36307903", "33433580", "35647957", "26909513", "28442683", "18417824", "17508036", "32343668", "27123557", "15663346", "29018725", "34179574", "18700453", "30296451", "2562546", "17937041", "23741132", "35366846"], "type": "yesno", "snippets": [{"offsetInBeginSection": 12, "offsetInEndSection": 175, "text": "Trans-scleral diode laser cycloablation (cyclodiode) is effective in the short-term management of refractory glaucoma where alternative treatments are not feasible", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36307903"}, {"offsetInBeginSection": 12, "offsetInEndSection": 155, "text": "Glaucoma is the most common cause of irreversible blindness worldwide. Many patients with glaucoma are asymptomatic early in the disease course", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33433580"}, {"offsetInBeginSection": 157, "offsetInEndSection": 306, "text": "Primary care clinicians should know which patients to refer to an eye care professional for a complete eye examination to check for signs of glaucoma", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33433580"}, {"offsetInBeginSection": 596, "offsetInEndSection": 785, "text": "Glaucoma is a chronic progressive optic neuropathy, characterized by damage to the optic nerve and retinal nerve fiber layer, that can lead to permanent loss of peripheral or central vision", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33433580"}, {"offsetInBeginSection": 1373, "offsetInEndSection": 1553, "text": " Treatment of glaucoma involves lowering intraocular pressure. This can be achieved with various classes of glaucoma medications as well as laser and incisional surgical procedures", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33433580"}, {"offsetInBeginSection": 1581, "offsetInEndSection": 1792, "text": "Vision loss from glaucoma can be minimized by recognizing systemic conditions and medications that increase a patient's risk of glaucoma and referring high-risk patients for a complete ophthalmologic examination", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33433580"}, {"offsetInBeginSection": 14, "offsetInEndSection": 53, "text": "irreversible vision loss from Glaucoma ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35647957"}, {"offsetInBeginSection": 127, "offsetInEndSection": 235, "text": "intraocular pressure (IOP) is the only modifiable risk factor identified to prevent glaucomatous vision loss", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35647957"}, {"offsetInBeginSection": 237, "offsetInEndSection": 315, "text": "Medical management remains the first-line of treatment in most adult glaucomas", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35647957"}, {"offsetInBeginSection": 85, "offsetInEndSection": 303, "text": "At present, all resources are directed towards reduction of intraocular pressure (IOP), the only known causal and treatable risk factor for glaucoma, and medical management is frequently the first choice in most cases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18417824"}, {"offsetInBeginSection": 483, "offsetInEndSection": 730, "text": "The philosophy of glaucoma management is to preserve the visual function and quality of life (QOL) of the individual with minimum effects on QOL in terms of cost, side effects, treatment regime, follow-up schedules as well as socioeconomic burden.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18417824"}, {"offsetInBeginSection": 465, "offsetInEndSection": 656, "text": "Thus, intraocular pressure-lowering strategies combined with neuroprotective therapies to protect visual neurons in the retina and brain may help to preserve vision in patients with glaucoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17508036"}, {"offsetInBeginSection": 803, "offsetInEndSection": 1225, "text": "In patients with manifest glaucoma, lowering the intraocular pressure prevents the progression of visual field defects, with a number needed to treat of 7.CONCLUSION: The diagnostic evaluation of glaucoma rests on multiple pillars, all of which must be considered for establishing the diagnosis and defining the desired target pressure: these are, among others, the intraocular pressure and ocular function and morphology.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32343668"}, {"offsetInBeginSection": 0, "offsetInEndSection": 326, "text": "INTRODUCTION: Medical therapy of glaucoma aims to maintain the patient's visual function and quality of life. This generally commences with monotherapy, but it is often difficult to reach the predetermined target pressure with this approach. Fixed combinations (FCs) are therefore selected as the next step of the medical ther", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27123557"}, {"offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Current management of glaucoma entails the medical, laser, or surgical reduction of intraocular pressure (IOP) to a predetermined level of target IOP, which is commensurate with either stability or delayed progression of visual loss.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26909513"}, {"offsetInBeginSection": 653, "offsetInEndSection": 889, "text": "Treatment of all forms of glaucoma consists of reducing IOP. With proper treatment, progression of this disease can often be delayed or prevented. Treatment options for glaucoma include medications, laser therapy and incisional surgery.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15663346"}, {"offsetInBeginSection": 229, "offsetInEndSection": 341, "text": "IOP reduction by medical, laser, or surgical therapies remains the only clinically proven treatment of glaucoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29018725"}, {"offsetInBeginSection": 0, "offsetInEndSection": 361, "text": "Over the past decade, results from prospective, randomized, clinical trials have confirmed the value of reducing intraocular pressure (IOP) in patients with ocular hypertension or primary open-angle glaucoma and have outlined the need to consider a target IOP in an individual glaucomatous patient and not an arbitrary value of 21 mm Hg as classically believed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18700453"}, {"offsetInBeginSection": 126, "offsetInEndSection": 382, "text": "Intraocular pressure is the main risk factor for glaucoma, and intraocular pressure-lowering treatment remains the mainstay of glaucoma treatment, but even successful intraocular pressure reduction does not stop the progression of glaucoma in all patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30296451"}, {"offsetInBeginSection": 445, "offsetInEndSection": 672, "text": "Knowing the type of glaucoma is vital, especially regarding an individualized treatment, since each patient is unique and needs to be treated accordingly, in order to prevent glaucomatous optic neuropathy and visual field loss.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34179574"}, {"offsetInBeginSection": 1288, "offsetInEndSection": 1552, "text": "n mean IOP respectively.CONCLUSIONS: The results from this study support the concept that the majority of glaucoma patients, who are responding inadequately to other glaucoma therapies, could benefit from a change to travoprost monotherapy or from the addition of ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17937041"}, {"offsetInBeginSection": 1526, "offsetInEndSection": 1720, "text": "Although the general rule is to initiate glaucoma management with medical treatment, the limits of medical therapy should be considered to identify those patients in need of surgical management.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28442683"}, {"offsetInBeginSection": 1152, "offsetInEndSection": 1387, "text": "Treatment for advanced glaucoma can be highly effective, and patients and their care partners should be informed that aggressive IOP lowering to the low teens or even single digits offers the best chance of protecting remaining vision.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23741132"}, {"offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "BACKGROUND: Treatment of open angle glaucoma (OAG) and/or ocular hypertension (OHT) focuses on achievement of target intraocular pressure (IOP), with the objective of slowing disease ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35366846"}]}
+{"question_id": "65cfab681930410b13000012", "question": "What is the mechanism of action of Pegozafermin?", "answer": "Pegozafermin is a long-acting glycopegylated fibroblast growth factor 21 (FGF21) analogue in development for the treatment of nonalcoholic steatohepatitis (NASH) and severe hypertriglyceridemia.", "relevant_passage_ids": ["37355760", "36521501", "37356033", "37696614", "37562970", "37889055", "37718721"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Pegozafermin, a long-acting glycopegylated analog of human fibroblast growth factor 21, is in development for the treatment of severe hypertriglyceridemia (SHTG) and nonalcoholic steatohepatitis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37355760"}, {"offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "The FGF21 analog pegozafermin in severe hypertriglyceridemia: a randomized phase 2 trial.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37355760"}, {"offsetInBeginSection": 0, "offsetInEndSection": 342, "text": "BACKGROUND: Management strategies for non-alcoholic steatohepatitis (NASH) are based predominantly on lifestyle modification, with no approved disease-modifying drugs yet available. We aimed to evaluate the safety, pharmacokinetics, and pharmacodynamics of pegozafermin (BIO89-100), a glycoPEGylated FGF21 analogue, in participants with NASH.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36521501"}, {"offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37356033"}, {"offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "BACKGROUND: Pegozafermin is a long-acting glycopegylated (pegylated with the use of site-specific glycosyltransferases) fibroblast growth factor 21 (FGF21) analogue in development for the treatment of nonalcoholic steatohepatitis (NASH) and severe hypertriglyceridemia. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37356033"}, {"offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Pegozafermin is a long-acting glycoPEGylated analog of fibroblast growth factor 21 (FGF21) in development for the treatment of nonalcoholic steatohepatitis (NASH) and severe hypertriglyceridemia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37696614"}, {"offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "The Novel GlycoPEGylated FGF21 Analog Pegozafermin Activates Human FGF Receptors and Improves Metabolic and Liver Outcomes in Diabetic Monkeys and Healthy Human Volunteers.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37562970"}, {"offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Pegozafermin (also known as BIO89-100) is a glycoPEGylated analog of fibroblast growth factor 21 (FGF21) under development to treat nonalcoholic steatohepatitis (NASH) and severe hypertriglyceridemia (SHTG).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37562970"}, {"offsetInBeginSection": 0, "offsetInEndSection": 423, "text": "BACKGROUND: An approved therapy for nonalcoholic steatohepatitis (NASH) and fibrosis remains a major unmet medical need.AIM: To investigate the histological and metabolic benefits of pegozafermin, a glycoPEGylated FGF21 analogue, in subjects with biopsy-confirmed NASH.METHODS: This proof-of-concept, open-label, single-cohort study, part 2 of a phase 1b/2a clinical trial, was conducted at 16 centres in the United States.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37718721"}, {"offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "BACKGROUND: Pegozafermin is a long-acting glycopegylated (pegylated with the use of site-specific glycosyltransferases) fibroblast growth factor 21 (FGF21) analogue in development for the treatment of nonalcoholic steatohepatitis (NASH) and severe hypertriglyceridemia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37356033"}, {"offsetInBeginSection": 1484, "offsetInEndSection": 1791, "text": "Studies presented here demonstrate that a novel long-acting FGF21 analog, pegozafermin, has similar pharmacologic properties as FGF21 and that repeated, subcutaneous dosing of pegozafermin in diabetic monkeys and healthy humans improves lipid metabolism, glucose metabolism, weight, and liver transaminases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37562970"}, {"offsetInBeginSection": 182, "offsetInEndSection": 831, "text": "We aimed to evaluate the safety, pharmacokinetics, and pharmacodynamics of pegozafermin (BIO89-100), a glycoPEGylated FGF21 analogue, in participants with NASH.METHODS: This randomised, double-blind, placebo-controlled, phase 1b/2a multiple-ascending-dose study enrolled adults (aged 21-75 years) who had NASH with stage F1-F3 fibrosis, or non-alcoholic fatty liver disease and a high risk of NASH (referred to in this study as phenotypic NASH) due to central obesity with type 2 diabetes, or central obesity with increased alanine aminotransferase (ALT) or a Fibroscan score of 7 kPa or greater, across 12 specialist centres and clinics in the USA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36521501"}, {"offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "Pegozafermin (PGZ), a novel glycopegylated version of human fibroblast growth factor 21 (FGF21), has demonstrated potential for addressing metabolic comorbidities, including severe hypertriglyceridemia, insulin resistance, nonalcoholic fatty liver disease, and obesity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37889055"}, {"offsetInBeginSection": 208, "offsetInEndSection": 400, "text": "In cell-based assays, pegozafermin had a similar receptor engagement profile as recombinant FGF21, with approximately eightfold higher potency at fibroblast growth factor receptor 1c (FGFR1c).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37562970"}, {"offsetInBeginSection": 0, "offsetInEndSection": 998, "text": "Pegozafermin (PGZ), a novel glycopegylated version of human fibroblast growth factor 21 (FGF21), has demonstrated potential for addressing metabolic comorbidities, including severe hypertriglyceridemia, insulin resistance, nonalcoholic fatty liver disease, and obesity. FGF21 is a naturally occurring peptide hormone primarily produced by the liver, with a half-life of 0.5 to 2 hours. It can influence metabolic processes through endocrine cellular effects. FGF21 receptors are found in the liver, adipose, skeletal muscles, and pancreatic tissues. Those receptors rely on the beta klotho (KLB) coreceptors, a transmembrane protein, to activate the FGF21 signaling pathway and FGF21's associated transcription factors. PGZ, through its extended half-life of 55 to 100 hours, has evidenced significant improvements in metabolic functions. Its mechanism of action includes promoting adiponectin levels, enhancing insulin sensitivity, increasing triglyceride uptake, and reducing de novo lipogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37889055"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Pegozafermin is a long-acting glycoPEGylated analog of fibroblast growth factor 21 (FGF21) in development for the treatment", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37696614"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Pegozafermin (also known as BIO89-100) is a glycoPEGylated analog of fibroblast growth factor 21 (FGF21)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37562970"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Pegozafermin, a long-acting glycopegylated analog of human fibroblast growth factor 21, is in development for the treatment", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37355760"}, {"offsetInBeginSection": 221, "offsetInEndSection": 330, "text": "cokinetics, and pharmacodynamics of pegozafermin (BIO89-100), a glycoPEGylated FGF21 analogue, in participant", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36521501"}, {"offsetInBeginSection": 164, "offsetInEndSection": 253, "text": "abolic benefits of pegozafermin, a glycoPEGylated FGF21 analogue, in subjects with biopsy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37718721"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Pegozafermin (PGZ), a novel glycopegylated version of human fibroblast growth factor 21 (FGF21), has demonstrated potential", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37889055"}, {"offsetInBeginSection": 0, "offsetInEndSection": 400, "text": "Pegozafermin (also known as BIO89-100) is a glycoPEGylated analog of fibroblast growth factor 21 (FGF21) under development to treat nonalcoholic steatohepatitis (NASH) and severe hypertriglyceridemia (SHTG). In cell-based assays, pegozafermin had a similar receptor engagement profile as recombinant FGF21, with approximately eightfold higher potency at fibroblast growth factor receptor 1c (FGFR1c).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37562970"}]}
+{"question_id": "65f70b9cc4010b4d7800001c", "question": "What is the indication for Alirocumab?", "answer": "Alirocumab, sold under the brand name Praluent, is a medication used as a second-line treatment for high cholesterol for adults whose cholesterol is not controlled by diet and statin treatment", "relevant_passage_ids": ["35052871", "27250613", "26785741", "28277798", "35974290", "25244623", "29171769", "26935836", "28395555", "26563849", "26370210", "27567901", "28618994", "26886466", "26798848", "26859553", "37939861", "28263403", "36440240", "28750828", "27186592", "28328015", "29802110"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "Effects of Alirocumab on Triglyceride Metabolism:", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35052871"}, {"offsetInBeginSection": 12, "offsetInEndSection": 290, "text": "PCSK9 antibodies strongly reduce LDL cholesterol. The effects of PCSK9 antibodies on triglyceride metabolism are less pronounced. The present study aimed to investigate in detail the effects of alirocumab on triglycerides, triglyceride-rich lipoproteins, and lipase regulators.M", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35052871"}, {"offsetInBeginSection": 290, "offsetInEndSection": 602, "text": "To achieve target LDL-cholesterol in these two groups of patients will be possible with new drugs - PCSK9 inhibitors, which decrease LDL-cholesterol by an additional 50-60 %. The first two PCSK9 inhibitors (alirocumab and evolocumab) already had been approved for clinical use by European regulatory authorities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27250613"}, {"offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "Alirocumab for the treatment of hypercholesterolaemia.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28395555"}, {"offsetInBeginSection": 503, "offsetInEndSection": 867, "text": "Areas covered: In 2015, the Food and Drug Administration and the European Medicines Agency approved alirocumab (Praluent\u00ae; Sanofi), a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), for the treatment of hypercholesterolaemic patients unable to meet LDL-C targets, as an adjunct to diet in addition/alternative to LLT.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28395555"}, {"offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "INTRODUCTION: Prescription of statins for low-density lipoprotein cholesterol (LDL-C) reduction is the standard of care in primary and secondary prevention of cardiovascular disease; nevertheless, a large number of patients treated with statins are unable to reach the recommended LDL-C targets.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28395555"}, {"offsetInBeginSection": 1177, "offsetInEndSection": 1689, "text": "Currently, alirocumab is approved by the US Food and Drug Administration (FDA) as an adjunct to diet and maximally tolerated statin therapy for use in adults with heterozygous familial hypercholesterolemia (FH) or those with atherosclerotic CV disease who require additional LDL-C lowering; it has also been recently approved by the European Medicines Agency (EMA) for use in patients with heterozygous FH, non-familial hypercholesterolemia or mixed dyslipidemia in whom statins are ineffective or not tolerated.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27567901"}, {"offsetInBeginSection": 1063, "offsetInEndSection": 1460, "text": "Expert commentary: Alirocumab causes a marked reduction in LDL-C, presents good safety and tolerability, and represents a promising approach for LDL-C lowering, particularly in patients with intolerance to statin or elevated LDL-C despite maximal statin therapy; nevertheless, further long-term data on safety and efficacy are necessary, such as data on the improvement of cardiovascular outcomes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28395555"}, {"offsetInBeginSection": 1063, "offsetInEndSection": 1621, "text": "Recently the fully human monoclonal antibodies against proprotein convertase subtilisin/kexin 9 (PCSK9), alirocumab (Praluent\u00ae) and evolocumab (Repatha\u00ae), which have been shown to decrease LDL-C by up to 70% have been approved in Europe for use in patients with primary hypercholesterolemia not at LDL-C target while on maximally tolerated lipid-lowering therapy and specifically for patients with statin intolerance and in the USA for patients with atherosclerotic cardiovascular disease or familial hypercholesterolemia requiring additional LDL-C lowering.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28618994"}, {"offsetInBeginSection": 272, "offsetInEndSection": 580, "text": "Alirocumab (Praluent; Sanofi/Regeneron, Bridgewater, NJ) and evolocumab (Repatha; Amgen, Thousand Oaks, CA) are currently available and approved for use in patients with heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, and clinical atherosclerotic cardiovascular disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26886466"}, {"offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Alirocumab: PCSK9 inhibitor for LDL cholesterol reduction.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25244623"}, {"offsetInBeginSection": 868, "offsetInEndSection": 1062, "text": "The authors review the pharmacological features, clinical efficacy, and safety of alirocumab in lowering LDL-C, and discuss its therapeutic perspectives based on the most recent clinical trials.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28395555"}, {"offsetInBeginSection": 0, "offsetInEndSection": 380, "text": "Alirocumab (Praluent\u00ae) is a fully human monoclonal antibody developed by Regeneron Pharmaceuticals and Sanofi that has been approved in the US as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolaemia (HeFH) or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL-C", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26370210"}, {"offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "Alirocumab (Praluent) for high cholesterol", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26535020"}, {"offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "BACKGROUND AND OBJECTIVES: Alirocumab is a cholesterol-lowering monoclonal antibody targeting proprotein convertase subtilisin kexin type 9 (PCSK9) indicated in the prevention of cardiovascular risk and exhibiting target-mediated drug disposition (TMDD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35974290"}, {"offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Alirocumab for the treatment of hypercholesterolemia.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28277798"}, {"offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "INTRODUCTION: Alirocumab is a fully human immunoglobulin G1 monoclonal antibody directed against proprotein convertase subtilisin/kexin type 9 (PCSK9) approved for the treatment of hypercholesterolemia in high-risk patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29171769"}, {"offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Alirocumab: targeting PCSK9 to treat hypercholesterolemia.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26798848"}, {"offsetInBeginSection": 924, "offsetInEndSection": 1309, "text": "The high cost and the current lack of long-term safety and efficacy data will restrict the use of alirocumab to patients who have high cardiovascular risk from established atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia and who are unable to achieve LDL-C targets with maximally tolerated dose of statins with or without other lipid-lowering drugs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28277798"}, {"offsetInBeginSection": 1287, "offsetInEndSection": 1565, "text": "Thus, alirocumab is a valuable emerging option for use in patients with hypercholesterolemia, particularly patients with statin intolerance or inadequately-controlled LDL-C despite statin therapy; however, more data are needed to establish its potential cardiovascular benefits.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26935836"}, {"offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "An evaluation of alirocumab for the treatment of hypercholesterolemia.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26563849"}, {"offsetInBeginSection": 294, "offsetInEndSection": 571, "text": "The clinical use of two monoclonal antibodies (alirocumab and evolocumab, approved in 2015) and one small interfering RNA (inclisiran, approved in 2020) which can inhibit PCSK9 function proved that they are very effective in lowering low density lipoprotein cholesterol (LDL-C)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37939861"}, {"offsetInBeginSection": 504, "offsetInEndSection": 852, "text": "reas covered: In 2015, the Food and Drug Administration and the European Medicines Agency approved alirocumab (Praluent\u00ae; Sanofi), a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), for the treatment of hypercholesterolaemic patients unable to meet LDL-C targets, as an adjunct to diet in addition/alte", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28395555"}, {"offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "INTRODUCTION: Alirocumab is a fully human immunoglobulin G1 monoclonal antibody directed against proprotein convertase subtilisin/kexin type 9 (PCSK9) approved for the treatment of hypercholesterolemia in high-", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29171769"}, {"offsetInBeginSection": 0, "offsetInEndSection": 660, "text": "Alirocumab and evolocumab are 2 human monoclonal antibodies that inhibit the proprotein convertase subtilisin/kexin type 9 (PCSK9). These antibodies can potently lower low-density lipoprotein cholesterol (LDLc) serum concentrations. The aims of this analysis were to develop a pharmacokinetic (PK) and pharmacodynamic (PD) model for both antibodies, to simulate and investigate different dosage and application regimens, and finally, to note the effects on LDLc levels. Alirocumab was clinically studied and approved with 2 doses, 75 and 150 mg every 2 weeks (Q2W), whereas evolocumab was tested and approved with 2 dosing intervals, 140 mg Q2W and 420 mg Q4W.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28263403"}, {"offsetInBeginSection": 0, "offsetInEndSection": 457, "text": "Background: Even though the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, alirocumab and evolocumab, have been approved to reduce plasma low-density lipoprotein cholesterol (LDL-C) and the risk of atherosclerotic cardiovascular disease in high-risk patients, real-world data showing comparisons of the lipid-lowering effects between alirocumab and evolocumab are scarce because of the low prescription rates of PCSK9 inhibitors in clinic", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36440240"}, {"offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "A new class of lipid-lowering drugs, inhibitors of PCSK9 has been generating impressive clinical trial data over the last several years, and alirocumab (Praluent) has become the first to be approved by the US FDA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26785741"}, {"offsetInBeginSection": 1063, "offsetInEndSection": 1619, "text": "Recently the fully human monoclonal antibodies against proprotein convertase subtilisin/kexin 9 (PCSK9), alirocumab (Praluent\u00ae) and evolocumab (Repatha\u00ae), which have been shown to decrease LDL-C by up to 70% have been approved in Europe for use in patients with primary hypercholesterolemia not at LDL-C target while on maximally tolerated lipid-lowering therapy and specifically for patients with statin intolerance and in the USA for patients with atherosclerotic cardiovascular disease or familial hypercholesterolemia requiring additional LDL-C lowerin", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28618994"}, {"offsetInBeginSection": 0, "offsetInEndSection": 485, "text": "In 2015 the U.S. Food and Drug Administration approved the first two proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, alirocumab (Praluent\u00ae; Sanofi/ Regeneron) and evolocumab (Repatha\u00ae; Amgen), for use in patients with heterozygous and homozygous familial hypercholesterolemia and for patients intolerant of statins or those with a major risk of cardiovascular disease (CVD) but unable to lower their LDL cholesterol (LDL-C) to optimal levels with statins and ezetimib", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27186592"}, {"offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "The proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab has been shown to substantially reduce low-density lipoprotein cholesterol (LDL-C).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28750828"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "BACKGROUND AND OBJECTIVES: Alirocumab is a cholesterol-lowering monoclonal antibody targeting proprotein convertase subtilisin kexin type 9 (PCSK9) indicated in the preven", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35974290"}, {"offsetInBeginSection": 606, "offsetInEndSection": 811, "text": "Alirocumab clinical trials with different doses on different administration schedules were shown to significantly reduce LDL cholesterol both as a mono-therapy and in combination with statins or ezetimibe.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25244623"}, {"offsetInBeginSection": 779, "offsetInEndSection": 1234, "text": "Large and comprehensive trials over the last 5 years also indicated good tolerability and safety and resulted in the 2015 regulatory approval in the USA and Europe for the marketing of two mAbs, evolocumab and alirocumab, for the treatment of LDL-C.SUMMARY: The background, clinical trials and approved indications for the current PCSK9 inhibitors are reviewed along with their likely role in the management of LDL-C and cardiovascular disease prevention.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26859553"}, {"offsetInBeginSection": 157, "offsetInEndSection": 425, "text": "In 2015 the US Food and Drug Administration approved both alirocumab and evolocumab for high-risk patients with familial hypercholesterolemia (FH) and clinical atherosclerotic cardiovascular disease requiring additional lowering of low-density lipoprotein cholesterol.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28328015"}, {"offsetInBeginSection": 332, "offsetInEndSection": 557, "text": "esterol (LDL-C). The currently available PCSK9 inhibitors alirocumab and evolocumab were shown to reduce LDL-C concentrations by approximately 55-60% relative to placebo use when used as monotherapy or added to other lipid-lo", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29802110"}]}
+{"question_id": "65f86a90c4010b4d78000057", "question": "Is there an approved vaccine against Helicobacter pylori?", "answer": "No. There is currently no approved vaccine against Helicobacter pylori.", "relevant_passage_ids": ["37018869", "37971157", "36641984", "9395760", "25400981", "24133496"], "type": "yesno", "snippets": [{"offsetInBeginSection": 183, "offsetInEndSection": 416, "text": "H. pylori, the development of an efficacious vaccine is a valid option to protect from disease or infection and ultimately prevent gastric cancer. However, despite more than 30 years of research, no vaccine has entered the market yet", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37018869"}, {"offsetInBeginSection": 2265, "offsetInEndSection": 2427, "text": "advances of H. pylori vaccines from two aspects, candidates of antigens and adjuvants, to provide references for the development of vaccine against this bacterium", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971157"}, {"offsetInBeginSection": 586, "offsetInEndSection": 697, "text": "Despite an extensive list of attempts to develop a vaccine, no approved vaccine against H. pylori is available.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36641984"}, {"offsetInBeginSection": 1297, "offsetInEndSection": 1447, "text": "Unfortunately, no vaccine against H. pylori is currently licensed, and protective immunity mechanisms against H. pylori are only partially understood.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24133496"}, {"offsetInBeginSection": 0, "offsetInEndSection": 351, "text": "After the discovery of Helicobacter pylori (H. pylori), and the evidence of its relationship with gastric diseases, antibiotic-based therapies were developed, which efficacy was however limited by antibiotic resistance and lack of patient compliance. A vaccine would overcome these drawbacks, but currently there is not any H. pylori vaccine licensed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25400981"}, {"offsetInBeginSection": 508, "offsetInEndSection": 560, "text": "An effective vaccine against H pylori is years away.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9395760"}, {"offsetInBeginSection": 293, "offsetInEndSection": 351, "text": "but currently there is not any H. pylori vaccine licensed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25400981"}, {"offsetInBeginSection": 251, "offsetInEndSection": 351, "text": "A vaccine would overcome these drawbacks, but currently there is not any H. pylori vaccine licensed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25400981"}]}
+{"question_id": "65cec1fb1930410b13000005", "question": "What disease can be treated with Tebentafusp?", "answer": "Tebentafusp is approved for uveal melanoma.", "relevant_passage_ids": ["37444540", "37483658", "36931146", "36970111", "36600005", "34551229", "31336704", "37595494", "35060440", "35172589", "36847626", "37207136", "35364557", "37650713", "38048850", "36102132", "35364798", "32816891", "37902386", "37473516", "37286303", "37141553", "34999237", "34885078", "35115315", "36785760", "37661909", "36229663", "36199496", "36710368", "37870955", "35236927", "36094043", "31344957", "36442912"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Tebentafusp in Patients with Metastatic Uveal Melanoma: A Real-Life Retrospective Multicenter Study.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37444540"}, {"offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "BACKGROUND: Tebentafusp has recently been approved for the treatment of metastatic uveal melanoma (mUM) after proving to have survival benefits in a first-line setting.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37444540"}, {"offsetInBeginSection": 1140, "offsetInEndSection": 1254, "text": "Treatment with ICI followed by tebentafusp may result in longer PFS/OS compared to the inverse treatment sequence.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37444540"}, {"offsetInBeginSection": 322, "offsetInEndSection": 446, "text": "Tebentafusp, a bispecific molecule, has recently become the first treatment in decades to improve overall survival for mUM. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37483658"}, {"offsetInBeginSection": 2309, "offsetInEndSection": 2563, "text": "CONCLUSIONS: Tebentafusp achieved the best results compared to combined ICB and other systemic treatments, although these results have to be interpreted with caution due to the approximative methodical approach and high heterogeneity of included studies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36931146"}, {"offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Tebentafusp: a first-in-class treatment for metastatic uveal melanoma.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36970111"}, {"offsetInBeginSection": 228, "offsetInEndSection": 460, "text": "Tebentafusp is both the first bispecific T-cell engager to show efficacy in the treatment of advanced solid cancer and the first anti-cancer treatment to demonstrate an overall survival benefit in patients with uveal melanoma (UM). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36970111"}, {"offsetInBeginSection": 881, "offsetInEndSection": 1065, "text": "These advances have driven the development of a number of novel emerging treatments, including tebentafusp, the first systemic therapy to achieve regulatory approval for this disease. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36600005"}, {"offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "INTRODUCTION: Tebentafusp is a novel bispecific immune mobilizing T cell receptor (TCR)-based agent developed for the treatment of metastatic uveal melanoma, a highly fatal disease with no currently approved treatment options.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35060440"}, {"offsetInBeginSection": 0, "offsetInEndSection": 315, "text": "On January 25, 2022, the U.S. Food and Drug Administration (FDA) approved the use of tebentafusp, a bispecific glycoprotein 100 (gp100) peptide-human leukocyte antigen (HLA)-directed CD3 T-cell activator, for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36847626"}, {"offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Tebentafusp: a novel drug for the treatment of metastatic uveal melanoma.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36847626"}, {"offsetInBeginSection": 228, "offsetInEndSection": 459, "text": "Tebentafusp is both the first bispecific T-cell engager to show efficacy in the treatment of advanced solid cancer and the first anti-cancer treatment to demonstrate an overall survival benefit in patients with uveal melanoma (UM).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36970111"}, {"offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Tebentafusp, a bispecific T-cell receptor fusion protein directed against gp100 and CD3, can improve survival in patients with metastatic uveal melanoma and was recently approved for the treatment of HLA-A*02:01-positive uveal melanoma patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37661909"}, {"offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Tebentafusp, the first drug shown to extend overall survival in people with uveal melanoma, was greenlighted by the FDA in late January to treat patients with inoperable or metastatic forms of the aggressive eye cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35115315"}, {"offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Tebentafusp: T Cell Redirection for the Treatment of Metastatic Uveal Melanoma.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31336704"}, {"offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "BACKGROUND: Tebentafusp demonstrated a superior overall survival (OS) benefit (hazard ratio [HR] 0.51) compared to investigator's choice (82% pembrolizumab) in a randomized, Phase 3 trial (IMCgp100-202; N=378) in untreated metastatic uveal mel", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38048850"}, {"offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Tebentafusp is a new T cell receptor bispecific fusion protein and the first approved treatment option for human leucocyte antigen-A*02:01 (HLA-A*02:01) metastatic uveal melanoma, with a proven benefit in overall survival versus the investigator's choice.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37595494"}, {"offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "INTRODUCTION: Tebentafusp is a novel bispecific immune mobilizing T cell receptor (TCR)-based agent developed for the treatment of metastatic uveal melanoma, a highly fatal disease with no currently approved trea", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35060440"}, {"offsetInBeginSection": 599, "offsetInEndSection": 742, "text": "Using tebentafusp as a case study, a CD3-bispecific approved for uveal melanoma, the model successfully captures the dynamics of five cytokines", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36710368"}, {"offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "BACKGROUND: Tebentafusp has recently been approved for the treatment of metastatic uveal melanoma (mUM) after proving to h", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37444540"}, {"offsetInBeginSection": 265, "offsetInEndSection": 425, "text": "Tebentafusp was granted full approval on January 25th 2022 in the setting of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35364557"}, {"offsetInBeginSection": 583, "offsetInEndSection": 751, "text": "Tebentafusp-tebn is now approved by the US Food and Drug Administration in HLA-A*02:01-positive uveal melanoma patients as first-line therapy in the metastatic setting.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36199496"}, {"offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "In January 2022, the US Food and Drug Administration granted regulatory approval to tebentafusp, a bispecific T cell receptor protein that targets melanoma antigen gp100 in the context of the human leucocyte antigen (HLA) A*0201 allele.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36442912"}]}
+{"question_id": "65f856a1c4010b4d7800004e", "question": "When was Havana Syndrome first recognized?", "answer": "Since 2016, an array of claims and public discourse have circulated in the medical community over the origin and nature of a mysterious condition dubbed \"Havana Syndrome,\" so named as it was first identified in Cuba.", "relevant_passage_ids": ["37965360", "35962646", "37976420", "32655474", "30828629"], "type": "factoid", "snippets": [{"offsetInBeginSection": 13, "offsetInEndSection": 206, "text": " In 2016 diplomatic personnel serving in Havana, Cuba, began reporting audible sensory phenomena paired with onset of complex and persistent neurological symptoms consistent with brain injury. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37965360"}, {"offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Since 2016, numerous American and Canadian diplomats and secret (intelligence) agents in Cuba, China, and other places in the world have experienced an abrupt onset of unusual clinical symptoms including, tinnitus, visual problems, vertigo, and cognitive difficulties,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35962646"}, {"offsetInBeginSection": 268, "offsetInEndSection": 438, "text": "This fact was illustrated in 2016 when U.S. diplomats serving in Havana, Cuba reported hearing strange noises accompanied by a constellation of unexplained health effects", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37976420"}, {"offsetInBeginSection": 0, "offsetInEndSection": 352, "text": "Since 2016, numerous American and Canadian diplomats and secret (intelligence) agents in Cuba, China, and other places in the world have experienced an abrupt onset of unusual clinical symptoms including, tinnitus, visual problems, vertigo, and cognitive difficulties, after they encountered strange sounds; this has been called \"Havana syndrome\" (HS).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35962646"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "In late 2016, diplomats in Havana, Cuba, began presenting with a unique symptom complex after perceiving a strange noise and/or feeling a pressure field in their domicile.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32655474"}, {"offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Introduction: In 2016 diplomatic personnel serving in Havana, Cuba, began reporting audible sensory phenomena paired with onset of complex and persistent neurological symptoms consistent with brain injury.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37965360"}, {"offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "BACKGROUND: In the Autumn of 2016, diplomatic personnel residing in Havana began to present with symptoms of dizziness, ear pain, and tinnitus that emerged after perception of high frequency noise and/or a pressure sensation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30828629"}]}
+{"question_id": "65f86f03c4010b4d7800005b", "question": "Is Marburg virus a member of the family of the Ebola virus (Filoviridae)?", "answer": "Yes, Marburg virus is a member of the family of the Ebola virus (Filoviridae).", "relevant_passage_ids": ["31021739", "36084314", "9721531", "21046175", "16026254", "37171813", "36242583", "25786917", "24713118", "15811650", "26656687", "17610952", "22935026", "37908613", "37880247", "37849404", "37647447", "37632081", "25118385", "27497688", "29593155", "28580138", "26038444", "36817425", "9448698", "21468930", "32320678", "27489272", "30332733", "16809329", "21994610", "29106386", "36920694", "18063023", "30192975", "21994800", "28076420", "22815803", "26047124", "35332563", "16355872", "30215737", "27268907", "31473342", "32093889"], "type": "yesno", "snippets": [{"offsetInBeginSection": 261, "offsetInEndSection": 313, "text": "Several filoviruses infect bats (e.g., Marburg virus", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31021739"}, {"offsetInBeginSection": 11, "offsetInEndSection": 48, "text": "African Filovirus (Ebola and Marburg)", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36084314"}, {"offsetInBeginSection": 527, "offsetInEndSection": 571, "text": "filoviruses (ebolaviruses and Marburg virus)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36084314"}, {"offsetInBeginSection": 171, "offsetInEndSection": 384, "text": "The Filoviridae family encompasses Ebola strains such as Sudan, Zaire, Bundibugyo, Tai Forest (formerly known as Ivory Coast), Reston, and Bombali, in addition to the closely related Marburg and Ravn virus strains", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37908613"}, {"offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Marburg and Ebola filoviruses are two of the deadliest infectious agents and several outbreaks have occurred in the last decades", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37880247"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Viruses in the family Filoviridae, including the commonly known Ebola (EBOV) and Marburg (MARV) viruses, can cause severe hemorrhagic fever in humans and nonhuman primates", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37849404"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Marburg virus, the prototype of the family Filoviridae, differs genetically, serologically, and morphologically from Ebola viruses.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9448698"}, {"offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "UNLABELLED: Ebola virus (EBOV) and Marburg virus (MARV) belong to the Filoviridae family and can cause outbreaks of severe hemorrhagic fever, with high mortality rates in humans.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27489272"}, {"offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Marburg virus (MARV) and Ebola virus (EBOV) belong to the family Filoviridae.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32320678"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Ebola viruses (EBOV) and Marburg virus belong to the family Filoviridae, order Mononegavirales.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17610952"}, {"offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Marburg virus (MARV) and Ebola virus (EBOV) are members of the family Filoviridae (\"filoviruses\") and cause severe hemorrhagic fever with human case fatality rates of up to 90%.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22935026"}, {"offsetInBeginSection": 121, "offsetInEndSection": 236, "text": "The Marburg virus is a lipid-enveloped virus from the Filoviridae family and is closely related to the Ebola virus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28580138"}, {"offsetInBeginSection": 1424, "offsetInEndSection": 1528, "text": "Comparative analyses showed that there are two lineages within the Marburg virus species of filoviruses.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9448698"}, {"offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Ebola virus and Marburg virus are members of the family of Filoviridae and are etiological agents of a deadly hemorrhagic fever disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26038444"}, {"offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Ebola virus (EBOV) and Marburg virus (MARV) belong to the family Filoviridae.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25118385"}, {"offsetInBeginSection": 237, "offsetInEndSection": 341, "text": "Marburg virus and Ebola virus, members of the family Filoviridae, cause highly lethal hemorrhagic fever.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29593155"}, {"offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Members of the family Filoviridae, including Ebola virus (EBOV) and Marburg virus (MARV), cause severe hemorrhagic fever in humans and nonhuman primates.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30332733"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Marburg virus (MARV) and the ebolaviruses belong to the family Filoviridae (the members of which are filoviruses) that cause severe hemorrhagic fever.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25786917"}, {"offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Filoviruses are filamentous enveloped viruses belonging to the family Filoviridae, in the order Mononegavirales. Some filovirus members, such as Ebola virus and Marburg virus, cause severe hemorrhagic fever in humans and non-human primates.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36242583"}, {"offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "UNLABELLED: Ebola virus (EBOV) and Marburg virus (MARV) belong to the Filoviridae family and can cause outbreaks of severe hemorrhagic fever, with high mortality rate", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27489272"}, {"offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Marburg virus (MARV) and Ebola virus (EBOV), members of the viral family Filoviridae, cause fatal hemorrhagic fevers in humans and nonhuman primates.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16809329"}, {"offsetInBeginSection": 0, "offsetInEndSection": 353, "text": "The members of the filoviruses are recognized as some of the most lethal viruses affecting human and non-human primates. The only two genera of the Filoviridae family, Marburg virus (MARV) and Ebola virus (EBOV), comprise the main etiologic agents of severe hemorrhagic fever outbreaks in central Africa, with case fatality rates ranging from 25 to 90%.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21994610"}, {"offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Ebolaviruses and marburgviruses belong to the family Filoviridae and cause high lethality in infected patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29106386"}, {"offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "The Marburg virus, which is a member of the same virus family as the Ebola virus called Filoviridae, causes the severe infectious disease known as Marburg virus disease (MVD)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37647447"}, {"offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "The Ebola virus and its close relative, the Marburg virus, both belong to the family Filoviridae and are highly hazardous and contagious viruses", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37632081"}, {"offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Marburg virus (MARV) and Ebola virus (EBOV) of the Filoviridae family are the most lethal viruses in terms of mortality rate.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36920694"}, {"offsetInBeginSection": 0, "offsetInEndSection": 393, "text": "Ebolavirus and Marburgvirus (belonging to the Filoviridae family) emerged four decades ago and cause epidemics of haemorrhagic fever with high case-fatality rates. The genome of filoviruses encodes seven proteins. No significant homology is observed between filovirus proteins and any known macromolecule. Moreover, Marburgvirus and Ebolavirus show significant differences in protein homology.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18063023"}, {"offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Ebola viruses (EBOV) and Marburg virus belong to the family Filoviridae, order Mononegavirales. The genus Ebolavirus consists of four species: Zaire ebolavirus (ZEBOV), Sudan ebolavirus (SEBOV), Ivory Coast ebolavirus (ICEBOV) and Reston ebolavirus (REBOV).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17610952"}, {"offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Marburg virus (MARV; family Filoviridae) causes sporadic outbreaks of Marburg hemorrhagic fever in sub-Saharan Africa with case fatality rates reaching 90%.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30192975"}, {"offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "The Filoviridae family of viruses, which includes the genera Ebolavirus (EBOV) and Marburgvirus (MARV), causes severe and often times lethal hemorrhagic fever in humans.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21994800"}, {"offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Marburg virus (MARV) and Ebola virus (EBOV), members of the family Filoviridae, represent a significant challenge to global public health.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24713118"}, {"offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Ebola virus (EBOV) and Marburg virus (MARV), belonging to the Filoviridae family, emerged four decades ago and caused severe viral hemorrhagic fever in human and other primates.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21468930"}, {"offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Ebola virus (EBOV) and Marburg virus (MARV) belong to the family Filoviridae and cause severe hemorrhagic fever in humans and nonhuman primates.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22815803"}, {"offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "The taxonomy of the family Filoviridae (marburgviruses and ebolaviruses) has changed several times since the discovery of its members, resulting in a plethora of species and virus names and abbreviations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21046175"}, {"offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "BACKGROUND: Ebola and Marburg viruses (family Filoviridae, genera Ebolavirus and Marburgvirus) cause haemorrhagic fevers in humans, often associated with high mort", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26047124"}, {"offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "The ability of viruses in the Filoviridae family (Ebola virus [EBOV] and Marburg virus [MARV]) to cause severe human disease and their pandemic potential makes all emerging filoviral pathogens a concern to humanity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35332563"}, {"offsetInBeginSection": 121, "offsetInEndSection": 303, "text": "The only two genera of the Filoviridae family, Marburg virus (MARV) and Ebola virus (EBOV), comprise the main etiologic agents of severe hemorrhagic fever outbreaks in central Africa", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21994610"}, {"offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "UNLABELLED: Marburg virus (MARV), a member of the filovirus family, causes severe hemorrhagic fever with up to 90", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26656687"}, {"offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Marburg virus (MARV), a member of the Filoviridae family that also includes Ebola virus (EBOV)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27497688"}, {"offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Marburg virus (MARV) and Ebola virus (EBOV), members of the family Filoviridae", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24713118"}, {"offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "The family Filoviridae is comprised of two genera: Marburgvirus and Ebolavirus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16355872"}, {"offsetInBeginSection": 173, "offsetInEndSection": 298, "text": "As members of the filovirus family, marburgviruses have caused similar devastating outbreaks, albeit with lower case numbers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30215737"}, {"offsetInBeginSection": 31, "offsetInEndSection": 112, "text": "ebolavirus (SUDV) and Marburg virus (MARV), are members of the Filoviridae family", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36817425"}, {"offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Marburg virus (MARV) and Ebola virus (EBOV), members of the family Filoviridae, represent a significant", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24713118"}, {"offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Ebola (EBOV) and Marburg (MARV) viruses are members of the Filoviridae family which cause outbreaks", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28076420"}, {"offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Marburg virus (MARV) and Ebola virus (EBOV), members of the viral family Filoviridae, cause fatal", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16809329"}, {"offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Ebola and Marburg viruses are members of the family Filoviridae, which cause severe hemorrhagic fevers", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16026254"}, {"offsetInBeginSection": 4, "offsetInEndSection": 171, "text": "GROUND: The family Filoviridae consists of several virus members known to cause significant mortality and disease in humans. Among these, Ebola virus (EBOV), Marburg v", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37171813"}, {"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Filoviridae family members Ebola (EBOV) and Marburg (MARV) viruses and Arenaviridae family member Lassa virus (LASV) are", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33536174"}, {"offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "The taxonomy of the family Filoviridae (marburgviruses and ebolaviruses) has changed several times since the discovery", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21046175"}, {"offsetInBeginSection": 73, "offsetInEndSection": 395, "text": "filoviruses Ebola virus (EBOV) and Marburg virus (MARV) cause highly lethal disease typified by unimpeded viral replication and severe hemorrhagic fever. Previously, we showed that expression of the homologous glycoprotein (GP) and matrix protein VP40 from a single filovirus, either EBOV or MARV, resulted in formation of", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15811650"}, {"offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Marburg virus (MARV), a member of the Filoviridae family that also includes Ebola virus (EBOV), causes lethal hemorrhagic fever with case fatality rates that have exceeded 50% in some outbreaks.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27497688"}, {"offsetInBeginSection": 354, "offsetInEndSection": 523, "text": "Ebola and Marburg viruses are members of the Filoviridae family and easily distinguishable from viruses of other families by the characteristic morphology of the virion.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9721531"}, {"offsetInBeginSection": 121, "offsetInEndSection": 353, "text": "The only two genera of the Filoviridae family, Marburg virus (MARV) and Ebola virus (EBOV), comprise the main etiologic agents of severe hemorrhagic fever outbreaks in central Africa, with case fatality rates ranging from 25 to 90%.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21994610"}, {"offsetInBeginSection": 0, "offsetInEndSection": 386, "text": "Filoviridae currently includes five official and one proposed genera. Genus Ebolavirus includes five established and one proposed ebolavirus species for Bombali virus (BOMV), Bundibugyo virus (BDBV), Ebola virus (EBOV), Reston virus (RESTV), Sudan virus (SUDV) and Ta\u00ef Forest virus (TAFV), and genus Marburgvirus includes a single species for Marburg virus (MARV) and Ravn virus (RAVV).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31473342"}, {"offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Eight viruses are currently assigned to the family Filoviridae Marburg virus, Sudan virus and, in particular, Ebola virus have received the most attention both by researchers and the public from 1967 to 2013.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27268907"}, {"offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "The family Filoviridae contains many important human viruses, including Marburg virus (MARV) and Ebola virus (EBOV).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32093889"}]}
+{"question_id": "65d140e71930410b1300003f", "question": "What medications were tested in the COSMIC-313 trial?", "answer": "The COSMIC-313 phase 3 randomized controlled trial tested the triplet combination of cabozantinib with nivolumab and ipilimumab in comparison with nivolumab plus ipilimumab control as fist-line systemic therapy in metastatic clear cell renal cell carcinoma.", "relevant_passage_ids": ["36239611", "37062953", "37246571", "37163623", "37207297"], "type": "list", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "The COSMIC-313 phase 3 randomized controlled trial tested the triplet combination of cabozantinib with nivolumab and ipilimumab in comparison with nivolumab plus ipilimumab control as fist-line systemic therapy in metastatic clear cell renal cell carcinoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36239611"}, {"offsetInBeginSection": 422, "offsetInEndSection": 651, "text": "A recently conducted trial (COSMIC-313) showed superior efficacy with a triplet combination of cabozantinib, nivolumab, and ipilimumab when compared to a placebo, nivolumab, and ipilimumab but at the cost of additional toxicity. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37062953"}, {"offsetInBeginSection": 697, "offsetInEndSection": 1074, "text": "As concern the triplet therapy (i.e. nivolumab+ipilumumab+cabozantinib), the updated analysis of the COSMIC-313 study confirmed a significant PFS advantage in the subgroup of mRCC patients at intermediate IMDC risk, while the lack of benefit in the poor risk group supports the critical role of immunotherapy (but not of VEGFR-TKIs) in this poor prognosis subgroup of patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37246571"}, {"offsetInBeginSection": 2009, "offsetInEndSection": 2480, "text": "CONCLUSIONS: Among patients with previously untreated, advanced renal-cell carcinoma who had intermediate or poor prognostic risk, treatment with cabozantinib plus nivolumab and ipilimumab resulted in significantly longer progression-free survival than treatment with nivolumab and ipilimumab alone. Grade 3 or 4 adverse events were more common in the experimental group than in the control group. (Funded by Exelixis; COSMIC-313 ClinicalTrials.gov number, NCT03937219.).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37163623"}, {"offsetInBeginSection": 734, "offsetInEndSection": 1073, "text": "nivolumab+ipilumumab+cabozantinib), the updated analysis of the COSMIC-313 study confirmed a significant PFS advantage in the subgroup of mRCC patients at intermediate IMDC risk, while the lack of benefit in the poor risk group supports the critical role of immunotherapy (but not of VEGFR-TKIs) in this poor prognosis subgroup of patients", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37246571"}, {"offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "The COSMIC-313 phase 3 randomized controlled trial tested the triplet combination of cabozantinib with nivolumab and ipilimumab in comparison with nivolumab plus ipilimumab control as fist-line systemic therapy in metastatic clear cell renal cell carcinoma", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36239611"}, {"offsetInBeginSection": 488, "offsetInEndSection": 716, "text": "In COSMIC-313, a randomized phase III trial for patients with untreated advanced ccRCC, the triplet combination of ipilimumab, nivolumab, and cabozantinib was compared with a contemporary control arm of ipilimumab and nivolumab.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37207297"}, {"offsetInBeginSection": 422, "offsetInEndSection": 650, "text": "A recently conducted trial (COSMIC-313) showed superior efficacy with a triplet combination of cabozantinib, nivolumab, and ipilimumab when compared to a placebo, nivolumab, and ipilimumab but at the cost of additional toxicity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37062953"}, {"offsetInBeginSection": 422, "offsetInEndSection": 649, "text": "A recently conducted trial (COSMIC-313) showed superior efficacy with a triplet combination of cabozantinib, nivolumab, and ipilimumab when compared to a placebo, nivolumab, and ipilimumab but at the cost of additional toxicity", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37062953"}, {"offsetInBeginSection": 734, "offsetInEndSection": 1074, "text": "nivolumab+ipilumumab+cabozantinib), the updated analysis of the COSMIC-313 study confirmed a significant PFS advantage in the subgroup of mRCC patients at intermediate IMDC risk, while the lack of benefit in the poor risk group supports the critical role of immunotherapy (but not of VEGFR-TKIs) in this poor prognosis subgroup of patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37246571"}, {"offsetInBeginSection": 4, "offsetInEndSection": 146, "text": "COSMIC-313 phase 3 randomized controlled trial tested the triplet combination of cabozantinib with nivolumab and ipilimumab in comparison with", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36239611"}, {"offsetInBeginSection": 720, "offsetInEndSection": 930, "text": "therapy (i.e. nivolumab+ipilumumab+cabozantinib), the updated analysis of the COSMIC-313 study confirmed a significant PFS advantage in the subgroup of mRCC patients at intermediate IMDC risk, while the lack of", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37246571"}]}
+{"question_id": "65f492bbc4010b4d78000011", "question": "Explain the action of Domperidone.", "answer": "Domperidone is a peripherally acting dopamine2-receptor antagonist", "relevant_passage_ids": ["37352416", "36958154", "24147629", "3527396", "4061095", "4087563", "3048796", "21894796", "6756878", "16997628", "8965601", "2960110", "7823770", "30233361", "9876882", "3949445", "6396519", "1851838", "7255146", "515866"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Domperidone is a dopamine-2 (D2) receptor antagonist that stimulates the release of stored prolactin in the anterior pituitary.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37352416"}, {"offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Domperidone is a dopamine D2 receptor inhibitor that stimulates pituitary gonadotropins.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36958154"}, {"offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "OBJECTIVE: Domperidone is a dopamine antagonist with anti-nausea and anti-emetic activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21894796"}, {"offsetInBeginSection": 0, "offsetInEndSection": 39, "text": "Domperidone, a new dopamine antagonist.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3527396"}, {"offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Domperidone is a dopamine antagonist that has recently been released in Canada.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3527396"}, {"offsetInBeginSection": 152, "offsetInEndSection": 323, "text": "Domperidone, a peripheral dopamine receptor antagonist, has been successfully used for decades in the US and marketed in many countries for the treatment of gastroparesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16997628"}, {"offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "OBJECTIVE: Domperidone is a dopamine antagonist with anti-nausea and anti-emeti", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21894796"}, {"offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Domperidone is a dopamine antagonist that does not readily enter the central nervous system. Given parenterally or orally it increases gastric emptying of liquids and increases lower oesophageal sphincter pressure in healthy subjects.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6756878"}, {"offsetInBeginSection": 339, "offsetInEndSection": 449, "text": "Domperidon is a pure dopaminantagonist. It accelerates gastric emptying but has less effect on bowel motility.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8965601"}, {"offsetInBeginSection": 366, "offsetInEndSection": 513, "text": "According to the current concepts, 3H-domperidone is a selective ligand of D2 dopamine receptors mediating the psychotropic effect of neuroleptics.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2960110"}, {"offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "INTRODUCTION: Domperidone is a dopamine D2-receptor antagonist developed as an antiemetic and pro", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24147629"}, {"offsetInBeginSection": 0, "offsetInEndSection": 886, "text": "Bromopride (BRO) and domperidone (DOMP) are dopamine D2 blocking agents used in gastroenterology clinics because of their anti emetic effect as well as their central and peripheral actions of increasing gastrointestinal motor activity. The rationale for these experiments was to compare BRO- and DOMP-effects on plasma, brain, and intestinal cholinesterase activity in vitro. BRO and DOMP effects on cholinesterase activity in plasma, striatum, duodenum and ileum of adult male rats were measured for drug concentrations ranging from 0.006 to 3.134 microM for BRO and from 0.006 to 125 microM for DOMP. The results demonstrate that both BRO and DOMP can inhibit cholinesterase activity in all tissues studied, with DOMP being more potent than BRO in plasma and intestinal tissues. These data suggest the existence of a cholinergic mechanism of action for these dopamine blocking agents.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7823770"}, {"offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "INTRODUCTION: Domperidone is a dopamine D2-receptor antagonist developed as an antiemetic and prokinetic agent.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24147629"}, {"offsetInBeginSection": 337, "offsetInEndSection": 1643, "text": "Major drug classes include: (i) Muscarinic receptor antagonists-originated from historical accounts of plant extracts containing atropine and hyoscine with development stimulated by the need to prevent sea-sickness among soldiers during beach landings; (ii) Histamine receptor antagonists-searching for replacements for the anti-malaria drug quinine, in short supply because of wartime shipping blockade, facilitated the discovery of histamine (H1) antagonists (e.g., dimenhydrinate), followed by serendipitous discovery of anti-emetic activity against motion sickness in a patient undergoing treatment for urticaria; (iii) Phenothiazines and dopamine receptor antagonists-investigations of their pharmacology as \"sedatives\" (e.g., chlorpromazine) implicated dopamine receptors in emesis, leading to development of selective dopamine (D2) receptor antagonists (e.g., domperidone with poor ability to penetrate the blood-brain barrier) as anti-emetics in chemotherapy and surgery; (iv) Metoclopramide and selective 5-hydroxytryptamine3(5-HT3) receptor antagonists-metoclopramide was initially assumed to act only via D2 receptor antagonism but subsequently its gastric motility stimulant effect (proposed to contribute to the anti-emetic action) was shown to be due to 5-hydroxytryptamine4 receptor agonism.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30233361"}, {"offsetInBeginSection": 907, "offsetInEndSection": 1072, "text": "Domperidone, a dopamine D2 receptor antagonist that does not cross the blood brain barrier is relatively free of the central side-effect liability of metoclopramide.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9876882"}, {"offsetInBeginSection": 0, "offsetInEndSection": 412, "text": "Domperidone is a dopamine antagonist that does not readily enter the central nervous system. Given parenterally or orally it increases gastric emptying of liquids and increases lower oesophageal sphincter pressure in healthy subjects. The antiemetic and pharmacodynamic profile of domperidone is similar to that of metoclopramide, although domperidone has a lower propensity to cause extrapyramidal side effects.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6756878"}, {"offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "OBJECTIVE: Domperidone is a dopamine antagonist with anti-nausea and anti-emetic activity. There have been several reports of sudden cardiac death (SCD) associated with the compound. Recently it was estimated to increase SCD nearl", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21894796"}, {"offsetInBeginSection": 0, "offsetInEndSection": 555, "text": "The effect of domperidone, a peripheral dopamine receptor antagonist, has been studied in the aspirin, phenylbutazone and reserpine induced gastric ulcers in rats. The gastric anti-ulcer activity of domperidone was evident following a single dose as well as a 5-day pretreatment against all the three ulcerogenic drugs. However, the protection in the five-day pretreatment group was greater than in the single dose pretreatment group. It appears that the gastrokinetic properties of domperidone play a significant role in producing this anti-ulcer effect.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3949445"}, {"offsetInBeginSection": 275, "offsetInEndSection": 1035, "text": "Dopamine, noradrenaline, adrenaline and apomorphine antagonised the contraction responses at all frequencies; the concentration-response curves were steep and the use of higher concentrations was precluded by changes in base line tension per se. That noradrenaline was approximately 10 fold more potent than dopamine, that the dopamine response was not antagonised by the dopamine antagonists haloperidol, domperidone or (-)sulpiride, but was mimicked by the alpha 2-agonist guanfacine and partially antagonised by the alpha 2-adrenoceptor antagonist yohimbine (which could also antagonise the inhibitory actions of guanfacine) would indicate that a component of dopamine's action to reduce cholinergic activity is effected via alpha 2-adrenoceptor mechanisms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6396519"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1706, "text": "The mechanism of action of clebopride on the motility of guinea pig stomach was examined by the receptor binding assay for bovine brain membrane and by measuring gastric contractility and the release of acetylcholine from the stomach. The receptor binding assay revealed that clebopride bound to the D2 dopamine receptor with a high affinity and to the alpha-2 adrenoceptor and 5-HT2 serotonin receptor with relatively lower affinity, and not to D1 dopamine, alpha-1 adrenergic, muscarinic acetylcholine, H1 histamine, or opioid receptor. In strips of the stomach, clebopride at 10(-8) M to 10(-5) M enhanced the electrical transmural stimulation-evoked contraction and the release of acetylcholine. This enhancement was attributed to the blockade of the D2 dopamine receptor and alpha-2 adrenoceptor because: 1) Maximum responses obtained with specific D2 dopamine receptor antagonist, domperidone, and with specific alpha-2 adrenoceptor antagonist, yohimbine, were smaller than that with clebopride, and the sum of the effects of these two specific receptor antagonists is approximately equal to the effect of clebopride. 2) The facilitatory effect of clebopride was partially eliminated by pretreatment of the sample with domperidone or yohimbine, and the facilitatory effect of clebopride was not observed in preparations treated with the combination of domperidone and yohimbine. Clebopride also antagonized the inhibitory effects of dopamine and clonidine on the electrical transmural stimulation-evoked responses. These results indicate that clebopride acts on post ganglionic cholinergic neurons at D2 and alpha-2 receptors in this preparation to enhance enteric nervous system stimulated motility.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1851838"}, {"offsetInBeginSection": 0, "offsetInEndSection": 682, "text": "The effects of domperidone, a peripheral dopamine receptor blocker which poorly crosses the blood-brain barrier, on copulatory and exploratory behaviour were studied in apomorphine (oestrogen + progesterone) treated ovariectomized rats. The dose of domperidone (1.0 mg/kg) which clearly prevented the inhibitory action of apomorphine on the lordotic response did not influence the effect of apomorphine in an exploratory test situation. This finding indicates that peripherally (intraperitoneally) administered domperidone influences dopaminergic mechanisms implicated in the copulatory behaviour of the female rat, but not dopaminergic mechanisms involved in exploratory behaviour.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4061095"}, {"offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "INTRODUCTION: Domperidone is a dopamine D2-receptor antagonist developed as an antiemetic and prokinetic agent. Oral domperidone is not approved in the United States, but it is used in many countries to treat nausea and vomiting, gastroparesis and as a galactogogue (to promo", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24147629"}, {"offsetInBeginSection": 0, "offsetInEndSection": 400, "text": "Administration of a dopamine (DA) antagonist, domperidone, increased circulating levels of LH in hyperprolactinaemic-amenorrhoeic women with pituitary microadenomas but not in normal women in the early follicular phase of the menstrual cycle. This drug does not readily cross the blood-brain barrier and therefore the site of action of domperidone could be the pituitary gland or the median eminence.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3048796"}, {"offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Domperidone is a dopamine antagonist that does not readily enter the central nervous system.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6756878"}, {"offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Domperidone is a peripheral antagonist of dopamine which does not cross the blood-brain barrier.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7255146"}, {"offsetInBeginSection": 339, "offsetInEndSection": 378, "text": "Domperidon is a pure dopaminantagonist.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8965601"}, {"offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "The effect of domperidone, a peripheral dopamine receptor antagonist, has been studied in the aspirin, phenylbutazone and reserpine induced gastric ulcers in rats.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3949445"}, {"offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "UNLABELLED: Domperidone (dopamine antagonist), metoclopramide and clebopride (both dopamine antagonists and stimulators of the intramural choliner", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4087563"}, {"offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Domperidone (Motilium), a dopamine receptor blocking agent, increased the resting tone of the lower oesophageal sphincter in 15 dogs and 6 baboons.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/515866"}, {"offsetInBeginSection": 235, "offsetInEndSection": 412, "text": "The antiemetic and pharmacodynamic profile of domperidone is similar to that of metoclopramide, although domperidone has a lower propensity to cause extrapyramidal side effects.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6756878"}, {"offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "Bromopride (BRO) and domperidone (DOMP) are dopamine D2 blocking agents used in gastroenterology clinics because of their anti emetic effect as well as their central and peripheral actions of increasing gastrointestinal motor activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7823770"}]}
+{"question_id": "65f86ba3c4010b4d78000059", "question": "Which age group should never be tested for HIV infection?", "answer": "There is no age group that should never be tested for HIV infection. In fact, the World Health Organization recommends that all people aged 15-64 years old get tested for HIV at least once in their lifetime, and those at high risk of infection get tested annually. Children born to mothers living with HIV also need to be tested regularly as they are at a higher risk of acquiring the virus through mother-to-child transmission. Early diagnosis and treatment of HIV can significantly improve health outcomes and reduce the risk of transmission. Therefore, it is important for all individuals, regardless of age, to know their HIV status and take appropriate measures to protect themselves and their partners.", "relevant_passage_ids": ["34949518", "37720974", "36629794", "36630307", "36630617", "18685551", "36589732", "25283353", "37993765", "36729993", "27435075", "21279431", "29583105", "24849622", "12126721", "25303208", "28883962", "19940800", "19303830", "17129866", "28796758", "37729175", "37632603", "10224192", "24789219", "8655933", "25960684", "20685813", "9611559", "22908365", "24964879"], "type": "factoid", "snippets": [{"offsetInBeginSection": 293, "offsetInEndSection": 410, "text": "social and clinical inequalities of more children infected with HIV and more children losing their fight against AIDS", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34949518"}, {"offsetInBeginSection": 475, "offsetInEndSection": 553, "text": "two out of five children living with HIV worldwide are unaware of their status", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34949518"}, {"offsetInBeginSection": 862, "offsetInEndSection": 882, "text": "maternal HIV testing", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34949518"}, {"offsetInBeginSection": 944, "offsetInEndSection": 968, "text": "pregnant people with HIV", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37720974"}, {"offsetInBeginSection": 1645, "offsetInEndSection": 1741, "text": "PPHIV experienced higher rates of LBW and VLBW newborns, and higher late pregnancy-related death", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37720974"}, {"offsetInBeginSection": 166, "offsetInEndSection": 196, "text": "adults diagnosed late with HIV", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36629794"}, {"offsetInBeginSection": 1545, "offsetInEndSection": 1720, "text": "HIV diagnosis could help develop effective strategies to reduce this burden of late presentation - particularly among heterosexual individuals, non-Europeans, and older people", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36629794"}, {"offsetInBeginSection": 926, "offsetInEndSection": 1010, "text": "Amongst MSM, those who were older, of an ethnicity other than European, acquired HIV", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36629794"}, {"offsetInBeginSection": 485, "offsetInEndSection": 581, "text": "penile cancer within HIV-positive individuals is significantly greater than in those without HIV", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36630307"}, {"offsetInBeginSection": 1000, "offsetInEndSection": 1109, "text": "HIV and penile carcinoma, with a higher risk of cancer in Hispanic, compared with Caucasian, HIV-positive men", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36630307"}, {"offsetInBeginSection": 12, "offsetInEndSection": 149, "text": "The vulnerability of female sex workers (FSWs) to HIV infection increases if unprotected heterosexual anal intercourse (HAI) is practiced", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36630617"}, {"offsetInBeginSection": 1000, "offsetInEndSection": 1254, "text": "Our analysis found that in Cameroon, women in polygamous relationships, Muslim women, married women with inadequate HIV knowledge, those who had never been tested for HIV and women with lower socioeconomic status are less likely to negotiate for safe sex", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37993765"}, {"offsetInBeginSection": 1508, "offsetInEndSection": 1631, "text": "Health-care providers should routinely screen all patients aged 13-64 years for HIV in accordance with CDC recommendations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18685551"}, {"offsetInBeginSection": 0, "offsetInEndSection": 843, "text": "BACKGROUND: The perinatal short-course zidovudine (ZDV) chemoprophylaxis that can reduce HIV-1 vertical transmission by 51% has been widely practiced in developing countries such as Thailand because of its simpler and less cost.OBJECTIVES: To investigate the effects of short-course regimen of oral ZDV for prophylaxis of HIV-1 subtype E vertical transmission among 'break-through' HIV-1 infected infants.STUDY DESIGN: The study analyzed clinical and virological outcomes of 80 infants, whose mothers received ZDV prophylaxis starting at 36 weeks gestation (group Z) and 37 infants whose mothers never received anti-retroviral drugs (group C), at the ages of 1-2, 4-6, and 12 months.RESULTS: Of the 12 HIV-1 infected infants, 5/7 (71.4%) from group Z and 1/5 (20%) from group C progressed to a symptomatic clinical stage by the age 4-6 months.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12126721"}, {"offsetInBeginSection": 540, "offsetInEndSection": 741, "text": "To reduce the number of persons with undiagnosed HIV infection, CDC issued recommendations in September 2006 to implement HIV screening as part of routine medical care for all persons aged 13-64 years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18685551"}, {"offsetInBeginSection": 121, "offsetInEndSection": 255, "text": "Yet many adolescents and young adults with high-risk behaviors for HIV are unaware of their HIV status and have never had an HIV test.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25283353"}, {"offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "HIV testing was assessed online among men accessing a sexual networking website for men who have sex with men.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21279431"}, {"offsetInBeginSection": 1071, "offsetInEndSection": 1143, "text": "An estimated 83.7% of sexually active older adults never tested for HIV.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29583105"}, {"offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "BACKGROUND: The human immunodeficiency virus (HIV) infection usually infects persons in the reproductive age group (15-49 years), but elderly people are also ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28883962"}, {"offsetInBeginSection": 1441, "offsetInEndSection": 1639, "text": "d HIV-infected adolescents in Zimbabwe. In resource-poor settings with maturing epidemics, the presence of skin disease should be regarded as a strong indication for HIV testing and especially as it", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19940800"}, {"offsetInBeginSection": 93, "offsetInEndSection": 174, "text": "This is the prime childbearing age group with an increasing mortality due to HIV.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19303830"}, {"offsetInBeginSection": 386, "offsetInEndSection": 829, "text": "No significant difference was observed in the association between HIV infection and gender (chi2=0.58, df = 1, P < 0.05). The highest prevalence of HIV infection (8.9%) was recorded among individuals in the 21-30 years age category, while the least HIV infection prevalence (5.3%) was observed among persons above 40 years old. There was no significant difference in the association between HIV infection and age (chi2=0.68, df = 3, P < 0.05).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17129866"}, {"offsetInBeginSection": 0, "offsetInEndSection": 334, "text": "CDC's 2006 recommendations for human immunodeficiency virus (HIV) testing state that all persons aged 13-64 years should be screened for HIV at least once, and that persons at higher risk for HIV infection, including sexually active gay, bisexual, and other men who have sex with men (MSM), should be rescreened at least annually (1).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28796758"}, {"offsetInBeginSection": 1944, "offsetInEndSection": 2091, "text": "Providers should target men aged \u2264 34 years, with primary education, visiting facilities for the first time and who have never been tested for HIV.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37729175"}, {"offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "The CDC recommends that persons aged 13-64 receive an HIV test at least once in their lifetime and that some groups test annually or more frequently", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37632603"}, {"offsetInBeginSection": 142, "offsetInEndSection": 408, "text": "The US Centers for Disease Control and Prevention recommends persons aged 13 to 64 years be tested for HIV at least once as part of routine health care; however, it is unclear how effectively these testing recommendations have been implemented in EHE priority areas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36729993"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1959, "text": "HIV testing continues to be a challenge among the young population in Tanzania. As of 2017, only 30% of 15-19-year-olds reported getting tested and receiving their results. This study will examine the demographic and socio-behavioral characteristics associated with HIV testing among adolescents and young adults in Tanzania. Interview data from the 2016-2017 Tanzania HIV Impact Survey (THIS) were analyzed on 10,128 adolescents and young adults 15-24 years of age, representing 10.5 million youth in Tanzania. Weighted logistic regression was used to model the relationship of HIV testing with demographic and socio-behavioral characteristics. Half (50%) of respondents reported ever having been tested for HIV. HIV testing was significantly lower among males compared with females (AOR = 0.5;95% confidence interval [CI] = 0.5-0.6; p<0.001), 15-19 year olds compared with 20-24 year olds (AOR = 0.4;95% CI = 0.4-0.5; p<0.001), no education compared with secondary or post-secondary education (AOR = 0.4;95% CI = 0.3-0.6; p<0.001), rural residents compared with urban residents (AOR = 0.7;95% CI = 0.6-0.9; p<0.001) and those who don't use condoms during sexual intercourse compared with those who do (AOR = 0.6;95% CI = 0.5-0.8; p<0.001). Among HIV-infected youth, younger age group, rural residents, education less than primary, single, high income, and sex workers were significantly associated with never testing for HIV. This study highlights the majority of characteristics affecting HIV testing among young people in Tanzania have not changed over the years, thus it is necessary to re-examine the current approaches to HIV testing. The COVID-19 pandemic will add to this challenge as it collides with the ongoing HIV epidemic and competes for needed medical supplies and health care provider resources. In light of this current situation, intensified and targeted HIV testing programs for at risk young populations in Tanzania should be prioritized.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36589732"}, {"offsetInBeginSection": 830, "offsetInEndSection": 1133, "text": "Mandatory pre-marital HIV screening could generate social stigmatization and infringement of the fundamental human rights of infected individuals. Voluntary counselling and confidential HIV testing and especially pre- and post-test counselling as the basis of pre-marital HIV testing are more desirable.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17129866"}, {"offsetInBeginSection": 0, "offsetInEndSection": 423, "text": "The Centers for Disease Control and Prevention recommends routine human immunodeficiency virus (HIV) testing of every client presenting for services in venues where HIV prevalence is high. Because older adults (aged \u226550 years) have particularly poor prognosis if they receive their diagnosis late in the course of HIV disease, any screening provided to younger adults in these venues should also be provided to older adults", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25303208"}, {"offsetInBeginSection": 526, "offsetInEndSection": 730, "text": "HIV-infected children, adolescents, and young adults who are severely immunocompromised (based on age-specific CD4 lymphocyte enumeration) attributable to HIV infection should not receive measles vaccine.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10224192"}, {"offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "HIV is often assumed to only affect younger people, and many older people do not realize that they might risk acquiring the virus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24789219"}, {"offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "The HIV infection primarily affects young adults, but older adults are also susceptible.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8655933"}, {"offsetInBeginSection": 1429, "offsetInEndSection": 1561, "text": "Physicians are less likely to discuss sexual risk behaviors with older adults and to test them for HIV compared with younger adults.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25960684"}, {"offsetInBeginSection": 546, "offsetInEndSection": 715, "text": "In 2007 the Centers for Disease Control and Prevention in the United States reported that 16.8% of new diagnoses of HIV that year were in individuals aged over 50 years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20685813"}, {"offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Adolescents and young adults are the fastest growing age group of human immunodeficiency virus (HIV) positive individuals in the US, and many who are infected do not know their HIV status.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24849622"}, {"offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Older Americans, 50 years of age and older, account for 10% of the 400,000 reported cases of AIDS nationwide (Centers for Disease Control and Prevention, 1994).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9611559"}, {"offsetInBeginSection": 258, "offsetInEndSection": 459, "text": "Since 2006, CDC has recommended that health-care providers screen for HIV all patients aged 13-64 years unless prevalence of undiagnosed HIV infection in their patients has been documented to be <0.1%.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24964879"}, {"offsetInBeginSection": 459, "offsetInEndSection": 700, "text": "In 2006, CDC recommended that all persons aged 13\u201364 years be screened for HIV in health-care settings in which the prevalence of undiagnosed HIV infection is >0.1%, and that persons with increased risk for HIV be retested at least annually.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22908365"}, {"offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Currently, the Centers for Disease Control and Prevention recommends that persons between 15 and 64\u00a0years get tested for human immunodeficiency virus (HIV) at least once in their lifetime and persons with HIV risk factors get tested more frequently.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27435075"}]}
+{"question_id": "65d12ae11930410b13000030", "question": "Can fingolimod be used during pregnancy?", "answer": "No. Fingolimod has teratogenic potential and therefore should not be used during pregnancy.", "relevant_passage_ids": ["37307691", "35428205", "35390594", "35088492", "33443836", "34310364", "32564333", "23961604", "37217309", "37341330", "28078140", "22926165", "30542374", "31185372"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1570, "offsetInEndSection": 1775, "text": "Interferon beta 1a SC was preferred over other treatments for patients with mild to moderate MS and planning for pregnancy (56.6%) or breastfeeding (60.2%). Fingolimod was not a choice for these patients. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37307691"}, {"offsetInBeginSection": 1985, "offsetInEndSection": 2389, "text": "In total, 45 patients (18.8%) permanently discontinued treatment because of AEs related to study drug; two patients reported pregnancy after treatment initiation and subsequently discontinued the\u00a0treatment; no deaths were reported.CONCLUSION: GOLEMS study demonstrated the sustained effectiveness and manageable safety profile of fingolimod under real-world conditions over 48\u00a0months in patients with MS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35428205"}, {"offsetInBeginSection": 1568, "offsetInEndSection": 1893, "text": "Concerns about COVID-19 had a noticeable impact on administering high efficacy drugs like rituximab and fingolimod. However, in male patients this approach has not been the case. It may be related to more aggressive disease course in this group. The other possible explanation could be planning for pregnancy in female cases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35390594"}, {"offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "BACKGROUND: Authorizations of fingolimod, teriflunomide and cladribine were accompanied by risk minimization measures concerning their teratogenic potential.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36174258"}, {"offsetInBeginSection": 503, "offsetInEndSection": 600, "text": "Fingolimod\u2005: contraindicated during pregnancy due to suspected risk of congenital malformations. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33443836"}, {"offsetInBeginSection": 489, "offsetInEndSection": 706, "text": "Drugs with a known potential of teratogenicity such as fingolimod or teriflunomide should be avoided and recommended wash-out times for medications such as cladribine, alemtuzumab or ocrelizumab should be considered. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34310364"}, {"offsetInBeginSection": 226, "offsetInEndSection": 433, "text": "Caution should be exercised when prescribing fingolimod and natalizumab to patients with multiple sclerosis who are of childbearing potential because of the risk of disease rebound when they are discontinued", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37341330"}, {"offsetInBeginSection": 980, "offsetInEndSection": 1095, "text": "Current evidence supports the contraindication for fingolimod during pregnancy; data on other DMTs remains limited.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28078140"}, {"offsetInBeginSection": 436, "offsetInEndSection": 604, "text": "Fingolimod is suspected to be harmful for fetal development, and the use of this drug should be stopped no later than two months before discontinuing the contraception.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23961604"}, {"offsetInBeginSection": 636, "offsetInEndSection": 770, "text": "Conception should be discouraged for patients on fingolimod, because of the limited information available on human pregnancy outcomes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22926165"}, {"offsetInBeginSection": 1081, "offsetInEndSection": 1308, "text": "If a patient becomes pregnant while taking fingolimod, and requires continued DMD treatment, a switch to interferon \u03b2 or natalizumab after a variable washout period may be prescribed, depending on the level of disease activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32564333"}, {"offsetInBeginSection": 254, "offsetInEndSection": 432, "text": "it is recommended that multiple sclerosis patients undergoing treatment with fingolimod use contraceptive methods for at least two months after discontinuation of the medication.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31185372"}, {"offsetInBeginSection": 0, "offsetInEndSection": 522, "text": "BACKGROUND AND METHODS: Limited data are available on the safety of fingolimod in pregnant women. We estimated the risk of adverse pregnancy outcomes in women with multiple sclerosis (MS) exposed to fingolimod either shortly before or during pregnancy in prospectively collected cases from clinical trials, observational studies, surveillance programs, and spontaneous reports.RESULTS: The prevalence of major malformations among live births does not appear to be significantly higher than those in the general population ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30542374"}, {"offsetInBeginSection": 26, "offsetInEndSection": 134, "text": "Discontinuation of fingolimod \u22652 months before pregnancy is recommended to minimize potential teratogenicity", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37217309"}, {"offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "BACKGROUND AND OBJECTIVE: Discontinuation of fingolimod \u22652 months before pregnancy is recommended to minimize potential teratogenicity. The magnitude of MS pregnancy relapse risk, particularly severe relapses, after fingolimod cessation is unclear, as is whether this risk is reduced by pregna", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37217309"}, {"offsetInBeginSection": 503, "offsetInEndSection": 599, "text": "Fingolimod\u2005: contraindicated during pregnancy due to suspected risk of congenital malformations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33443836"}]}
+{"question_id": "65f38059c4010b4d7800000e", "question": "What does capnography measure?", "answer": "Capnography provides real-time measurement of carbon dioxide (CO2) in respiratory gases.", "relevant_passage_ids": ["37507472", "37259022", "34008907", "30523011", "24785676", "7736268", "7889801", "7792768", "9390853", "26638570", "24685942", "31692301", "18156957", "26264607", "2511789", "1643689", "25436022", "1489871", "26714621"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "A secondary analysis of a randomized study was performed to study the relationship between volumetric capnography (VCAP) and arterial CO2 partial pressure (PCO2) during cardiopulmonary resuscitation", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37507472"}, {"offsetInBeginSection": 11, "offsetInEndSection": 140, "text": " By continually monitoring end-tidal carbon dioxide concentrations, capnography can detect abnormal ventilation or apnoea early. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37259022"}, {"offsetInBeginSection": 139, "offsetInEndSection": 228, "text": "Capnography is the measurement and numerical display of end-tidal carbon dioxide (EtCO2).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24685942"}, {"offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Capnography measures exhaled carbon dioxide and is most useful when applied directly to patient care.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9390853"}, {"offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Capnography is the measurement of carbon dioxide (CO2) concentration in a gas mixture.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7736268"}, {"offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Capnography, often referred to by emergency clinicians as end-tidal carbon dioxide monitoring, is a noninvasive method of measuring cardiopulmonary and metabolic parameters that can be utilized in many clinical applications.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31692301"}, {"offsetInBeginSection": 494, "offsetInEndSection": 614, "text": "Capnography measures exhaled carbon dioxide and provides early identification of airway obstruction and hypoventilation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30523011"}, {"offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "An end-tidal CO2 monitor (capnometer) is used most often as a noninvasive substitute for PaCO2 in anesthesia, anesthetic recovery, and intensive care. Additionally, the wide spread on-site use of portable capnometers in emergency and trauma situations is now observed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26264607"}, {"offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Capnometers measure carbon dioxide (CO2) in expired air and provide clinicians with a noninvasive measure of systemic metabolism, circulation, and ventilation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2511789"}, {"offsetInBeginSection": 101, "offsetInEndSection": 255, "text": "Capnography provides a continuous and non-invasive measure of arterial partial pressure of carbon dioxide (PaCO2) throughout the entire respiratory cycle.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7889801"}, {"offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "MONITORING RESPIRATORY and metabolic function by using capnography to measure end tidal carbon dioxide is standard practice in anaesthesia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26638570"}, {"offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Capnometers measure carbon dioxide (CO2) in expired air and provide clinicians with a noninvasive measure of systemic metabolism, circulation, and ventilation. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2511789"}, {"offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "PURPOSE OF REVIEW: Volumetric capnography (VCap) measures the kinetics of carbon dioxide (CO2) elimination on a breath-by-breath basis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24785676"}, {"offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Capnography measures carbon dioxide concentration or partial pressure of the respiratory gas continuously and non-invasively.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7792768"}, {"offsetInBeginSection": 216, "offsetInEndSection": 452, "text": "Capnography is the non-invasive measurement of a sample of the exhaled carbon dioxide which has multiple clinical uses including as a method to confirm placement of a tracheal tube and/or to assess ventilation, perfusion and metabolism.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34008907"}, {"offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "BACKGROUND: Capnography provides a continuous, non-invasive monitoring of the CO2 to assess adequacy of ventilation and provide added safety features in mechanically ventilated patients by allowing for quick identification of unplanned", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25436022"}, {"offsetInBeginSection": 277, "offsetInEndSection": 518, "text": "Capnography, a noninvasive monitoring technique designed to measure expired carbon dioxide (CO2) levels, has been used previously to identify respiratory placement of nasogastric tubes in adults; however, its use in children is understudied.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18156957"}, {"offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Capnometers measure carbon dioxide (CO2) in inspired and expired air.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1489871"}, {"offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "INTRODUCTION: Capnography is used to monitor the endtidal carbon dioxide tension (EtCO2) i", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26714621"}, {"offsetInBeginSection": 340, "offsetInEndSection": 583, "text": "This review of capnography includes the methods available to determine carbon dioxide in expired air, and an analysis of the physiology of capnograms, which are followed by a description of the applications of capnography in clinical practice.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1643689"}]}
+{"question_id": "65f8611dc4010b4d78000055", "question": "Should men be immunized against Human Papilloma Virus?", "answer": "Yes, HPV is one of the most common causes of STD, and can cause genital warts and cancer (cervical, anal, vulvar, vaginal, penile, and oropharyngeal) in men and women.", "relevant_passage_ids": ["36691362", "36305982", "37264392", "31992466", "25553242", "26554731", "33145777", "27354258", "22021967", "22371460", "25167164", "25811679", "29769961", "27486020", "18830138", "30591254", "35577640", "23391351", "37661628", "25756144", "20547286", "23167429", "32154741", "26734596", "35471242", "29517117", "24553168", "28346275", "28538494", "20138347", "36897868"], "type": "summary", "snippets": [{"offsetInBeginSection": 384, "offsetInEndSection": 518, "text": "As scientific knowledge of HPV-related cancers has advanced, it has become evident that HPV vaccination is a priority for both genders", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36691362"}, {"offsetInBeginSection": 520, "offsetInEndSection": 634, "text": "HPV is known to contribute to male cancers of the mouth, throat, anus, and penis, as well as causing genital warts", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36691362"}, {"offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "The human papillomavirus (HPV) vaccine is one of the most effective public health measures for preventing HPV-related cancers and other diseases", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36305982"}, {"offsetInBeginSection": 12, "offsetInEndSection": 107, "text": "Almost all cases of cervical and anal cancer have been linked to the human papillomavirus (HPV)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37264392"}, {"offsetInBeginSection": 180, "offsetInEndSection": 291, "text": "both men and women can also develop cancers of the anus, oral cavity, and oropharynx that are attributed to HPV", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37264392"}, {"offsetInBeginSection": 790, "offsetInEndSection": 1134, "text": "Gardasil(\u00ae) is a quadrivalent vaccine against HPV types 6, 11, 16, and 18 and is recommended for use in females 9-26 years of age, for the prevention of cervical, vulvar, and vaginal cancers and intraepithelial neoplasia and condyloma acuminata and recently for vaccination in boys and men 9-26 years of age for the prevention of genital warts.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22021967"}, {"offsetInBeginSection": 1288, "offsetInEndSection": 1420, "text": "HPV vaccines are safe and efficacious against type-specific HPV-induced anogenital warts, precancerous lesions, and cervical cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22021967"}, {"offsetInBeginSection": 418, "offsetInEndSection": 567, "text": "HPV infection is considered to contribute to almost 100% cervical cancers and at least 80% of anal and 40-60% of vulvar, vaginal, and penile cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22021967"}, {"offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "On October 25, 2011, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommended that the quadrivalent human papillomavirus vaccine (Gardasil; Merck & Co, Inc, Whitehouse Station, NJ) be used routinely in males.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22371460"}, {"offsetInBeginSection": 1048, "offsetInEndSection": 1178, "text": "ACIP recommends routine vaccination with HPV4 or HPV2 for females aged 11 or 12 years and with HPV4 for males aged 11 or 12 years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25167164"}, {"offsetInBeginSection": 155, "offsetInEndSection": 635, "text": "HPV vaccine efficacy varies in relationship to when the vaccine is administered, with greater efficacy obtained if administered prior to sexual debut. Historically, this vaccine was created to protect women from cervical cancer. As scientific knowledge of HPV-related cancers has advanced, it has become evident that HPV vaccination is a priority for both genders. HPV is known to contribute to male cancers of the mouth, throat, anus, and penis, as well as causing genital warts.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36691362"}, {"offsetInBeginSection": 259, "offsetInEndSection": 464, "text": "HPV vaccine is recommended for routine vaccination at age 11 or 12 years. ACIP also recommends vaccination for females aged 13 through 26 years and males aged 13 through 21 years not vaccinated previously.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25811679"}, {"offsetInBeginSection": 253, "offsetInEndSection": 497, "text": "heir lives. Canada's National Advisory Committee on Immunization (NACI) has recommended a three-dose immunization schedule with HPV vaccine for females 9 years of age and older and for males between 9 and 26 years of age, since 2007 and 2012, r", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29769961"}, {"offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "BACKGROUND: Rates of routine human papillomavirus (HPV) vaccination of adolescent males in the United States are low. Leading health organizations advocate consistent and strong physician recommendations to improve HPV vaccine di", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27486020"}, {"offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "BACKGROUND: For human papillomavirus (HPV) vaccination to have maximum benefit to public health, both men and women should be vaccinated. Although efficacy trials in men are still ongoing, the HPV vaccine will likely be licensed for men in the ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18830138"}, {"offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "In the United States, human papillomavirus (HPV) vaccine has been recommended for females since 2006 and for males since 2011.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30591254"}, {"offsetInBeginSection": 875, "offsetInEndSection": 1334, "text": "vaccine recommendations.CONCLUSION: HPV is responsible for 50.8% of penile cancers globally, 79.8% of PeIN, and 90% of genital warts. In 2009 the Food and Drug Administration licensed the quadrivalent HPV vaccine for use in males, with a potential efficacy of 90% and 77.5% to reduce genital warts and anal intraepithelial neoplasia, respectively. However, the uptake of HPV vaccination in men is low, and gender-neutral vaccination is estimated to be impleme", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35577640"}, {"offsetInBeginSection": 2398, "offsetInEndSection": 2627, "text": "Accordingly, for prevention purposes and social fairness and equality, as both sexes are affected by the disease, the vaccination of 12-year-old males against HPV should be recommended in order to guaranty protection to everyone.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23391351"}, {"offsetInBeginSection": 1421, "offsetInEndSection": 1590, "text": "The quadrivalent vaccine against HPV has proved to be effective in preventing external genital lesions in males aged 16-26 years in 90.4%; (95%; CI: 69.2-98.1) of cases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23391351"}, {"offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "MSM are a high-risk population for HPV infection and related diseases. MSM can be effectively protected by quadrivalent and nine-valent HPV vaccines.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37661628"}, {"offsetInBeginSection": 306, "offsetInEndSection": 401, "text": " boys and girls. The quadrivalent HPV vaccination is approved and recommended for both boys and", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25756144"}, {"offsetInBeginSection": 0, "offsetInEndSection": 512, "text": "BACKGROUND: For human papillomavirus (HPV) vaccination to have maximum benefit to public health, both men and women should be vaccinated. Although efficacy trials in men are still ongoing, the HPV vaccine will likely be licensed for men in the near future. Little is known about men's interest in HPV vaccination. This study assessed whether informing men about the benefits of male HPV vaccination for their female sexual partner(s) boosted interest in the HPV vaccine beyond informing them about the benefits t", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18830138"}, {"offsetInBeginSection": 0, "offsetInEndSection": 466, "text": "PURPOSE: We assessed U.S. physicians' attitudes and perceptions regarding potential human papillomavirus (HPV) vaccination of males.METHODS: We surveyed a random sample of 2,714 pediatricians and family practitioners identified in administrative claims of a U.S. health plan as HPV vaccinators of females; 595 pediatricians and 499 family practitioners participated.RESULTS: Most physicians would recommend HPV vaccination to males aged 11-12 (63.9%), 13-18 (93.4%),", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20547286"}, {"offsetInBeginSection": 304, "offsetInEndSection": 658, "text": "HPV vaccination of boys should help reduce anal cancer in homosexual men and cervical cancer in women, it will have little or no impact on penile or prostate cancer. Male circumcision can reduce cervical, penile and possibly prostate cancer. Promotion of both HPV vaccination and male circumcision will synergistically maximize genital cancer prevention.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23167429"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1138, "text": "Human papillomavirus (HPV) remains the most common sexually transmitted infection with a lifetime incidence of over 75%. Based on US data from the Centers for Disease Control and Prevention (CDC), 64% of invasive HPV-associated cancers are attributable to HPV 16 or 18 (65% for females; 63% males) and may be prevented by vaccination with either the quadrivalent or nonavalent HPV vaccine. Public HPV vaccination programs are now the norm for women aged 9-45 years and men aged 9-26 years in Canada. Yet, only recently have guidelines begun to consider vaccination of men older than 26 years of age. There now exist compelling reasons to recommend vaccination against HPV amongst males >26 years of age. Recognizing that the risks posed by HPV infection persist beyond 26 years of age, that the vaccination of men aged 26-45 years with HPV vaccine confers immunogenicity at levels demonstrably efficacious against HPV-related diseases, and that the Food and Drug Administration recently expanded the HPV vaccination to include older men, it is argued that HPV vaccination in men older than 26 years of age should be routinely recommended.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32154741"}, {"offsetInBeginSection": 138, "offsetInEndSection": 558, "text": "Despite the proven safety and efficacy of available vaccines, HPV remains the most common sexually transmitted infection. Underlying the high prevalence of HPV infection is the poor adherence to the Centers for Disease Control recommendation to vaccinate all 11- to 12-year-old males and females. In fact, only about 38 and 14% of eligible females and males, respectively, receive the complete, three-dose immunization. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26734596"}, {"offsetInBeginSection": 0, "offsetInEndSection": 448, "text": "BACKGROUND: Despite the high risks associated with human papillomavirus (HPV), the HPV vaccination rate of men is far lower than women. Most previous review studies have focused on female vaccination and related affecting factors. However, previous studies have reported that the factors affecting HPV vaccination differ by gender.OBJECTIVE: The aim of this review was to identify the factors affecting HPV vaccine initiation in men through a syste", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35471242"}, {"offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "AIMS: Human papilloma virus (HPV) is 1 of the most common sexually transmitted infection responsible for different types of cancer: cervical, penile, vulvar, anal and oropharyngeal.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33145777"}, {"offsetInBeginSection": 1117, "offsetInEndSection": 1401, "text": "The 9vHPV and qHPV vaccines showed comparable safety profiles.CONCLUSIONS: In addition to immune responses to HPV 31/33/45/52/58, a three-dose regimen of the 9vHPV vaccine elicited a similar immune response to HPV 6/11/16/18 when compared with the qHPV vaccine in men aged 16-26years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27354258"}, {"offsetInBeginSection": 0, "offsetInEndSection": 370, "text": "The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommends that human papillomavirus (HPV) vaccination routinely be targeted to females and males aged 11 years or 12 years as part of the adolescent immunization platform to help reduce the incidence of anogenital cancers and genital warts associated with HPV infection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24553168"}, {"offsetInBeginSection": 333, "offsetInEndSection": 464, "text": "ACIP also recommends vaccination for females aged 13 through 26 years and males aged 13 through 21 years not vaccinated previously.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25811679"}, {"offsetInBeginSection": 895, "offsetInEndSection": 1291, "text": "The Advisory Committee on Immunization Practices and the American College of Obstetricians and Gynecologists recommend routine HPV vaccination for girls and boys at the target age of 11-12 years (but it may be given from the age of 9 years) as part of the adolescent immunization platform in order to help reduce the incidence of anogenital cancer and genital warts associated with HPV infection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28346275"}, {"offsetInBeginSection": 895, "offsetInEndSection": 1291, "text": "The Advisory Committee on Immunization Practices and the American College of Obstetricians and Gynecologists recommend routine HPV vaccination for girls and boys at the target age of 11-12 years (but it may be given from the age of 9 years) as part of the adolescent immunization platform in order to help reduce the incidence of anogenital cancer and genital warts associated with HPV infection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28538494"}, {"offsetInBeginSection": 308, "offsetInEndSection": 682, "text": "We also present the recommendations of the Qu\u00e9bec Immunization Committee (CIQ) in this regard, which are: to provide targeted vaccination for MSM up to 26\u00a0years of age and in-school vaccination of preadolescent boys since this is the best approach to take to have a real impact on the burden related to HPV in the MSM population and to provide direct protection for all men.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26554731"}, {"offsetInBeginSection": 232, "offsetInEndSection": 487, "text": "Even though a fall in cervical cancer rates has been reported worldwide, the subsequent rise in HPV-associated head and neck cancers among men and women have been reported from developed countries, necessitating the vaccination of adolescent boys as well.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29517117"}, {"offsetInBeginSection": 918, "offsetInEndSection": 1195, "text": "Extension of immunization offer to young women and to adolescent male subjects has become an important additional opportunity for several countries, with a special focus needed on homosexual men with HIV infection who are at particularly increased risk of HPV-related diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25553242"}, {"offsetInBeginSection": 390, "offsetInEndSection": 499, "text": "Public HPV vaccination programs are now the norm for women aged 9-45 years and men aged 9-26 years in Canada.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32154741"}, {"offsetInBeginSection": 704, "offsetInEndSection": 1138, "text": "Recognizing that the risks posed by HPV infection persist beyond 26 years of age, that the vaccination of men aged 26-45 years with HPV vaccine confers immunogenicity at levels demonstrably efficacious against HPV-related diseases, and that the Food and Drug Administration recently expanded the HPV vaccination to include older men, it is argued that HPV vaccination in men older than 26 years of age should be routinely recommended.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32154741"}, {"offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "Human Papilloma Virus (HPV) has been implicated in the initiation of several types of cancers in both females and males. Therefore, it is imperative that national immunization programs should ensure that both young women and young men receive full immunization for herd immunity in their teenage years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31992466"}, {"offsetInBeginSection": 542, "offsetInEndSection": 831, "text": "Male sexual behavior, with consequent HPV infection and disease contribute to considerable disease burden in females. Hence, inclusion of males in prophylactic HPV vaccination programs should prevent HPV-related disease in males as well as substantially reducing disease burden in females.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20138347"}, {"offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Human Papillomavirus (HPV) vaccination is of paramount importance to reduce HPV-associated cancers in both genders.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36897868"}, {"offsetInBeginSection": 1605, "offsetInEndSection": 1788, "text": "Therefore, inclusion of males in an HPV vaccination program is likely to have significant health and economic benefits over and above those observed from current female-only programs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20138347"}]}
+{"question_id": "65cfd68a1930410b13000021", "question": "Is sectoral Heterochromia associated with Crohn's disease?", "answer": "No. There are no published reports to suggest an association of sectoral Heterochromia with Crohn's disease.", "relevant_passage_ids": ["34189344", "17933676", "3792843"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "A case of unilateral sectoral iris heterochromia in an infant with Beckwith-Wiedemann syndrome.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34189344"}, {"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "PURPOSE: To report a case of unilateral sectoral iris heterochromia in an infant with Beckwith-Wiedemann syndrome (BWS).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34189344"}, {"offsetInBeginSection": 367, "offsetInEndSection": 451, "text": "CONCLUSIONS: This is the first reported case of iris heterochromia in a BWS patient.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34189344"}, {"offsetInBeginSection": 51, "offsetInEndSection": 262, "text": "The first case is an example of Waardenburg's type II (without dystopia canthorum) with bilateral sectoral iris heterochromia and fundus bicolor, hyperpigmented skin patches, characteristic facies and deafness. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3792843"}]}
+{"question_id": "65f377d5c4010b4d78000009", "question": "List the most effective treatment methods for Madelung disease.", "answer": "Lipectomy and liposuction are considered to be the most effective treatment methods for Madelung disease;", "relevant_passage_ids": ["37060787", "37363562", "21813877", "1582619", "33492475", "30461459", "28785324", "26246230", "1780727", "12627249", "12755508"], "type": "list", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 484, "text": "Madelung disease (MD) was first described by Brodie in 1846 as a rare multiple lipoma. It is a benign tumor characterized by symmetrical diffuse adipose tissue deposition in the proximal extremities and neck. Until now, the etiology and pathogenesis of the disease have not been fully explained, resulting in difficulties in diagnosis and treatment; moreover, palliative treatment, such as surgical resection of adipose tissue or liposuction, is still the mainstream treatment for MD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37060787"}, {"offsetInBeginSection": 0, "offsetInEndSection": 331, "text": "Madelung's disease is a rare disfiguring disorder that affects both function and esthetic appearance in the head and/or shoulder, neck, and arms regions. Lipectomy is typically necessary but such treatment can encounter difficulties due to the large sizes of the tumors, interspersed with important organs in the surrounding region", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37363562"}, {"offsetInBeginSection": 0, "offsetInEndSection": 689, "text": "Benign symmetrical lipomatosis (Madelung disease) is a rare metabolic disorder characterized by the presence of multiple, symmetric, nonencapsulated fat masses in the face, neck, and shoulders. The clinical course is slow, typically one of slow progressive enlargement with cosmetic and functional sequelae. The authors describe a case in which an open surgical approach was performed to treat this disorder, with good results. There are many aspects of treatment currently lacking a consensus, and the authors discuss these, principally in relation to the location of the fat, the role of liposuction versus surgery, the staging of surgical procedures, and the placement of the incisions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21813877"}, {"offsetInBeginSection": 1634, "offsetInEndSection": 1988, "text": "Lipectomy and liposuction are considered to be the most effective treatment methods for Madelung disease; however, choice of surgery should be based on comprehensive consideration of the disease, such as severity, mass location, and patient expectations.LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33492475"}, {"offsetInBeginSection": 1529, "offsetInEndSection": 1755, "text": "Severe complications were not observed.CONCLUSIONS: According to our experience, surgical resection is the main method of improving the appearance, ensuring eradication of the tumor, and reducing the possibility of recurrence.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30461459"}, {"offsetInBeginSection": 677, "offsetInEndSection": 1003, "text": "Severe complications were not observed.CONCLUSIONS: According to our experience, combined lipectomy and liposuction represents a successful procedure in treating benign symmetric lipomatosis in the head and neck region.Nevertheless, advantages and drawbacks of the two techniques should be equally considered prior to surgery.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12627249"}, {"offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "A patient with benign symmetrical lipomatosis of the neck (Madelung's disease) was successfully treated with liposuction rather than classic surgical lipectomy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1780727"}, {"offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Madelung's Disease - Case Series and Treatment by Tumescent Liposuction or Lipectomy.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28785324"}, {"offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Rhytidectomy approach for recurrent Madelung disease.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21813877"}, {"offsetInBeginSection": 1595, "offsetInEndSection": 1849, "text": "e helpful for diagnosis and cognition. Lipectomy and liposuction are considered to be the most effective treatment methods for Madelung disease; however, choice of surgery should be based on comprehensive consideration of the disease, such as severity, m", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33492475"}, {"offsetInBeginSection": 0, "offsetInEndSection": 350, "text": "Madelung's disease is a rare disfiguring lipomatosis of unknown etiology. The only effective therapy is the palliative surgical removal of the fatty tissue by lipectomy or liposuction. Experience with eighteen surgically treated patients shows that despite a high rate of complications and the tendency to recur, both techniques might be very useful.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1582619"}, {"offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "Benign symmetrical lipomatosis (Madelung's disease) is a rare condition of unclear aetiology characterized by numerous, unencapsulated lipomatous deposits. The only effective treatment is by surgical intervention; however, there is no consensus in the optimal approach.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26246230"}, {"offsetInBeginSection": 852, "offsetInEndSection": 999, "text": "We think that combined lipectomy and liposuction is a successful procedure for treating benign symmetrical lipomatosis in the head and neck region.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12755508"}]}
+{"question_id": "65f847c5c4010b4d78000046", "question": "What are common side effects of the progesterone-only pill (POP)?", "answer": "The progestogen-only pill may change your periods (lighter, more frequent or stop altogether). \nBleeding (spotting) between periods.\nAcne. \nMood swings.\nWeight gain. \nChanges to libido.\n\nSpeak to a pharmacist or doctor if you have side effects that are a problem for you.", "relevant_passage_ids": ["32538188", "31321765", "21080791", "36720088", "38002722", "8982741", "37962511", "20569066"], "type": "list", "snippets": [{"offsetInBeginSection": 25, "offsetInEndSection": 144, "text": "progestin-only pills (POPs) is still relatively infrequent, mainly for their unpredictable effect on menstrual bleeding", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32538188"}, {"offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Breakthrough bleeding is a side effect of progesterone-only pills (POPs) in 40% of women, and is reduced to 10% with combined hormonal contraceptives (CHCs)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36720088"}, {"offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "PURPOSE: Progestin-only pills (POPs), compared to combined, are not associated with an increased risk of venous thromboembolism, but are associated with a poor cycle control.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37962511"}, {"offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "The Risk of Breakthrough Bleeding Justifies the Use of Combined Hormonal Contraception Over Progesterone-Only Pills While Breastfeeding.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36720088"}, {"offsetInBeginSection": 800, "offsetInEndSection": 884, "text": "The most commonly reported complaints in women using all POPs are bleeding problems.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21080791"}, {"offsetInBeginSection": 166, "offsetInEndSection": 366, "text": "The main reason for this is that women on POP often have abnormal bleeding patterns, with an increased frequency of bleeding, lengthened cycles, breakthrough bleeding, spotting and prolonged bleeding.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8982741"}, {"offsetInBeginSection": 9, "offsetInEndSection": 173, "text": "Progestin-only pills (POPs), compared to combined, are not associated with an increased risk of venous thromboembolism, but are associated with a poor cycle control", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37962511"}, {"offsetInBeginSection": 183, "offsetInEndSection": 304, "text": "POPs are often associated with breakthrough bleeding (BTB), and irregular spotting is often a reason for their cessation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38002722"}, {"offsetInBeginSection": 1019, "offsetInEndSection": 1194, "text": "ative studies are available. Progestogen-only pills are associated with a more irregular bleeding pattern than contraceptive pills containing oestrogens, especially during the", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20569066"}]}
+{"question_id": "65d128f81930410b1300002d", "question": "What is the mechanism of action of Peresolimab?", "answer": "Peresolimab is a humanized IgG1 monoclonal antibody designed to stimulate the endogenous programmed cell death protein 1 (PD-1) inhibitory pathway.", "relevant_passage_ids": ["37195941"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "BACKGROUND: Peresolimab is a humanized IgG1 monoclonal antibody designed to stimulate the endogenous programmed cell death protein 1 (PD-1) inhibitory pathway. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37195941"}, {"offsetInBeginSection": 1941, "offsetInEndSection": 2175, "text": "CONCLUSIONS: Peresolimab showed efficacy in a phase 2a trial in patients with rheumatoid arthritis. These results provide evidence that stimulation of the PD-1 receptor has potential efficacy in the treatment of rheumatoid arthritis. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37195941"}, {"offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "BACKGROUND: Peresolimab is a humanized IgG1 monoclonal antibody designed to stimulate the endogenous programmed cell death protein 1 (PD-1) inhibitory pathway.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37195941"}, {"offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "BACKGROUND: Peresolimab is a humanized IgG1 monoclonal antibody designed to stimulate the endogenous programmed cell death protein 1 (PD-1) inhibitory pathway. Stimulation of this pathway would be a no", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37195941"}]}
+{"question_id": "65f1d021c4010b4d78000004", "question": "Explain the difference between eosinophilic esophagitis and reflux-induced esophagitis.", "answer": "EoE can be distinguished from GERD using a scoring system of clinical and endoscopic features. Many aspects of EoE were statistically distinct from GERD when controlling for age. Male sex, dysphagia, history of food impaction, absence of pain/heartburn, linear furrowing, and white papules were the distinguishing variables", "relevant_passage_ids": ["37814560", "36351516", "37064719", "20353445", "23085895", "18322968", "22794699", "24813513", "23459046", "19733260", "22075653", "26020633"], "type": "summary", "snippets": [{"offsetInBeginSection": 334, "offsetInEndSection": 557, "text": "asal cell hyperplasia may occur in patients with gastroesophageal reflux disease (GERD), a condition in which acid from the stomach enters the esophagus, or eosinophilic esophagitis (EoE), an emerging form of food allergy. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37064719"}, {"offsetInBeginSection": 27, "offsetInEndSection": 232, "text": "Eosinophilic esophagitis (EoE) is a food allergen-induced disease of the esophagus. Chronic, eosinophil-predominant inflammation eventually leads to fibrosis, esophageal dysfunction and severe morbidity. S", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37814560"}, {"offsetInBeginSection": 0, "offsetInEndSection": 313, "text": "BACKGROUND AND OBJECTIVES: Diagnosing eosinophilic esophagitis (EoE) depends on intraepithelial eosinophil count of \u226515 eosinophils per high-power field (HPF); however, differentiating EoE from gastroesophageal reflux disease (GERD) continues to be a challenge because no true \"criterion standard\" criteria exist.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23085895"}, {"offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Eosinophilic esophagitis (EoE) is distinguished from gastroesophageal reflux disease (GERD) by persistent esophageal eosinophilia despite medical therapy with proton-pump inhibitors for 4-6 weeks.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22794699"}, {"offsetInBeginSection": 102, "offsetInEndSection": 369, "text": "The notion that GERD and EoE can be distinguished by the response to proton pump inhibitor (PPI) treatment is based on the mistaken assumption that gastric acid suppression is the only important therapeutic effect of PPIs, and therefore only GERD can respond to PPIs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24813513"}, {"offsetInBeginSection": 178, "offsetInEndSection": 515, "text": "While studies from the '80s identified the presence of esophageal eosinophilia as being a histologic marker for the diagnosis of GERD, studies in the '90s demonstrated that high levels of esophageal eosinophilia were characteristic for a novel immune/antigen-mediated esophageal disease, EoE, that was seemingly quite distinct from GERD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23459046"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1637, "text": "BACKGROUND & AIMS: Features of eosinophilic esophagitis (EoE) and gastroesophageal reflux disease (GERD) overlap; because they cannot be differentiated on the basis of eosinophil counts alone, it can be a challenge to distinguish these disorders. We aimed to characterize the clinical, endoscopic, and histologic features of EoE and GERD and to identify factors that might be used to differentiate them.METHODS: We performed a retrospective case-control study on data collected from 2000 to 2007. Cases were patients of any age with EoE, as defined by recent consensus guidelines; controls were patients of any age with GERD. Clinical and endoscopic data were collected, and all esophageal biopsy specimens were reassessed by gastrointestinal pathologists. Cases and controls were compared, unconditional logistic regression was performed to develop a model to predict EoE, and receiver operator characteristic curves were constructed.RESULTS: Data from 151 patients with EoE and 226 with GERD were analyzed. Compared with GERD, features that independently predicted EoE included younger age; symptoms of dysphagia; documented food allergies; observations of esophageal rings, linear furrows, white plaques, or exudates by upper endoscopy; an absence of a hiatal hernia, observed by upper endoscopy; a higher maximum eosinophil count; and the presence of eosinophil degranulation observed in biopsy specimens. The area under the curve for this model was 0.934.CONCLUSIONS: We identified a set of readily available and routinely measured variables that differentiate EoE from GERD. Use of this type of analysis with patients suspected to ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19733260"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1581, "text": "Eosinophilic esophagitis (EE) and gastroesophageal reflux disease (GERD) have overlapping clinical, manometric, endoscopic and histopathologic features. The diagnosis of EE is nowadays based upon the presence of 15 or more eosinophils per high power field (eo/HPF) in esophageal biopsies. We report the cases of two young males suffering from dysphagia and recurrent food impaction with reflux esophagitis and more than 20 eo/HPF in upper-mid esophagus biopsies, both of which became asymptomatic on proton pump inhibitor (PPI) therapy. The first patient also achieved a histologic response, while EE remained in the other patient after effective PPI treatment, as shown by 24-h esophageal pH monitoring. Topical steroid therapy combined with PPI led to complete remission in this latter patient. GERD and EE may be undistinguishable, even by histology, so diagnosis of EE should only be established after a careful correlation of clinical, endoscopic and pathologic data obtained under vigorous acid suppression. These diagnostic difficulties are maximal when both diseases overlap. Limited data are available about this topic, and the interaction between EE and GERD is a matter of debate. In this setting, upper-mid esophagus step biopsies and esophageal pH monitoring of patients on PPI therapy are pivotal to evaluate the role of each disease. A PPI trial is mandatory in patients with a histopathologic diagnosis of EE; in those unresponsive to PPI treatment, EE should be suggested. However, a clinical response to PPI may not rule out quiescent EE, as shown in this report.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18322968"}, {"offsetInBeginSection": 106, "offsetInEndSection": 1705, "text": " diseases. The mucosa affected by eosinophilic esophagitis (EoE) is composed of a stratified squamous epithelia and contains intraepithelial eosinophils. To date, no studies have identified the esophageal microbiome in patients with EoE or the impact of treatment on these organisms. The aim of this study was to identify the esophageal microbiome in EoE and determine whether treatments change this profile. We hypothesized that clinically relevant alterations in bacterial populations are present in different forms of esophagitis.DESIGN: In this prospective study, secretions from the esophageal mucosa were collected from children and adults with EoE, Gastroesophageal Reflux Disease (GERD) and normal mucosa using the Esophageal String Test (EST). Bacterial load was determined using quantitative PCR. Bacterial communities, determined by 16S rRNA gene amplification and 454 pyrosequencing, were compared between health and disease.RESULTS: Samples from a total of 70 children and adult subjects were examined. Bacterial load was increased in both EoE and GERD relative to normal subjects. In subjects with EoE, load was increased regardless of treatment status or degree of mucosal eosinophilia compared with normal. Haemophilus was significantly increased in untreated EoE subjects as compared with normal subjects. Streptococcus was decreased in GERD subjects on proton pump inhibition as compared with normal subjects.CONCLUSIONS: Diseases associated with mucosal eosinophilia are characterized by a different microbiome from that found in the normal mucosa. Microbiota may contribute to es", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26020633"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1680, "text": "Eosinophilic esophagitis (EoE) and reflux esophagitis (RE) overlap clinically and histologically. RE is characterized by epithelial infiltration with small numbers of neutrophils and eosinophils, EoE by a prominent eosinophilic infiltrate. Lymphocytic esophagitis (LE), a new entity characterized by peripapillary lymphocytosis, questions the role lymphocytes play in esophageal inflammation. We test the hypothesis that lymphocyte infiltration in RE differs from EoE. One blinded pathologist read esophageal biopsies from 39 RE and 39 EoE patients. Both groups demonstrated significant numbers of lymphocytes (RE 22.7 +/- 2.2/HPF, EoE 19.8 +/- 1.8/HPF). Eosinophils/HPF in RE and EoE were 2.8 +/- 0.7 and 74.9 +/- 8.2, respectively (P < 0.001). Neutrophils were uncommon in RE (0.26 +/- 0.16/HPF) and EoE (0.09 +/- 0.04; P = 0.07). Eight of the 39 RE specimens had >or=50 lymphocytes in >or=1 HPF. Two were consistent with LE. There was an inverse correlation between numbers of eosinophils and lymphocytes in EoE (R = -0.47; P = 0.002), and no correlation between them in RE (R = 0.18; P = 0.36). The patients with EoE who used antireflux medications had fewer lymphocytes (16.3 +/- 1.3 vs 22.2 +/- 2.3/HPF; P = 0.030) and eosinophils (55.6 +/- 5.2 vs 76.0 +/- 8.7/HPF; P = 0.042) than those who did not. The pathological role of lymphocytes in RE and EoE may be underestimated. Our observation that 5% of the RE specimens meet histopathological criteria for LE potentially blurs the line between these entities. The observation that eosinophil counts are lower in EoE when antireflux meds are used supports the notion that reflux plays a role in the clinical expression of EoE.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20353445"}, {"offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Eosinophilic esophagitis (EoE) and reflux esophagitis (RE) overlap clinically and histologically. RE is characterized by epithelial infiltration with small numbers of neutrophils and eosinophils, EoE by a prominent eosinophilic infiltrate.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20353445"}]}
+{"question_id": "65f84aa5c4010b4d78000047", "question": "What are the most common symptoms of fibroids?", "answer": "heavy/painful periods\nabdominal pain\nlower back pain\na frequent need to urinate\nconstipation\npain or discomfort during sex", "relevant_passage_ids": ["36759100", "36989026", "18372219", "37609293", "25145720", "33016950", "29483852", "35957805", "29564309", "36436959", "22482961", "31960950", "16754159", "29628616", "29511672", "35968245", "36471219", "24310827", "34640407", "25713613", "37575346", "19646564", "18618119", "30766459", "16504807", "33388011"], "type": "list", "snippets": [{"offsetInBeginSection": 66, "offsetInEndSection": 162, "text": "Fibroids can be asymptomatic or present with heavy menstrual bleeding, pelvic pressure, and pain", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36759100"}, {"offsetInBeginSection": 309, "offsetInEndSection": 755, "text": "Uterine fibroid symptoms include abnormal menstrual bleeding leading to anaemia, tiredness, chronic vaginal discharge, and pain during periods. Other symptoms include protrusion of the abdomen, pain during intercourse, dysfunctions of bladder/bowel leading to urinary incontinence/retention, pain, and constipation. It is also associated with reproductive issues like impaired fertility, conceiving complications, and adverse obstetric outcomes. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36989026"}, {"offsetInBeginSection": 201, "offsetInEndSection": 322, "text": "Common symptoms associated with fibroids include abnormal uterine bleeding, pelvic pressure and reproductive dysfunction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16754159"}, {"offsetInBeginSection": 79, "offsetInEndSection": 277, "text": "The most common reported symptoms of fibroids are heavy menstrual bleeding and painful menstruation, pelvic pain, urinary problems, constipation, as well as infertility and recurrent pregnancy loss.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29483852"}, {"offsetInBeginSection": 204, "offsetInEndSection": 427, "text": "Approximately 50% of women with fibroids experience symptoms which may include menorrhagia that may result in anemia, bulk symptoms with bladder and bowel dysfunction and abdominal protrusion, dysmenorrhea, and infertility.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29628616"}, {"offsetInBeginSection": 1500, "offsetInEndSection": 1678, "text": "In conclusion, women with UFs have significantly higher levels of perceived stress and menstrual distress than controls and HMB plays a major role in determining such conditions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36471219"}, {"offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Uterine fibroids are the most common benign pelvic tumor of the female genital tract and tend to increase with age; they cause menorrhagia, dysmenorrhea, pelvic pressure symptoms, back pain, and subfertility.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29511672"}, {"offsetInBeginSection": 208, "offsetInEndSection": 374, "text": "Symptoms for up to 50 percent of women experiencing fibroids include heavy menstrual bleeding, pelvic pressure or pain and gastrointestinal and genitourinary changes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25145720"}, {"offsetInBeginSection": 0, "offsetInEndSection": 608, "text": "Uterine fibroids (also called leiomyomas or myomas) are the most common disorder among women of reproductive age, with an incidence of between 20% and 80%; they are often detected incidentally in routine healthy examinations, through bimanual pelvic and/or ultrasound examination, because uterine fibroids are rarely associated with symptoms. Sometimes, uterine fibroids may be complicated by a variety of symptoms, including menstrual disturbance (e.g., menorrhagia, dysmenorrhea, intermenstrual bleeding), pressure symptoms, bloated sensation, increased urinary frequency, bowel disturbance, or pelvic pain", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22482961"}, {"offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Heavy menstrual bleeding (HMB), distress in the pelvis, infertile, and stressed feelings are all indications of fibroids in the uterus, the most prevalent type of benign uterine tumor.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35957805"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "(1) Background: Uterine fibroids are the most common form of benign uterine tumors, causing heavy menstrual bleeding (HMB), pelvic pain, infertility and pressure symptoms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34640407"}, {"offsetInBeginSection": 258, "offsetInEndSection": 377, "text": "The main symptoms of uterine fibroids are profuse menstrual bleeding, abnormal uterine bleeding, and pressure symptoms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33016950"}, {"offsetInBeginSection": 250, "offsetInEndSection": 493, "text": "The symptoms usually reported by women with fibroids are the following: abnormal gynaecologic haemorrhage, chronic pelvic pain, dyspareunia, as well as urinary and bowel symptoms, urinary frequency or retention and, in some cases, infertility.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25713613"}, {"offsetInBeginSection": 191, "offsetInEndSection": 467, "text": "Approximately 50% of women with fibroids experience symptoms which can range from heavy menstrual bleeding and bulk-related symptoms such as pelvic pressure with bladder and bowel dysfunction to reproductive dysfunction (e.g., infertility or obstetric complications) and pain.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37575346"}, {"offsetInBeginSection": 98, "offsetInEndSection": 228, "text": "Fibroids can become symptomatic with symptoms such as menorrhagia and menometrorrhagia, pelvic pain, and reproductive dysfunction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24310827"}, {"offsetInBeginSection": 376, "offsetInEndSection": 655, "text": "Though most women with fibroids are asymptomatic, approximately 30% of them will present with severe symptoms which can include abnormal uterine bleeding, anemia, pelvic pain and pressure, back pain, urinary frequency, constipation, or infertility, and will require intervention.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31960950"}, {"offsetInBeginSection": 174, "offsetInEndSection": 427, "text": "Symptomatic uterine fibroids present with menstrual problems, anemia, infertility, miscarriages, an enlarged abdomen, pressure symptoms involving the bladder and bowels (such as frequent urination or constipation), and sometimes coital-related problems.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35968245"}, {"offsetInBeginSection": 109, "offsetInEndSection": 224, "text": "Common symptoms associated with fibroids include pelvic pain, heavy menstrual bleeding, anemia, and pelvic pressure", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37609293"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1022, "text": "Uterine fibroids, the most common tumours in women of reproductive age, are asymptomatic in at least 50% of afflicted women. However, in other women, they cause significant morbidity and affect quality of life. Clinically, they present with a variety of symptoms: menstrual disturbances including menorrhagia, dysmenorrhoea and intermenstrual bleeding; pelvic pain unrelated to menstruation; and pressure symptoms such as a sensation of bloatedness, increased urinary frequency and bowel disturbance. In addition, they may compromise reproductive function, possibly contributing to subfertility, early pregnancy loss and later pregnancy complications such as pain, preterm labour, malpresentations, increased need for caesarean section, and postpartum haemorrhage. Large fibroids may distend the abdomen, which may be aesthetically displeasing to many women. Abnormal bleeding occurs in 30% of symptomatic women, and abnormal bleeding, bloating and pelvic discomfort due to mass effect constitute the most common symptoms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18372219"}, {"offsetInBeginSection": 0, "offsetInEndSection": 652, "text": "Uterine fibroids (also called leiomyomas or myomas) are the most common disorder among women of reproductive age, with an incidence of between 20% and 80%; they are often detected incidentally in routine healthy examinations, through bimanual pelvic and/or ultrasound examination, because uterine fibroids are rarely associated with symptoms. Sometimes, uterine fibroids may be complicated by a variety of symptoms, including menstrual disturbance (e.g., menorrhagia, dysmenorrhea, intermenstrual bleeding), pressure symptoms, bloated sensation, increased urinary frequency, bowel disturbance, or pelvic pain; therefore definite treatment is requested.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22482961"}, {"offsetInBeginSection": 0, "offsetInEndSection": 624, "text": "Uterine fibroids (UFs), leiomyomas or myomas, are a type of malignancy that affects the smooth muscle of the uterus, and it is most commonly detected in women of reproductive age. Uterine fibroids are benign monoclonal growths that emerge from uterine smooth muscle cells (myometrium) as well as fibroblasts. Uterine fibroid symptoms include abnormal menstrual bleeding leading to anaemia, tiredness, chronic vaginal discharge, and pain during periods. Other symptoms include protrusion of the abdomen, pain during intercourse, dysfunctions of bladder/bowel leading to urinary incontinence/retention, pain, and constipation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36989026"}, {"offsetInBeginSection": 111, "offsetInEndSection": 300, "text": "Heavy or prolonged menstrual bleeding, abnormal uterine bleeding, resultant anemia, pelvic pain, infertility, and/or recurrent pregnancy loss are generally associated with uterine fibroids.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29564309"}, {"offsetInBeginSection": 174, "offsetInEndSection": 391, "text": "Symptomatic fibroids, with ailments such as abnormal uterine bleeding, dysmenorrhoea, pelvic pain, impaired urination, bowel dysfunction, infertility, and recurrent pregnancy loss, are indicated for medical treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30766459"}, {"offsetInBeginSection": 109, "offsetInEndSection": 225, "text": "Common symptoms associated with fibroids include pelvic pain, heavy menstrual bleeding, anemia, and pelvic pressure.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37609293"}, {"offsetInBeginSection": 146, "offsetInEndSection": 287, "text": "The most common symptoms associated with uterine myomas are abnormal uterine bleeding and pelvic discomfort mostly caused by the mass effect.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16504807"}, {"offsetInBeginSection": 309, "offsetInEndSection": 452, "text": "Uterine fibroid symptoms include abnormal menstrual bleeding leading to anaemia, tiredness, chronic vaginal discharge, and pain during periods.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36989026"}, {"offsetInBeginSection": 86, "offsetInEndSection": 269, "text": "Heavy menstrual bleeding with resultant anemia, dysmenorrhea, chronic pelvic pain, infertility, urinary symptoms and constipation are generally associated with uterine fibroids (UFs).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33388011"}, {"offsetInBeginSection": 421, "offsetInEndSection": 484, "text": "Fibroid symptoms are protean, and menorrhagia is most frequent.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36436959"}, {"offsetInBeginSection": 19, "offsetInEndSection": 185, "text": "(fibroids), the most common benign tumor in women of childbearing age, can cause symptoms including dysmenorrhea, menorrhagia, urinary symptoms, pain and infertility.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18618119"}, {"offsetInBeginSection": 309, "offsetInEndSection": 624, "text": "Uterine fibroid symptoms include abnormal menstrual bleeding leading to anaemia, tiredness, chronic vaginal discharge, and pain during periods. Other symptoms include protrusion of the abdomen, pain during intercourse, dysfunctions of bladder/bowel leading to urinary incontinence/retention, pain, and constipation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36989026"}, {"offsetInBeginSection": 98, "offsetInEndSection": 244, "text": "Symptomatic fibroids present with menorrhagia, pelvic pain, leukorrhea, pressure and bloating, increased abdominal girth, and severe dysmenorrhea.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19646564"}]}
+{"question_id": "65cfa22b1930410b1300000c", "question": "What is the target of Selpercatinib?", "answer": "Selpercatinib is an orally-administered, selective inhibitor of rearranged during transfection (RET) kinase approved for the treatment of advanced RET fusion-positive non-small cell lung cancer (NSCLC).", "relevant_passage_ids": ["36729098", "36568522", "36572992", "36626081", "36632846", "36422787", "36416226", "34649088", "37265026", "36469155", "35726802", "34832869", "37131086", "37059058", "36198171", "36825106", "33082208", "37360768", "32557397", "37795873", "38050583", "37972337", "37718634", "32493697", "37070927", "34713870", "34099825", "33150799", "35950566", "33161056", "33169506", "33771190", "35647935", "37603207", "33489819", "34505490", "33007380", "32846060", "35582449", "36122315", "33314236", "32416592", "37870973", "35704797", "31988000", "37565829", "37317595", "33455880", "32083997", "36075388", "35304457", "35969032", "36481304", "34402300", "36996322", "37525669", "37274265", "32703767", "37265412", "37425604", "33239432", "32846061", "35799394", "37051304", "34237031", "31768065", "35425116", "36108661", "36657661", "35007206"], "type": "factoid", "snippets": [{"offsetInBeginSection": 359, "offsetInEndSection": 486, "text": "More recently, two selective RET inhibitors, selpercatinib and pralsetinib, demonstrated higher efficacy and good tolerability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36729098"}, {"offsetInBeginSection": 1515, "offsetInEndSection": 1641, "text": "Drug exposure of RET inhibitors is expected to increase with CYP 3A4 inhibition, with selpercatinib being the least affected. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36568522"}, {"offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "An overview of the role of selpercatinib and pralsetinib in RET-fusion-positive non-small cell lung cancer (NSCLC).", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36572992"}, {"offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "OBJECTIVE: Selpercatinib and pralsetinib are new targeted therapies used to treat patients with non-small cell lung cancer (NSCLC) due to RET gene rearrangements.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36572992"}, {"offsetInBeginSection": 1606, "offsetInEndSection": 1671, "text": "Three RET-mutant patients received selpercatinib; all showed PR. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36626081"}, {"offsetInBeginSection": 828, "offsetInEndSection": 981, "text": "Rapid translation and regulatory approval of selective RET inhibitors, selpercatinib and pralsetinib, have opened up the field of RET precision oncology.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36632846"}, {"offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Selpercatinib: A Review in Advanced RET Fusion-Positive NSCLC.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36422787"}, {"offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "Selpercatinib (Retevmo\u00ae/Retsevmo\u00ae) is an orally-administered, selective inhibitor of rearranged during transfection (RET) kinase approved for the treatment of advanced RET fusion-positive non-small cell lung cancer (NSCLC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36422787"}, {"offsetInBeginSection": 927, "offsetInEndSection": 1090, "text": "Thus, currently available evidence suggests that selpercatinib is a promising new RET-targeted therapy option for patients with advanced RET fusion-positive NSCLC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36422787"}, {"offsetInBeginSection": 74, "offsetInEndSection": 169, "text": "Selpercatinib is a highly selective RET inhibitor for treatment of metastatic RET-altered MTC. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36416226"}, {"offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Selpercatinib (RETEVMO\u2122) is a receptor tyrosine kinase RET (rearranged during transfection) inhibitor being developed by Loxo Oncology for the treatment of cancers harbouring RET alterations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32557397"}, {"offsetInBeginSection": 1663, "offsetInEndSection": 1824, "text": "Conclusions Selective RET inhibitors Pralsetinib and Selpercatinib have shown a good effect on RET fusion-positive NSCLC, with a low incidence of adverse events.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37603207"}, {"offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Selpercatinib is a targeted, FDA-approved, oral, small-molecule inhibitor for the treatment of rearranged during transfection (RET) proto-oncogene mutation-positive cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34832869"}, {"offsetInBeginSection": 192, "offsetInEndSection": 443, "text": "Based on results from the phase I/II LIBRETTO-001 trial, selpercatinib was recently approved by the US FDA for the treatment of RET fusion-positive non-small-cell lung cancer, RET fusion-positive thyroid cancer and RET-mutant medullary thyroid cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32557397"}, {"offsetInBeginSection": 629, "offsetInEndSection": 815, "text": "Selpercatinib (LOXO-292) and pralsetinib (BLU-667) are potent and selective inhibitors that target RET alterations, including fusions and mutations, irrespective of the tissue of origin.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33771190"}, {"offsetInBeginSection": 117, "offsetInEndSection": 232, "text": "Selpercatinib is a highly selective RET inhibitor that has demonstrated anti-tumor activity in RET-mutated cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37795873"}, {"offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Selpercatinib is a small molecule that binds at the RET kinase active site.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37059058"}, {"offsetInBeginSection": 620, "offsetInEndSection": 871, "text": "In 2020, the US Food and Drug Administration approved selpercatinib, a selective RET inhibitor, for adults with lung and thyroid cancers with RET rearrangements or mutations, making it the first targeted therapy to be approved for RET-altered cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33489819"}, {"offsetInBeginSection": 267, "offsetInEndSection": 449, "text": "Here, we describe a case of a sarcoma, associated with a RET::TRIM33-fusion gene with an exceptional response to a neoadjuvant therapy with the selective RET inhibitor selpercatinib.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36469155"}, {"offsetInBeginSection": 80, "offsetInEndSection": 466, "text": "Oncogenic RET fusions or mutations are found most often in non-small cell lung cancer (NSCLC) and in thyroid cancer, but also increasingly in various types of cancers at low rates. In the last few years, two potent and selective RET protein tyrosine kinase inhibitors (TKIs), pralsetinib (BLU-667) and selpercatinib (LOXO-292, LY3527723) were developed and received regulatory approval.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37131086"}, {"offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "INTRODUCTION: Novel rearranged in transfection (RET)-specific tyrosine kinase inhibitors (TKIs) such as selpercatinib (LOXO-292) have shown unprecedented efficacy in tumors positive for RET fusions or mutations, notably RET fusion-positive NSCLC and RET-mutated medullary thyroid", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31988000"}, {"offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "P-Glycoprotein (ABCB1/MDR1) and BCRP (ABCG2) Limit Brain Accumulation and Cytochrome P450-3A (CYP3A) Restricts Oral Exposure of the RET Inhibitor Selpercatinib (RETEVMO).", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34832869"}, {"offsetInBeginSection": 145, "offsetInEndSection": 383, "text": "Selpercatinib and pralsetinib are tyrosine kinase inhibitors selectively targeting RET and with clinical activity in RET-positive NSCLC.CASE PRESENTATION: A male never-smoker in his forties was diagnosed with advanced lung adenocarcinoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34505490"}, {"offsetInBeginSection": 314, "offsetInEndSection": 504, "text": "Fortunately, two selective RET inhibitors (sRETi), namely pralsetinib and selpercatinib, have been approved for treating RET fusion NSCLC due to their remarkable efficacy and safety profiles", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37718634"}, {"offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Sustained Response with Dose-reduced Selpercatinib in a Pediatric Patient with Metastatic NCOA4-RET Fusion Papillary Thyroid Carcinoma.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37565829"}, {"offsetInBeginSection": 308, "offsetInEndSection": 558, "text": "In addition to these approvals, dostarlimab for mismatch repair deficiency(dMMR), dabrafenib and trametinib for BRAF V600E, and selpercatinib for RET fusion gene have been approved in the United States as tumor agnostic biomarkers and their treatment", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37317595"}, {"offsetInBeginSection": 410, "offsetInEndSection": 643, "text": "To overcome these issues, new selective RET inhibitors such as pralsetinib (BLU-667) and selpercatinib (LOXO-292) have been developed in clinical trials, with selpercatinib recently approved by the Food and Drug Administration (FDA).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33455880"}, {"offsetInBeginSection": 112, "offsetInEndSection": 389, "text": "er (NSCLC). RET-selective inhibitors selpercatinib (LOXO-292) and pralsetinib (BLU-667) recently demonstrated favorable antitumor activity and safety profiles in advanced RET fusion-positive NSCLC, and both have received approval by the US Food and Drug Administration for this", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33007380"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1634, "text": "Activating receptor tyrosine kinase RET (rarranged during transfection) gene alterations have been identified as oncogenic in multiple malignancies. RET gene rearrangements retaining the kinase domain are oncogenic drivers in papillary thyroid cancer, non-small-cell lung cancer, and multiple other cancers. Activating RET mutations are associated with different phenotypes of multiple endocrine neoplasia type 2 as well as sporadic medullary thyroid cancer. RET is thus an attractive therapeutic target in patients with oncogenic RET alterations. Multikinase inhibitors with RET inhibitor activity, such as cabozantinib and vandetanib, have been explored in the clinic for tumors with activating RET gene alterations with modest clinical efficacy. As a result of the nonselective nature of these multikinase inhibitors, patients had off-target adverse effects, such as hypertension, rash, and diarrhea. This resulted in a narrow therapeutic index of these drugs, limiting ability to dose for clinically effective RET inhibition. In contrast, the recent discovery and clinical validation of highly potent selective RET inhibitors (pralsetinib, selpercatinib) demonstrating improved efficacy and a more favorable toxicity profile are poised to alter the landscape of RET-dependent cancers. These drugs appear to have broad activity across tumors with activating RET alterations. The mechanisms of resistance to these next-generation highly selective RET inhibitors is an area of active research. This review summarizes the current understanding of RET alterations and the state-of-the-art treatment strategies in RET-dependent cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32083997"}, {"offsetInBeginSection": 185, "offsetInEndSection": 465, "text": "o carcinomas. Six inhibitors have been approved for the treatment of RET-driven cancers: vandetanib, cabozantinib, lenvatinib, sorafenib, selpercatinib, and pralsetinib. Only selpercatinib and pralsetinib have been developed specifically for RET, while the remaining are multikina", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36198171"}, {"offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Selpercatinib is a first-in-class, highly selective and potent, central nervous system-active RET kinase inhibitor.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35969032"}, {"offsetInBeginSection": 603, "offsetInEndSection": 715, "text": "Recently, two potent and selective RET TKIs, pralsetinib (BLU-667) and selpercatinib (LOXO-292), were developed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35582449"}, {"offsetInBeginSection": 250, "offsetInEndSection": 404, "text": "nt benefit. Selective RET inhibitors Pralsetinib and Selpercatinib are targeted drugs approved by the US Food and Drug Administration for treating RET-mut", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37603207"}, {"offsetInBeginSection": 185, "offsetInEndSection": 340, "text": "o carcinomas. Six inhibitors have been approved for the treatment of RET-driven cancers: vandetanib, cabozantinib, lenvatinib, sorafenib, selpercatinib, an", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36198171"}, {"offsetInBeginSection": 356, "offsetInEndSection": 550, "text": "Recent advancements in targeted therapies have led to the development of ret proto-oncogene (RET) inhibitors, such as selpercatinib and pralsetinib, which have been approved for the treatment of", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37525669"}, {"offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "OBJECTIVE: Selpercatinib and pralsetinib are new targeted therapies used to treat patients with non-small cell lung cancer (NSCLC) due to RET gene rear", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36572992"}, {"offsetInBeginSection": 173, "offsetInEndSection": 229, "text": "r types. Selpercatinib is a highly selective RET kinase ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33082208"}, {"offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "INTRODUCTION: Selpercatinib is a RET selective tyrosine kinase inhibitor with nanomolar potency against diverse RE", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35726802"}, {"offsetInBeginSection": 299, "offsetInEndSection": 436, "text": "selective RET protein tyrosine kinase inhibitors (TKIs), pralsetinib (BLU-667) and selpercatinib (LOXO-292, LY3527723) were developed and", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37131086"}, {"offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Selpercatinib (LOXO-292) is a selective and potent RET inhibitor.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33314236"}, {"offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Selpercatinib (RETEVMO\u2122) is a receptor tyrosine kinase RET (rearranged during transfection) inhibitor being developed by Loxo Oncology for the treatment of cancers harbouring RET alterations. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32557397"}, {"offsetInBeginSection": 197, "offsetInEndSection": 311, "text": "er treatment. Selpercatinib (LOXO-292) is a highly selective RET kinase inhibitor indicated in advanced RET-mutant", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35007206"}, {"offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Recently Food and Drug Administration (FDA)-approved pralsetinib (BLU-667) and selpercatinib (LOXO-292) are RET-selective protein tyrosine kinase inhibitors for treating RET-altered cancers, but whether they have distinct activity was unknown.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34099825"}, {"offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "BACKGROUND: Selpercatinib (LOXO-292) and pralsetinib (BLU-667) are highly potent RET-selective protein tyrosine kinase inhibitors (TKIs) for treating advanced RET-altered thyroid cancers and non-small-cell lung can", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33161056"}]}
+{"question_id": "65f5a319c4010b4d78000016", "question": "What is IL-35?", "answer": "IL-35 is a member of the IL-12 family and is an immunosuppressive and anti-inflammatory cytokine secreted mainly by regulatory cells. Structurally, IL-35 is a heterodimeric cytokine. Interleukin 35 (IL-35) is involved in the pathogenesis of endometriosis by suppressing immunoreaction and promoting endometrial cell proliferation", "relevant_passage_ids": ["36731088", "36579639", "37464473", "36314719", "29371247", "31966444", "27734415", "25619872", "29749583", "24273881", "34054534", "22427377", "25752977", "31333002", "33128920", "26872697", "35420296", "32276581", "27996283", "24970690", "27582486", "29641433", "33865428", "25640666", "35434379", "26530251", "31974915", "26369677", "34788131", "29054137", "28936965", "35759811"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "INTERLEUKIN-35 DOWNREGULATES THE IMMUNE RESPONSE OF EFFECTOR CD4 + T CELLS VIA RESTRICTING HIGH MOBILITY GROUP BOX-1 PROTEIN-DEPENDENT AUTOPHAGY IN SEPSIS.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36731088"}, {"offsetInBeginSection": 138, "offsetInEndSection": 216, "text": "The novel role of the anti-inflammatory cytokine IL-35 in sepsis was examined.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36731088"}, {"offsetInBeginSection": 9, "offsetInEndSection": 157, "text": "Interleukin 35 (IL-35) is involved in the pathogenesis of endometriosis by suppressing immunoreaction and promoting endometrial cell proliferation. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36579639"}, {"offsetInBeginSection": 12, "offsetInEndSection": 161, "text": "Interleukin-35 (IL-35), secreted by regulatory T cells (Treg) and B cells, is immunosuppressive under both physiological and pathological conditions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37464473"}, {"offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Interleukin 35 (IL-35) mediates immunosuppression of T cells in autoimmune diseases", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36314719"}, {"offsetInBeginSection": 342, "offsetInEndSection": 525, "text": "IL-35 (Interleukin-35) is a new member of the IL-12 (Interleukin-12) family, which is an immunosuppressive and anti-inflammatory cytokine secreted mainly by Treg (T regulatory cells).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34054534"}, {"offsetInBeginSection": 122, "offsetInEndSection": 260, "text": "IL-35 is an anti-inflammatory cytokine comprising the p35 subunit of IL-12 and the subunit Epstein-Barr virus (EBV) -induced gene 3(EBI3).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24273881"}, {"offsetInBeginSection": 182, "offsetInEndSection": 318, "text": "Since its discovery, IL-35 has been shown to exhibit immunosuppressive activities which are distinct from other members of IL-12 family.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27734415"}, {"offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "IL-35 is a relatively new cytokine that emerges as an important immunomodulator.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29749583"}, {"offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Interleukin 35 (IL-35) is the most recently identified member of the IL-12 family of cytokines and offers the potential to be a target for new therapies for autoimmune, inflammatory, and infectious diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25619872"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Interleukin (IL)-35 is a newly identified inhibitory cytokine used by T regulatory cells to control T cell-driven immune responses.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22427377"}, {"offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Interleukin 35 (IL-35) functions in an anti-inflammatory fashion by inhibiting T-cell proliferation, whereas CD4(+) T cells play an important role in cellular immunity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25752977"}, {"offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "Interleukin-35 (IL-35), is a recently identified cytokine that belongs to the IL-12 family, it is a potent anti-inflammatory and immunosuppressive cytokine which was first recognized to be produced by regulatory T cells (Tregs) cells, and recently was found to be produced by regulatory B cells (Bregs).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31333002"}, {"offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "OBJECTIVE: IL-35 (interleukin-35) is an anti-inflammatory cytokine, which inhibits immune responses by inducing regulatory T cells and regulatory B cells and suppressing effector T cells and m", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29371247"}, {"offsetInBeginSection": 292, "offsetInEndSection": 396, "text": "Interleukin-35 (IL-35) is a Treg cell-secreted cytokine that inhibits T cell proliferation and function.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26872697"}, {"offsetInBeginSection": 452, "offsetInEndSection": 569, "text": "IL-35 can directly suppress effector T-cell proliferation and function and inhibit the differentiation of Th17 cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27734415"}, {"offsetInBeginSection": 319, "offsetInEndSection": 451, "text": "IL-35 is also unique in that it is expressed primarily by regulatory T-cells (Tregs) rather than by antigen-presenting cells (APCs).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27734415"}, {"offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "BACKGROUND: Interleukin (IL)-35 is a newly indentified cytokine and induces immunotolerance via suppres", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31974915"}, {"offsetInBeginSection": 0, "offsetInEndSection": 394, "text": "BACKGROUND: Interleukin-35 (IL-35) is a recently described heterodimeric cytokine that belongs to the IL-12 family and consists of p35 (IL-12a) and EBI3 (IL-27b) subunits. The expression of IL-35 in humans is inducible in response to inflammatory stimuli. Increased IL-35 levels were documented in several autoimmune inflammatory diseases, suggesting a possible immunomodulatory role in their p", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33128920"}, {"offsetInBeginSection": 821, "offsetInEndSection": 954, "text": "Among the cytokines, interleukin (IL)-35 is the one most recently discovered that suppresses inflammatory responses of immune cells. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26530251"}, {"offsetInBeginSection": 821, "offsetInEndSection": 1108, "text": "Among the cytokines, interleukin (IL)-35 is the one most recently discovered that suppresses inflammatory responses of immune cells. Accumulating evidence suggests that IL-35 represents an attractive target for anti-atherosclerotic therapy based on its several atheroprotective features.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26369677"}, {"offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "BACKGROUND: Interleukin-35 (IL-35) is a newly identified IL-12 cytokine family member, which regulates the activity of immune cells in infectious diseases and autoimmune", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32276581"}, {"offsetInBeginSection": 0, "offsetInEndSection": 379, "text": "Interleukin-35 (IL-35) is a lately observed cytokine and is part of the IL-12 cytokine family. IL-35 includes two subunits, p35 and Epstein-Barr virus-induced gene 3, and activates subsequent signaling pathways by binding to receptors to mediate signal transduction, thereby modulating the immunoregulatory functions of T cells, B cells, macrophages, and other immune cell types.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35434379"}, {"offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "IL-35 is the newest member of IL-12 family. A dimeric protein consisting of two separate subunits has manifested suppressive actions on immune system, which is counterproductive in the context of cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31205568"}, {"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Interleukin (IL)-35 is a novel member of the IL-12 cytokine family, which exhibits a unique immune regulatory function.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31186721"}, {"offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "BACKGROUND: IL-35 is a novel cytokine suppressing the immune response through the expansion of regulatory T cells and suppression of Th17 cell ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27996283"}, {"offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Interleukin-35 (IL-35) is a novel anti-inflammatory cytokine and has been shown to play an important role in maintaining immune homeostasis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24970690"}, {"offsetInBeginSection": 125, "offsetInEndSection": 192, "text": "IL35 has recently emerged as a novel regulator of immune responses.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27582486"}, {"offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "The recently identified cytokines-interleukin (IL)-35 and interleukin (IL)-37-have been described for their anti-inflammatory and immune-modulating actions in numerous inflammatory diseases, auto-immune disorders, malignancies, infectious diseases and sepsis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29641433"}, {"offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "BACKGROUND: IL-35 is a newly anti-inflammatory cytokine that belongs to the I", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33865428"}, {"offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Interleukin-35 (IL-35) is a novel immunosuppressive and anti-inflammatory cytokine.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31966444"}, {"offsetInBeginSection": 65, "offsetInEndSection": 188, "text": "Interleukin-35 (IL35) can suppress T cell proliferation and elicit the development of inducible regulatory T cells (Tregs).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25640666"}, {"offsetInBeginSection": 698, "offsetInEndSection": 841, "text": "IL35 is overexpressed in a variety of cancers and may exert its function both on antitumor immune responses as well as directly on tumor cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27582486"}, {"offsetInBeginSection": 95, "offsetInEndSection": 379, "text": "IL-35 includes two subunits, p35 and Epstein-Barr virus-induced gene 3, and activates subsequent signaling pathways by binding to receptors to mediate signal transduction, thereby modulating the immunoregulatory functions of T cells, B cells, macrophages, and other immune cell types.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35434379"}, {"offsetInBeginSection": 1057, "offsetInEndSection": 1197, "text": ", IL35 appears to contribute to the loss of immunological self-tolerance in ITP patients by modulating T cells and immunoregulatory cytokine", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25640666"}, {"offsetInBeginSection": 821, "offsetInEndSection": 953, "text": "Among the cytokines, interleukin (IL)-35 is the one most recently discovered that suppresses inflammatory responses of immune cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26530251"}, {"offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Interleukin 35 (IL-35) is a relatively newly identified cytokine required for the regulatory and suppressive functions of regulatory T cells (Treg), playing an important role in the prevention of autoimmune diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29054137"}, {"offsetInBeginSection": 161, "offsetInEndSection": 394, "text": "Interleukin-35 (IL-35), an inhibitory cytokine that belongs to the IL-12 family, is capable of potently suppressing T cell proliferation and inducing IL-35-producing induced regulatory T cells (iTr35) to limit inflammatory responses.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34788131"}, {"offsetInBeginSection": 423, "offsetInEndSection": 569, "text": "meostasis. Interleukin-35 (IL-35), as a newly identified member of IL-12 family, exerts suppressive effect on immune response by means of a specif", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28936965"}, {"offsetInBeginSection": 168, "offsetInEndSection": 365, "text": "Interleukin-35 (IL-35), a cytokine of the interleukin-12 family, is a novel anti-inflammation and immunosuppressive cytokine, maintaining inflammatory suppression and regulating immune homeostasis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35759811"}, {"offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "OBJECTIVE: IL-35 is a potent immunosuppressive and anti-inflammatory cytokine, consisting of a p35 subunit and an Epstein-Barr virus-induced gene 3 (EBI3) subunit, which sup", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35420296"}]}
+{"question_id": "65f84535c4010b4d78000044", "question": "What are the transmission mechanisms of the human Ebola infection?", "answer": "Ebolaviruses spread through contact via broken skin or mucous membranes in the eyes, nose, or mouth with:\nBlood or body fluids of a person who is sick with or has died from Ebola disease.\nObjects contaminated with body fluids from a person who is sick with or has died from Ebola disease.\nInfected fruit bats and primates.\nSemen from men survivors of Ebola disease (via oral, vaginal, or anal sex).", "relevant_passage_ids": ["33080902", "30513823", "30381349", "25719678", "18981410", "32487785", "30609455", "28058346", "28653186"], "type": "list", "snippets": [{"offsetInBeginSection": 233, "offsetInEndSection": 424, "text": "EBOV has been described to occur via contact with infected bodily fluids, supported by data indicating that infectious EBOV could be cultured from blood, semen, saliva, urine, and breast milk", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30381349"}, {"offsetInBeginSection": 257, "offsetInEndSection": 284, "text": "human-to-human transmission", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30513823"}, {"offsetInBeginSection": 360, "offsetInEndSection": 438, "text": "persistent EBOV infections and included sexual transmission from EVD survivors", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30513823"}, {"offsetInBeginSection": 440, "offsetInEndSection": 511, "text": "Asymptomatic infection and long-term viral persistence in EVD survivors", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30513823"}, {"offsetInBeginSection": 686, "offsetInEndSection": 756, "text": "persistence of filoviruses and their potential for sexual transmission", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30513823"}, {"offsetInBeginSection": 273, "offsetInEndSection": 296, "text": "nosocomial transmission", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26910462"}, {"offsetInBeginSection": 192, "offsetInEndSection": 399, "text": "The sporadic human outbreaks are believed to result when EBOV \"jumps\" from an infected animal to a person and is subsequently transmitted between persons by direct contact with infected blood or body fluids.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18981410"}, {"offsetInBeginSection": 379, "offsetInEndSection": 524, "text": "Transmission of EBoV has been reported in various ways, including human to human transmission through close contact with blood and bodily fluids.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32487785"}, {"offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "Ebola virus disease (EVD), formerly known as Ebola hemorrhagic fever, is a severe, often fatal illness in humans. Ebola virus (EBOV) is transmitted through contact with blood or body fluids of a person who contracted or died from EVD, contaminated objects like needles and infected animals or bush meat.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28058346"}, {"offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Viruses of the Ebolavirus genus cause sporadic epidemics of severe and systemic febrile disease that are fueled by human-to-human transmission.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28653186"}, {"offsetInBeginSection": 683, "offsetInEndSection": 801, "text": "People were infected by touching body fluids of blood, secretions, vomit, and other discharges from patients with EVD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30609455"}, {"offsetInBeginSection": 217, "offsetInEndSection": 425, "text": "Transmission of EBOV has been described to occur via contact with infected bodily fluids, supported by data indicating that infectious EBOV could be cultured from blood, semen, saliva, urine, and breast milk.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30381349"}]}
+{"question_id": "65ce88be1930410b13000002", "question": "What is the mechanisms of action of Sotorasib?", "answer": "Sotorasib was the first-in-class KRAS inhibitor to reach the US and European market, and its pharmacological inhibition is restricted to the KRAS p.G12C mutation.", "relevant_passage_ids": ["36690705", "36563789", "36566134", "36764316", "36581205", "36577165", "35412531", "36077640", "37627169", "34715449", "36529835", "36929750", "37386628", "37831779", "36217844", "36319849", "34365406", "34715459", "34675734", "36901764", "38093368", "38072173", "38070479", "38067288", "38061200", "38049578", "38044989", "37101895", "37008835", "36315377", "37190303", "37101896", "35153196", "34357500", "37673617", "34137282", "34590053", "34158284", "32955176", "37504336", "35192958", "38023987", "35864332", "35267628", "34004237", "34607583", "33971321", "36388799", "34144959", "34919824", "35260176", "33824136", "36546651", "37666686", "37557065", "37336286", "34471232", "34864132", "36980522", "35083149", "36358848", "35101229", "36394791", "36928090", "37700573", "37110848", "34776511", "36675641", "35832439", "38010044", "33466360", "33957355", "34096690", "34504076", "34161704", "37703579"], "type": "summary", "snippets": [{"offsetInBeginSection": 467, "offsetInEndSection": 582, "text": "At progression, the patient continued entrectinib and started sotorasib, a small molecule inhibitor of KRAS p.G12C.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36690705"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1218, "text": "Patients with metastatic NSCLC bearing a ROS1 gene fusion usually experience prolonged disease control with ROS1-targeting tyrosine kinase inhibitors (TKI), but significant clinical heterogeneity exists in part due to the presence of co-occurring genomic alterations. Here, we report on a patient with metastatic NSCLC with a concurrent ROS1 fusion and KRAS p.G12C mutation at diagnosis who experienced a short duration of disease control on entrectinib, a ROS1 TKI. At progression, the patient continued entrectinib and started sotorasib, a small molecule inhibitor of KRAS p.G12C. A patient-derived cell line generated at progression on entrectinib demonstrated improved TKI responsiveness when treated with entrectinib and sotorasib. Cell-line growth dependence on both ROS1 and KRAS p.G12C was further reflected in the distinct downstream signaling pathways activated by each driver. Clinical benefit was not observed with combined therapy of entrectinib and sotorasib possibly related to an evolving KRAS p.G12C amplification identified on repeated molecular testing. This case supports the need for broad molecular profiling in patients with metastatic NSCLC for potential therapeutic and prognostic information.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36690705"}, {"offsetInBeginSection": 198, "offsetInEndSection": 481, "text": "ecent breakthroughs in the development of mutant-specific KRAS inhibitors include the FDA approved drug Lumakras (Sotorasib, AMG510) for KRAS G12C-mutated non-small cell lung cancer (NSCLC), and MRTX1133, a promising clinical candidate for the treatment of KRAS G12D-mutated cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36563789"}, {"offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "[Sotorasib treatment in KRAS G12C-mutated non-small cell lung cancer: Experience in the Tours university hospital].", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36566134"}, {"offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Following the CodeBreak 100 study, since 2021 sotorasib has been available in France, with authorization for early access in treatment of non-small cell lung cancer with a KRAS G12C mutation. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36566134"}, {"offsetInBeginSection": 0, "offsetInEndSection": 315, "text": "BACKGROUND: Sotorasib is a specific, irreversible inhibitor of the GTPase protein, KRASG12C. We compared the efficacy and safety of sotorasib with a standard-of-care treatment in patients with non-small-cell lung cancer (NSCLC) with the KRASG12C mutation who had been previously treated with other anticancer drugs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36764316"}, {"offsetInBeginSection": 639, "offsetInEndSection": 802, "text": "This discovery stemmed from our finding that Survivin expression is downregulated upon treatment of pancreatic cancer cells with the KRASG12C inhibitor Sotorasib. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36581205"}, {"offsetInBeginSection": 96, "offsetInEndSection": 258, "text": "Sotorasib was the first-in-class KRAS inhibitor to reach the US and European market, and its pharmacological inhibition is restricted to the KRAS p.G12C mutation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36577165"}, {"offsetInBeginSection": 271, "offsetInEndSection": 388, "text": "Evidence indicates that treatment with KRAS G12C inhibitors (sotorasib) triggers the MRAS:SHOC2:PP1C trimeric complex", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38072173"}, {"offsetInBeginSection": 904, "offsetInEndSection": 1141, "text": "In summary, sotorasib is a promising KRASG12C inhibitor that increases the available treatment options for patients with KRAS G12C mutation-positive NSCLC who were previously treated with platinum-based chemotherapy and/or immunotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36315377"}, {"offsetInBeginSection": 219, "offsetInEndSection": 425, "text": "Sotorasib is a small molecule that selectively and irreversibly targets KRASG12C.METHODS: We conducted a phase 1 trial of sotorasib in patients with advanced solid tumors harboring the KRAS p.G12C mutation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32955176"}, {"offsetInBeginSection": 341, "offsetInEndSection": 473, "text": "Sotorasib, a first-in-class specific small molecule that irreversibly inhibits KRAS G12C, has since obtained Health Canada approval.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37504336"}, {"offsetInBeginSection": 132, "offsetInEndSection": 277, "text": "By binding irreversibly to KRASG12C, sotorasib inhibits downstream signalling pathways which are associated with cell growth and differentiation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36315377"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Sotorasib (LUMAKRAS\u2122 in the USA and LUMYKRAS\u2122 in the EU) is an orally active, first-in-class G12C-mutant KRAS (KRASG12C) inhibitor.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36315377"}, {"offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Sotorasib (LUMAKRAS\u00ae) is the first RAS inhibitor that selectively binds to KRAS G12C and irreversibly inhibits the conformational change from the inactive to active form of KRAS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37673617"}, {"offsetInBeginSection": 1177, "offsetInEndSection": 1334, "text": "Using this approach, we characterised how the interactome of KRAS wild-type and mutants is regulated by the clinically approved KRASG12C inhibitor Sotorasib.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37627169"}, {"offsetInBeginSection": 1701, "offsetInEndSection": 1964, "text": "Responses were also observed in patients with pancreatic, endometrial, and appendiceal cancers and melanoma.CONCLUSIONS: Sotorasib showed encouraging anticancer activity in patients with heavily pretreated advanced solid tumors harboring the KRAS p.G12C mutation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32955176"}, {"offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Sotorasib (LUMAKRAS\u2122) is a RAS GTPase family inhibitor being developed by Amgen for the treatment of solid tumours with KRAS mutations, including non-small cell lung cancer (NSCLC) and colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34357500"}, {"offsetInBeginSection": 426, "offsetInEndSection": 681, "text": "Sotorasib, a first-in-class covalent KRAS G12C inhibitor that binds to the switch pocket II in the KRAS G12C-GDP \"off\" state, received US FDA accelerated approval on May 21, 2021 in the US, based on a Phase II dose expansion cohort of CodeBreaK 100 trial.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37101896"}, {"offsetInBeginSection": 329, "offsetInEndSection": 689, "text": "Their foremost mechanism of action utilizes the Switch II binding pocket and Cys12 residue of GDP-bound KRAS proteins in G12C mutants, confining them to their inactive state. Sotorasib and Adagrasib, both FDA-approved for the treatment of non-small cell lung cancer (NSCLC), have been pivotal in paving the way for KRAS G12C inhibitors in the clinical setting.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37190303"}, {"offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "BACKGROUND: Clinical trials of the KRAS inhibitors adagrasib and sotorasib have shown promising activity in cancers harboring KRAS glycine-to-cysteine amino acid substitutions at co", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34161704"}, {"offsetInBeginSection": 539, "offsetInEndSection": 949, "text": "We identified compounds, such as flupentixol, amlodipine, and fluvoxamine, for the G12C mutant and paroxetine, flupentixol, and zuclopenthixol for the G12D mutant with significant inhibitory functions. All five compounds bound to the H95 cryptic groove of mutant K-Ras with high efficiency and, like sotorasib, retained a novel binding mechanism with additional hydrophobic interactions at the molecular level.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34715554"}, {"offsetInBeginSection": 113, "offsetInEndSection": 269, "text": "The recently approved mutant selective small-molecule cysteine-reactive covalent inhibitor of the G12C mutant of K-Ras, sotorasib, provides a case in point.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35864332"}, {"offsetInBeginSection": 504, "offsetInEndSection": 688, "text": "Sotorasib and Adagrasib, both FDA-approved for the treatment of non-small cell lung cancer (NSCLC), have been pivotal in paving the way for KRAS G12C inhibitors in the clinical setting", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37190303"}, {"offsetInBeginSection": 278, "offsetInEndSection": 496, "text": "Sotorasib is indicated for the treatment of adults with advanced, previously treated, KRAS G12C mutation-positive non-small cell lung cancer (NSCLC) in multiple countries, including the countries of the EU and the USA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36315377"}, {"offsetInBeginSection": 855, "offsetInEndSection": 1001, "text": "We will comment on the group with KRAS G12C mutation and the targeted therapy with sotorasib for its efficiency and toxicity based on new studies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37666686"}, {"offsetInBeginSection": 0, "offsetInEndSection": 565, "text": "Sotorasib, a direct inhibitor of the enzyme Kirsten rat sarcoma viral oncogene (KRAS) with the G12C mutation, was approved by the U.S. Food and Drug Administration (FDA), as a second-line treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) containing the KRAS G12C mutation, on the basis of results of a phase II clinical trial (Code- BreaK100). In this article, we review the mechanism of action of KRAS G12C inhibitors and the latest clinical trials with sotorasib to provide a comprehensive understanding of its efficacy and toxicity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35412531"}, {"offsetInBeginSection": 224, "offsetInEndSection": 402, "text": "In particular, the covalent KRAS-G12C inhibitors sotorasib and adagrasib are used to treat patients with advanced non-small cell lung cancer (NSCLC) carrying KRAS-G12C mutations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34471232"}, {"offsetInBeginSection": 81, "offsetInEndSection": 409, "text": "Recent efforts have witnessed a revolutionary strategy for KRAS G12C inhibitors with exhibiting conspicuous clinical responses across multiple tumor types, providing new impetus for renewed drug development and culminating in sotorasib with approximately 6-month median progression-free survival in KRAS G12C-driven lung cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34864132"}, {"offsetInBeginSection": 574, "offsetInEndSection": 837, "text": "This discovery led to the development of a new class of selective small-molecule inhibitors against the KRAS G12C isoform. Sotorasib and adagrasib are approved in locally advanced or metastatic NSCLC patients who have received at least one prior systemic therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36980522"}, {"offsetInBeginSection": 526, "offsetInEndSection": 789, "text": "Recently, the discovery of a new pocket under the effector binding switch II region of KRAS G12C has allowed the development of direct KRAS inhibitors such as sotorasib, the first FDA-approved drug targeting KRAS G12C, or adagrasib, initiating a new exciting era.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35083149"}, {"offsetInBeginSection": 598, "offsetInEndSection": 819, "text": "Sotorasib and adagrasib are novel KRAS inhibitors that recently gained FDA approval for pre-treated KRAS mutant NSCLC patients, and other molecules such as GDC-6036 are currently being investigated with promising results.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36358848"}, {"offsetInBeginSection": 368, "offsetInEndSection": 505, "text": "Advances over the past decade with KRAS(G12C) mutation-specific inhibitors have culminated in the first FDA-approved RAS drug, sotorasib.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35101229"}, {"offsetInBeginSection": 197, "offsetInEndSection": 387, "text": "Recent breakthroughs in the development of mutant-specific KRAS inhibitors include the FDA approved drug Lumakras (Sotorasib, AMG510) for KRAS G12C-mutated non-small cell lung cancer (NSCLC)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36563789"}, {"offsetInBeginSection": 0, "offsetInEndSection": 373, "text": "Sotorasib, a direct inhibitor of the enzyme Kirsten rat sarcoma viral oncogene (KRAS) with the G12C mutation, was approved by the U.S. Food and Drug Administration (FDA), as a second-line treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) containing the KRAS G12C mutation, on the basis of results of a phase II clinical trial (Code- BreaK100).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35412531"}, {"offsetInBeginSection": 374, "offsetInEndSection": 565, "text": "In this article, we review the mechanism of action of KRAS G12C inhibitors and the latest clinical trials with sotorasib to provide a comprehensive understanding of its efficacy and toxicity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35412531"}, {"offsetInBeginSection": 504, "offsetInEndSection": 689, "text": "Sotorasib and Adagrasib, both FDA-approved for the treatment of non-small cell lung cancer (NSCLC), have been pivotal in paving the way for KRAS G12C inhibitors in the clinical setting.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37190303"}, {"offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Sotorasib, a direct inhibitor of the enzyme Kirsten rat sarcoma viral oncogene (KRAS) with the G12C", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35412531"}, {"offsetInBeginSection": 1215, "offsetInEndSection": 1337, "text": "how the interactome of KRAS wild-type and mutants is regulated by the clinically approved KRASG12C inhibitor Sotorasib. In", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37627169"}, {"offsetInBeginSection": 194, "offsetInEndSection": 281, "text": "cancer. Until the recent approval of sotorasib, a KRAS G12C inhibitor, lack of targeted", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34715449"}, {"offsetInBeginSection": 271, "offsetInEndSection": 389, "text": "Evidence indicates that treatment with KRAS G12C inhibitors (sotorasib) triggers the MRAS:SHOC2:PP1C trimeric complex.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38072173"}, {"offsetInBeginSection": 698, "offsetInEndSection": 940, "text": "Sotorasib, has been approved by the U.S. Food and Drug Administration (FDA) and by the European Medicines Agency. Another KRAS inhibitor targeting c.34G > T (p.G12C), Adagrasib, is currently being reviewed by the FDA for accelerated approval.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36077640"}]}
+{"question_id": "65f039fdc4010b4d78000002", "question": "What is the vector for coxiella burnetii transmission?", "answer": "Ticks are the common vector for Coxiella burnetii", "relevant_passage_ids": ["37387368", "35190334", "37866329", "26458781", "33406079", "32059686", "36439350", "32141019", "33113791", "37107481", "37025192", "26186513", "21771522", "32173315", "28502643"], "type": "factoid", "snippets": [{"offsetInBeginSection": 334, "offsetInEndSection": 484, "text": "transmitted by ticks include bacteria of the genus Borrelia and the species Francisella tularensis, Anaplasma phagophytophilum and Coxiella burnetii; ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37387368"}, {"offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Prevalence of Coxiella-infections in ticks - review and meta-analysis.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35190334"}, {"offsetInBeginSection": 238, "offsetInEndSection": 394, "text": "Excretion of C. burnetii in tick feces and saliva is well documented but the role of these findings or the epidemiological context is discussed controversia", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35190334"}, {"offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "Exploring the diversity of tick-borne pathogens: The case of bacteria (Anaplasma, Rickettsia, Coxiella and Borrelia) protozoa (Babesia and Theileria) and viruses (Orthonairovirus, tick-borne encephalitis virus and louping ill virus) in the European continent.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37866329"}, {"offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Vector competence of the African argasid tick Ornithodoros moubata for the Q fever agent Coxiella burnetii.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33406079"}, {"offsetInBeginSection": 908, "offsetInEndSection": 1103, "text": "Although C. burnetii transmission is mainly airborne, ticks may act as vectors and play an important role in the natural cycle of transmission of coxiellosis among wild vertebrates and livestock.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36439350"}, {"offsetInBeginSection": 1354, "offsetInEndSection": 1586, "text": "Finally, we detected only a sporadic presence of C. burnetii DNA in tick faeces, but no living bacterium was further isolated in culture assays, suggesting that excretion in faeces is not a common mode of transmission in O. moubata.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33406079"}, {"offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Transstadial Transmission from Nymph to Adult of Coxiella burnetii by Naturally Infected Hyalomma lusitanicum.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33113791"}, {"offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Coxiella burnetii (Derrick) Philip, the causative agent of Q fever, is mainly transmitted by aerosols, but ticks can also be a source of infection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33113791"}, {"offsetInBeginSection": 1225, "offsetInEndSection": 1311, "text": "Furthermore, the transmission of C. burnetii is most likely via vectors (i.e., ticks).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37107481"}, {"offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Query (Q) fever is a vector-borne zoonosis caused by the obligate intracellular pathogen Coxiella burnetii. Animals, including dogs, cats, cattle, and sheep, can be infected by C. burnetii.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26186513"}, {"offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Q fever is a global zoonotic infection caused by the intracellular Gram-negative bacterium Coxiella burnetii. Historically, it is considered a vector-borne disease, but the role of ticks in transmission has not fully been elucidated yet.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35190334"}, {"offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Q fever is a widespread zoonotic disease caused by\u00a0Coxiella burnetii that most commonly infects not only a variety of mammals but also arthropods and in particularly ticks.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32173315"}, {"offsetInBeginSection": 426, "offsetInEndSection": 1093, "text": "In this study, we re-evaluated the vector competence of the African soft tick Ornithodoros moubata for an avirulent strain of C. burnetii. To this end, we used an artificial feeding system to initiate infection of ticks, specific molecular tools to monitor further infections, and culture assays in axenic and cell media to check for the viability of C. burnetii excreted by ticks. We observed typical traits associated with vector competence: The exposure to an infected blood meal resulted in viable and persistent infections in ticks, trans-stadial transmissions of infection from nymphs to adults and the ability of adult ticks to transmit infectious C. burnetii.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33406079"}, {"offsetInBeginSection": 0, "offsetInEndSection": 387, "text": "The dramatic spread of Q fever in Poland among cattle kept in isolation from natural environment (ticks, wild animals) has suggested the possibility that the infection may also be transmitted sexually. To test this hypothesis series of experiments have been performed in controlled laboratory conditions. Male mice infected with C. burnetii were allowed to mate with healthy female mice.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1350178"}, {"offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Background: Q fever is a zoonotic disease caused by Coxiella burnetii infection, with domestic ruminants as the main source of infection and tick bites as one of the transmission vectors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37025192"}, {"offsetInBeginSection": 1201, "offsetInEndSection": 1353, "text": "In addition, while adult female ticks were infected, we did not observe C. burnetii in eggs, suggesting that transovarial transmission is not effective.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33406079"}, {"offsetInBeginSection": 426, "offsetInEndSection": 564, "text": "In this study, we re-evaluated the vector competence of the African soft tick Ornithodoros moubata for an avirulent strain of C. burnetii.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33406079"}, {"offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Coxiella burnetii, the causative agent of Q fever, and Rickettsia spp. are bacterial pathogens that can be transmitted by ticks of the genus Dermacentor (i.e., Dermacentor marginatus and D. reticulatus).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21771522"}, {"offsetInBeginSection": 1217, "offsetInEndSection": 1410, "text": "Our data suggest that zebus as well as Amblyomma and Boophilus ticks have to be considered as a natural reservoir or vector for C. burnetii, but the risk of cattle-to-human transmission is low.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28502643"}, {"offsetInBeginSection": 78, "offsetInEndSection": 115, "text": "ticks in the transmission of Coxiella", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32141019"}, {"offsetInBeginSection": 0, "offsetInEndSection": 353, "text": "BACKGROUND: The bacterium Coxiella burnetii is the etiological agent of Q fever and is mainly transmitted via inhalation of infectious aerosols. DNA of C. burnetii is frequently detected in ticks, but the role of ticks as vectors in the epidemiology of this agent is still controversial. In this study, Ixodes ricinus and Dermacentor marginatus adults a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32059686"}, {"offsetInBeginSection": 51, "offsetInEndSection": 374, "text": "Coxiella burnetii, a ubiquitous intracellular bacterium infecting humans and a variety of animals. Transmission is primarily but not exclusively airborne, and ticks are usually thought to act as vectors. We argue that, although ticks may readily transmit C. burnetii in experimental systems, they only occasionally transmit", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26458781"}]}
+{"question_id": "65f82fe1c4010b4d7800003f", "question": "Methotrexate is an antifolate medication.", "answer": "Yes", "relevant_passage_ids": ["36946211", "36508886", "22111860", "20579471", "12583828", "22388607", "23394392", "25161385", "7510620", "27758143", "26783755", "9713954", "24651961", "27993660", "19337845", "27920680", "8247309", "18020507", "29226354", "33572934", "24986327", "37973683", "37527941", "37493925", "37405586", "37384801", "37104530", "36443884", "26547381", "34132539", "22806879", "15753437", "19838716", "3178237", "17534933", "24348319", "31890337", "24704904", "36532750", "8852336", "11817030", "3896745", "30452231", "9479873"], "type": "yesno", "snippets": [{"offsetInBeginSection": 14, "offsetInEndSection": 49, "text": "Methotrexate (MTX) is an antifolate", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36946211"}, {"offsetInBeginSection": 662, "offsetInEndSection": 706, "text": "antifolate medications, such as methotrexate", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36508886"}, {"offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Methotrexate (MTX) is an antimetabolite and antifolate drug used in the treatment of cancer and autoimmune diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20579471"}, {"offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "INTRODUCTION: Methotrexate is an antifolate medication frequently used in the treatment of malignant and nonmalignant diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22388607"}, {"offsetInBeginSection": 230, "offsetInEndSection": 270, "text": "Methotrexate is a well known antifolate.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7510620"}, {"offsetInBeginSection": 176, "offsetInEndSection": 315, "text": "Antifolate methotrexate (MTX), a drug commonly used in chemotherapy of several types of cancer, is a strong inhibitor of folate metabolism.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26783755"}, {"offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Methotrexate (MTX), an antifolate drug, is the first-line disease-modifying agent for the treatment of rheumatoid arthritis (RA) worldwide.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23394392"}, {"offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Methotrexate is an antimetabolite and antifolate drug that is widely used in the treatment of malignancies and auto-immune disorders.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24651961"}, {"offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Methotrexate (MTX), the antifolate drug widely used as both an anticancer chemotherapeutic drug and as an immunosuppressive agent, mimics natural folates to inhibit critical cellular biosynthetic pathways.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9713954"}, {"offsetInBeginSection": 215, "offsetInEndSection": 299, "text": "Methotrexate, the most studied folate antagonist, is effective in many malignancies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12583828"}, {"offsetInBeginSection": 300, "offsetInEndSection": 502, "text": "Methotrexate inhibits dihydrofolate reductase, which leads to accumulation of polyglutamated folates, causing further inhibition of thymidylate synthase and glycinamide ribonucleotide formyltransferase.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12583828"}, {"offsetInBeginSection": 0, "offsetInEndSection": 292, "text": "INTRODUCTION: Antifolates are structural analogs of folates, which have been used as antitumor drugs for more than 60\u00a0years. The antifolate drug most commonly used for treating human tumors is methotrexate (MTX), which is utilized widely in first-line treatment protocols of high-grade osteos", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27758143"}, {"offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "BACKGROUND: For decades, methotrexate (MTX; amethopterin) has been known as an antifolate inhibitor of dihydrofolate reductase (DHFR), and it is widely used for the treatment of various malignancies and autoimmu", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27993660"}, {"offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Antifolates, such as methotrexate (MTX), are the treatment of choice for numerous cancers. MTX inhibits dihydrofolate reductase (DHFR), which is essential for cell growth and proliferation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19337845"}, {"offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Methotrexate (MTX) is an antifolic drug used in the treatment of immune-mediated and neoplastic diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27920680"}, {"offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Methotrexate (MTX) is an antifolate cytotoxic medication used to treat certain types of cancer and at lower doses for rheumatic diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25161385"}, {"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "(1) Background: Antifolate methotrexate (MTX) is the most common disease-modifying antirheumatic drug (DMARD) for treating human rheumatoid arthritis (RA).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33572934"}, {"offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Methotrexate is an antifolate agent used in the treatment of various cancers and some autoimmune diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22111860"}, {"offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Methotrexate (MTX) is an antifolate drug used for several diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29226354"}, {"offsetInBeginSection": 131, "offsetInEndSection": 259, "text": "Methotrexate is an antifolate that inhibits methylation reactions and reactions of amino acid, purine and pyrimidine metabolism.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18020507"}, {"offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Methotrexate (MTX) is an antifolic drug that in recent years has been largely employed in the treatment of Rheumatoid Arthritis (RA).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8247309"}, {"offsetInBeginSection": 14, "offsetInEndSection": 122, "text": "Methotrexate (MTX), a folate antagonist, is often used as second-line treatment in patients with sarcoidosis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37973683"}, {"offsetInBeginSection": 12, "offsetInEndSection": 192, "text": "The folate antagonist high-dose methotrexate (HD-MTX) is integral to induction chemotherapy for primary CNS lymphoma (PCNSL); however, it can be associated with leukoencephalopathy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37527941"}, {"offsetInBeginSection": 327, "offsetInEndSection": 431, "text": "6MP is combined with weekly oral methotrexate (MTX), an antifolate drug, to augment therapeutic activity", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37493925"}, {"offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Methotrexate (MTX) is an antifolate that is inescapable and widely used to treat autoimmune diseases and is the gold standard medicine for the arthritic condition", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37405586"}, {"offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Most of our understanding of folate metabolism in the parasite Leishmania is derived from studies of resistance to the antifolate methotrexate (MTX)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37384801"}, {"offsetInBeginSection": 440, "offsetInEndSection": 548, "text": "Recent studies have shown that known antifolate compounds, including methotrexate, inhibit the activity of W", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37104530"}, {"offsetInBeginSection": 14, "offsetInEndSection": 132, "text": "Methotrexate (MTX) is an antifolate and immunosuppressive drug prescribed for various malignancies and immune diseases", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36946211"}, {"offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "BACKGROUND: Methotrexate is an antifolate antimetabolite that inhibits the activity of dihydrofolate reductase by acting as a false substrate, which leads to defects of DNA synthesis, specifically the inhibition of purine and pyrimidine synthesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36443884"}, {"offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Methotrexate (MTX), a folate antagonist drug, has been widely used for treating various cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34132539"}, {"offsetInBeginSection": 284, "offsetInEndSection": 403, "text": "Methotrexate (MTX) is a specific folate antagonist that competitively inhibits dihydrofolate reductase (DHFR) activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22806879"}, {"offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Antifolates, such as methotrexate (MTX), are the treatment of choice for numerous cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19337845"}, {"offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Methotrexate (MTX) is a folate antagonist inhibiting nucleic acid and methionine synthesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15753437"}, {"offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Methotrexate (MTX) is a folate inhibitor which has gained a major role in the treatment of rheumatoid arthritis (RA).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19838716"}, {"offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Methotrexate (MTX), a folate antagonist which blocks de novo nucleotide biosynthesis and DNA replication, is an anchor drug in acute lymphoblastic leukemia (ALL) treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26547381"}, {"offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Methotrexate (MTX), a folic acid antagonist, is among the most active known drugs for clinical cancer therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3178237"}, {"offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "The folate inhibitor methotrexate (MTX) is an important component of osteosarcoma (OS) treatment regimens.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17534933"}, {"offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Methotrexate (MTX), a folic acid antagonist, is widely used in the treatment of neoplasms, psoriasis and rheumatoid arthritis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24348319"}, {"offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Methotrexate (MTX) is a folate antagonist drug used for several diseases, such as cancers, various malignancies, rheumatoid arthritis (RA) and inflammatory bowel disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31890337"}, {"offsetInBeginSection": 69, "offsetInEndSection": 265, "text": "Methotrexate (MTX) is a folic acid antagonist used in high doses as antimetabolite in anti-cancer treatment as well as in low doses for the treatment of rheumatoid arthritis and adults' psoriasis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24704904"}, {"offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Methotrexate (MTX) is a folic acid antagonist, the mechanism of action is to inhibit DNA synthesis, repair and cell proliferation by decreasing the activities of several folate-dependent enzymes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36532750"}, {"offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Methotrexate (MTX) is an antifolate cytotoxic medication used to treat certain types of cancer and", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25161385"}, {"offsetInBeginSection": 25, "offsetInEndSection": 119, "text": "e (MTX) is an antifolate and immunosuppressive drug prescribed for various malignancies and im", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36946211"}, {"offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Methotrexate (MTX) is a clinically important antifolate that has been used in combination with other chemotherapeutic agents in the treatment of malignancies including acute lymphocytic leukemia, osteosarcoma, carcinomas of the breast, head and neck, choriocarcinoma and non-Hodgkin's lymphoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8852336"}, {"offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "Methotrexate (MTX) is the prototype folate antagonist cytotoxic drug, employed in the therapy of solid tumors and leukaemias, and recently also as an immunosuppressive agent in organ transplantation, in the treatment of some autoimmune diseases and in the therapy of severe asthma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11817030"}, {"offsetInBeginSection": 299, "offsetInEndSection": 493, "text": "A number of drugs such as aminopterin, methotrexate (amethopterin), pyrimethamine, trimethoprim and triamterene act as folate antagonists and produce folate deficiency by inhibiting this enzyme.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3896745"}, {"offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "The folate antagonist methotrexate is a cytotoxic drug used in the treatment of several cancer types.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30452231"}, {"offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "Amethopterin (methotrexate, MTX) is an antimetabolite and antifolate drug with antiflammatory properities and is used to treat autoimmune diseases, such as psoriasis, rheumatoid arthritis and certain types of cancer, such as breast, lymphoma and lung.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24986327"}, {"offsetInBeginSection": 0, "offsetInEndSection": 353, "text": "A number of antifolate drugs, which inhibit the key enzymes in the 'thymidylate cycle', dihydrofolate reductase (DHFR) and thymidylate synthase (TS), have been developed as part of the search for analogues with superior antitumor efficacy to a 'classical' antifolate, methotrexate (MTX), and those which are active against the MTX-resistant tumor cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9479873"}]}
+{"question_id": "65d131451930410b13000034", "question": "Is GC1118 effective for glioblastoma?", "answer": "No. GC1118 did not prolong progression free survival of patients with glioblastoma.", "relevant_passage_ids": ["37537946"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1455, "offsetInEndSection": 1721, "text": "CONCLUSION: This study did not meet the primary endpoint (PFS6); however, we found that immune signatures were significantly upregulated in the tumors with regression upon GC1118 therapy, which signifies the potential of immune-mediated antitumor efficacy of GC1118.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37537946"}]}
+{"question_id": "65f70d71c4010b4d7800001e", "question": "Is COACH syndrome a rare autosomal recessive genetic disease characterized by liver fibrosis and related to portal hypertension.", "answer": "COACH syndrome is a rare autosomal recessive genetic disease characterized by liver fibrosis, which leads to severe complications related to portal hypertension.", "relevant_passage_ids": ["36617405", "37965976", "19058225", "28860541", "8669436", "19261004", "8862632", "19574260", "16313315", "12390436"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "The clinical features of cerebellar vermis hypoplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis (COACH) characterize the rare autosomal recessive multisystem disorder called COACH syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36617405"}, {"offsetInBeginSection": 12, "offsetInEndSection": 174, "text": "COACH syndrome is a rare autosomal recessive genetic disease characterized by liver fibrosis, which leads to severe complications related to portal hypertension. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37965976"}, {"offsetInBeginSection": 12, "offsetInEndSection": 172, "text": "COACH syndrome is a rare autosomal recessive genetic disease characterized by liver fibrosis, which leads to severe complications related to portal hypertension", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37965976"}, {"offsetInBeginSection": 1203, "offsetInEndSection": 1371, "text": "Physicians should be aware of COACH syndrome when they examine young patients who present with hepatopathy, portal hypertension of unknown origin and cerebellar ataxia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19261004"}, {"offsetInBeginSection": 446, "offsetInEndSection": 549, "text": "We describe a 28-yr-old female with COACH syndrome resulting in chronic renal and hepatic insufficiency", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16313315"}, {"offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Hepatic insufficiency and liver transplantation in a patient with COACH syndrome.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12390436"}, {"offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "BACKGROUND: COACH syndrome is a rare autosomal recessive genetic disease characterized by liver fibrosis, which leads to severe complications related to portal hypertension.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37965976"}, {"offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "The acronym COACH defines an autosomal recessive condition of Cerebellar vermis hypo/aplasia, Oligophrenia, congenital Ataxia, Coloboma and Hepatic fibrosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19058225"}, {"offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "OBJECTIVE: To identify genetic causes of COACH syndromeBACKGROUND: COACH syndrome is a rare autosomal recessive disorder characterised by Cerebellar vermis hypoplasia, Oligophrenia (developmental delay/mental retardation), Ataxia, Coloboma, and Hepatic fibrosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19574260"}, {"offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "MKS3/TMEM67 mutations are a major cause of COACH Syndrome, a Joubert Syndrome related disorder with liver involvement.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19058225"}, {"offsetInBeginSection": 304, "offsetInEndSection": 426, "text": "The main feature of COACH is congenital hepatic fibrosis (CHF), resulting from malformation of the embryonic ductal plate.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19058225"}, {"offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "BACKGROUND: COACH syndrome is a rare autosomal recessive genetic disease characterized by liver fibrosis, which leads to severe complications related to portal h", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37965976"}, {"offsetInBeginSection": 1319, "offsetInEndSection": 1552, "text": "Of these three previous patients, one died from hepatic failure due to de novo HCV infection 3\u2009years after LT.CONCLUSIONS: LT should be considered an effective treatment for COACH syndrome in patients with severe portal hypertension.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37965976"}, {"offsetInBeginSection": 174, "offsetInEndSection": 653, "text": "However, only a few patients with COACH syndrome undergoing liver transplantation (LT) have been reported.MATERIALS AND METHODS: We herein report the outcomes of four children who underwent LT for COACH syndrome at our institute and review three previously reported cases to elucidate the role of LT in COACH syndrome.RESULTS: All four patients in our institute were female, and three received living donors LT. All patients were diagnosed with COACH syndrome by genetic testing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37965976"}, {"offsetInBeginSection": 305, "offsetInEndSection": 497, "text": "This combination of findings suggested a diagnosis of COACH syndrome which is characterized by hypoplasia of cerebellar vermis, oligophrenia, congenital ataxia, coloboma, and hepatic fibrosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8669436"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "The COACH syndrome is a very rare disorder with cerebellar vermis hypoplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16313315"}, {"offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "BACKGROUND: COACH syndrome is a rare autosomal recessive genetic disease characterized by liver fibrosis, which leads to severe complications related to portal hypertensi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37965976"}, {"offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "COACH syndrome is an autosomal recessive developmental disorder, a subtype of Joubert syndrome and related disorders, characterized by cerebellar vermis hypoplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28860541"}, {"offsetInBeginSection": 894, "offsetInEndSection": 1105, "text": "This pattern of defects is consistent with COACH syndrome (Cerebellar vermis hypoplasia, Oligophrenia, congenital Ataxia, Coloboma, Hepatic fibrocirrhosis) which has previously been reported in five other cases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8862632"}]}
+{"question_id": "65f86f62c4010b4d7800005c", "question": "Which symptoms could indicate depression in young children?", "answer": "sadness\nirritability\nabulia\nfatigue\ninability to concentrate\neat too little or too much\nsleep too little or too much\nhave big changes in weight\nfeelings of guilt, worthlessness, emptiness\nhave thoughts about suicide \nself-harming", "relevant_passage_ids": ["33436094", "876801", "28520097", "31515716", "30911869"], "type": "list", "snippets": [{"offsetInBeginSection": 12, "offsetInEndSection": 196, "text": "Major depressive disorder is common, debilitating, and affects feelings, thoughts, mood, and behaviors. Childhood and adolescence are critical periods for the development of depression", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33436094"}, {"offsetInBeginSection": 852, "offsetInEndSection": 1048, "text": "The domain of negative self-concept during the toddler period evidenced by self-deprecation and difficulty making choices emerged as the two strongest variables predictive of preschool depression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28520097"}, {"offsetInBeginSection": 73, "offsetInEndSection": 404, "text": "Childhood depression is an episodic disorder characterized by 10 criteria, symptoms of dysphoric mood, self-deprecatory ideation, agitation, loss of energy, reduced socialization, altered school performance, altered school attitude, sleep disturbance, appetite disturbance, and somatic compliants persisting for at least one month.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/876801"}, {"offsetInBeginSection": 0, "offsetInEndSection": 313, "text": "Reductions in positive affect are a salient feature of preschool-onset major depressive disorder. Yet, little is known about the psychophysiological correlates of this blunted positive affect and whether reduced physiological responding to pleasant stimuli may differentiate depressed and healthy young children. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31515716"}, {"offsetInBeginSection": 0, "offsetInEndSection": 432, "text": "Depressive disorders can be observed in early childhood and are associated with significant concurrent and prospective impairment; however, little is known about day-to-day variations in common depressive behaviors in children. This study examined the day-to-day variability of two common depressive behaviors in preschool-aged children, sadness and irritability, and factors associated with the daily occurrence of these behaviors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30911869"}, {"offsetInBeginSection": 755, "offsetInEndSection": 1048, "text": "Findings suggest that clinical-level symptoms of depression may arise as early as age 24 months. The domain of negative self-concept during the toddler period evidenced by self-deprecation and difficulty making choices emerged as the two strongest variables predictive of preschool depression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28520097"}]}
+{"question_id": "65d136bc1930410b1300003c", "question": "What are active ingredients of Paxlovid?", "answer": "Paxlovid is composed of nirmatrelvir and ritonavir.", "relevant_passage_ids": ["37839266", "36703601", "36568522", "37969744", "36181334", "37510996", "36465589", "35101563", "37231296", "36345404", "35881032", "35153195", "36154584"], "type": "list", "snippets": [{"offsetInBeginSection": 147, "offsetInEndSection": 214, "text": " Paxlovid\u00ae is composed of two tablets, nirmatrelvir and ritonavir. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37839266"}, {"offsetInBeginSection": 580, "offsetInEndSection": 783, "text": "The anti-COVID drugs explored via other approaches include nirmatrelvir (used in combination with ritonavir as Paxlovid), tixagevimab and cilgavimab (both used in combination with each other) and others.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36703601"}, {"offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Overview of Drug-Drug Interactions Between Ritonavir-Boosted Nirmatrelvir (Paxlovid) and Targeted Therapy and Supportive Care for Lung Cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36568522"}, {"offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Introduction: Oral administration of ritonavir-boosted nirmatrelvir (Paxlovid) was found to be promising in the treatment of coronavirus disease 2019. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36568522"}, {"offsetInBeginSection": 1111, "offsetInEndSection": 1269, "text": "Paxlovid, as used in the clinic, is a combination of Nirmatrelvir (viral protease inhibitor) and Ritonavir (a \"booster\" inhibitor of Nirmatrelvir metabolism).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37510996"}, {"offsetInBeginSection": 195, "offsetInEndSection": 455, "text": "PAXLOVID, comprised of nirmatrelvir and ritonavir (used as a pharmacokinetic enhancer), is an oral therapy currently in development as a therapeutic option for those infected with SARS-CoV-2 to prevent progression to severe disease, hospitalization, and death.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35101563"}, {"offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Interactions of the Anti-SARS-CoV-2 Agents Molnupiravir and Nirmatrelvir/Paxlovid with Human Drug Transporters.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37510996"}, {"offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Pfizer's drug for the treatment of patients infected with COVID-19, Paxlovid, contains most notably nirmatrelvir, along with ritonavir.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36465589"}, {"offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "On December 22, 2021, the United States Food and Drug Administration approved the first main protease inhibitor, i.e., oral antiviral nirmatrelvir (PF-07321332)/ritonavir (Paxlovid), for the treatment of early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36345404"}, {"offsetInBeginSection": 0, "offsetInEndSection": 333, "text": "The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease inhibitor PF-07321332 (nirmatrelvir), in combination with ritonavir (Paxlovid), was recently granted emergency use authorization by multiple regulatory agencies for the treatment of coronavirus disease 2019 (COVID-19) in adults and pediatric patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35153195"}, {"offsetInBeginSection": 34, "offsetInEndSection": 236, "text": "Paxlovid, a combination of Nirmatrelvir and Ritonavir, was granted emergency use authorization by the United States Food and Drug Administration (FDA) for the treatment of COVID-19 on December 22, 2021.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36154584"}, {"offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Paxlovid is a nirmatrelvir (NMV) and ritonavir (RTV) co-packaged medication used for the treatment of coronavirus disease 2019 (COVID-19). The active component of Paxlovid is NMV and RTV is a pharmacokinetic booster.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37969744"}, {"offsetInBeginSection": 580, "offsetInEndSection": 700, "text": "The anti-COVID drugs explored via other approaches include nirmatrelvir (used in combination with ritonavir as Paxlovid)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36703601"}, {"offsetInBeginSection": 172, "offsetInEndSection": 353, "text": "antiviral treatment. Most case reports of rebound COVID-19 have been associated with cessation of treatment with the combined oral antiviral agent nirmatrelvir/ritonavir (Paxlovid).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36181334"}, {"offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Paxlovid, a copackaged medication of nirmatrelvir tablets (150\u2009mg) and ritonavir tablets (100\u2009mg) developed by Pfizer, is one of the first orally accessible COVID-19 antiviral medicines to be approved for emergency usage.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35881032"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Introduction: Oral administration of ritonavir-boosted nirmatrelvir (Paxlovid) was found to be promising in the treatment of coronavirus disease 2019.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36568522"}, {"offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "PURPOSE: PAXLOVID\u2122 is nirmatrelvir tablets co-packaged with ritonavir tablets. Ritonavir is used as a pharmacokinetics (PK) enhancer to reduce metabolism and increase exposure of nirma", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37231296"}, {"offsetInBeginSection": 137, "offsetInEndSection": 271, "text": "disease 2019. The active antiviral component nirmatrelvir in Paxlovid is co-formulated with ritonavir, a strong cytochrome P450 (CYP) ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36568522"}]}
+{"question_id": "65f37997c4010b4d7800000b", "question": "What is an Albatross plot used for?", "answer": "The albatross plot is a novel graphical tool for presenting results of diversely reported studies in a systematic review", "relevant_passage_ids": ["28453179", "34035181", "32423407"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "The albatross plot: A novel graphical tool for presenting results of diversely reported studies in a systematic review.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28453179"}, {"offsetInBeginSection": 1111, "offsetInEndSection": 1284, "text": "We provide examples of albatross plots using data from previous meta-analyses, allowing for comparison of results, and an example from when a meta-analysis was not possible.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28453179"}, {"offsetInBeginSection": 766, "offsetInEndSection": 1127, "text": "For interpretation of the results across studies, we produced albatross plots for all studies combined and by age-groups, sex of the parents, sex of the child, methodology of assessment of parental PA, and type of PA.RESULTS: Thirty-nine papers were included with sample size of parent-child dyads ranging from 15 to 1267 (mean\u2009=\u2009319 dyads, median\u2009=\u2009227 dyads).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32423407"}, {"offsetInBeginSection": 612, "offsetInEndSection": 955, "text": "We propose a novel plot, the albatross plot, which requires only a 1-sided P value and a total sample size from each study (or equivalently a 2-sided P value, direction of effect and total sample size). The plot allows an approximate examination of underlying effect sizes and the potential to identify sources of heterogeneity across studies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28453179"}, {"offsetInBeginSection": 679, "offsetInEndSection": 926, "text": "To assess the quality of evidence, Cochrane Collaboration's Risk of Bias Tool was used. Due to the heterogeneity of reported outcomes, meta-analysis was performed for only some outcomes and a narrative synthesis with albatross plots was presented.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34035181"}, {"offsetInBeginSection": 612, "offsetInEndSection": 1110, "text": "We propose a novel plot, the albatross plot, which requires only a 1-sided P value and a total sample size from each study (or equivalently a 2-sided P value, direction of effect and total sample size). The plot allows an approximate examination of underlying effect sizes and the potential to identify sources of heterogeneity across studies. This is achieved by drawing contours showing the range of effect sizes that might lead to each P value for given sample sizes, under simple study designs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28453179"}]}
+{"question_id": "65f85df3c4010b4d78000051", "question": "What should you do if you find an individual that you suspect has overdosed?", "answer": "Call emergency services.\nTry to wake the person up.\nAdminister naloxone if you have it.\nCardiopulmonary resuscitation.\nStay until emergency services arrive.", "relevant_passage_ids": ["33771150", "31420089", "36123614", "33682423", "30924736", "16002027", "20967505"], "type": "list", "snippets": [{"offsetInBeginSection": 112, "offsetInEndSection": 462, "text": "The implementation of naloxone programs, such as 'take-home naloxone' (THN), has emerged as a key intervention in reducing opioid overdose deaths. These programs aim to train individuals at risk of witnessing or experiencing an opioid overdose to recognize an opioid overdose and respond with naloxone. Naloxone effectively reverses opioid overdoses ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33771150"}, {"offsetInBeginSection": 1233, "offsetInEndSection": 1438, "text": "Another medication mode of minimizing risk of overdose is take-home naloxone. Naloxone is an opioid antagonist used to reverse opioid overdose, and take-home naloxone programs aim to prevent fatal overdose", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31420089"}, {"offsetInBeginSection": 1869, "offsetInEndSection": 2153, "text": "Data indicated the aided survived the suspected overdose in 87.4% of cases.CONCLUSIONS: With appropriate training, law enforcement personnel were able to recognize opioid overdoses and prevent fatalities by administering naloxone and carrying out time-sensitive medical interventions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36123614"}, {"offsetInBeginSection": 1532, "offsetInEndSection": 1844, "text": "Current American Heart Association recommendations call for laypeople and others who cannot reliably establish the presence of a pulse to initiate cardiopulmonary resuscitation in any individual who is unconscious and not breathing normally; if opioid overdose is suspected, naloxone should also be administered.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33682423"}, {"offsetInBeginSection": 136, "offsetInEndSection": 339, "text": "An adjunct to respiratory support that can reduce this high mortality rate is the administration of naloxone by Emergency Medical Services (EMS) practitioners for patients with suspected opioid overdose.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30924736"}, {"offsetInBeginSection": 1159, "offsetInEndSection": 1416, "text": "Efforts to equip drug users to manage overdoses effectively, including training in first aid and the provision of naloxone, and the reduction of police involvement at overdose events may have a substantial impact on overdose-related morbidity and mortality.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16002027"}, {"offsetInBeginSection": 113, "offsetInEndSection": 193, "text": "Opiate overdose can be reversed by administering naloxone, an opiate antagonist.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20967505"}]}
+{"question_id": "65cebf371930410b13000004", "question": "What is the mechanism of action of sparsentan?", "answer": "Sparsentan is a single-molecule dual endothelin type-A and angiotensin II type 1 receptor antagonist for the treatment of immunoglobulin A (IgA) nephropathy and focal segmental glomerulosclerosis (FSGS).", "relevant_passage_ids": ["37180506", "37022667", "37256677", "37221817", "36852566", "38041499", "35052766", "29142983", "32274453", "37706310", "30361325", "35514086", "37762309", "37015244", "37921461", "36834836", "35224732", "37931634", "35547199", "35291039", "31749142"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Introduction: Sparsentan is a novel single-molecule dual endothelin angiotensin receptor antagonist with hemodynamic and anti-inflammatory properties and is not an immunosuppressant. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37180506"}, {"offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Sparsentan (FILSPARI\u2122) is an oral, dual endothelin angiotensin receptor antagonist that is being developed by Travere Therapeutics for the treatment of immunoglobulin A (IgA) nephropathy and focal segmental glomerulosclerosis (FSGS).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37022667"}, {"offsetInBeginSection": 275, "offsetInEndSection": 471, "text": "Sparsentan is a single-molecule dual endothelin type-A and angiotensin II type 1 receptor antagonist (DEARA) under clinical development for focal segmental glomerulosclerosis and IgA nephropathy. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37256677"}, {"offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Sparsentan is a single-molecule dual endothelin angiotensin receptor antagonist (DEARA) currently under investigation as a treatment for focal segmental glomerulosclerosis (FSGS) and IgA nephropathy (IgAN).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37221817"}, {"offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Sparsentan is a single-molecule dual antagonist of the endothelin type A receptor and angiotensin II type 1 receptor under investigation for the treatment of focal segmental glomerulosclerosis and immunoglobulin A nephropathy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36852566"}, {"offsetInBeginSection": 388, "offsetInEndSection": 935, "text": "A Randomized, Multicenter, Double-Blind, Parallel, Active-Control Study of the Effects of Sparsentan, a Dual Endothelin Receptor and Angiotensin Receptor Blocker, on Renal Outcomes in Patients With Primary FSGS (DUPLEX) study evaluates the long-term antiproteinuric efficacy, nephroprotective potential, and safety profile of sparsentan compared with an AT1 receptor blocker alone in patients with FSGS.METHODS: DUPLEX is a multicenter, international, phase 3, randomized, double-blind, active-controlled study of sparsentan in patients with FSGS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32274453"}, {"offsetInBeginSection": 275, "offsetInEndSection": 470, "text": "Sparsentan is a single-molecule dual endothelin type-A and angiotensin II type 1 receptor antagonist (DEARA) under clinical development for focal segmental glomerulosclerosis and IgA nephropathy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37256677"}, {"offsetInBeginSection": 1063, "offsetInEndSection": 1233, "text": "Sparsentan, a dual-acting antagonist of the angiotensin II receptor and endothelin type A receptors, was found to suppress the amplitude of peak and late INa effectively.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37762309"}, {"offsetInBeginSection": 813, "offsetInEndSection": 1036, "text": "Interestingly, Sparsentan, the dual angiotensin II (Ang II) receptor and endothelin type A receptor antagonist, can also reduce TRM cell responses by intervening IL-15 signaling, exploring its new pharmacological functions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35514086"}, {"offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "BACKGROUND: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37015244"}, {"offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Sparsentan is a dual endothelin/angiotensin II receptor antagonist indicated to reduce proteinuria in patients with primary IgA nephropathy at high risk of disease progression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38041499"}]}
+{"question_id": "65f70915c4010b4d7800001a", "question": "Please summarize MuSK Antibody positive Myasthenia Gravis.", "answer": "Myasthenia gravis (MG) is a chronic autoimmune disorder in which antibodies destroy the communication between nerves and muscle, resulting in weakness of the skeletal muscles Approximately 5% of patients with MG, show positive results on muscle-specific kinase (MuSK) antibody testing and usually have severe symptoms, refractory disease, residual muscle atrophy, and poor prognosis.", "relevant_passage_ids": ["36396811", "37455510", "36527328", "37150596", "37564637", "35747537", "20613516", "25557356", "21822490", "19882635", "15989843", "27697312", "16155434", "30472069", "22013178", "17718696", "34992891", "34491934", "23706725", "22981737", "31177576"], "type": "summary", "snippets": [{"offsetInBeginSection": 102, "offsetInEndSection": 338, "text": "for anti-muscle specific tyrosine kinase (MuSK) antibody (Ab) in a large cohort of anti-acetylcholine receptor (AChR) Ab-negative generalized myasthenia gravis (MG), and also to investigate clinical contexts for the diagnosis of MuSK MG", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36396811"}, {"offsetInBeginSection": 334, "offsetInEndSection": 558, "text": "We compared the plasma concentrations of 15 myokines in 63 patients with acetylcholine receptor antibody (Ab)-positive MG and 14 with muscle-specific tyrosine kinase Ab-positive MG (MuSK MG) with those in 15 healthy controls", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37455510"}, {"offsetInBeginSection": 296, "offsetInEndSection": 378, "text": "In this report, we describe three patients with anti-muscle-specific kinase (MuSK)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36527328"}, {"offsetInBeginSection": 18, "offsetInEndSection": 155, "text": " Myasthenia gravis (MG) with muscle-specific tyrosine kinase (MuSK) antibodies (MMG) is predominantly seen in women of childbearing age. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37150596"}, {"offsetInBeginSection": 0, "offsetInEndSection": 372, "text": "Muscle-specific kinase (MuSK) Myasthenia Gravis (MG) represents a prototypical antibody-mediated disease characterized by predominantly focal muscle weakness (neck, facial, and bulbar muscles) and fatigability. The pathogenic antibodies mostly belong to the immunoglobulin subclass (Ig)G4, a feature which attributes them their specific properties and pathogenic profile. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37564637"}, {"offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "OBJECTIVE: Muscle-specific receptor tyrosine kinase (MuSK) antibody-positive myasthenia gravis (MG) accounts for 5%-15% of autoimmune MG. MuSK mediates the agrin-signaling pathway and also anchors the collagenic tail subunit (ColQ) of acetylcholinesterase (AChE).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22013178"}, {"offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Muscle specific tyrosine kinase antibody positive myasthenia gravis (MuSK- MG) is characterized by autoantibodies against the MuSK protein of the neuromuscular junction resulting in weakness of bulbar and proximal muscles.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30472069"}, {"offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Muscle-specific tyrosine kinase- (MuSK-) antibodies-positive Myasthenia Gravis accounts for about one third of Seronegative Myasthenia Gravis and is clinically characterized by early onset of prominent bulbar, neck, shoulder girdle, and respiratory weakness.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21822490"}, {"offsetInBeginSection": 567, "offsetInEndSection": 778, "text": "myasthenia gravis.RECENT FINDINGS: MuSK antibodies are found in a variable proportion of AChR antibody negative myasthenia gravis patients who are often, but not exclusively, young adult females, with bulbar, ne", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16155434"}, {"offsetInBeginSection": 1315, "offsetInEndSection": 1463, "text": "ted to randomized clinical trials.SUMMARY: MuSK antibodies define a form of myasthenia gravis that can be difficult to diagnose, can be life threate", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16155434"}, {"offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Background and Objectives: Muscle-specific kinase (MuSK) antibody-positive myasthenia gravis (MuSK + MG) is a form of MG with bulbar-predominant symptoms often resistant ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35747537"}, {"offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "PURPOSE OF REVIEW: Some of the 20% of myasthenia gravis patients who do not have antibodies to acetylcholine receptors (AChRs) have antibodies to muscle specific kinase (MuSK), but a full understanding of their frequency, the associated clinical phenotype and the mechanisms of action of the antibodies has not", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16155434"}, {"offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Muscle-specific kinase (MuSK) Myasthenia Gravis (MG) represents a prototypical antibody-mediated disease characterized by predominantly focal muscle weakness (neck, facial, and bulbar muscles) and fatigability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37564637"}, {"offsetInBeginSection": 1406, "offsetInEndSection": 1571, "text": "The role of thymectomy in the management of these patients remains uncertain.SUMMARY: MuSK antibody positive patients represent a unique subset of myasthenia gravis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20613516"}, {"offsetInBeginSection": 27, "offsetInEndSection": 196, "text": "Muscle-specific kinase (MuSK) antibody-positive myasthenia gravis (MuSK + MG) is a form of MG with bulbar-predominant symptoms often resistant to conventional treatments", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35747537"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1235, "text": "We investigated the presence of antibodies (Abs) against muscle-specific tyrosine kinase (MuSK) in Japanese myasthenia gravis (MG) patients. MuSK Abs were found in 23 (27%) of 85 generalized seronegative MG (SNMG) patients but not in any of the ocular MG patients. MuSK Ab-positive patients were characterized as having female dominance (M:F, 5:18), age range at onset 18 to 72 (median 45) years old, and prominent oculobulbar symptoms (100%) with neck (57%) or respiratory (35%) muscle weakness. Limb muscle weakness was comparatively less severe (52%), thymoma absent. Most patients had good responses to simple plasma exchange and steroid therapy. MuSK IgG from all 18 patients was exclusively the IgG 4 subclass and bound mainly with the MuSK Ig 1-2 domain. Serial studies of 12 individuals showed a close correlation between the variation in MuSK Ab titers and MG clinical severity (P = 0.01 by Kruskal-Wallis). MuSK Ab titers were sharply decreased in patients who had a good response to early steroid therapy or simple plasma exchange, but there was no change, or a rapid increase on exacerbation after thymectomy. Measurement of MuSK Ab titers aids in the diagnosis of MG and the monitoring of clinical courses after treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17718696"}, {"offsetInBeginSection": 668, "offsetInEndSection": 1057, "text": "Muscle-specific tyrosine kinase myasthenia gravis (MuSK-Ab MG) is a rare subtype of myasthenia gravis with distinct pathogenesis and unique clinical features. Diagnosis can be challenging due to its atypical presentation as compared to seropositive myasthenia gravis. It responds inconsistently to steroids, but plasma exchange and immunosuppressive therapies have shown promising results.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34992891"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1623, "text": "PURPOSE OF REVIEW: Important concepts regarding the pathogenesis, clinical features, diagnosis and treatment of muscle-specific tyrosine kinase (MuSK) antibody positive myasthenia gravis will be reviewed. Special attention will be paid to clinical phenotypes and treatment, particularly encouraging responses that have been reported to rituximab.RECENT FINDINGS: Worldwide studies confirm three major phenotypes in MuSK antibody positive myasthenia gravis (MMG) patients: indistinguishable from acetylcholine receptor antibody positive patients, prominent faciopharyngeal weakness, usually with marked muscle atrophy, and relatively isolated neck extensor and respiratory weakness. MMG predominates in women and weakness is typically more severe, with more frequent respiratory crises than non-MuSK myasthenia gravis. Patients with sub-acute bulbar, shoulder, and neck weakness pose unique challenges in terms of differential diagnosis and electrodiagnosis. Electrodiagnostic studies evaluating for disorders of neuromuscular transmission should focus on proximal limb and facial muscles, as well as clinically weak muscles. The response to acetylcholinesterase inhibitors is often disappointing. Long-term outcomes appear favorable though patients typically require more aggressive immunosuppression. Uncontrolled observations report encouraging results with rituximab in the treatment of refractory MMG. The role of thymectomy in the management of these patients remains uncertain.SUMMARY: MuSK antibody positive patients represent a unique subset of myasthenia gravis. Identification of these patients has important diag", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20613516"}, {"offsetInBeginSection": 0, "offsetInEndSection": 541, "text": "INTRODUCTION: Approximately 39% to 49% of patients with previously diagnosed acetylcholine receptor antibody-negative myasthenia gravis have been found to be muscle-specific tyrosine kinase (MuSK) antibody positive. These patients have a presentation that typically includes oculobulbar weakness, poorer response to cholinesterase inhibitors, and higher risk for acute clinical decompensation that necessitates plasma exchange. MuSK patients can require more aggressive maintenance immunosuppression earlier-on to maintain stability, often w", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34491934"}, {"offsetInBeginSection": 0, "offsetInEndSection": 771, "text": "Antibodies (Abs) to muscle-specific tyrosine kinase (MuSK) are detected in approximately 40% of generalized acetylcholine receptor antibody-negative myasthenia gravis (MG). Anti-MuSK Abs are nearly always associated with generalized symptoms, with prevalent involvement of craniobulbar, cervical and respiratory muscles and with a striking preponderance in women. The typical course of MuSK-MG is acute onset, rapid progression, brittle course in the first years, early respiratory crises and unprovoked relapses in spite of high-dose immunosuppression. Patients often require long-term management with multiple immunosuppressive (IS) agents and many of them remain dependent on IS treatment. The majority of anti-MuSK Abs are of the non-complement-binding IgG4 subclass.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23706725"}, {"offsetInBeginSection": 1119, "offsetInEndSection": 1404, "text": "MuSK antibody-positive myasthenia gravis (MG) accounts for 5-15% of autoimmune MG. As AChR deficiency is typically mild and as cholinesterase inhibitors are generally ineffective or worsen myasthenic symptoms, we asked if the patient's MuSK-IgG interferes with binding of ColQ to MuSK.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22981737"}, {"offsetInBeginSection": 0, "offsetInEndSection": 445, "text": "BACKGROUND AND OBJECTIVE: Recently, the presence of antibodies to a muscle-specific tyrosine kinase (MuSK) has been reported in some patients with seronegative generalized myasthenia gravis. Our objective was to describe a group of patients who were positive for anti-MuSK antibodies.PATIENTS AND METHOD: Detection of antibodies using a radioimmunoassay was performed in the serum of 26 patients with generalized myasthenia gravis. We identified", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15989843"}, {"offsetInBeginSection": 0, "offsetInEndSection": 378, "text": "BACKGROUND: Adult and pediatric patients suffering from MuSK (muscle-specific kinase) -antibody positive myasthenia gravis exhibit similar features to individuals with acetylcholine receptor (AChR) antibodies, but they differ in several characteristics such as a predominant bulbar, respiratory and neck weakness, a generally worse disease severity and a tendency to develop mus", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27697312"}, {"offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "BACKGROUND: Anti-muscle specific kinase antibody positive myasthenia gravis (MuSK MG) is often characterized by a relatively severe and progressive course, refractoriness to standard myasthenia gravis (MG) medications, and an increased risk of myasth", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25557356"}, {"offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "INTRODUCTION: Muscle-specific tyrosine kinase (MuSK) autoantibody related myasthenia gravis is characterized by bulbar and respiratory manifestations, a poor response to anticholinergics, and a generally good response to plasma exchange ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31177576"}, {"offsetInBeginSection": 752, "offsetInEndSection": 1153, "text": "This survey reinforces several cardinal features of MuSK-Ab-positive MG, including prominent bulbar involvement and anticholinesterase nonresponsiveness. Facial or tongue atrophy was rare. Most patients respond favorably to immunotherapy. The best clinical response was to corticosteroids and plasma exchange, and the poorest response was to IVIG. Long-term outcome is favorable in about 60% of cases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19882635"}]}
+{"question_id": "65f8418fc4010b4d78000041", "question": "Is it advisable to bring the fever down when it is supposedly meant to assist in the fight of disease?", "answer": "While fever is a common symptom in children and can cause distress, it's important to note that antipyretics, or fever-reducing medications, are typically used to alleviate discomfort rather than solely to reduce body temperature. Fever is part of the body's natural defense mechanism against illness, so the primary goal of treatment is to relieve distress, not necessarily to lower the fever. Therefore, it's not always advisable to bring the fever down just for the sake of reducing body temperature. It's more about managing the child's comfort level.", "relevant_passage_ids": ["35967183", "35511631", "33912381", "9578327", "33738101", "21357332", "22436665", "16617919", "35822579", "2200377", "12856055"], "type": "summary", "snippets": [{"offsetInBeginSection": 13, "offsetInEndSection": 112, "text": "Fever is the most common presenting symptom in children and causes distress in patients and parents", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35967183"}, {"offsetInBeginSection": 500, "offsetInEndSection": 546, "text": "antipyretics are indicated only for discomfort", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35511631"}, {"offsetInBeginSection": 1504, "offsetInEndSection": 1680, "text": "relief from distress is the primary indication for prescribing pharmacotherapy, and antipyretics should not be administered with the sole intention of reducing body temperature", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33912381"}, {"offsetInBeginSection": 830, "offsetInEndSection": 1056, "text": "The two thermoregulatory responses represent two complementary strategies of survival in systemic inflammation: fever ensures the active attack against the pathogen; hypothermia secures the defense of the host's vital systems.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9578327"}, {"offsetInBeginSection": 200, "offsetInEndSection": 308, "text": "In contrast, high temperature in non-infectious intensive care patients is associated with higher mortality.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22436665"}, {"offsetInBeginSection": 1228, "offsetInEndSection": 1350, "text": "There is little evidence that fever facilitates recovery from disease or assists the immune system in mounting a response.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16617919"}, {"offsetInBeginSection": 0, "offsetInEndSection": 986, "text": "Although fever is one of the main presenting symptoms of COVID-19 infection, little public attention has been given to fever as an evolved defense. Fever, the regulated increase in the body temperature, is part of the evolved systemic reaction to infection known as the acute phase response. The heat of fever augments the performance of immune cells, induces stress on pathogens and infected cells directly, and combines with other stressors to provide a nonspecific immune defense. Observational trials in humans suggest a survival benefit from fever, and randomized trials published before COVID-19 do not support fever reduction in patients with infection. Like public health measures that seem burdensome and excessive, fevers involve costly trade-offs but they can prevent infection from getting out of control. For infections with novel SARS-CoV-2, the precautionary principle applies: unless evidence suggests otherwise, we advise that fever should be allowed to run its course.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33738101"}, {"offsetInBeginSection": 1126, "offsetInEndSection": 1270, "text": "Even though this is a common practice, lowering body temperature has not improved survival in laboratory animals or in patients with infections.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33738101"}, {"offsetInBeginSection": 484, "offsetInEndSection": 660, "text": "Observational trials in humans suggest a survival benefit from fever, and randomized trials published before COVID-19 do not support fever reduction in patients with infection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33738101"}, {"offsetInBeginSection": 292, "offsetInEndSection": 483, "text": "The heat of fever augments the performance of immune cells, induces stress on pathogens and infected cells directly, and combines with other stressors to provide a nonspecific immune defense.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33738101"}, {"offsetInBeginSection": 661, "offsetInEndSection": 817, "text": "Like public health measures that seem burdensome and excessive, fevers involve costly trade-offs but they can prevent infection from getting out of control.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33738101"}, {"offsetInBeginSection": 317, "offsetInEndSection": 729, "text": "Fever, however, is not the primary illness but is a physiologic mechanism that has beneficial effects in fighting infection. There is no evidence that fever itself worsens the course of an illness or that it causes long-term neurologic complications. Thus, the primary goal of treating the febrile child should be to improve the child's overall comfort rather than focus on the normalization of body temperature.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21357332"}, {"offsetInBeginSection": 362, "offsetInEndSection": 586, "text": "According to research, we are at a crossroad, with strong research evidence accumulating over the last few decades supporting a positive role for fever and the ongoing pressures of current practice to lower body temperature.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35822579"}, {"offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "While understanding of the mechanisms of fever has progressed in recent years, much uncertainty remains as to whether fever in itself (as distinct from its cause) is beneficial or harmful, and what circumstances warrant antipyretic therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2200377"}, {"offsetInBeginSection": 986, "offsetInEndSection": 1189, "text": "No evidence shows that it is beneficial to treat febrile children with paracetamol. Treatment should be given only to children who are in obvious discomfort and those with conditions known to be painful.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12856055"}, {"offsetInBeginSection": 373, "offsetInEndSection": 528, "text": "No studies showed any clear benefit for the use of paracetamol in therapeutic doses in febrile children with viral or bacterial infections or with malaria.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12856055"}]}
+{"question_id": "65cfd13f1930410b1300001d", "question": "Can syphilis cause proctitis?", "answer": "Yes. Syphilis can cause proctitis.", "relevant_passage_ids": ["36703251", "37267792", "35969837", "27365889", "30516724", "21998411", "33370929", "879137"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "A 26-year-old man in Australia who has sex with men had severe perianal ulceration, proctitis, and skin lesions develop. Testing revealed primary syphilis, mpox, and primary HIV infection. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36703251"}, {"offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Syphilitic proctitis presenting as locally advanced rectal cancer: A case report.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37267792"}, {"offsetInBeginSection": 101, "offsetInEndSection": 248, "text": "We present a case of severe syphilitic proctitis leading to large bowel obstruction with imaging findings mimicking locally advanced rectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37267792"}, {"offsetInBeginSection": 1513, "offsetInEndSection": 1715, "text": "CONCLUSION: Severe proctitis leading to large bowel obstruction is a possible presentation of syphilis, and a high degree of clinical suspicion is necessary to be able to accurately identify the cause. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37267792"}, {"offsetInBeginSection": 0, "offsetInEndSection": 376, "text": "ABSTRACT: We analyzed microbiologic etiologies of proctitis among patients seen in an urban sexual health clinic during 2011 to 2021. Among 759 cases, 179 (24%) tested positive for Neisseria gonorrhoeae , 171 (23%) for Chlamydia trachomatis , 21 (3%) for herpes simplex virus, 30 (4%) for syphilis, and 73 (10%) for multiple pathogens; no pathogen was identified in 425 (56%).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35969837"}, {"offsetInBeginSection": 822, "offsetInEndSection": 906, "text": "The patient tested positive for syphilis and was diagnosed with syphilitic proctitis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37267792"}, {"offsetInBeginSection": 1049, "offsetInEndSection": 1714, "text": "Final pathology on the rectal biopsies demonstrated positive Warthin-Starry and spirochete immunohistochemical stain.DISCUSSION: This case illustrates key aspects in the care of a patient with syphilitic proctitis mimicking an obstructing rectal cancer, including the need for high clinical suspicion, thorough evaluation including sexual and sexually transmitted disease history, multidisciplinary communication, and management of the Jarisch-Herxheimer reaction.CONCLUSION: Severe proctitis leading to large bowel obstruction is a possible presentation of syphilis, and a high degree of clinical suspicion is necessary to be able to accurately identify the cause.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37267792"}, {"offsetInBeginSection": 41, "offsetInEndSection": 161, "text": "Syphilitic proctitis involving the rectal mucosa often presents with pain on defecation, rectal bleeding, or ulceration.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30516724"}, {"offsetInBeginSection": 162, "offsetInEndSection": 264, "text": "We present a case of asymptomatic syphilitic proctitis diagnosed upon a routine screening colonoscopy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30516724"}, {"offsetInBeginSection": 0, "offsetInEndSection": 44, "text": "A Case of Asymptomatic Syphilitic Proctitis.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30516724"}, {"offsetInBeginSection": 822, "offsetInEndSection": 907, "text": "The patient tested positive for syphilis and was diagnosed with syphilitic proctitis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37267792"}, {"offsetInBeginSection": 101, "offsetInEndSection": 384, "text": "We present a case of severe syphilitic proctitis leading to large bowel obstruction with imaging findings mimicking locally advanced rectal cancer.PRESENTATION OF CASE: A 38-year-old man who had sex with men presented to the emergency department with a 2\u00a0week history of obstipation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37267792"}, {"offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Case of secondary syphilis presenting with unusual complications: syphilitic proctitis, gastritis, and hepatitis.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21998411"}, {"offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Syphilitic proctitis is a rare presentation of sexually transmitted infection that poses a diagnostic challenge as it mimics rectal cancer clinically, radiologically and endoscopically.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33370929"}, {"offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Syphilitic proctitis is a rare disease that usually presents as proctitis, ulcer, and neoplasm but lacks pathognomonic clinical symptoms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27365889"}, {"offsetInBeginSection": 1468, "offsetInEndSection": 1657, "text": "anagement of the Jarisch-Herxheimer reaction.CONCLUSION: Severe proctitis leading to large bowel obstruction is a possible presentation of syphilis, and a high degree of clinical suspicion ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37267792"}, {"offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Two adult male homosexuals with syphilitic proctitis and without any detectable anal lesions are reported.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/879137"}]}
+{"question_id": "65f493cac4010b4d78000012", "question": "What disorder is considered off label use for domperidone?", "answer": "A major side effect of domperidone is prolactinemia, allowing it to be used off-label for the purpose of inducing lactation.", "relevant_passage_ids": ["35793516", "37352416", "36367713", "37159421", "25475074", "24600732", "25306766", "27280111", "27296864", "25825854", "30481478"], "type": "factoid", "snippets": [{"offsetInBeginSection": 12, "offsetInEndSection": 113, "text": "Domperidone is an antiemetic that is commonly used as an off-label prescription to induce lactation. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35793516"}, {"offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Domperidone is a dopamine-2 (D2) receptor antagonist that stimulates the release of stored prolactin in the anterior pituitary. It is prescribed off-label in Canada and Australia to promote lactation in prolactin-deficient women. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37352416"}, {"offsetInBeginSection": 12, "offsetInEndSection": 100, "text": "Domperidone is a dopamine-2 antagonist used off-label to increase breast milk production", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36367713"}, {"offsetInBeginSection": 312, "offsetInEndSection": 538, "text": "However, among (pediatric) gastroenterologists, domperidone is also used outside its authorized indication (\"off label\") for treatment of symptoms associated with gastro-esophageal reflux disease, dyspepsia, and gastroparesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37159421"}, {"offsetInBeginSection": 819, "offsetInEndSection": 1058, "text": "Based on this, the purpose of this review is to summarize all evidence on the efficacy of domperidone for the treatment of GI disorders in infants and children and to report an overview of its pharmacological properties and safety profile.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37159421"}, {"offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "OBJECTIVES: Domperidone and metoclopramide are prokinetics commonly prescribed off-label to infants and younger children in an attempt to treat gastro-oesophageal reflux symptoms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25825854"}, {"offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Objectives: Domperidone is an antiemetic that is commonly used as an off-label prescription to induce lactation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35793516"}, {"offsetInBeginSection": 312, "offsetInEndSection": 537, "text": "However, among (pediatric) gastroenterologists, domperidone is also used outside its authorized indication (\"off label\") for treatment of symptoms associated with gastro-esophageal reflux disease, dyspepsia, and gastroparesis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37159421"}, {"offsetInBeginSection": 160, "offsetInEndSection": 256, "text": "on, such as domperidone, an off-label galactagogue, are often prescribed. Domperidone is controv", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30481478"}, {"offsetInBeginSection": 12, "offsetInEndSection": 137, "text": "Domperidone is an antiemetic that is commonly used as an off-label prescription to induce lactation. Neuropsychiatric adverse", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35793516"}, {"offsetInBeginSection": 12, "offsetInEndSection": 118, "text": "Domperidone is a dopamine-2 antagonist used off-label to increase breast milk production. Dosages commonly", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36367713"}, {"offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Domperidone is a prokinetic agent used as a second-line treatment option for gastroparesis in those unable to tolerate", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25306766"}, {"offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Domperidone is a peripheral dopamine-2 receptor antagonist with prokinetic and antiemetic properties. Its prokinetic effects are mainly manifest in the upper gastrointestinal (GI) tract. Currently its use is restricted", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37159421"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "BACKGROUND: Domperidone is commonly used off-label to stimulate milk production in mothers who have low ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27280111"}, {"offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Domperidone is a dopamine-2 (D2) receptor antagonist that stimulates the release of stored prolactin in the anterior pituitary. It is prescribed off-label in Canada and Australia to promote lactation in prolactin-deficient women.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37352416"}, {"offsetInBeginSection": 105, "offsetInEndSection": 221, "text": "astfeeding. Medications that can increase milk production, such as domperidone, an off-label galactagogue, are often", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30481478"}, {"offsetInBeginSection": 338, "offsetInEndSection": 462, "text": "A major side effect of domperidone is prolactinemia, allowing it to be used off-label for the purpose of inducing lactation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25306766"}, {"offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "PURPOSE: The aim of this study is to examine the relationship between domperidone (commonly used off-label for lactation stimulation), ventricular arrhythmia and all-cause mortality during the postpartu", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27296864"}, {"offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "OBJECTIVES: Domperidone and metoclopramide are prokinetics commonly prescribed off-label to infants and younger children in an attempt to treat gastro-oesophageal refl", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25825854"}, {"offsetInBeginSection": 1214, "offsetInEndSection": 1481, "text": "The use of domperidone as a galactagogue is worrisome as drug-induced long QT syndrome occurred mostly in women. In these circumstances, an improvement of breastfeeding practices seems to be more effective and safer than the use of an off-label domperidone treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25475074"}, {"offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "The use of domperidone in accordance with the terms of its marketing authorisation, or off-label to increase breast milk production, exposes patients to serious cardiac risk.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24600732"}]}
+{"question_id": "65f8721ec4010b4d7800005d", "question": "Which neurotransmitters are thought to play a role in obsessive compulsive disorder?", "answer": "The neurotransmitters thought to play a role in obsessive-compulsive disorder (OCD) include:\n\n1. Serotonin\n2. Dopamine \n3. Glutamate\n4. Gamma-aminobutyric acid (GABA)\n\nDysregulation of these neurotransmitter systems, especially serotonin, dopamine, and glutamate, within cortico-striatal-thalamo-cortical circuits is implicated in the pathophysiology of OCD. An imbalance between excitatory glutamate and inhibitory GABA neurotransmission may be particularly important.", "relevant_passage_ids": ["33751503", "21963369", "24576790", "31146727", "28950396", "21938084", "16650712", "11267629", "9924841", "20136383", "2692636", "9108814", "9829023", "21424418", "16213689"], "type": "list", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 339, "text": "A large body of evidence suggests that the neuropathology of obsessive-compulsive disorder (OCD) lies in the complex neurotransmitter network of the cortico-striatal-thalamo-cortical (CSTC) circuit, where dopamine (DA), serotonin (5HT), glutamate (Glu), and gamma-amino butyric acid (GABA) dysfunction have been implicated in the disorder.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11267629"}, {"offsetInBeginSection": 850, "offsetInEndSection": 929, "text": "Neurotransmitters implicated in OCD include serotonin, dopamine, and glutamate.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24576790"}, {"offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "The serotonin (5-HT) neurotransmitter system has been implicated in the pathophysiology of several neuropsychiatric disorders, especially obsessive-compulsive disorder (OCD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9924841"}, {"offsetInBeginSection": 0, "offsetInEndSection": 637, "text": "The differential effects of serotonin-reuptake inhibitors on obsessive-compulsive disorder (OCD) were sufficient to presume that a serotonin regulatory disorder is the most essential part of the pathophysiology of OCD. In patients with OCD, however, a high-dose of serotonin-reuptake inhibitor monotherapy may not be sufficient, and approximately half of patients were noted to be treatment-resistant. As results from previous studies have shown, there have been positive treatment responses to the dopaminergic antagonists. This suggests that other neurotransmitter systems, such as dopamine, are involved in the pathophysiology of OCD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20136383"}, {"offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Involvement of the brain serotonin (5-HT) neurotransmitter system in obsessive-compulsive disorder (OCD) was originally suggested on the basis of therapeutic effects found with the semiselective serotonin uptake inhibitor, clomipramine.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2692636"}, {"offsetInBeginSection": 1190, "offsetInEndSection": 1462, "text": "Similarly, the involvement of serotonergic neurotransmitters in OCD suggests that these neurotransmitters are central to defining spectrum disorders.Again, however, serotonin plays a role in many functions (including impulse control) and mediates many different disorders.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16650712"}, {"offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "BACKGROUND: While serotonin is the neurotransmitter most commonly implicated in obsessive-compulsive and related disorders, there is also evidence for dopaminergic mediation of these conditions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9108814"}, {"offsetInBeginSection": 1507, "offsetInEndSection": 1754, "text": "The MRS measures did not vary by subgroup and showed no correlations with demographic and clinical variables.CONCLUSIONS: These results indicate that GABA abnormalities within the anterior cingulate cortex contribute to the pathophysiology of OCD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31146727"}, {"offsetInBeginSection": 543, "offsetInEndSection": 732, "text": "Recent evidence suggests that the ubiquitous excitatory neurotransmitter glutamate is dysregulated in OCD, and that this dysregulation may contribute to the pathophysiology of the disorder.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21963369"}, {"offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "BACKGROUND: There is a major role for serotonin in the mechanism of anti-obsessional drug action. Drugs that block uptake of noradrenaline are not effective in the treatment of obsessive-compulsive disorder (OCD), while drugs that potently bock serotonin reuptake ar", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9829023"}, {"offsetInBeginSection": 473, "offsetInEndSection": 612, "text": "Significant overlap in neurotransmitter dysfunction (serotonin, glutamate, and dopamine) has been documented between schizophrenia and OCD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21938084"}, {"offsetInBeginSection": 600, "offsetInEndSection": 848, "text": "Neurochemical studies have shown that OCD is linked to changes of the central modulatory transmitter system, especially, the serotonin and dopamine system, which probably contribute to a direct and indirect dysregulation in various neural networks.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21424418"}, {"offsetInBeginSection": 788, "offsetInEndSection": 929, "text": "in the cortico-striato-thalamo-cortical circuit in the brain. Neurotransmitters implicated in OCD include serotonin, dopamine, and glutamate.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24576790"}, {"offsetInBeginSection": 520, "offsetInEndSection": 707, "text": "Recently, there is extensive evidence showing a key role of glutamate pathways abnormalities within the cortico-striatal-thalamo-cortical circuitry and temporal lobes in OCD pathogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28950396"}, {"offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "In obsessive-compulsive disorder (OCD), the success of pharmacological treatment with serotonin re-uptake inhibitors and atypical antipsychotic drugs suggests that both the central serotonergic and dopaminergic systems are involved in the pathophysiology of the disorder.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16213689"}]}
+{"question_id": "65d126d21930410b1300002c", "question": "Can denosumab cause jaw necrosis?", "answer": "Yes. Denosumab can cause jaw necrosis", "relevant_passage_ids": ["32307659", "29063702", "28684826", "25497376", "23830772", "23645723", "26964445", "30560961", "23159111", "24582013", "28555210", "37389685", "25131835", "38028038", "29576576", "22093187", "29983309", "31299805", "27648313", "26859582", "24804929", "24490612"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is an infrequent, but potentially serious, adverse event that can occur after exposure to bone-modifying agents (BMAs; e.g., bisphosphonates, denosumab, and antiangiogenic therapies). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32307659"}, {"offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Osteonecrosis of the jaw (ONJ) is a severe complication of therapy with antiresorptive agents (e.g. bisphosphonates and denosumab), which are used to manage bone metastases from cancer, to reduce the incidence of skeletal-related events.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29063702"}, {"offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Aggressive denosumab-related jaw necrosis - a case series.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28684826"}, {"offsetInBeginSection": 203, "offsetInEndSection": 329, "text": "We are presenting four cases of MRONJ related to denosumab treatment showing increasingly aggressive pictures of the disease. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28684826"}, {"offsetInBeginSection": 476, "offsetInEndSection": 767, "text": "A total of 383 cases were registered: 369 were described as BRONJ, 5 as avascular necrosis, and 9 were unknown. Bisphosphonates had been given orally in 207 (56%), intravenously in 125 (34%), both orally and intravenously in 27 (7%), and was unknown in 9 (2%); one had been given denosumab. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25497376"}, {"offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Osteonecrosis of the jaw has recently been described in patients receiving subcutaneous administration of RANKL-inhibitors (denosumab).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23830772"}, {"offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Medication-related osteonecrosis of the jaws (MRONJ) is a serious debilitating disease resulting from long-term treatment with Antiresorptive drugs such as Bisphosphonates or Denosumab, which significantly affects patients' quality of life", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38028038"}, {"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "PURPOSE: Osteonecrosis of the jaw has been recently reported in patients receiving denosumab for the treatment of metastatic bone disease and osteoporosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29983309"}, {"offsetInBeginSection": 2195, "offsetInEndSection": 2283, "text": "33 (5%) patients on denosumab developed osteonecrosis of the jaw versus none on placebo.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22093187"}, {"offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Denosumab and anti-angiogenetic drug-related osteonecrosis of the jaw: an uncommon but potentially severe disease.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23645723"}, {"offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Denosumab, an Alternative to Bisphosphonates but also Associated with Osteonecrosis of the Jaw--What is the Risk?", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26964445"}, {"offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "PURPOSE: To report a case of osteonecrosis of the jaw (ONJ) occurring in an implant area possibly related to denosumab, a relatively new antiosteoporot", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28555210"}, {"offsetInBeginSection": 83, "offsetInEndSection": 259, "text": "Osteonecrosis of the jaw (ONJ) is a rare but serious clinical condition. It affects patients treated with bisphosphonates, and also with denosumab, mainly in oncological doses.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21365586"}, {"offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "We report a case of osteonecrosis of the jaw (ONJ) associated with denosumab therapy in a 62-year-old female patient being treated for bone metastases from breast cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29576576"}, {"offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Denosumab, an Alternative to Bisphosphonates but also Associated with Osteonecrosis of the Jaw--What is the Risk?.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26964445"}, {"offsetInBeginSection": 0, "offsetInEndSection": 402, "text": "PURPOSE: To report a case of osteonecrosis of the jaw (ONJ) occurring in an implant area possibly related to denosumab, a relatively new antiosteoporotic agent.MATERIALS AND METHODS: Two months following the extraction of both maxillary first molars, a bilateral maxillary sinus floor elevation was performed on a 64-year-old female patient under a biannual \u202860\u2005mg denosumab antiosteoporotic treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28555210"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Denosumab Related Osteonecrosis of the Jaw with Spontaneous Necrosis of the Soft Palate: Report of a Life Threatening Case.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27648313"}, {"offsetInBeginSection": 510, "offsetInEndSection": 1069, "text": "After 3\u2005months, the implants underwent prosthetic rehabilitation at one side, and a series of failures that led to an ONJ instalment at the other side.RESULTS: The ONJ persisted over 7\u2005months and was only resolved by a surgical approach consisting of a piezoelectric osteotomy and platelet-rich fibrin with a tension-free wound closure.CONCLUSIONS: A cumulative effect of denosumab is likely to be associated with a jaw osteonecrosis, which in this case was manageable using a surgical approach with no need to interrupt the appropriate drug treatment course.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28555210"}, {"offsetInBeginSection": 0, "offsetInEndSection": 403, "text": "Osteonecrosis of the jaw (ONJ) is a severe complication of therapy with antiresorptive agents (e.g. bisphosphonates and denosumab), which are used to manage bone metastases from cancer, to reduce the incidence of skeletal-related events. Available data indicate that 0-27, 5% of patients exposed to antiresorptive agents may develop ONJ, depending on the number of infusions and the duration of therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29063702"}, {"offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Denosumab-related osteonecrosis of the jaws (DRONJ) is a recently described entity that shares many common clinical and radiological features with bisphosphonate-related osteonecrosis of the jaws (BRONJ).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26859582"}, {"offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "We report the first case of teriparatide adjuvant role in the management of a denosumab-induced osteonecrosis of the jaw in a male subject with idiopathic osteoporosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24804929"}, {"offsetInBeginSection": 807, "offsetInEndSection": 1017, "text": "brin with a tension-free wound closure.CONCLUSIONS: A cumulative effect of denosumab is likely to be associated with a jaw osteonecrosis, which in this case was manageable using a surgical approach with no need", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28555210"}, {"offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Osteonecrosis of the jaw as a result of treatment with receptor activators of nuclear factor kappa-B ligand (RANKL) inhibitors (denosumab)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24582013"}, {"offsetInBeginSection": 244, "offsetInEndSection": 318, "text": "A severe side effect of denosumab is the osteonecrosis of the jaw (DRONJ).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31299805"}, {"offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Ultrasonic Piezoelectric Bone Surgery Combined With Leukocyte and Platelet-Rich Fibrin and Pedicled Buccal Fat Pad Flap in Denosumab-Related Osteonecrosis of the Jaw.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31299805"}, {"offsetInBeginSection": 511, "offsetInEndSection": 763, "text": "While Medication Related Osteonecrosis of the Jaw (MRONJ) is most commonly seen in patients treated with bisphosphonates, in the past decade, it has become apparent that other types of medication, most notably denosumab, can cause comparable disorders.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30560961"}, {"offsetInBeginSection": 1, "offsetInEndSection": 240, "text": "Osteonecrosis of the jaws (ONJ) is an adverse side event of bisphosphonates and denosumab, antiresorptive agents that effectively reduce the incidence of skeletal-related events in patients with metastatic bone cancer and multiple myeloma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24490612"}, {"offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "BACKGROUND: Denosumab (DMB) is a bone antiresorptive agent used to treat osteoporosis or metastatic cancer of the bones. However, denosumab-associated osteonecrosis of the jaw (DRONJ) has become a common complication in canc", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37389685"}, {"offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "Denosumab is a new bone antiresorptive agent that has received approval by the Food and Drug Administration for use in patients with osteoporosis and metastatic cancer to the bones. Like the bisphosponates that are used as antiresorptive medications, denosumab has been associated with osteonecrosis of the jaws (ONJ).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23159111"}, {"offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "Denosumab (Amgen, Thousand Oaks, California, USA) is a new bone antiresorptive agent used in patients with osteoporosis or metastatic cancer to the bones. As with the bisphosphonates that are used as antiresorptive medications, denosumab has been associated with osteonecrosis of the jaws (ONJ).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25131835"}]}
+{"question_id": "65f37871c4010b4d7800000a", "question": "What is DEXTR", "answer": "DEXTR is a semi-automated data extraction tool for public health literature-based reviews: Dextr provides similar performance to manual extraction in terms of recall and precision and greatly reduces data extraction time.", "relevant_passage_ids": ["34920276", "32856160"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Evaluation of a semi-automated data extraction tool for public health literature-based reviews: Dextr.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34920276"}, {"offsetInBeginSection": 1876, "offsetInEndSection": 2247, "text": "The Dextr tool addresses data-extraction challenges associated with environmental health sciences literature with a simple user interface, incorporates the key capabilities of user verification and entity connecting, provides a platform for further automation developments, and has the potential to improve data extraction for literature reviews in this and other fields.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34920276"}, {"offsetInBeginSection": 1824, "offsetInEndSection": 2017, "text": "rs to generate machine-readable, annotated exports. The Dextr tool addresses data-extraction challenges associated with environmental health sciences literature with a simple user interface, in", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34920276"}, {"offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Data extraction for epidemiological research (DExtER): a novel tool for automated clinical epidemiology studies.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32856160"}]}
+{"question_id": "65f85ec7c4010b4d78000052", "question": "What is the most common surgical treatment for hydrocephalus?", "answer": "The most common surgical treatment for hydrocephalus is the placement of a ventriculoperitoneal shunt.", "relevant_passage_ids": ["37402676", "34152450", "34774581", "21961546", "31286305", "17946960", "27203135", "25569424", "36314835", "26889393", "1474973", "35609726", "36780037", "31036124", "29122895", "20045747", "22222434", "11441995", "15630948", "36324983", "30459864", "22650109", "19725301"], "type": "factoid", "snippets": [{"offsetInBeginSection": 207, "offsetInEndSection": 360, "text": "Gravitation-assisted shunt valves are designed to prevent hydrostatic over-drainage frequently observed in the long course of shunt-treated hydrocephalus", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34152450"}, {"offsetInBeginSection": 11, "offsetInEndSection": 205, "text": "Shunt treatment for hydrocephalus in children should aim for sustainable flexibility in regard to optional, perspective pressure level adjustment during advancing physical and mental development", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34152450"}, {"offsetInBeginSection": 637, "offsetInEndSection": 741, "text": "hydrocephalic neonates and infants who received initial VP-shunt insertion in the early post-natal phase", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34152450"}, {"offsetInBeginSection": 1424, "offsetInEndSection": 1477, "text": "primary VP-shunt insertion at a mean age of 10 weeks ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34152450"}, {"offsetInBeginSection": 947, "offsetInEndSection": 1057, "text": "Shunt surgery is preferred for secondary hydrocephalus, especially for secondary normal pressure hydrocephalus", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37402676"}, {"offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Ventriculoperitoneal (VP) shunt placement is the most common surgical treatment for hydrocephalus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21961546"}, {"offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "BACKGROUND: Cerebrospinal fluid (CSF) diversion by shunts is the most common surgical treatment for hydrocephalus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34774581"}, {"offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "OBJECTIVE The surgical placement of a shunt designed to resolve the brain's impaired ability to drain excess CSF is one of the most common treatments for hydrocephalus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27203135"}, {"offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "The most common treatment for patients with hydrocephalus is the surgical implantation of a cerebrospinal fluid (CSF) shunt.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17946960"}, {"offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "INTRODUCTION: Ventriculoperitoneal (V-P) shunt surgery is the most common technique used for the treatment of hydrocephalus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26889393"}, {"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Two hundred eight patients with non-tumoral congenital hydrocephalus underwent CSF shunting below the age of one month.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1474973"}, {"offsetInBeginSection": 1305, "offsetInEndSection": 1365, "text": " All patients received VP shunts for hydrocephalus managemen", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31286305"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Cerebrospinal fluid shunt placement is the most common surgical intervention for hydrocephalus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25569424"}, {"offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "OBJECTIVE: Ventriculoperitoneal shunt (VPS) surgery is a common treatment for hydrocephalus in children and adults, making it one of the most common procedures in ne", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36780037"}, {"offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Ventriculoperitoneal shunt (VPS) placement is an effective and most frequently used surgical method in the treatment of hydrocephalus, but the mechanical and infective complications are often seen after this surgical procedure.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31036124"}, {"offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Ventriculoperitoneal (VP) shunt surgery remains the most widely used neurosurgical procedure for the management of hydrocephalus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29122895"}, {"offsetInBeginSection": 985, "offsetInEndSection": 1139, "text": "Hydrocephalus is treated with a ventriculo-peritoneal shunt but shunts in these patients suffer from frequent obstructions and require multiple revisions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20045747"}, {"offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Ventriculoperitoneal (VP) shunt surgery is the most common technique used in the treatment of hydrocephalus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22222434"}, {"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Ventriculoperitoneal (VP) shunts are among the most frequently performed operations in the management of hydrocephalus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11441995"}, {"offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Hydrocephalus is a common adult neurosurgical condition typically requiring treatment with a cerebrospinal fluid (CSF) shunt, of which the ventriculoperitoneal (VP) shunt is the most common type.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36314835"}, {"offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Ventriculoperitoneal (VP) shunts are the most common treatment modality for hydrocephalus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15630948"}, {"offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Background: Ventriculoperitoneal shunt (VPS) insertion and endoscopic third ventriculostomy (ETV) are common surgical procedures used to treat pediatric hydrocephalus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36324983"}, {"offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "CONTEXT: Ventriculoperitoneal (VP) shunt and endoscopic third ventriculostomy (ETV) are the established surgical treatments for obstructive hydrocephalus (HCP).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30459864"}, {"offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "INTRODUCTION: Insertion of a ventriculoperitoneal (VP) shunt, the method of choice in the treatment of hydrocephalus, is often followed by various mechanical and/or infective ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22650109"}, {"offsetInBeginSection": 1043, "offsetInEndSection": 1303, "text": "lved without any consequences.CONCLUSION: Insertion of a VP shunt represents the most frequent method of choice of the surgical treatment of hydrocephalus, but also potentially a highly risky procedure followed by various complications about which parents shou", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22650109"}, {"offsetInBeginSection": 811, "offsetInEndSection": 900, "text": "VP shunts are presently regarded as the standard of care for uncomplicated hydrocephalus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19725301"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "OBJECTIVE: Although ventriculoperitoneal shunt surgery is the most common method for hydrocephalus treatment, it may lead to serious complications and require surgical int", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35609726"}]}
+{"question_id": "65d126471930410b1300002b", "question": "Is Upadacitinib effective for Crohn\u2019s Disease?", "answer": "Yes. Upadacitinib is effective for Crohn\u2019s Disease.", "relevant_passage_ids": ["36272109", "36968986", "35695972", "31781755", "36898598"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "BACKGROUND: Upadacitinib is a selective Janus kinase inhibitor approved for the management of ulcerative colitis and is under evaluation for the management of Crohn's disease [CD] in Phase 3 clinical trials.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36272109"}, {"offsetInBeginSection": 1557, "offsetInEndSection": 1715, "text": "CONCLUSION: In this real-world cohort of highly refractory CD patients, upadacitinib was effective in inducing remission and had an acceptable safety profile.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36272109"}, {"offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Successful treatment of concomitant alopecia universalis and Crohn's disease with upadacitinib: A case report.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36968986"}, {"offsetInBeginSection": 494, "offsetInEndSection": 620, "text": "Upadacitinib, an oral JAK1 inhibitor, has demonstrated efficacy in treating Crohn's disease during phase III clinical trials. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36968986"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Upadacitinib Is Safe and Effective for Crohn's Disease: Real-World Data from a Tertiary Center.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35695972"}, {"offsetInBeginSection": 134, "offsetInEndSection": 263, "text": "Phase II trials demonstrated that upadacitinib induces endoscopic remission in patients with moderate-to-severe Crohn's disease. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35695972"}, {"offsetInBeginSection": 415, "offsetInEndSection": 734, "text": "In this cohort of medically refractory patients with CD, treatment with upadacitinib resulted in subjective and objective responses in 25 and 42% of patients, respectively. Even at doses that are considered lower than currently being studied for CD, upadacitinib was associated with a favorable benefit-to-risk profile.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35695972"}, {"offsetInBeginSection": 709, "offsetInEndSection": 798, "text": "Upadacitinib also showed promising results in a phase II trial in moderate to severe CD. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31781755"}, {"offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "BACKGROUND & AIMS: Upadacitinib is a novel selective Janus kinase 1 inhibitor that has shown efficacy in the treatment of moderate to severe ulcerative colitis (UC) and Crohn's disease (CD), and has received Food and Drug Administration approval for UC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36898598"}, {"offsetInBeginSection": 134, "offsetInEndSection": 262, "text": "Phase II trials demonstrated that upadacitinib induces endoscopic remission in patients with moderate-to-severe Crohn's disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35695972"}, {"offsetInBeginSection": 494, "offsetInEndSection": 619, "text": "Upadacitinib, an oral JAK1 inhibitor, has demonstrated efficacy in treating Crohn's disease during phase III clinical trials.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36968986"}, {"offsetInBeginSection": 709, "offsetInEndSection": 797, "text": "Upadacitinib also showed promising results in a phase II trial in moderate to severe CD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31781755"}, {"offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "BACKGROUND & AIMS: Upadacitinib is a novel selective Janus kinase 1 inhibitor that has shown efficacy in the treatment of moderate to severe ulcerative colitis (UC) and Crohn's disease (CD), and has received Food and Drug Administrati", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36898598"}]}
+{"question_id": "65f0369bc4010b4d78000001", "question": "Is melatonin beneficial in the treatment of in cerebral ischemia-reperfusion injury:", "answer": "Yes, melatonin is beneficial in treating cerebral ischemia-reperfusion injury:", "relevant_passage_ids": ["37301531", "37321200", "35219702", "12614473", "24646622", "34800293", "15673559", "31697951", "37327371", "37600520", "30476721", "35841976", "37923146", "18194199", "19552637", "12853293", "11068944", "12579834", "21160589", "15033929", "27620136", "35572137", "33063739", "24530291", "15298666", "12667942", "17123867", "12074100", "33777317", "35301664", "34118791", "32599143"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Melatonin regulates microglial polarization and protects against ischemic stroke-induced brain injury in mice.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37301531"}, {"offsetInBeginSection": 331, "offsetInEndSection": 461, "text": "Melatonin is a promising neuroprotective agent that can regulate microglial polarization in central nervous system (CNS) diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37301531"}, {"offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Melatonin Attenuates Cerebral Ischemia/Reperfusion Injury through Inducing Autophagy", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37321200"}, {"offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Melatonin improves cognitive function by suppressing endoplasmic reticulum stress and promoting synaptic plasticity during chronic cerebral hypoperfusion in rats.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35219702"}, {"offsetInBeginSection": 282, "offsetInEndSection": 462, "text": "Melatonin is neuroprotective against cerebral ischemia-reperfusion injury (CIRI) in non-DM, normoglycemic animals through anti-oxidant effect, anti-inflammation, and anti-apoptosis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37327371"}, {"offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Melatonin Attenuates Cerebral Ischemia/Reperfusion Injury through Inducing Autophagy.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37321200"}, {"offsetInBeginSection": 1429, "offsetInEndSection": 1807, "text": "Melatonin potentiated intrinsic antioxidant status, inhibited acid mediated rise in intracellular calcium levels, decreased apoptotic cell death and also markedly inhibited protein kinase C (PKC) influenced AQP4 expression in the cerebral cortex and dorsal striatum.SIGNIFICANCE: Melatonin confers neuroprotection by protein kinase C mediated AQP4 inhibition in ischemic stroke.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24530291"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Melatonin, the secretory product of the pineal gland, is known to be neuroprotective in cerebral ischemia, which is so far mostly attributed to its antioxidant properties.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15033929"}, {"offsetInBeginSection": 1529, "offsetInEndSection": 1650, "text": "Melatonin treatment diminished the loss of neurons and decreased the infarct volume as compared with untreated MCAO rats.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15033929"}, {"offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Melatonin: a promising neuroprotective agent for cerebral ischemia-reperfusion injury.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37600520"}, {"offsetInBeginSection": 870, "offsetInEndSection": 1147, "text": "These findings suggest that melatonin can improve microvessel abnormalities in the cerebral cortex and hippocampus by lowering the expression of vascular endothelial growth factor and its receptors, thereby improving the cognitive function of patients with Alzheimer's disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33063739"}, {"offsetInBeginSection": 406, "offsetInEndSection": 631, "text": "Post administration of melatonin following ischemic stroke reduces AQP4 mediated brain edema and confers neuroprotection.MATERIALS AND METHODS: An in-silico approach was undertaken to confirm effective melatonin-AQP4 binding.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24530291"}, {"offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "This brief review summarizes the recently obtained evidence which illustrates the beneficial effects of the endogenously produced antioxidant, melatonin, in reducing tissue damage and reversing cardiac pathophysiology in models of experimental ischemia/reperfusion.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12667942"}, {"offsetInBeginSection": 0, "offsetInEndSection": 421, "text": "BACKGROUND: Experimental studies have documented the beneficial effects of the endogenously produced antioxidant, melatonin, in reducing tissue damage and limiting cardiac pathophysiology in models of experimental ischemia-reperfusion. Melatonin confers cardioprotection against ischemia-reperfusion injury most likely through its direct free radical scavenging activities and its indirect actions in stimulating antioxid", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17123867"}, {"offsetInBeginSection": 0, "offsetInEndSection": 345, "text": "Melatonin, a natural product of the pineal gland, has been shown to protect against ischemic stroke, but the molecular mechanisms underlying its protective function are not fully understood. In the present study, we tested whether melatonin could protect against ischemia-reperfusion (I/R) injury to rat brain by targeting the autophagy pathway.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24646622"}, {"offsetInBeginSection": 443, "offsetInEndSection": 1058, "text": "The exogenous administration of melatonin in these experimental stroke models reduced infarct volume, lowered the frequency of apoptosis, increased the number of surviving neurons, reduced reactive gliosis, lowered the oxidation of neural lipids and oxidatively damaged DNA, induced bcl-2 gene expression (the activity of which improves cell survival), upregulated excision repair cross-complementing factor 6 (an essential gene for preferential DNA excision repair), restrained poly(ADP ribose) synthetase (which depletes cellular NAD resulting in the loss of ATP) activity, and improved neurophysiologic outcomes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12853293"}, {"offsetInBeginSection": 170, "offsetInEndSection": 442, "text": "In these investigations, which have used three species (rat, gerbil, and cat), melatonin was universally found to reduce brain damage that normally occurs as a consequence of the temporary interruption of blood flow followed by the reflow of oxygenated blood to the brain.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12853293"}, {"offsetInBeginSection": 1224, "offsetInEndSection": 1367, "text": "Melatonin attenuates molecular and cellular damage resulting from cardiac ischemia-reperfusion in which destructive free radicals are involved.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21160589"}, {"offsetInBeginSection": 1125, "offsetInEndSection": 1290, "text": "Taken together, our results document that melatonin provides neuroprotective effects in CCH by attenuating oxidative stress and stress protein expression in neurons.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19552637"}, {"offsetInBeginSection": 557, "offsetInEndSection": 1083, "text": "Neuronal damage was assessed in CA1 pyramidal layer of gerbil hippocampus and evaluated 7 days after ischemia.RESULTS: MT significantly reversed the locomotor activity increases, ameliorated learning and working memory deficit, and reduced the extent of CA1 hippocampal pyramidal cells injury after transient global cerebral ischemia in the Mongolian gerbil.CONCLUSION: MT provides significantly protective effect against both histological and behavioral consequences of global cerebral ischemia-reperfusion injury in gerbils.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12579834"}, {"offsetInBeginSection": 882, "offsetInEndSection": 1074, "text": "Therefore, understanding the underlying intracellular and molecular mechanisms is crucial before investigating the neuroprotective effects of melatonin in cerebral ischemia-reperfusion injury.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37600520"}, {"offsetInBeginSection": 1503, "offsetInEndSection": 1674, "text": "Our results suggest that melatonin treatment mediates neuroprotection against ischemia/reperfusion injury partly via inhibition of the consequential inflammatory response.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15298666"}, {"offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Intranasally administered melatonin core-shell polymeric nanocapsules: A promising treatment modality for cerebral ischemia.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35841976"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1085, "text": "The role of OPA1-related mitochondrial fusion in brain reperfusion stress has remained elusive. The aim of our study is to explore whether melatonin alleviates cerebral IR injury by modulating OPA1-related mitochondrial fusion. We found that melatonin reduced infarct area and suppressed neuron death during reperfusion stress. Biological studies have revealed that IR-inhibited mitochondrial fusion was largely reversed by melatonin via upregulated OPA1 expression. Knocking down OPA1 abrogated the protective effects of melatonin on mitochondrial energy metabolism and mitochondrial apoptosis. In addition, we also found that melatonin modified OPA1 expression via the Yap-Hippo pathway; blockade of the Yap-Hippo pathway induced neuron death and mitochondrial damage despite treatment with melatonin. Altogether, our data demonstrated that cerebral IR injury is closely associated with defective OPA1-related mitochondrial fusion. Melatonin supplementation enhances OPA1-related mitochondrial fusion by activating the Yap-Hippo pathway, ultimately reducing brain reperfusion stress.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30476721"}, {"offsetInBeginSection": 205, "offsetInEndSection": 1184, "text": "Melatonin regulates a large number of physiological actions and its beneficial properties have been reported. The aim of this study was to investigate whether melatonin mediates neuroprotection in rat hippocampal slices subjected to oxygen-glucose-deprivation (OGD) and glutamate excitotoxicity. Thus, we describe here that melatonin significantly reduced the amount of lactate dehydrogenase released in the OGD-treated slices, reverted neuronal injury caused by OGD-reoxygenation in CA1 and CA3 hippocampal regions, restored the reduction of GSH content of the hippocampal slices induced by OGD, and diminished the oxidative stress produced in the reoxygenation period. Furthermore, melatonin afforded maximum protection against glutamate-induced toxicity and reversed the glutamate released almost basal levels, at 10 and 30\u03bcM concentration, respectively. Consequently, we propose that melatonin might strongly and positively influence the outcome of brain ischemia/reperfusion", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27620136"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1226, "text": "Melatonin is a potent scavenger of free radicals and an indirect antioxidant. Recent studies have shown that melatonin possesses beneficial effects in experimental models of brain trauma and global cerebral ischemia. The effects of pretreatment with melatonin on volume of cerebral infarction were investigated in the present study. Adult male Sprague-Dawley rats were anesthetized with sodium pentobarbital to undergo right-sided endovascular middle cerebral artery occlusion (MCAO) for 3 hr. A single dose of melatonin (1.5, 5, 15, or 50 mg/kg in 1 mL normal saline) or its vehicle was given via an intraperitoneal injection at 0.5 hr before MCAO. Relative infarction volumes on day 3 after MCAO were significantly reduced in the groups treated with melatonin at 5 (mean +/- S.E.M., 15.7 +/- 2.5%) or 15 (21.4 +/- 3.1 %) mg/kg but not at 1.5 (30.6 +/- 3.5%) or 50 (26.7 +/- 2.8%) mg/ kg when compared with the vehicle group (33.9 +/- 3.5%). There was no significant difference in the arterial blood pressure (BP), heart rate (HR) and relative cerebral blood flow among the experimental groups. These results indicate that pretreatment with melatonin at a dose between 5 and 15 mg/kg protects against focal cerebral ischemia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12074100"}, {"offsetInBeginSection": 0, "offsetInEndSection": 957, "text": "Melatonin, a natural product of the pineal gland, has been shown to protect against ischemic stroke, but the molecular mechanisms underlying its protective function are not fully understood. In the present study, we tested whether melatonin could protect against ischemia-reperfusion (I/R) injury to rat brain by targeting the autophagy pathway. The I/R brain injury was induced by the established rat transient middle cerebral artery occlusion model. We found intraperitoneal injection of melatonin can ameliorate rat brain injury as evidenced by multiple morphological and behavioral criteria, such as infarct size, neurological score, serum creatine kinase, and lactate dehydrogenase content, as well as pyknotic-positive cells. Further studies revealed that the beneficial effects of melatonin is through targeting the autophagy pathway by inhibiting expression of beclin-1 and conversion of LC3, as well as activating the PI3K/Akt pro-survival pathway.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24646622"}, {"offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Melatonin as a Potential Neuroprotectant: Mechanisms in Subarachnoid Hemorrhage-Induced Early Brain Injury.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35572137"}, {"offsetInBeginSection": 173, "offsetInEndSection": 438, "text": "f diseases. In this study, the neuroprotective effects of melatonin (Mel) on a rat model of cerebral ischemia/reperfusion injury (CIRI) were assessed by multi-parametric MRI combined with histopathological techniques for longitudinal monitoring of the lesion microe", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37923146"}, {"offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "Melatonin is a strong antioxidant which beneficially protects against middle cerebral artery occlusion (MCAO) followed by hemorrhagic transformation in rats; protection includes the reduction of neurological deficits, infarction, and hematoma volume.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33777317"}, {"offsetInBeginSection": 187, "offsetInEndSection": 1642, "text": "Nonetheless, the mechanisms of the anti-inflammatory effects of EA are unclear. Cerebral I/R injury was induced in rats by middle cerebral artery occlusion (MCAO). Following I/R injury, the rats underwent EA therapy at the Shenting (DU24) and Baihui (DU20) acupoints for seven successive days. The Morris water maze test, magnetic resonance imaging (MRI) and molecular biology assays were utilized to assess the establishment of the rat stroke model with cognitive impairment and the therapeutic effect of EA. EA treatment of rats subjected to MCAO showed a significant reduction in infarct volumes accompanied by cognitive recovery, as observed in Morris water maze test outcomes. The possible mechanisms by which EA treatment attenuates cognitive impairment are by regulating endogenous melatonin secretion through aralkylamine N-acetyltransferase gene (AANAT, a rate-limiting enzyme of melatonin) synthesis in the pineal gland in stroke rats. Simultaneously, through melatonin regulation, EA exerts neuroprotective effects by upregulating mitophagy-associated proteins and suppressing reactive oxygen species (ROS)-induced NLRP3 inflammasome activation after I/R injury. However, melatonin receptor inhibitor (luzindole) treatment reversed these changes. The findings from this research suggested that EA ameliorates cognitive impairment through the inhibition of NLRP3 inflammasome activation by regulating melatonin-mediated mitophagy in stroke rats.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35301664"}, {"offsetInBeginSection": 152, "offsetInEndSection": 230, "text": "Melatonin has protective effects against cerebral ischemia/reperfusion injury.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19552637"}, {"offsetInBeginSection": 1435, "offsetInEndSection": 1598, "text": "e damage in neurons after CI.CONCLUSION: Melatonin treatment following CI reduced the infarct area and induced the autophagic proteins Beclin-1, LC3, and p62 by in", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37321200"}, {"offsetInBeginSection": 1300, "offsetInEndSection": 1513, "text": "In conclusion, these results indicate that melatonin treatment can protect against CIR-induced brain damage in diabetic mice, which may be achieved by the autophagy enhancement mediated by the SIRT1-BMAL1 pathway.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34800293"}, {"offsetInBeginSection": 1626, "offsetInEndSection": 1762, "text": "lls, and better neuronal survival.CONCLUSIONS: T1DM aggravates CIRI. Melatonin treatment is neuroprotective against CIRI in T1DM rats vi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37327371"}, {"offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "AIMS: The neurohormone melatonin (MEL) has been reported as a promising neuroprotective molecule, however it suffers pharmaceutical limitations such as poor solubility and low bioavailability, which hinder its pharmacological and clinical pote", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35841976"}, {"offsetInBeginSection": 228, "offsetInEndSection": 327, "text": "We found that melatonin reduced infarct area and suppressed neuron death during reperfusion stress.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30476721"}, {"offsetInBeginSection": 1139, "offsetInEndSection": 1289, "text": "tosis through SIRT3 activation.SIGNIFICANCE: Our research proved that melatonin promoted SIRT3 expression after tMCAO and alleviated cerebral I/R inju", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31697951"}, {"offsetInBeginSection": 1256, "offsetInEndSection": 1546, "text": "stroke. Melatonin treatment significantly decreased infarct volume and cerebral apoptosis; mitigated endoplasmic reticulum stress and mitochondrial dysfunction; and inhibited CI/R injury-induced oxidative/nitrative stress and nuclear factor-\u03baB activation, which was eradicated in ROR\u03b1-defic", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32599143"}, {"offsetInBeginSection": 1648, "offsetInEndSection": 1762, "text": "al survival.CONCLUSIONS: T1DM aggravates CIRI. Melatonin treatment is neuroprotective against CIRI in T1DM rats vi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37327371"}, {"offsetInBeginSection": 934, "offsetInEndSection": 1085, "text": "Melatonin supplementation enhances OPA1-related mitochondrial fusion by activating the Yap-Hippo pathway, ultimately reducing brain reperfusion stress.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30476721"}, {"offsetInBeginSection": 655, "offsetInEndSection": 894, "text": "er ischemia.RESULTS: MT significantly reversed the locomotor activity increases, ameliorated learning and working memory deficit, and reduced the extent of CA1 hippocampal pyramidal cells injury after transient global cerebral ischemia in ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12579834"}, {"offsetInBeginSection": 273, "offsetInEndSection": 463, "text": "Melatonin's efficacy in curtailing neural damage under conditions of transitory interruption of the blood supply to the brain has been documented in models of both focal and global ischemia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15673559"}, {"offsetInBeginSection": 566, "offsetInEndSection": 826, "text": "For example, when given at the time of ischemia or reperfusion onset, melatonin reduces neurophysiological deficits, infarct volume, the degree of neural edema, lipid peroxidation, protein carbonyls, DNA damage, neuron and glial loss, and death of the animals.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15673559"}, {"offsetInBeginSection": 1112, "offsetInEndSection": 1373, "text": "Considering its high efficacy in overcoming much of the damage associated with ischemia/reperfusion injury, not only in the brain but in other organs as well, its use in clinical trials for the purpose of improving stroke outcome should be seriously considered.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15673559"}, {"offsetInBeginSection": 87, "offsetInEndSection": 151, "text": "melatonin against ischemia/reperfusion brain injury. The studies", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18194199"}, {"offsetInBeginSection": 35, "offsetInEndSection": 118, "text": " that melatonin plays a critical role in protecting against cerebral ischemia/reper", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31697951"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1724, "text": "The brain is highly susceptible to focal or global ischemia. Unless ischemia is promptly reversed, reperfusion produces further cerebral damage. Acute thrombolysis or defibrinogenation is effective only in selective patients with ischemic stroke and carries a significant risk of bleeding complications. Whereas numerous neuroprotectants were shown to be effective in experimental studies, none of them have been shown to work in clinical trials. The major pathogenetic mechanisms of ischemia/reperfusion injury include excitotoxicity, disturbed calcium ion homeostasis, overproduction of nitric oxide and other free radicals, inflammation, and apoptosis. Nitric oxide and other free radicals, the key mediators of excitotoxicity and disturbed calcium ion homeostasis, cause direct injury and also indirectly damage via inflammation and apoptosis. Melatonin is a potent free radical scavenger and an indirect antioxidant. This mini review summarizes the in vivo and in vitro evidence that melatonin protects against ischemia/reperfusion injury. There is convincing evidence from the literature that melatonin treatment is highly effective in different in vivo and in vitro models of excitotoxicity or ischemia/reperfusion in multiple animal species. Melatonin is safe and non-toxic in humans, and its administration via the oral route or intravenous injection is convenient. While more experimental studies should be conducted to further explore the neuroprotective mechanisms and to document any synergistic or additive protection from combining melatonin with thrombolysis, defibrinogenation or other neuroprotectants, interested clinical scientists should consider planning phase II and III studies to confirm the benefit", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12614473"}, {"offsetInBeginSection": 1317, "offsetInEndSection": 1527, "text": "ischemia and reperfusion. Histological observations of the pyramidal layer of CA-1 showed a reduction of neuronal loss in animals that received melatonin. These results show that melatonin improves brain injury", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11068944"}, {"offsetInBeginSection": 910, "offsetInEndSection": 1255, "text": "Brains were harvested for infarct size estimation, water content measurement, biochemical analysis, apoptosis study and western blot experiments.KEY FINDINGS: Melatonin at 60 min post ischemia rendered neuroprotection as evident by reduction in cerebral infarct volume, improvement in motor and neurological deficit and reduction in brain edema.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24530291"}, {"offsetInBeginSection": 1472, "offsetInEndSection": 1567, "text": "These results show that melatonin improves brain injury induced by transient cerebral ischemia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11068944"}, {"offsetInBeginSection": 1256, "offsetInEndSection": 1428, "text": "Furthermore, ischemia induced surge in levels of nitrite and malondialdehyde (MDA) were also found to be significantly reduced in ischemic brain regions in treated animals.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24530291"}, {"offsetInBeginSection": 809, "offsetInEndSection": 1334, "text": "Then, we observed the changes in the SIRT3 and downstream relative proteins, infarction volume, neurological score, Nissl, H&E and TUNEL staining, and the expression of apoptosis proteins after tMCAO.KEY FINDINGS: Melatonin upregulated the expression of SIRT3 after tMCAO, and alleviated the neurological dysfunction and cell apoptosis through SIRT3 activation.SIGNIFICANCE: Our research proved that melatonin promoted SIRT3 expression after tMCAO and alleviated cerebral I/R injury by activating the SIRT3 signaling pathway.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31697951"}, {"offsetInBeginSection": 1366, "offsetInEndSection": 1534, "text": "Overall, we demonstrate that melatonin can alleviate CIR injury in diabetic mice by activating Akt-SIRT3-SOD2 signaling and subsequently improving mitochondrial damage.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34118791"}]}
+{"question_id": "65f84b5ec4010b4d78000048", "question": "Are Hemoglobin-Based Oxygen Carriers approved for human use?", "answer": "Hemoglobin-Based Oxygen Carriers (HBOCs) are not widely approved for human use. As of now, no HBOC has been approved by the FDA and EMA, except for compassionate use. However, some products like Hemopure are in clinical use in South Africa and Russia. HemO2life has also been approved for organ preservation in organ transplantation in the European Union. Other products like OxyVita and Sanguinate are still undergoing active clinical studies. It's important to note that while these products are in use or under study, there is currently no widely accepted product used as an alternative to human blood in clinical settings with severe anemic conditions.", "relevant_passage_ids": ["36837597", "34776270", "17591302", "11805546", "15168238", "31513123", "30177214", "17021438", "11336435", "31836032", "24418449", "25697570", "36443351", "12783619", "14562565", "29592539", "18494389", "18694360", "28099525"], "type": "yesno", "snippets": [{"offsetInBeginSection": 118, "offsetInEndSection": 257, "text": "As of today, there is no widely accepted product used as an alternative to human blood in clinical settings with severe anemic condition(s)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36837597"}, {"offsetInBeginSection": 504, "offsetInEndSection": 598, "text": "products still in active clinical research in the category of hemoglobin-based oxygen carriers", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36837597"}, {"offsetInBeginSection": 739, "offsetInEndSection": 1027, "text": "Hemopure is in clinical use in South Africa and Russia. Oxyglobin, the sister product of Hemopure, has been approved for veterinary use in the European Union and the United States. HemO2life has recently been approved for organ preservation in organ transplantation in the European Union.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36837597"}, {"offsetInBeginSection": 1028, "offsetInEndSection": 1096, "text": "OxyVita and Sanguinate are still undergoing active clinical studies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36837597"}, {"offsetInBeginSection": 1301, "offsetInEndSection": 1395, "text": "Unfortunately, so far, no HBOC has been approved by FDA and EMA, except for compassionate use.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34776270"}, {"offsetInBeginSection": 957, "offsetInEndSection": 1347, "text": "Safety and cost effectiveness are being evaluated for their use as an alternative to blood transfusion or along with other strategies of blood conservation in cardiac surgery.SUMMARY: One hemoglobin-based oxygen carrier (Hemopure) has been approved for use in humans in South Africa as well as another hemoglobin-based oxygen carrier (Gelenpol) and a perfluorocarbon (Perfluoron) in Russia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17021438"}, {"offsetInBeginSection": 1541, "offsetInEndSection": 1839, "text": "Four cross-linked hemoglobin products have been tested in Phase III clinical trials.CONCLUSION: While no product has yet been approved for clinical use, preliminary studies with oxygen therapeutics show promising results, with effective oxygen carrying capacity and acceptable side effect profiles.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11336435"}, {"offsetInBeginSection": 1229, "offsetInEndSection": 1382, "text": "Several of these HBOCs have undergone rigorous preclinical and clinical evaluation, but have not yet received clinical approval in the USA for human use.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31513123"}, {"offsetInBeginSection": 1365, "offsetInEndSection": 1549, "text": "While there is no FDA approved hemoglobin-based oxygen carrier approved for use in injured patients at this writing, phase III studies are currently either underway or being developed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11805546"}, {"offsetInBeginSection": 277, "offsetInEndSection": 583, "text": "No artificial oxygen carriers are currently approved for clinical use in the United States. Hemopure has been approved for use in South Africa. The companies producing Hemopure and PolyHeme, both of which are hemoglobin-based oxygen carriers, have filed a Biologic License Application in the United States.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17591302"}, {"offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "For the past thirty years, hemoglobin-based oxygen carriers (HBOCs) have been under development\u00a0as a red blood cell substitute. Side-effects such as vasoconstriction, oxidative injury, and cardiac toxicity have prevented clinical approval of HBOCs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36443351"}, {"offsetInBeginSection": 904, "offsetInEndSection": 1020, "text": "HBOC-201, which is a preparation of cell-free bovine hemoglobin, has been approved for clinical use in South Africa.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15168238"}, {"offsetInBeginSection": 262, "offsetInEndSection": 412, "text": "Hemopure (HBOC-201, bovine Hb glutamer-250; OPK Biotech, Cambridge, MA), one such HBOC, has been approved for clinical use in South Africa and Russia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24418449"}, {"offsetInBeginSection": 1373, "offsetInEndSection": 1604, "text": "HBOC-201 is generally well-tolerated and is approved for use in South Africa, where it is indicated for use in adult surgical patients who are acutely anaemic, and is used to eliminate, delay or reduce the need for allogeneic RBCs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12783619"}, {"offsetInBeginSection": 1605, "offsetInEndSection": 1690, "text": "A Biologics License Application for HBOC-201 is currently under review by the US FDA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12783619"}, {"offsetInBeginSection": 436, "offsetInEndSection": 544, "text": "South Africa recently approved one HBOC for use as a transfusion alternative in patients with chronic anemia", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14562565"}, {"offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Bovine-derived hemoglobin-based oxygen carriers (HBOCs) have been investigated for use in humans (HBOC-201) and approved for veterinary medicine (HBOC-301).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25697570"}, {"offsetInBeginSection": 1198, "offsetInEndSection": 1294, "text": "Hemoglobin-based oxygen carriers (HBOCs) are currently not Food and Drug Administration approved", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29592539"}, {"offsetInBeginSection": 277, "offsetInEndSection": 420, "text": "No artificial oxygen carriers are currently approved for clinical use in the United States. Hemopure has been approved for use in South Africa.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17591302"}, {"offsetInBeginSection": 0, "offsetInEndSection": 429, "text": "Hemoglobin based oxygen carriers (HBOCs) have been developed as alternative oxygen transporting formulations for the acute treatment of anemia and ischemia. Efficacy has been demonstrated in a variety of preclinical models and selected human patients; however, a higher overall incidence of mortality and myocardial infarction in those dosed with HBOCs in later stage clinical trials has prevented widespread regulatory approval.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31836032"}, {"offsetInBeginSection": 1235, "offsetInEndSection": 1661, "text": "There are at least three agents presently under development that use different techniques to alter the basic hemoglobin tetramer. While there is no FDA approved hemoglobin-based oxygen carrier approved for use in injured patients at this writing, phase III studies are currently either underway or being developed. There is high likelihood that one or more of these agents will be approved for clinical use in the near future.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11805546"}, {"offsetInBeginSection": 606, "offsetInEndSection": 1020, "text": "HBOCs have been the most extensively studied and tested in preclinical and clinical trials that have shown success in diminishing the number of blood transfusions as well as an overall favorable side-effect profile. This has been demonstrated in vascular, cardiothoracic, and orthopaedic patients. HBOC-201, which is a preparation of cell-free bovine hemoglobin, has been approved for clinical use in South Africa.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15168238"}, {"offsetInBeginSection": 515, "offsetInEndSection": 1252, "text": "Preparations undergoing experimental and clinical assessment include Human Polymerized Haemoglobin (Polyheme), Polymerized Bovine Haemoglobin-based Oxygen Carrier (HBOC-201, Hemopure), Haemoglobin Raffimer (HemoLink), Diaspirin Cross-linked Haemoglobin (HemAssist), Human Recombinant Haemoglobin (rHb), Enzyme Cross-linked Poly-haemoglobin, Maleimide-activated Polyethylene-glycol Modified Haemoglobin (MP4, Hemospan), Zero-linked Haemoglobin (ZL-HbBv) and Recombinant Hybrid of Human-alpha-chains and Bovine-beta-chains and Perflubron (Oxygent). Research into some of these compounds has been discontinued, while others have advanced into clinical phase III trials, but none has achieved market approval for Europe, US or Canada so far.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18494389"}, {"offsetInBeginSection": 791, "offsetInEndSection": 1984, "text": "ted in Phase III clinical trials. Hemoglobin-based oxygen carriers (HBOCs) are either cross-linked or microencapsulated hemoglobin molecules. Modification of the human hemoglobin molecule with intra- and inter-molecular cross-linking eliminates renal toxicity and improves the oxygen dissociation characteristics of the molecule. These modifications are necessary because stroma-free hemoglobin (Hb) does not release oxygen in the physiologic range and dissociates into dimers which can be rapidly filtered by the kidney, leading to renal toxicity. In addition to human Hb, bovine hemoglobin is another source of raw material for HBOC products. Recombinant human Hb has also been produced, using an E. coli expression system, for HBOC manufacturing. Four cross-linked hemoglobin products have been tested in Phase III clinical trials.CONCLUSION: While no product has yet been approved for clinical use, preliminary studies with oxygen therapeutics show promising results, with effective oxygen carrying capacity and acceptable side effect profiles. In the future, the formation of a hybrid product which combines the best features from several of the products currently undergoing development ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11336435"}, {"offsetInBeginSection": 739, "offsetInEndSection": 794, "text": "Hemopure is in clinical use in South Africa and Russia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36837597"}, {"offsetInBeginSection": 795, "offsetInEndSection": 919, "text": "Oxyglobin, the sister product of Hemopure, has been approved for veterinary use in the European Union and the United States.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36837597"}, {"offsetInBeginSection": 920, "offsetInEndSection": 1027, "text": "HemO2life has recently been approved for organ preservation in organ transplantation in the European Union.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36837597"}, {"offsetInBeginSection": 261, "offsetInEndSection": 429, "text": "a higher overall incidence of mortality and myocardial infarction in those dosed with HBOCs in later stage clinical trials has prevented widespread regulatory approval.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31836032"}, {"offsetInBeginSection": 277, "offsetInEndSection": 368, "text": "No artificial oxygen carriers are currently approved for clinical use in the United States.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17591302"}, {"offsetInBeginSection": 369, "offsetInEndSection": 420, "text": "Hemopure has been approved for use in South Africa.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17591302"}, {"offsetInBeginSection": 128, "offsetInEndSection": 248, "text": "Side-effects such as vasoconstriction, oxidative injury, and cardiac toxicity have prevented clinical approval of HBOCs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36443351"}, {"offsetInBeginSection": 1110, "offsetInEndSection": 1581, "text": "Hb-based oxygen carriers (HBOCs) can potentially provide therapeutic oxygenation when blood or RBCs are not available. Several of these HBOCs have undergone rigorous preclinical and clinical evaluation, but have not yet received clinical approval in the USA for human use. While these designs are being optimized for clinical translations, several new HBOC designs and molecules have been reported in recent years, with unique properties. The current article will provide", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31513123"}, {"offsetInBeginSection": 1102, "offsetInEndSection": 1479, "text": "nservation in cardiac surgery.SUMMARY: One hemoglobin-based oxygen carrier (Hemopure) has been approved for use in humans in South Africa as well as another hemoglobin-based oxygen carrier (Gelenpol) and a perfluorocarbon (Perfluoron) in Russia. Phase III trials in Europe and North America will be concluded very soon. We anticipate seeing one or two products approved in Nort", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17021438"}, {"offsetInBeginSection": 432, "offsetInEndSection": 1201, "text": "In this article, we reviewed the most developed but failed products and products still in active clinical research in the category of hemoglobin-based oxygen carriers. Among all of the discussed hemoglobin-based oxygen therapeutics, HemAssist, PolyHeme, Hemolink, Hemospan, and Hemoximer were discontinued. Hemopure is in clinical use in South Africa and Russia. Oxyglobin, the sister product of Hemopure, has been approved for veterinary use in the European Union and the United States. HemO2life has recently been approved for organ preservation in organ transplantation in the European Union. OxyVita and Sanguinate are still undergoing active clinical studies. The field of oxygen therapeutics seems to be entering a phase of rapid growth in the coming 10-20 years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36837597"}, {"offsetInBeginSection": 392, "offsetInEndSection": 1534, "text": "With a worldwide shortage of donor blood that is expected to increase over time, the creation of oxygen-carriers with long storage life and compatibility without typing and cross-matching, persists as one of the foremost important challenges in biomedicine. However, research has so far failed to produce FDA approved RBCs substitutes (RBCSs) for human usage. As such, due to unacceptable toxicities, the first generation of oxygen-carriers has been withdrawn from the market. Being hemoglobin (Hb) the main component of RBCs, a lot of effort is being devoted in assembling semi-synthetic RBCS utilizing Hb as the oxygen-carrier component, the so-called Hb-based oxygen carriers (HBOCs). However, a native RBC also contains a multi-enzyme system to prevent the conversion of Hb into non-functional methemoglobin (metHb). Thus, the challenge for the fabrication of next-generation HBOCs relies in creating a system that takes advantage of the excellent oxygen-carrying capabilities of Hb, while preserving the redox environment of native RBCs that prevents or reverts the conversion of Hb into metHb. In this review, we feature the most recent", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30177214"}, {"offsetInBeginSection": 110, "offsetInEndSection": 514, "text": "Hemoglobin-based oxygen carriers (HBOCs) derived from purified human or bovine hemoglobin have been studied for clinical use and one product is currently available in the United States and European Union for veterinary use, and another in South Africa for human use.OBJECTIVE: HBOC-201, bovine purified hemoglobin crosslinked and polymerized with glutaraldehyde, has been studied extensively in patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18694360"}, {"offsetInBeginSection": 294, "offsetInEndSection": 452, "text": "Despite decades of research to develop hemoglobin (Hb) based oxygen (O2) carriers (HBOCs) as RBC substitutes, there are no products approved for clinical use.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28099525"}, {"offsetInBeginSection": 600, "offsetInEndSection": 1027, "text": "Among all of the discussed hemoglobin-based oxygen therapeutics, HemAssist, PolyHeme, Hemolink, Hemospan, and Hemoximer were discontinued. Hemopure is in clinical use in South Africa and Russia. Oxyglobin, the sister product of Hemopure, has been approved for veterinary use in the European Union and the United States. HemO2life has recently been approved for organ preservation in organ transplantation in the European Union.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36837597"}]}
+{"question_id": "65cfa37c1930410b1300000d", "question": "Gantenerumab was developed for treatment of which disease?", "answer": "Gantenerumab was developed for Alzheimer's disease.", "relevant_passage_ids": ["35841240", "36447240", "37017737", "36751779", "36281062", "36515320", "36388611", "28754630", "35100444", "36457865", "35493943", "37823690", "22583155", "21987394", "36348972", "37966285", "21955818", "29221491", "25081412", "32787971", "38026755", "24255592", "30261916", "29181492", "24490853", "22277519", "31883703", "34155411", "33336218", "26433971", "26721364", "37881360", "25164658", "31831056", "28720101", "25483498", "36253511", "24445401", "29037101", "36151869", "33321511", "28066098", "34110536", "35290498", "24981190", "27678025", "35676943", "35320578", "36454709", "32991803", "35401412", "29686315"], "type": "factoid", "snippets": [{"offsetInBeginSection": 259, "offsetInEndSection": 442, "text": "Other anti-amyloid antibodies are under investigation in phase III (donanemab, lecanemab, gantenerumab) and have shown preliminary evidence of a cognitive benefit in phase II trials. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35841240"}, {"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Gantenerumab: an anti-amyloid monoclonal antibody with potential disease-modifying effects in early Alzheimer's disease.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36447240"}, {"offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "BACKGROUND: This review describes the research and development process of gantenerumab, a fully human anti-amyloid monoclonal antibody in development to treat early symptomatic and asymptomatic Alzheimer's disease (AD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36447240"}, {"offsetInBeginSection": 1026, "offsetInEndSection": 1157, "text": "BODY: Here, we review over 2 decades of gantenerumab development in the context of scientific discoveries in the broader AD field. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36447240"}, {"offsetInBeginSection": 1666, "offsetInEndSection": 1865, "text": "CONCLUSION: The results from the gantenerumab phase 3 programs are expected by the end of 2022 and will add critical information to the collective knowledge on the search for effective AD treatments.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36447240"}, {"offsetInBeginSection": 604, "offsetInEndSection": 901, "text": "METHODS: Sixty-six mutation-positive participants enrolled in the gantenerumab and placebo arms of the first Dominantly Inherited Alzheimer Network Trials Unit clinical trial (DIAN-TU-001) underwent both 11C-PiB and 18F-florbetapir PET imaging at baseline and during at least one follow-up visit. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37017737"}, {"offsetInBeginSection": 543, "offsetInEndSection": 847, "text": "Two long-term, controlled trials on three anti-\u03b2-amyloid monoclonal antibodies (solanezumab, gantenerumab and crenezumab) in subjects carrying Alzheimer's disease-linked mutated genes encoding for amyloid precursor protein or presenilin 1 or presenilin 2 failed to show cognitive or functional benefits. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36751779"}, {"offsetInBeginSection": 776, "offsetInEndSection": 1062, "text": "The model components were calibrated to data from the literature and internal studies, including quantitative data supporting the underlying AD biology and clinical data from clinical trials for anti-A\u03b2 monoclonal antibodies (mAbs) aducanumab, crenezumab, gantenerumab, and solanezumab.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36281062"}, {"offsetInBeginSection": 0, "offsetInEndSection": 573, "text": "INTRODUCTION: Recent published clinical trial safety data showed that 41% of Alzheimer patients experienced amyloid-related imaging abnormalities (ARIA), marks of microhemorrhages and edema in the brain, following administration of Biogen's Aduhelm/aducanumab (amino acids 3-7 of the A\u03b2 peptide). Similarly, Janssen/Pfizer's Bapineuzumab (amino acids 1-5 of the A\u03b2 peptide) and Roche's Gantenerumab (amino acids 2-11/18-27 of the A\u03b2 peptide) also displayed ARIA in clinical trials, including microhemorrhage and focal areas of inflammation or vasogenic edema, respectively.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36515320"}, {"offsetInBeginSection": 0, "offsetInEndSection": 332, "text": "Patients with Alzheimer's disease who have been given monoclonal antibodies targeting amyloid-\u03b2 (A\u03b2) (eg, gantenerumab, donanemab, lecanemab, and aducanumab) for scientific purposes may have a spectrum of imaging findings known as amyloid-related imaging abnormalities (ARIA), shown on brain magnetic resonance imaging (MRI) scans. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36388611"}, {"offsetInBeginSection": 167, "offsetInEndSection": 362, "text": "Gantenerumab is a subcutaneously administered, fully human, anti-A\u03b2 IgG1 monoclonal antibody with highest affinity for aggregated A\u03b2 that has been tested for the treatment of Alzheimer's disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37966285"}, {"offsetInBeginSection": 260, "offsetInEndSection": 546, "text": "This study investigates a bispecific modular fusion protein composed of gantenerumab, a fully human monoclonal anti- amyloid-beta (A\u03b2) antibody under investigation for AD treatment, with a human transferrin receptor 1-directed Brainshuttle\u2122 module (trontinemab; RG6102, INN trontinemab)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37823690"}, {"offsetInBeginSection": 167, "offsetInEndSection": 650, "text": "Gantenerumab is a subcutaneously administered, fully human, anti-A\u03b2 IgG1 monoclonal antibody with highest affinity for aggregated A\u03b2 that has been tested for the treatment of Alzheimer's disease.METHODS: We conducted two phase 3 trials (GRADUATE I and II) involving participants 50 to 90 years of age with mild cognitive impairment or mild dementia due to Alzheimer's disease and evidence of amyloid plaques on positron-emission tomography (PET) or cerebrospinal fluid (CSF) testing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37966285"}, {"offsetInBeginSection": 2025, "offsetInEndSection": 2383, "text": "Amyloid-related imaging abnormalities with edema (ARIA-E) occurred in 24.9% of the participants receiving gantenerumab, and symptomatic ARIA-E occurred in 5.0%.CONCLUSIONS: Among persons with early Alzheimer's disease, the use of gantenerumab led to a lower amyloid plaque burden than placebo at 116 weeks but was not associated with slower clinical decline.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37966285"}, {"offsetInBeginSection": 0, "offsetInEndSection": 445, "text": "BACKGROUND: Gantenerumab is a fully human anti-A\u03b2 monoclonal antibody in clinical development for the treatment of Alzheimer disease (AD).OBJECTIVES: To investigate whether treatment with gantenerumab leads to a measurable reduction in the level of A\u03b2 amyloid in the brain and to elucidate the mechanism of amyloid reduction.DESIGN: A multicenter, randomized, double-blind, placebo-controlled, ascending-dose positron emission tomographic study.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21987394"}, {"offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Profile of gantenerumab and its potential in the treatment of Alzheimer's disease.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24255592"}, {"offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Two Phase 3 Trials of Gantenerumab in Early Alzheimer's Disease.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37966285"}, {"offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Gantenerumab is intended for the treatment of Alzheimer's disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28754630"}, {"offsetInBeginSection": 1332, "offsetInEndSection": 1515, "text": " gantenerumab, and an anti-tau monoclonal antibody, RO7105705, as well as a robust biomarker platform to aid in the early identification of people at risk or in the early stages of AD", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29181492"}, {"offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "PURPOSE: Gantenerumab, a fully human anti-amyloid-\u03b2 IgG1 monoclonal antibody that binds to aggregated forms of amyloid-\u03b2, is being investigated as a potential disease-modifying treatment for early (prodromal to mild) Alzheimer disease (AD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31883703"}, {"offsetInBeginSection": 729, "offsetInEndSection": 1045, "text": "Gantenerumab is an investigational fully human anti-amyloid beta monoclonal antibody with a high capacity to bind and remove beta-amyloid plaques in the brain. This compound, currently undergoing Phase II and III clinical trials represents a promising agent with a disease-modifying potential in Alzheimer's disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24255592"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1065, "text": "Both active and passive anti-\u03b2-amyloid (A\u03b2) immunotherapies for the treatment of Alzheimer's disease (AD) have demonstrated clearance of brain A\u03b2 deposits. Among passive immunotherapeutics, two Phase III clinical trials in mild-to-moderate AD patients with bapineuzumab, a humanized monoclonal antibody directed at the N-terminal sequence of A\u03b2, were disappointing. Also solanezumab, directed at the mid-region of A\u03b2, failed in two Phase III trials in mild-to-moderate AD. Another Phase III trial with solanezumab is ongoing in mildly affected AD patients based on encouraging results in this subgroup. Second-generation active A\u03b2 vaccines (CAD106, ACC-001, and Affitope AD02) and new passive anti-A\u03b2 immunotherapies (gantenerumab and crenezumab) have been developed and are under clinical testing. These new anti-A\u03b2 immunotherapies are being tested in prodromal AD, in presymptomatic subjects with AD-related mutations, or in asymptomatic subjects at risk of developing AD. These primary and secondary prevention trials will definitely test the A\u03b2 cascade hypothes", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24490853"}, {"offsetInBeginSection": 1080, "offsetInEndSection": 1496, "text": " encouraging results in this subgroup of patients. Second-generation active A\u03b2 vaccines (ACC-001, CAD106, and Affitope AD02) and new passive anti-A\u03b2 immunotherapies (gantenerumab and crenezumab) are being tested in prodromal Alzheimer's disease patients, in presymptomatic individuals with Alzheimer's disease-related mutations, or in asymptomatic individuals at risk of developing Alzheimer's disease to definitely ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24445401"}, {"offsetInBeginSection": 0, "offsetInEndSection": 798, "text": "INTRODUCTION: The recent failure of several clinical trials on anti-\u03b2-amyloid (A\u03b2) drugs in Alzheimer's disease (AD) suggested earlier intervention in the disease course. Secondary prevention trials have been started in autosomal-dominant AD (ADAD) individuals without cognitive dysfunction and in cognitively healthy subjects at risk of developing sporadic AD (SAD).AREAS COVERED: Herein, the authors discuss prevention trials in ADAD and SAD, with a focus on the anti-A\u03b2 monoclonal antibodies solanezumab and gantenerumab presently in Phase III clinical development. These therapies are also being tested in the Dominantly Inherited Alzheimer's Network Trials Unit (DIAN-TU).EXPERT OPINION: Anti-A\u03b2 monoclonal antibodies are being tested in subjects at the preclinical stage of ADAD and even in s", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29037101"}, {"offsetInBeginSection": 246, "offsetInEndSection": 490, "text": "Gantenerumab, a fully human monoclonal antibody (mAb) that binds to aggregated amyloid-beta, was tested in two 24-month phase III studies (NCT01224106, NCT02051608) in participants with prodromal and mild Alzheimer's disease (AD), respectively.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35100444"}, {"offsetInBeginSection": 522, "offsetInEndSection": 928, "text": "The 16 compounds selected include disease-modifying therapies and symptomatic therapies. The research and development pipeline now focuses on disease-modifying therapies such as gantenerumab, aducanumab, ALZ-801, ALZT-OP1, donanemab, lecanemab, simufilam, NE3107, semaglutide, and GV-971, which could put an end to the situation where Alzheimer's patients in China have no effective treatment alternatives.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36457865"}, {"offsetInBeginSection": 372, "offsetInEndSection": 592, "text": "en-label extension of SCarlet RoAD (a study of gantenerumab in participants with prodromal Alzheimer's disease) and Marguerite RoAD (as study of Gantenerumab in participants with mild Alzheimer's disease) studies were us", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35676943"}, {"offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Gantenerumab is intended for the treatment of Alzheimer's disease. It is a fully human recombinant", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28754630"}]}
+{"question_id": "65f70a55c4010b4d7800001b", "question": "Please list the congenital fibrinogen disorders.", "answer": "Congenital fibrinogen disorders are rare pathologies of the haemostasis, comprising afibrinogenaemia, hypofibrinogenaemia, dysfibrinogenaemia and hypodysfibrinogenaemia.", "relevant_passage_ids": ["37823427", "36055263", "35853369", "35821906", "35207353", "34261148", "36276905", "34829490", "31797863", "27019463", "27293018", "29844251", "35073585", "32871307", "23852822", "27019462", "27492693", "16855369", "32852326", "33030793", "16999847", "17430139", "23439004", "918595", "31542854", "15004306", "26430672", "29316703"], "type": "list", "snippets": [{"offsetInBeginSection": 12, "offsetInEndSection": 352, "text": "Congenital fibrinogen deficiencies (CFD) are a group of rare bleeding disorders (RBD). Afibrinogenemia as a subclass of these disorders would occurs as a result of mutations in fibrinogen gene. Here in, the sequences of A\u03b1 chain of fibrinogen (FGA) in patients with inherited afibrinogenemia disorder in south-eastern of Iran were analysed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37823427"}, {"offsetInBeginSection": 134, "offsetInEndSection": 295, "text": " From the first clinical description of afibrinogenemia in 1920, many major achievements have contributed to a better understanding of these complex disorders. T", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36055263"}, {"offsetInBeginSection": 1431, "offsetInEndSection": 1514, "text": "congenital fibrinogen disorders, focusing on afibrinogenemia and dysfibrinogenemia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36055263"}, {"offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Ranging from bleeding to thrombosis, the clinical features of congenital fibrinogen qualitative disorders, including dysfibrinogenemia and hypodysfibrinogenemia, ar", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35853369"}, {"offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Congenital (hypo-)dysfibrinogenemia and bleeding: A systematic literature review.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35853369"}, {"offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Fibrinogen deficiencies are very rare. Qualitative fibrinogen deficiencies (dysfibrinogenaemia and hypodysfibrinogenemia) are functional disorders that can present with both haemorrhagic symptoms and with thro", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35821906"}, {"offsetInBeginSection": 582, "offsetInEndSection": 773, "text": "In this paper, we focused on familial hypofibrinogenemia, a rare inherited quantitative fibrinogen disorder characterized by decreased fibrinogen levels with a high phenotypic heterogeneity. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35207353"}, {"offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "The congenital dysfibrinogenemias, most often associated with bleeding disorders, encompass mutations in the amino-terminal end of fibrinogen \u03b1-chain consisting of Gly17-Pro18-Arg19-Val20, known as knob A, which is a critical site for fibrin polymerization. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34261148"}, {"offsetInBeginSection": 1, "offsetInEndSection": 88, "text": " case of congenital afibrinogenemia with multiple thrombotic and hemorrhagic disorders.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36276905"}, {"offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Congenital fibrinogen disorders are rare pathologies of the hemostasis, comprising quantitative (afibrinogenemia, hypofibrinogenemia) and qualitative (dysfibrinogenemia and hypodysfibrinogenemia) disorders. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34829490"}, {"offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "INTRODUCTION: Congenital fibrinogen disorders (CFDs) are classified as afibrinogenemia or hypofibrinogenemia (Hypo), dysfibrinogenemia (Dys), or hypodysfibrinogenemia (Hypodys), according to functional and antigenic fibrinogen concentrations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33030793"}, {"offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Congenital fibrinogen disorders are rare diseases affecting either the quantity (afibrinogenemia and hypofibrinogenemia) or the quality (dysfibrinogenemia) or both (hypodysfibrinogenemia) of plasmatic fibrinogen.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27019462"}, {"offsetInBeginSection": 323, "offsetInEndSection": 619, "text": "Afibrinogenemia and hypofibrinogenemia are the consequence of mutations in the homozygous, heterozygous, or compound heterozygous state in one of three genes encoding the fibrinogen chains, which can affect the synthesis, assembly, intracellular processing, stability, or secretion of fibrinogen.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34829490"}, {"offsetInBeginSection": 250, "offsetInEndSection": 563, "text": "Congenital fibrinogen disorders (CFDs) are divided into qualitative deficiencies (dysfibrinogenemia, hypodysfibrinogenemia) in which the mutant fibrinogen molecule is present in the circulation and quantitative deficiencies (afibrinogenemia, hypofibrinogenemia) with no mutant molecule present in the bloodstream.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35073585"}, {"offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Congenital Afibrinogenemia and Hypofibrinogenemia: Laboratory and Genetic Testing in Rare Bleeding Disorders with Life-Threatening Clinical Manifestations and Challenging Management.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34829490"}, {"offsetInBeginSection": 0, "offsetInEndSection": 483, "text": "Congenital fibrinogen disorders are classified into two types of plasma fibrinogen defects: type I (quantitative fibrinogen deficiencies), that is, hypofibrinogenemia or afibrinogenemia, in which there are low or absent plasma fibrinogen antigen levels, respectively, and type II (qualitative fibrinogen deficiencies), that is, dysfibrinogenemia or hypodysfibrinogenemia, in which there are normal or reduced antigen levels associated with disproportionately low functional activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27019463"}, {"offsetInBeginSection": 49, "offsetInEndSection": 321, "text": "Congenital fibrinogen disorders (afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia and hypodysfibrinogenemia), caused by pathogenic variants in the genes FGA, FGB and FGG, have the potential of causing bleeding diathesis and/or thrombotic events of variable severity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32852326"}, {"offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Congenital fibrinogen disorders are rare diseases affecting either the quantity (afibrinogenaemia and hypofibrinogenaemia) or the quality (dysfibrinogenaemia) or both (hypodysfibrinogenaemia) of fibrinogen.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27293018"}, {"offsetInBeginSection": 0, "offsetInEndSection": 581, "text": "Congenital fibrinogen disorders are classified into two types of plasma fibrinogen defects: type I (quantitative fibrinogen deficiencies), that is, hypofibrinogenemia or afibrinogenemia, in which there are low or absent plasma fibrinogen antigen levels, respectively, and type II (qualitative fibrinogen deficiencies), that is, dysfibrinogenemia or hypodysfibrinogenemia, in which there are normal or reduced antigen levels associated with disproportionately low functional activity. These disorders are caused by mutations in the three fibrinogen-encoding genes FGA, FGB, and FGG.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27019463"}, {"offsetInBeginSection": 0, "offsetInEndSection": 430, "text": "Hereditary fibrinogen abnormalities comprise two classes of plasma fibrinogen defects: Type I, afibrinogenemia or hypofibrinogenemia, which has absent or low plasma fibrinogen antigen levels (quantitative fibrinogen deficiencies), and Type II, dysfibrinogenemia or hypodysfibrinogenemia, which shows normal or reduced antigen levels associated with disproportionately low functional activity (qualitative fibrinogen deficiencies).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23852822"}, {"offsetInBeginSection": 0, "offsetInEndSection": 333, "text": "Congenital qualitative and quantitative fibrinogen disorders represent heterogeneous rare abnormalities caused by mutations in one of the 3 genes encoding individual fibrinogen polypeptide chains, located on chromosome 4q28. It is estimated that congenital fibrinogen disorder accounts for 8% of rare coagulation factor deficiencies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31797863"}, {"offsetInBeginSection": 0, "offsetInEndSection": 370, "text": "Hereditary fibrinogen disorders include type I deficiencies (afibrinogenemia and hypofibrinogenemia, i.e. quantitative defects), with low or unmeasurable levels of immunoreactive protein; and type II deficiencies (dysfibrinogenemia and hypodysfibrinogenemia, i.e. qualitative defects), showing normal or altered antigen levels associated with reduced coagulant activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16999847"}, {"offsetInBeginSection": 0, "offsetInEndSection": 312, "text": "INTRODUCTION: Congenital fibrinogen disorders result from genetic mutations in FGA, FGB, or FGG resulting in quantitative fibrinogen deficiencies (afibrinogenemia or hypofibrinogenemia) or qualitative fibrinogen deficiencies (dysfibrinogenemia). Hypodysfibrinogenemia sharing features with hypo- and dysfibrinoge", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32871307"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Congenital fibrinogen disorders can be quantitative (afibrinogenemia, hypofibrinogenemia) or functional (dysfibrinognemia).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29844251"}, {"offsetInBeginSection": 0, "offsetInEndSection": 346, "text": "Congenital fibrinogen disorders comprise quantitative disorders defined by a complete absence (afibrinogenemia) or by a decreased level (hypofibrinogenemia) of circulating fibrinogen and qualitative disorders characterized by a discrepancy between the activity and the antigenic levels of fibrinogen (dysfibrinogenemia and hypodysfibrinogenemia).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27492693"}, {"offsetInBeginSection": 389, "offsetInEndSection": 837, "text": "Among congenital fibrinogen deficiencies, quantitative defects (also called type I deficiencies; i.e. congenital afibrino-genemia [CAF] and hypofibrinogenemia) are characterized by the concomitant absence or reduction of coagulant activity and immunoreactive protein, while qualitative defects (type II deficiencies; i.e. dysfibrinogenemia and hypodysfibrino-genemia) show low clotting protein in contrast with normal or moderately reduced antigen.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17430139"}, {"offsetInBeginSection": 0, "offsetInEndSection": 557, "text": "Inherited fibrinogen disorders can be classified into qualitative and quantitative anomalies: dysfibrinogenemia is characterised by normal circulating levels of fibrinogen with abnormal function; hypofibrinogenemia and afibrinogenemia are characterised by reduced or absent fibrinogen in circulation respectively,while hypodysfibrinogenemia is defined by reduced fibrinogen with reduced function. All are due to mutations in one of the three fibrinogen genes, FGA, FGB and FGG, which are clustered in a region of 50 kb on the long arm of human chromosome 4.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16855369"}, {"offsetInBeginSection": 0, "offsetInEndSection": 396, "text": "Inherited fibrinogen disorders can be classified into qualitative and quantitative anomalies: dysfibrinogenemia is characterised by normal circulating levels of fibrinogen with abnormal function; hypofibrinogenemia and afibrinogenemia are characterised by reduced or absent fibrinogen in circulation respectively,while hypodysfibrinogenemia is defined by reduced fibrinogen with reduced function.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16855369"}, {"offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Congenital fibrinogen deficiency is a rare bleeding disorder, affecting either the quantity (afibrinogenemia, hypofibrinogenemia) or quality (dysfibrinogenemia) of circulating fibrinogen.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23439004"}, {"offsetInBeginSection": 212, "offsetInEndSection": 399, "text": "Congenital hypofibrinogenemia appears to be a separate entity which can be distinguished from heterozygous individuals of congenital afibrinogenemia and from congenital dysfibrinogenemia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/918595"}, {"offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Congenital dysfibrinogenemia is characterized with undetectable or low fibrinogen level by Clauss assay complicated by bleeding and/or thrombosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31542854"}, {"offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Congenital afibrinogenemia/hypofibrinogenemia is an extremely rare coagulation disorder.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15004306"}, {"offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Congenital afibrinogenemia/hypofibrinogenemia is a rare inherited hematologic disorder in which a patient lacks or has insufficient level of fibrinogen, the blood coagulation factor I.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26430672"}, {"offsetInBeginSection": 267, "offsetInEndSection": 654, "text": "Since the identification of the first causative mutation for congenital afibrinogenemia, studies have elucidated the underlying molecular pathophysiology of numerous causative mutations leading to fibrinogen deficiency, developed cell-based and animal models to study human fibrinogen disorders, and further explored the clinical consequences of absent, low, or dysfunctional fibrinogen.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29316703"}, {"offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Congenital fibrinogen disorders are rare pathologies of the hemostasis, comprising quantitative (afibrinogenemia, hypofibrinogenemia) and qualitative (dysfibrinogenemia and hypodysfibrinogenemia) disorders. The clinical", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34829490"}, {"offsetInBeginSection": 247, "offsetInEndSection": 1059, "text": "4. Congenital fibrinogen disorders (CFDs) are divided into qualitative deficiencies (dysfibrinogenemia, hypodysfibrinogenemia) in which the mutant fibrinogen molecule is present in the circulation and quantitative deficiencies (afibrinogenemia, hypofibrinogenemia) with no mutant molecule present in the bloodstream. Phenotypic manifestations are variable, patients may be asymptomatic, or suffer from bleeding or thrombosis. Causative mutations can occur in any of the three fibrinogen genes and can affect one or both alleles. Given the large number of studies reporting on novel causative mutations for CFDs since the review on the same topic published in 2016, we performed an extensive search of the literature and list here 120 additional mutations described in both quantitative and qualitative disorders.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35073585"}]}
+{"question_id": "65f82218c4010b4d7800003e", "question": "What are the current indications for thalidomide?", "answer": "Current indications are as follows: erythema nodosum leprosum, multiple myeloma,  Graft versus host disease, mycobacterial infection,  severe recurrent aphthous stomatitis,  primary brain malignancies, HIV- associated wasting syndrome, Crohn disease, Kaposi sarcoma, myelodysplastic syndrome, hematopoietic stem cell transplantation, hereditary hemorrhagic telangiectasia", "relevant_passage_ids": ["25617013", "21048383", "11235821", "12423428", "21338284", "10781782", "14713870", "23830554", "37206489", "36884210", "12749503", "12696209", "11734114", "11809002", "18034532", "15148528", "9170807", "15934472", "25828060", "10487395", "31175889", "23858438", "25852850", "10992277", "17076653", "20510766", "18023317"], "type": "list", "snippets": [{"offsetInBeginSection": 231, "offsetInEndSection": 366, "text": "erythema nodosum leprosum, aphthous ulceration and cachexia in HIV disease, inflammatory bowel diseases, and several malignant diseases", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21048383"}, {"offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Thalidomide is resurging in the management of adult rheumatologic skin conditions, especially lupus erythematosus", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25617013"}, {"offsetInBeginSection": 463, "offsetInEndSection": 532, "text": "aphthous stomatitis and chronic graft-versus-host disease in children", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25617013"}, {"offsetInBeginSection": 593, "offsetInEndSection": 646, "text": "actinic prurigo and epidermolysis bullosa pruriginosa", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25617013"}, {"offsetInBeginSection": 1000, "offsetInEndSection": 1200, "text": "She was diagnosed with\u00a0International Staging System (ISS) stage 3 multiple myeloma, which was successfully treated with bortezomib, thalidomide and dexamethasone with regular bisphosphonates that year", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37206489"}, {"offsetInBeginSection": 429, "offsetInEndSection": 634, "text": "With this definition, only three drugs are repurposed for cancer: Bacillus Calmette-Guerin (BCG) vaccine (superficial bladder cancer, thalidomide [multiple myeloma], and propranolol [infantile hemangioma])", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36884210"}, {"offsetInBeginSection": 1103, "offsetInEndSection": 1314, "text": "The anti-angiogenic effects of thalidomide may make this compound valuable as single-drug therapy or as an adjunct to chemotherapy in patients with cancer, particularly those with metastases or multiple myeloma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11809002"}, {"offsetInBeginSection": 157, "offsetInEndSection": 456, "text": "Gradually, thalidomide was reintroduced for the treatment of a few skin diseases including leprous erythema nodosum, severe mucosal ulcers (e.g., associated with HIV infection or Beh\u00e7et's disease), lymphocytic skin infiltrations, cutaneous lupus erythematosus, and chronic graft-versus-host disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11809002"}, {"offsetInBeginSection": 138, "offsetInEndSection": 391, "text": "Thalidomide has been used in several cutaneous inflammatory disorders (such as erythema nodosum leprosum in lepromatous leprosy, cutaneous lupus erythematosus, severe aphtosis), cancers (relapsed/refractory multiple myeloma) and inflammatory conditions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15934472"}, {"offsetInBeginSection": 447, "offsetInEndSection": 610, "text": "Thalidomide is currently being used clinically to treat such conditions as cachexia associated with HIV and cancer, mycobacterial disease, and autoimmune diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9170807"}, {"offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Thalidomide was approved for the treatment of multiple myeloma in Japan under a risk management program, named TERMS, in 2008.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26234426"}, {"offsetInBeginSection": 191, "offsetInEndSection": 572, "text": "Current evidence indicates that thalidomide reduces the activity of the inflammatory cytokine tumor necrosis factor (TNF)-alpha by accelerating the degradation of its messenger RNA. Thalidomide also inhibits angiogenesis. Recently, the drug was approved for sale in the United States for the treatment of erythema nodosum leprosum, an inflammatory complication of Hansen's disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10781782"}, {"offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Thalidomide, the drug that caused a worldwide epidemic of serious birth defects in the late 1950s and early 1960s, was recently approved by the US Food and Drug Administration (FDA) for use in treating the skin disease erythema nodosum leprosum, a complication of leprosy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10487395"}, {"offsetInBeginSection": 0, "offsetInEndSection": 969, "text": "Thalidomide is a synthetic glutamic acid derivative first introduced in 1956 in Germany as an over the counter medications. It was thought to be one of the safest sedatives ever produced as it was effective in small doses, was not addictive, and did not have acute side-effects such as motor impairment, but was quickly removed from market after it was linked to cases of severe birth defects. The Food and Drug Administration approved use in the treatment of erythema nodosum leprosum. Further, it was shown its effectiveness in unresponsive dermatological conditions such as actinic prurigo, adult Langerhans cell hystiocytosis, aphthous stomatitis, Beh\u00e7et syndrome, graft-versus-host disease, cutaneous sarcoidosis, erythema multiforme, Jessner-Kanof lymphocytic infiltration of the skin, Kaposi sarcoma, lichen planus, lupus erythematosus, melanoma, prurigo nodularis, pyoderma gangrenosum and others. In May 2006, it was approved for the treating multiple myeloma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23830554"}, {"offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "Thalidomide has gained an infamous history due to severe birth defects observed in patients who had taken the drug to control nausea during pregnancy. The medication was withdrawn from the market because of its teratogenicity, but was approved by the FDA in 1998 for the treatment of erythema nodosum leprosum.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15696990"}, {"offsetInBeginSection": 146, "offsetInEndSection": 405, "text": "Thalidomide was later found to very effectively suppress erythema nodosum leprosum (ENL). The US Food and Drug Administration (FDA) has approved Thalomid (thalidomide) capsules for the acute treatment of the cutaneous manifestations of moderate to severe ENL.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11235821"}, {"offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "BACKGROUND: Thalidomide is best known as a major teratogen that caused birth defects in up to 12,000 children in the 1960s. More recently, this agent has been approved by the US Food and Drug Administration for the treatment of erythema nodosum leprosum (ENL) through a restricted-", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12749503"}, {"offsetInBeginSection": 0, "offsetInEndSection": 312, "text": "Thalidomide was first used in the late 1950s but it was withdrawn from the market in the 1960s for its notorious teratogenic effects. This drug was more recently rediscovered as a powerful immunomodulatory and antiinflammatory agent and was approved by the FDA in 1998 for treatment of erythema nodosum leprosum.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15148528"}, {"offsetInBeginSection": 500, "offsetInEndSection": 672, "text": "Thalidomide is US Food and Drug Administration (FDA)-approved for use in acute erythema nodosum leprosum and, in combination with dexamethasone, in newly diagnosed myeloma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21338284"}, {"offsetInBeginSection": 97, "offsetInEndSection": 727, "text": "Currently, it is used for a few indications; in Brazil, where leprosy is endemic, thalidomide is used for the treatment of erythema nodosum leprosum, and recent cases of thalidomide embryopathy have been reported.METHODS: We analyzed the frequency of births with phenotypes consistent with thalidomide embryopathy (TEP) and correlated this with the distribution of thalidomide and the prevalence of leprosy between 2005 and 2010 in Brazil.RESULTS: A total of 5,889,210 thalidomide tablets were distributed; the prevalence of limb reduction defects was 1.60 (CI95%: 1.54-1.66) and TEP was 0.11 (CI95%: 0.10-0.13) per 10,000 births.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25828060"}, {"offsetInBeginSection": 0, "offsetInEndSection": 970, "text": "Thalidomide is a synthetic glutamic acid derivative first introduced in 1956 in Germany as an over the counter medications. It was thought to be one of the safest sedatives ever produced as it was effective in small doses, was not addictive, and did not have acute side-effects such as motor impairment, but was quickly removed from market after it was linked to cases of severe birth defects. The Food and Drug Administration approved use in the treatment of erythema nodosum leprosum. Further, it was shown its effectiveness in unresponsive dermatological conditions such as actinic prurigo, adult Langerhans cell hystiocytosis, aphthous stomatitis, Beh\u00e7et syndrome, graft-versus-host disease, cutaneous sarcoidosis, erythema multiforme, Jessner-Kanof lymphocytic infiltration of the skin, Kaposi sarcoma, lichen planus, lupus erythematosus, melanoma, prurigo nodularis, pyoderma gangrenosum and others. In May 2006, it was approved for the treating multiple myeloma. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23830554"}, {"offsetInBeginSection": 83, "offsetInEndSection": 296, "text": "tion defects. Currently, it is used for a few indications; in Brazil, where leprosy is endemic, thalidomide is used for the treatment of erythema nodosum leprosum, and recent cases of thalidomide embryopathy have ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25828060"}, {"offsetInBeginSection": 146, "offsetInEndSection": 788, "text": "Thalidomide was later found to very effectively suppress erythema nodosum leprosum (ENL). The US Food and Drug Administration (FDA) has approved Thalomid (thalidomide) capsules for the acute treatment of the cutaneous manifestations of moderate to severe ENL. Thalidomide is currently under investigation for the treatment of a wide variety of diseases, including conditions thought to have an inflammatory or immune basis, malignancies and complications of infection with HIV. Interest in the potential anti-inflammatory, immunomodulatory and anti- angiogenic effects of thalidomide has resulted in off-label use of prescription thalidomide.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11235821"}, {"offsetInBeginSection": 0, "offsetInEndSection": 335, "text": "Thalidomide currently is used to treat relapsed and refractory multiple myeloma. The drug also is being actively investigated in patients newly diagnosed with multiple myeloma. The therapeutic applications of thalidomide are expected to grow as clinical trials document its activity in treating other neoplastic disorders and diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12696209"}, {"offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Thalidomide is an effective agent to treat over 25 seemingly unrelated dermatological conditions that have an inflammatory or autoimmune basis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12423428"}, {"offsetInBeginSection": 0, "offsetInEndSection": 716, "text": "Thalidomide, the drug that caused a worldwide epidemic of serious birth defects in the late 1950s and early 1960s, was recently approved by the US Food and Drug Administration (FDA) for use in treating the skin disease erythema nodosum leprosum, a complication of leprosy. The drug has also shown promise in the treatment of other serious diseases. If thalidomide is eventually approved for use in the US and other countries for treatment of diseases more prevalent than erythema nodosum leprosum, or if use of the drug for non-approved indications becomes widespread, hundreds of thousands of women with childbearing ability could be treated. If this should happen, can we prevent another epidemic of birth defects?", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10487395"}, {"offsetInBeginSection": 0, "offsetInEndSection": 605, "text": "BACKGROUND: Thalidomide is best known as a major teratogen that caused birth defects in up to 12,000 children in the 1960s. More recently, this agent has been approved by the US Food and Drug Administration for the treatment of erythema nodosum leprosum (ENL) through a restricted-use program. Its immunomodulatory, anti-inflammatory, and antiangiogenic properties are currently under study in a number of clinical conditions.OBJECTIVE: This article reviews the pharmacology of thalidomide; its approved and off-label uses in dermatologic, oncologic, and gastrointestinal conditions; and adverse events as", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12749503"}, {"offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Thalidomide currently is used to treat relapsed and refractory multiple myeloma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12696209"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "BACKGROUND: Thalidomide is a sedative/hypnotic agent that is currently used to treat patients suffering from multiple myeloma, myelodysplastic syndromes and erythema nodos", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31175889"}, {"offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Thalidomide and its analog, Lenalidomide, are in current use clinically for treatment of multiple myeloma, complications of leprosy and cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23858438"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Immunomodulatory drugs (IMiDs) currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25852850"}, {"offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Thalomid is the FDA-approved commercial formulation of thalidomide currently used in the US to treat erythema nodosum leprosum, a complication of leprosy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10992277"}, {"offsetInBeginSection": 236, "offsetInEndSection": 405, "text": "The US Food and Drug Administration (FDA) has approved Thalomid (thalidomide) capsules for the acute treatment of the cutaneous manifestations of moderate to severe ENL.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11235821"}, {"offsetInBeginSection": 13, "offsetInEndSection": 561, "text": "DRUG WITH A TEMPORARY MARKETING AUTHORISATION: Thalidomide is currently available in France for nominative or cohort use with a temporary marketing authorisation (TMA). It is only prescribed and delivered in hospital settings. SIX OFFICIAL INDICATIONS: Its current indications are principally lepromatous nodular erythema, severe aphtosis, Jessner-Kanoff's cutaneous lymphocyte infiltration, discoid lupus erythematosis, chronic graft-versus-host reactions, and relapsed and or refractory multiple myeloma (after the failure of standard therapies).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14713870"}, {"offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Thalidomide is approved for treating erythema nodosum leprosum and multiple myeloma, but it has also emerged as a useful treatment option for many refractory dermatologic disorders.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20510766"}, {"offsetInBeginSection": 1287, "offsetInEndSection": 1820, "text": "icularly tumor necrosis factor-alpha. In addition to its approved indication for ENL, thalidomide has been studied in various other conditions, including graft-versus-host disease, discoid lupus erythematosus, sarcoidosis, relapsed/refractory multiple myeloma, Waldenstrom's macroglobulinemia, myelodysplastic syndromes, acute myeloid leukemia, myelofibrosis with myeloid metaplasia, renal cell carcinoma, malignant gliomas, prostate cancer, Kaposi's sarcoma, colorectal carcinoma, oral aphthous ulcers, Beh\u00e7et's disease, Crohn's dis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12749503"}, {"offsetInBeginSection": 0, "offsetInEndSection": 628, "text": "Thalidomide was first used in the late 1950s but it was withdrawn from the market in the 1960s for its notorious teratogenic effects. This drug was more recently rediscovered as a powerful immunomodulatory and antiinflammatory agent and was approved by the FDA in 1998 for treatment of erythema nodosum leprosum. Thalidomide has shown great promise in advanced or refractory multiple myeloma either alone or in combination with other agents. It has also demonstrated benefits in a wide variety of disparate conditions such as aphthous and genital ulcers, cancer cachexia, HIV, tuberculosis and chronic graft versus host disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15148528"}, {"offsetInBeginSection": 102, "offsetInEndSection": 222, "text": "Thalidomide was approved by the FDA in July 1998 for the treatment of erythema nodusum leprosum associated with leprosy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18023317"}, {"offsetInBeginSection": 423, "offsetInEndSection": 585, "text": "Recently, thalidomide was approved for sale in the United States for the treatment of erythema nodosum leprosum, an inflammatory complication of Hansen's disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11734114"}, {"offsetInBeginSection": 82, "offsetInEndSection": 280, "text": "Thalidomide has established its own niche market particularly for the dermatological manifestations associated with HIV, Beh\u00e7et's disease, graft-versus-host disease and systemic lupus erythematosus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18034532"}]}
+{"question_id": "65d1357c1930410b13000039", "question": "What is the administration route of zavegepant?", "answer": "Zavegepant is administered intranasally and used for migraine attacks.", "relevant_passage_ids": ["37345774", "37038933", "37227596", "36804093", "37363553", "36189708", "36239038", "37904462", "33096162"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Zavegepant (Zavzpret), a nasal spray, is approved to treat adults with acute migraine with or without aura.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37345774"}, {"offsetInBeginSection": 405, "offsetInEndSection": 658, "text": "Ubrogepant is ratified for acute migraine treatment, atogepant is validated for preventive therapy, whereas rimegepant is ratified for both indications, all via oral administration and while zavegepant is administered intranasally for migraine attacks. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37038933"}, {"offsetInBeginSection": 246, "offsetInEndSection": 403, "text": "In March 2023, zavegepant nasal spray (ZAVZPRET\u2122) received its first approval in the USA for the acute treatment of migraine with or without aura in adults. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37227596"}, {"offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Safety, tolerability, and efficacy of zavegepant 10 mg nasal spray for the acute treatment of migraine in the USA: a phase 3, double-blind, randomised, placebo-controlled multicentre trial.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36804093"}, {"offsetInBeginSection": 187, "offsetInEndSection": 349, "text": "Zavegepant, an intranasally administered small molecule calcitonin gene-related peptide (CGRP) receptor antagonist, was previously assessed in a phase 2/3 trial. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36804093"}, {"offsetInBeginSection": 2868, "offsetInEndSection": 3015, "text": "INTERPRETATION: Zavegepant 10 mg nasal spray was efficacious in the acute treatment of migraine, with favourable tolerability and safety profiles. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36804093"}, {"offsetInBeginSection": 267, "offsetInEndSection": 457, "text": "Zavegepant is a novel, first-in-class, intranasally administered calcitonin gene-related peptide (CGRP) receptor antagonist that has recently been approved for use in acute migraine attacks.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37363553"}, {"offsetInBeginSection": 817, "offsetInEndSection": 1034, "text": "Moreover, the intranasal method of administration is a characteristic advantage of Zavegepant, as patients suffering from acute migraine attacks cannot easily ingest oral medication, due to severe nausea and vomiting.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37363553"}, {"offsetInBeginSection": 1035, "offsetInEndSection": 1280, "text": "In this mini-review, the efficacy and safety of Zavegepant will be compared with those of alternative treatments available for migraines, including oral triptans, intranasal triptans, and other CGRP antagonists currently available in the market.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37363553"}, {"offsetInBeginSection": 405, "offsetInEndSection": 657, "text": "Ubrogepant is ratified for acute migraine treatment, atogepant is validated for preventive therapy, whereas rimegepant is ratified for both indications, all via oral administration and while zavegepant is administered intranasally for migraine attacks.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37038933"}, {"offsetInBeginSection": 128, "offsetInEndSection": 410, "text": "Zavegepant (BHV-3500, BMS-742413) is a high affinity antagonist of the CGRP receptor (hCGRP Ki\u00a0=\u00a00.023\u00a0nM) that has demonstrated efficacy in the acute treatment of migraine with intranasal delivery in a Phase 2/3 trial, despite showing low oral bioavailability in rats (FPO\u00a0=\u00a01.7%).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33096162"}, {"offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Focus on zavegepant: the first intranasal third-generation gepant.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36189708"}, {"offsetInBeginSection": 12, "offsetInEndSection": 194, "text": "Zavegepant nasal spray is a novel CGRP receptor antagonist that has been developed for the acute treatment of migraine - a prevalent disease leading to disability and economic burden", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37904462"}, {"offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "BACKGROUND: Zavegepant nasal spray is a novel CGRP receptor antagonist that has been developed for the acu", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37904462"}, {"offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "OBJECTIVE: Evaluate the efficacy, safety, and tolerability of zavegepant nasal spray in the acute treatment of migraine.BACKGROUND: Calci", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36239038"}, {"offsetInBeginSection": 175, "offsetInEndSection": 336, "text": "d vomiting. Zavegepant, an intranasally administered small molecule calcitonin gene-related peptide (CGRP) receptor antagonist, was previously assessed in a phas", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36804093"}, {"offsetInBeginSection": 169, "offsetInEndSection": 350, "text": "Newly approved small molecules that antagonize the\u00a0CGRP receptor, gepants, have advanced\u00a0from the hepatotoxic first-generation telcagepant to\u00a0third-generation intranasal zavegepant;", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36189708"}, {"offsetInBeginSection": 281, "offsetInEndSection": 491, "text": " for acute treatment. Zavegepant, a high-affinity, selective, and structurally unique calcitonin gene-related peptide-receptor antagonist in late-stage development, is formulated as a nasal spray for the acute ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36239038"}, {"offsetInBeginSection": 809, "offsetInEndSection": 982, "text": "e attacks per month. Participants were randomly assigned (1:1) to zavegepant 10 mg nasal spray or matching placebo and self-treated a single migraine attack of moderate or s", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36804093"}]}
+{"question_id": "65f59db8c4010b4d78000014", "question": "Brunner's gland hamartoma (BGH) is often asymptomatic and so how is it usually diagnosed?", "answer": "Brunner's gland hamartoma (BGH) is a rare, benign tumor of the duodenum. It is mostly asymptomatic and usually found incidentally on routine esophagogastroduodenoscopy (EGD).", "relevant_passage_ids": ["30671231", "27737521", "22303509", "15034292", "31443637", "28408987", "28584807", "31427914", "30971558", "27055413", "36891571", "37073689", "29694312", "29201733", "7824865", "31451057", "33832073", "33314802", "19924571", "34194867", "32637056", "19140240", "31080246", "22836185", "27426650", "16006686", "33215668", "16955152"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Brunner's gland hamartoma is a rare benign duodenal tumor. It occurs in Brunner's glands, which are found in the duodenum and produce secretions that protect the duodenum from pancreatic enzymes, gastric acid, and other agents.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30671231"}, {"offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Brunner's gland hamartomas are small benign lesions that are most commonly found in the bulb of the duodenum. They are very uncommon, and most are found incidentally during upper gastrointestinal series or esophagogastroduodenoscopy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27737521"}, {"offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Brunner's gland hamartoma is an extremely uncommon benign tumor of the duodenum. Most of the lesions are small, asymptomatic and are detected incidentally. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22303509"}, {"offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Brunner's gland hamartomas are rare tumors of duodenum, they are often discovered incidentally during esophagogastroduodenoscopy or upper gastrointestinal series", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15034292"}, {"offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Brunner's gland adenoma (BGA), also known as Brunneroma or polypoid hamartoma, is a rare benign duodenal tumor that proliferates from Brunner's glands of the duodenum", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37073689"}, {"offsetInBeginSection": 566, "offsetInEndSection": 840, "text": "Most patients with Brunner's gland hamartoma are asymptomatic or have nonspecific complaints.CONCLUSION: BHG is a rare tumor arising from the Brunner's gland of the duodenum, considered entirely benign, although there have been occasionally reports of malignant foci inside.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29694312"}, {"offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "INTRODUCTION: Brunner's gland hyperplasia (BGH) of the duodenum is an uncommon finding at endoscopy and is usually asymptomatic.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19924571"}, {"offsetInBeginSection": 0, "offsetInEndSection": 328, "text": "BACKGROUND: Brunner's gland hamartomas are very uncommon lesions and are usually asymptomatic.METHODS: A 77-year-old man was urgently operated on for massive upper gastrointestinal bleeding, associated with haematemesis.RESULTS: A 3.5 x 3 x 3 cm mass arising from the anterior aspect of the first part of the duodenum was found.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7824865"}, {"offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Brunner's gland adenoma (hyperplasia) (BGA/H) is a benign gastrointestinal lesion, usually asymptomatic and frequently detected incidentally by endoscopy as a submucosal nodule.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33314802"}, {"offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "RATIONALE: Brunner gland hamartoma (BGH) is a rare tumor of the duodenum.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33832073"}, {"offsetInBeginSection": 0, "offsetInEndSection": 571, "text": "Brunner's gland hamartoma (BGH) is a rare sub-epithelial tumour of the duodenum, which may cause haemorrhagic or obstructive gastrointestinal symptoms. Their accurate histological diagnosis often remains elusive before resection. Although endoscopic ultrasonography (EUS) is considered an excellent modality to study lesions within the gastrointestinal wall, only a few reports have described endosonographic characteristics of BGHs. A reliable pre-resection diagnosis with EUS may not only allay fear of malignancy but may as well avert a major surgery for the patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31427914"}, {"offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Brunner's gland hamartomas are rare, benign small bowel tumours. There were fewer than 150 cases reported in the English literature until the end of the last century. These hamartomas may be discovered incidentally during an upper gastrointestinal tract endoscopy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16955152"}, {"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Brunner's gland hamartoma is an extremely uncommon benign tumor of the duodenum. Most of the lesions are small, asymptomatic and are detected incidentally.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22303509"}, {"offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "BACKGROUND: Brunner's gland adenoma is a rare benign tumor arising from Brunner's glands. It is mostly small in size, and patients with this tumor are a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33817211"}, {"offsetInBeginSection": 0, "offsetInEndSection": 501, "text": "Brunner's gland hamartoma (or Brunneroma) is an uncommon tumour with an incidence of <0.01%, accounting for approximately 5-10% of benign duodenal tumours. Usually asymptomatic, it may manifest occasionally with duodenal obstruction or upper gastrointestinal haemorrhage and rarely with biliary fistulation, cholestatic jaundice and intussusception. It may be associated with uraemia and chronic pancreatitis. The diagnosis is usually confirmed by imaging studies and upper gastrointestinal endoscopy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31451057"}, {"offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Brunner's gland hyperplasia (BGH) is an unusual entity that presents with large duodenal polyp or mass and rarely causes gastrointestinal bleeding", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32637056"}, {"offsetInBeginSection": 184, "offsetInEndSection": 250, "text": "Brunner's gland hamartoma (BGH) is a rare benign small bowel tumor", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31443637"}, {"offsetInBeginSection": 14, "offsetInEndSection": 128, "text": "Brunner's gland hamartoma (BGH) is an infrequently encountered, benign, polypoid proliferation of Brunner's glands", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28408987"}, {"offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "Brunner's gland adenoma is a rare benign tumor of small bowel, often incidentally discovered during endoscopy or radiological imaging. Mostly they are asymptomatic or often present with nonspecific symptoms such as nausea, vomiting, gastrointestinal hemorrhage, iron deficiency anemia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31080246"}, {"offsetInBeginSection": 617, "offsetInEndSection": 910, "text": "ding to their tissue components. Brunner's gland hamartoma commonly occurred in the duodenal bulb and exhibited a polypoid appearance, while Brunner's gland hyperplasia was primarily observed in the second portion of duodenum as a submucosal mass and was accompanied by symptoms more frequentl", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22836185"}, {"offsetInBeginSection": 11, "offsetInEndSection": 410, "text": "Brunner's gland hyperplasia is a rare benign tumour and occurs most frequently in the upper part of the duodenum, mostly in the fifth or the sixth decade. Pathogenesis is still unknown. Symptoms are mostly absent, but larger lesions can cause gastric outlet obstruction or bleeding. Biopsies are necessary for differential diagnosis and to rule out cancerous changes. Mostly a resection is required.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27426650"}, {"offsetInBeginSection": 0, "offsetInEndSection": 714, "text": "CONTEXT: Brunner's gland hyperplasia is rarely associated with clinical symptoms. Most of the lesions are less than 1 cm in diameter and accounts for about 6.8% of all endoscopically removed duodenal polyps. When symptoms occur, this hyperplasia can be effectively treated with endoscopy. However, when the lesion is too large to pass through the endoscopic snare, endoscopic treatment is not possible and surgical treatment is necessary. This treatment may vary from local excision to more complex operations. When Brunner's gland hyperplasia does not have common dimensions, it may also mimic a malignancy of the duodenal-pancreatic area. In this case, a biopsy is indicated even though its result may be not inf", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16006686"}, {"offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "INTRODUCTION: Brunner's gland hamartoma (BGH) is an infrequently encountered, benign, polypoid proliferation of Brunner's glands. Usually these lesions are asymptomatic, just only occasionally presenting with duodenal obstruction or bleeding signs and mimicking a t", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28408987"}, {"offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Brunner's gland hyperplasia (BGH) is an unusual entity that presents with large duodenal polyp or mass and rarely causes gastrointestinal bleeding. It is usually asymptomatic and often an incidental finding during the esophagoduodenoscopy (EGD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32637056"}, {"offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "INTRODUCTION: Brunner's gland hyperplasia (BGH) of the duodenum is an uncommon finding at endoscopy and is usually asymptomatic. Symptomatic BGH presenting with biliary obstruction and pancreatitis is extremely rare and the literature is limited to a few", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19924571"}, {"offsetInBeginSection": 0, "offsetInEndSection": 375, "text": "Brunner gland hamartoma (BGH) is a rare condition that requires a high clinical suspicion to diagnose. Large hamartomas may initially present with iron deficiency anemia (IDA) or symptoms suggesting intestinal obstruction. Barium swallow may demonstrate the lesion, but endoscopic evaluation is the acceptable first line management unless a concern for underlying malignancy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36891571"}, {"offsetInBeginSection": 922, "offsetInEndSection": 1098, "text": ". Most cases of BGH are benign and asymptomatic; however, it is important to be aware that some patients have severe anemia, gastrointestinal obstruction, or malignant potentia", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34194867"}, {"offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Brunner gland hamartoma (brunneroma) is a rare benign tumor of the duodenum. It is usually asymptomatic and detected incidentally by endoscopy or other imaging modality.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29201733"}, {"offsetInBeginSection": 134, "offsetInEndSection": 371, "text": "Brunner's gland hamartomas (BGHs), which are uncommon, asymptomatic and usually found incidentally. They are predominantly benign lesions, but instances of malignant transformation have been reported. Case History We describe a rare case", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27055413"}, {"offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Brunner's gland hamartoma (BGH) is an extremely rare benign digestive tumor, generally located in the duodenal bulb. We report the case of a 51-year-old asymptomatic man", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28584807"}, {"offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Brunner's gland hamartomas (BGHs) are rare, benign, primary duodenal tumors. The clinical presentations can vary, and confirming a diagnosis can be challenging", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33215668"}, {"offsetInBeginSection": 172, "offsetInEndSection": 427, "text": "tomy (HSP). Brunner's gland hamartoma (BGH) is a rare benign small bowel tumor. The majority of BGH measuring about 2\u2009cm in diameter, rarely larger than 5\u2009cm. Most patients are asymptomatic, some may present with gastrointestinal hemorrhage or intestinal ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31443637"}, {"offsetInBeginSection": 0, "offsetInEndSection": 383, "text": "Brunner's gland hamartomas (BGHs) are uncommon lesions of duodenum which show hyperplasia of these glands along with smooth muscle bundles, adipose tissue and lymphoid aggregates. These are usually benign, solitary, pedunculated, polypoidal lesions. Dysplastic changes in BGH are extremely rare and even rarer is the multiplicity of this lesion. We hereby report an index case of BGH", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30971558"}, {"offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Brunner's gland hamartoma (BGH) is a rare sub-epithelial tumour of the duodenum, which may cause haemorrhagic or obstructive gastrointestinal symptoms. Their accurate histological diagnosis often remains elusive", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31427914"}, {"offsetInBeginSection": 23, "offsetInEndSection": 106, "text": "Brunner's gland hamartoma (BGH) of the duodenum causing upper gastrointestinal (GI)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19140240"}]}
+{"question_id": "65f86e06c4010b4d7800005a", "question": "Is peritoneal dialysis the best option for infants with kidney failure?", "answer": "Yes, peritoneal dialysis is often the preferred method for infants with kidney failure.", "relevant_passage_ids": ["36449100", "32063210", "2739769", "10723344", "34648058", "17990805", "35589990", "26591190", "11998382", "21907533", "22371780", "23350610", "26438039", "32063141"], "type": "yesno", "snippets": [{"offsetInBeginSection": 48, "offsetInEndSection": 83, "text": "automated peritoneal dialysis (APD)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36449100"}, {"offsetInBeginSection": 1703, "offsetInEndSection": 1706, "text": "APD", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36449100"}, {"offsetInBeginSection": 1826, "offsetInEndSection": 1828, "text": "PD", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36449100"}, {"offsetInBeginSection": 12, "offsetInEndSection": 141, "text": "Peritoneal dialysis (PD) remains the most widely used modality for chronic dialysis in children, particularly in younger children", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32063210"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Chronic ambulatory peritoneal dialysis (CAPD) is the treatment most often used in neonates and infants with chronic kidney failure.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10723344"}, {"offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "BACKGROUND: Peritoneal dialysis (PD) is the preferred mode of kidney replacement therapy (KRT) in infants and young children with kidney failure.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34648058"}, {"offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Peritoneal dialysis remains the treatment of choice for acute renal failure in infancy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2739769"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Peritoneal dialysis is the most commonly prescribed dialysis modality for infants and young children with kidney failure worldwide.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35589990"}, {"offsetInBeginSection": 282, "offsetInEndSection": 419, "text": "The authors demonstrate that peritoneal dialysis is an effective, safe, and available method for treating acute renal failure in infants.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11998382"}, {"offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "BACKGROUND: Peritoneal dialysis (PD) is the preferred mode of kidney replacement therapy (KRT) in infants and young children with kidney failure. Hemodialysis (HD) is used less often due to the technical challenges and risk of complications in small", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34648058"}, {"offsetInBeginSection": 1411, "offsetInEndSection": 1636, "text": "cannula, venous catheter).CONCLUSION: Peritoneal dialysis is the method of choice in newborns with acute renal failure, and it is used in the treatment of neonatal asphyxia till the restoration of kidney function is achieved.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17990805"}, {"offsetInBeginSection": 2154, "offsetInEndSection": 2241, "text": "Peritoneal dialysis is the treatment of choice for infants with chronic kidney failure.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26591190"}, {"offsetInBeginSection": 364, "offsetInEndSection": 504, "text": "Peritoneal dialysis is the renal replacement therapy of choice, especially in children under 2 years, with an important risk of peritonitis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21907533"}, {"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Peritoneal dialysis (PD) is considered as the most common form of renal replacement therapy for newborns including preterms with acute kidney injury (AKI).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23350610"}, {"offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "BACKGROUND: Peritoneal dialysis is the preferred mode of renal replacement therapy in infants with end-stage renal disease (ESRD). Hemodialysis (HD) is seldom used in neonates and infants due to the risk of major complications in the", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26438039"}, {"offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "BACKGROUND: Peritoneal dialysis (PD) is the preferred mode of kidney replacement therapy (KRT) in infants and young children with kid", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34648058"}, {"offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "BACKGROUND: Peritoneal dialysis (PD) is the preferred modality of renal replacement therapy in children with end-stage renal dis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32063141"}, {"offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "INTRODUCTION: Peritoneal dialysis (PD) is a preferred method of renal replacement therapy for end-stage renal disease in children. Recent advances have allowed chronic PD to be provided to children of all a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22371780"}]}
+{"question_id": "65ce88b71930410b13000001", "question": "Is Lecanemab approved for Alzheimer\u2019s Disease?", "answer": "Yes. Lecanemab (Leqembi\u00ae) is approved in the United States for the treatment of Alzheimer's disease (AD) to be initiated in early AD (mild cognitive impairment due to AD or mild AD dementia) with confirmed brain amyloid pathology.", "relevant_passage_ids": ["37490245", "37389302", "37414156", "37334596", "37357276", "36856953", "37902139", "37676096", "36931947", "38017568", "37831471", "37682322", "38095822", "37479527", "38067098", "38021811", "37955845", "37927263", "37251789", "37060386", "37639602", "37045461"], "type": "yesno", "snippets": [{"offsetInBeginSection": 819, "offsetInEndSection": 1069, "text": "Data from recent trials implicate these agents as the first effective disease-modifying therapies against AD and has led to the US Food and Drug Administration (FDA) recent approval of aducanumab and lecanemab, under an accelerated approval pathway. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37490245"}, {"offsetInBeginSection": 819, "offsetInEndSection": 1068, "text": "Data from recent trials implicate these agents as the first effective disease-modifying therapies against AD and has led to the US Food and Drug Administration (FDA) recent approval of aducanumab and lecanemab, under an accelerated approval pathway.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37490245"}, {"offsetInBeginSection": 220, "offsetInEndSection": 462, "text": "At the time of writing, two amyloid-lowering antibodies, aducanumab and lecanemab, have obtained United States Food and Drug Administration accelerated approval, with further agents of this class in the Alzheimer's disease treatment pipeline.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37490245"}, {"offsetInBeginSection": 220, "offsetInEndSection": 461, "text": "At the time of writing, two amyloid-lowering antibodies, aducanumab and lecanemab, have obtained United States Food and Drug Administration accelerated approval, with further agents of this class in the Alzheimer's disease treatment pipeline", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37389302"}, {"offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "The US Food and Drug Administration (FDA)'s recent accelerated approval of two anti-amyloid antibodies for treatment of Alzheimer's disease (AD), aducanumab and lecanemab, has caused substantial debate. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37414156"}, {"offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "After the CLARITY-AD clinical trial results of lecanemab were interpreted as positive, and supporting the amyloid hypothesis, the drug received accelerated Food and Drug Administration approval.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37334596"}, {"offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Lecanemab (Leqembi\u00ae) is approved in the United States for the treatment of Alzheimer's disease (AD) to be initiated in early AD (mild cognitive impairment [MCI] due to AD or mild AD dementia) with confirmed brain amyloid pathology. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37357276"}, {"offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "The approval of lecanemab by the US Food and Drug Administration has been touted as a defining moment in the treatment of Alzheimer's disease", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38095822"}, {"offsetInBeginSection": 506, "offsetInEndSection": 659, "text": "Finally, in the last two years, the Food and Drug Administration (FDA) approved the first-ever medications to treat Alzheimer's, aducanumab and lecanemab", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38067098"}, {"offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "The approval of lecanemab by the US Food and Drug Administration has been touted as a defining moment in the treatment of Alzheimer's disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38095822"}, {"offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "BACKGROUND: Lecanemab is the latest monoclonal antibody that targets beta-amyloid approved exclusively for treatment of Alzheimer's disease with mild cognitive impairment or mild dementia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37902139"}, {"offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Commentaries: Lecanemab: pioneering the way as the first approved drug for Alzheimer's disease treatment.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37682322"}, {"offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Two anti-amyloid monoclonal antibodies (MABs)-lecanemab (Leqembi\u00ae) and aducanumab (Aduhelm\u00ae)-have been approved in the USA for the treatment of Alzheimer's disease (AD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37060386"}, {"offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "BACKGROUND: Lecanemab is the latest monoclonal antibody that targets beta-amyloid approved exclusively for treatment of Alzheimer's disease with mild cognitive impairment or mi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37902139"}, {"offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "On July 6, 2023, the U.S. Food and Drug Administration (FDA) approved lecanemab (Leqembi) for the treatment of Alzheimer's dementia (AD) patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37676096"}, {"offsetInBeginSection": 1329, "offsetInEndSection": 1418, "text": "Lecanemab has been recently approved by the FDA for the treatment of Alzheimer's disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36931947"}, {"offsetInBeginSection": 443, "offsetInEndSection": 540, "text": " Full FDA approval was granted for lecanemab due to its ability to eliminate toxic brain amyloids", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37682322"}, {"offsetInBeginSection": 398, "offsetInEndSection": 492, "text": "Lecanemab was the second amyloid antibody to receive accelerated approval for use in early AD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37045461"}, {"offsetInBeginSection": 1002, "offsetInEndSection": 1145, "text": "This article summarizes the milestones in the development of lecanemab leading to this first approval for the treatment of Alzheimer's disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36856953"}, {"offsetInBeginSection": 0, "offsetInEndSection": 337, "text": "The approval of lecanemab by the US Food and Drug Administration has been touted as a defining moment in the treatment of Alzheimer's disease. Lecanemab, an anti-amyloid beta monoclonal antibody, is the first Alzheimer's disease drug targeting amyloid beta that has shown statistically significant cognitive benefits in phase III trials.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38095822"}, {"offsetInBeginSection": 0, "offsetInEndSection": 358, "text": "Two monoclonal antibodies (mAbs), aducanumab and lecanemab, have received accelerated approval from the US FDA for initiation of treatment in early Alzheimer's disease patients who have proven \u03b2-amyloid pathology (A\u03b2). One of these, lecanemab, has subsequently received full approval and other monoclonal antibodies are poised for positive review and approva", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37955845"}, {"offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "Recently, the U.S. Food and Drug Administration (FDA) approved 2 anti-amyloid monoclonal antibodies, aducanumab (June 7, 2021) and lecanemab (July 6, 2023), for the treatment of Alzheimer's disease (AD) patients, and will most likely also approve a 3rd one, donanemab, soon.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37831471"}, {"offsetInBeginSection": 269, "offsetInEndSection": 454, "text": "n. Consistent with a critical role for this form of A\u03b2 in AD, a recently FDA-approved therapeutic antibody targeted against protofibrils, lecanemab, slows the progression of AD in patie", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37639602"}, {"offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "BACKGROUND: The approval of lecanemab for the treatment of Alzheimer's disease (AD) by the Food and Drug Administration in the United States has sparked controversy over issues of safety, cost, a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37927263"}, {"offsetInBeginSection": 997, "offsetInEndSection": 1186, "text": "ed in the analysis.RESULTS: The FDA approved lecanemab for Alzheimer's disease in January 2023 which acts as a novel disease-modifying anti-amyloid-beta (A\u03b2) human monoclonal antibody and i", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37902139"}, {"offsetInBeginSection": 55, "offsetInEndSection": 237, "text": "(FDA) approved lecanemab (Leqembi) for the treatment of Alzheimer's dementia (AD) patients. In 2 clinical trials, lecanemab reduced amyloid in the brain and slowed cognitive decline.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37676096"}, {"offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "BACKGROUND: Lecanemab is the latest monoclonal antibody that targets beta-amyloid approved exclusively for treatment of Alzheimer's disease with mild cognitive impairment or mild dementia. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37902139"}, {"offsetInBeginSection": 0, "offsetInEndSection": 452, "text": "Lecanemab (lecanemab-irmb; LEQEMBI\u2122) is a humanized immunoglobulin gamma 1 (IgG1) against aggregated soluble and insoluble forms of amyloid-\u03b2 peptide. It is being developed by Eisai, under a global licence from BioArctic (formerly BioArctic Neuroscience), and in collaboration with Biogen, for the treatment of Alzheimer's disease, and received its first approval for this indication on 6\u00a0January 2023 in the USA under the Accelerated Approval Pathway.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36856953"}, {"offsetInBeginSection": 88, "offsetInEndSection": 334, "text": "lt to cure. Drugs aimed at slowing the progression of the disease have been developed, with the Food and Drug Administration (FDA) granting accelerated approval for aducanumab on June 21, 2021 and a new accelerated approval for lecanemab on Janua", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38017568"}]}
+{"question_id": "65f5a3efc4010b4d78000017", "question": "Can Ultrasonography be used to detect tumors in dogs and cats?", "answer": "Ultrasonography can be used as screening tests for dogs and cats, potentially representing an alternative to the invasive sampling methods required for cytological and histopathological analysis.", "relevant_passage_ids": ["36790748", "15005361", "7591927", "7358560", "6698841", "34617607", "29530040", "22331324", "21486639", "17153071", "34828010", "34521571", "11130788", "31579524", "10955496", "25028432", "9402711", "15017037", "18418997"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Ultrasonography (US) and computed\u00a0tomography\u00a0(CT) are used to diagnose neoplastic and non-neoplastic focal renal lesions\u00a0in\u00a0dogs\u00a0and\u00a0cats", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36790748"}, {"offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "A retrospective survey from January 1989 to January 1999 of Tufts University Foster Hospital for Small Animals radiology records of 12 dogs and seven cats with cytologically or histopathologically confirmed abdominal mast cell disease was perform", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15005361"}, {"offsetInBeginSection": 1257, "offsetInEndSection": 1520, "text": "Although these findings are not specific to the disease in either species, abdominal ultrasound is considered a useful tool for determining the extent of disease in small-animal patients with mast cell tumor if used in conjunction with histopathology or cytology.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15005361"}, {"offsetInBeginSection": 937, "offsetInEndSection": 1050, "text": "In the 2 dogs with intradural masses, intraoperative ultrasonography helped to delineate the extent of the tumor.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7591927"}, {"offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Two-dimensional, gray-scale ultrasonography for assessment of hepatic and splenic neoplasia in the dog and cat.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6698841"}, {"offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "BACKGROUND: In veterinary medicine, contrast-enhanced ultrasonography allowed the accurate quantification of liver, splenic and kidney vascularization in healthy dogs and the differentiation between malignant and benign hepatic, renal, and splenic nodules in dogs and cats based on perfusion patterns.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29530040"}, {"offsetInBeginSection": 982, "offsetInEndSection": 1455, "text": "In dogs, an ultrasonographically normal liver was associated with not having lymphomatous infiltration, leopard-spotted splenic parenchyma and splenomegaly were independently associated with lymphomatous infiltration and leopard-spotted splenic parenchyma was also associated with the B cell immunophenotype of multi-centric lymphoma.CLINICAL SIGNIFICANCE: Ultrasonography of the spleen and liver is specific but not sensitive in the detection of lymphomatous infiltration.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34617607"}, {"offsetInBeginSection": 0, "offsetInEndSection": 532, "text": "CASE SUMMARY: A 14-year-old cat was presented with a 2-week history of ataxia, seizure-like episodes, vomiting and weight loss. Serum biochemistry revealed severe hypoglycaemia, associated with low serum fructosamine and high insulin concentrations. On abdominal ultrasound, a focal hypoechoic well-defined mass in the left limb of the pancreas was identified and the presence of an additional smaller nodule was suspected. Contrast-enhanced ultrasonography (CEUS) confirmed the presence of both lesions and revealed a third, even s", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31579524"}, {"offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "A 12-year-old fox-terrier dog presented with forelimb lameness of 3-weeks duration. Ultrasonography revealed a mass within the thoracic wall and osteolysis of the left third rib.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16901271"}, {"offsetInBeginSection": 412, "offsetInEndSection": 593, "text": "Abdominal ultrasound was performed in three cats and one dog, findings included the presence of hyperechoic masses with associated acoustic shadowing, some with a hypoechoic centre.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10955496"}, {"offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "OBJECTIVES: To determine the diagnostic accuracy of ultrasonography in the detection of lymphomatous infiltration of the liver and spleen in a population of dogs and cats with lymphoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34617607"}, {"offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Ultrasonography, which has become a mainstay of diagnosing intestinal diseases in dogs and cats, is often one of the first diagnostic tools used to differentiate inflammatory from neoplastic infiltration of the small intestine.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21486639"}, {"offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Lung Ultrasound for Imaging of B-Lines in Dogs and Cats-A Prospective Study Investigating Agreement between Three Types of Transducers and the Accuracy in Diagnosing Cardiogenic Pulmonary Edema, Pneumonia and Lung Neoplasia.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34828010"}, {"offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Diagnostic accuracy of ultrasonography to detect hepatic and splenic lymphomatous infiltration in dogs and cats.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34617607"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Focused Ultrasound of Superficial-Soft Tissue Swellings, Masses, and Fluid Collections in Dogs and Cats.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34521571"}, {"offsetInBeginSection": 124, "offsetInEndSection": 271, "text": "This report describes four dogs with pheochromocytoma in which radiography, ultrasonography and computed tomography (CT) were key diagnostic tools.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11130788"}, {"offsetInBeginSection": 152, "offsetInEndSection": 270, "text": "Mural lesions representing lymphoma affecting the urinary bladder were identified ultrasonographically in all animals.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17153071"}, {"offsetInBeginSection": 139, "offsetInEndSection": 239, "text": "Abdominal ultrasound and MRI were performed on 8 dogs having a mass lesion on abdominal radiography.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9402711"}, {"offsetInBeginSection": 444, "offsetInEndSection": 609, "text": "Ultrasonography revealed masses in all dogs with uterine body/cervical tumors and could delineate the origin of the mass in one of two dogs with uterine horn tumors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25028432"}, {"offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "The presence of a heart-base tumor was diagnosed by ultrasound imaging in a 10-year-old, female, domestic shorthaired cat presenting with dyspnea and pleural effusion because of the presence of a modified transudate.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15017037"}, {"offsetInBeginSection": 10, "offsetInEndSection": 274, "text": "ultrasonography was found to be useful in the diagnosis of hydronephrosis, renal calculi, and renal neoplasia in the dog and cat. One dog with hydronephorsis, one with renal calculi, and a cat with a renal neoplasm were scanned with a real-time ultrasonic scanner.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7358560"}, {"offsetInBeginSection": 283, "offsetInEndSection": 603, "text": "l disease.MATERIAL AND METHODS: Ultrasonography and MRI were performed in 15 dogs and 15 cats with intraocular neoplasia or intraocular inflammatory disease.RESULTS: In all patients with intraocular neoplasia, sonography revealed masses with increased echogenicity and fairly uniform echotexture, thus allowing the tenta", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22331324"}, {"offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Contrast-enhanced ultrasound was used to study focal and multifocal lesions of the spleen in 26 dogs and two cats affected by 11 benign and 18 malignant splenic diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18418997"}, {"offsetInBeginSection": 1, "offsetInEndSection": 90, "text": "ltrasonography of small intestinal inflammatory and neoplastic diseases in dogs and cats.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21486639"}]}
+{"question_id": "65f82058c4010b4d7800003d", "question": "What is the first line treatment for severe Plasmodium falciparum malaria?", "answer": "First line treatment in severe Plasmodium falciparum malaria is artesunate.", "relevant_passage_ids": ["36056897", "37666798", "36126008", "17402835", "30885541", "25217396", "22453057", "35916842", "25069406", "27089770", "27809844", "23121274", "22818552", "26832999", "27613271", "15642960", "16923176", "33685888", "35326891", "25163350", "33344893", "25348537", "19881520", "26880088", "22966778", "27449110", "24659706", "30983213", "31843017", "34561157", "26483118", "32228566", "35857773", "23350023"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Intravenous artesunate has been the global standard of care for severe malaria", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36056897"}, {"offsetInBeginSection": 67, "offsetInEndSection": 152, "text": "Parenteral artesunate (ARS) is the first-line treatment for severe falciparum malaria", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37666798"}, {"offsetInBeginSection": 1560, "offsetInEndSection": 1628, "text": "Intravenous artesunate is the treatment of choice for severe malaria", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36126008"}, {"offsetInBeginSection": 243, "offsetInEndSection": 421, "text": "The first line treatments for Plasmodium falciparum are artemisinin combination therapies, chloroquine in most non-falciparum and intravenous artesunate if any severity criteria.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26832999"}, {"offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "BACKGROUND: In Zambia, unacceptably high resistance to commonly used antimalarial drugs prompted the choice of artemether-lumefantrine (AL) as first line treatment for uncomplicated Plasmodium falciparum malaria.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16923176"}, {"offsetInBeginSection": 1338, "offsetInEndSection": 1646, "text": "Total treatment failure was significantly higher in the SP group (96/393; 19.3%) as compared to the AL (22/403; 5.4%) group (OR: 4.15; 95% CI: 2.52-6.83; P < 0.001).CONCLUSION: In Zambia, the new first line regimen AL is far more efficacious than SP in treating uncomplicated P. falciparum malaria in adults.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16923176"}, {"offsetInBeginSection": 668, "offsetInEndSection": 745, "text": "Artesunate should constitute first-line treatment for severe malaria in Asia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17402835"}, {"offsetInBeginSection": 84, "offsetInEndSection": 268, "text": "Artesunate has become the treatment of choice for severe malaria, and artemisinin-based combination therapies (ACTs) are the foundation of modern falciparum malaria treatment globally.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27613271"}, {"offsetInBeginSection": 284, "offsetInEndSection": 469, "text": "Combination therapy through coadministration of sulfadoxine-pyrimethamine plus artesunate was introduced as a first-line treatment for uncomplicated malaria in one district in Tanzania.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15642960"}, {"offsetInBeginSection": 1368, "offsetInEndSection": 1471, "text": "First-line therapy for P falciparum malaria in the US is combination therapy that includes artemisinin.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35916842"}, {"offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Intravenous (i.v.) artesunate is now the recommended first-line treatment of severe falciparum malaria in adults and children by WHO guidelines.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22453057"}, {"offsetInBeginSection": 92, "offsetInEndSection": 179, "text": "Intravenous (i.v.) artesunate is the first-line treatment for severe falciparum malaria", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33685888"}, {"offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Parenteral artesunate (AS) is the WHO first-line treatment recommended in adults and children for severe malaria.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35326891"}, {"offsetInBeginSection": 1410, "offsetInEndSection": 1511, "text": "IV artesunate is now recommended as the first-line treatment for severe falciparum malaria in France.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25163350"}, {"offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "The majority of deaths from malaria are in young African children. Parenteral artesunate (ARS) is the first-line treatment for severe falciparum malaria.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37666798"}, {"offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "BACKGROUND: In sub-Saharan Africa, artemisinin-based combination therapy (ACT) and injectable artesunate are the first-line treatments for uncomplicated and severe Plasmodium falciparum malaria, respectively.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25217396"}, {"offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "The first-line treatments for uncomplicated Plasmodium falciparum malaria are artemisinin-based combination therapies (ACTs), consisting of an artemisinin derivative combined with a longer acting partner drug.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33344893"}, {"offsetInBeginSection": 2762, "offsetInEndSection": 2826, "text": "Intravenous artesunate is first-line therapy for severe malaria.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35916842"}, {"offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Artemisinin-based combination therapy (ACT) is the recommended first-line treatment for Plasmodium falciparum malaria.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25348537"}, {"offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Plasmodium falciparum resistance to chloroquine and sulphadoxine-pyrimethamine has led to the recent adoption of artemisinin-based combination therapies (ACTs) as the first line of treatment against malaria.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19881520"}, {"offsetInBeginSection": 1121, "offsetInEndSection": 1200, "text": "First-line treatment of severe P. falciparum malaria is based on IV artesunate.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25069406"}, {"offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "BACKGROUND: Artemisinin combination therapy (ACT) is used worldwide as the first-line treatment against uncomplicated Plasmodium falcipa", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27809844"}, {"offsetInBeginSection": 0, "offsetInEndSection": 329, "text": "Artemisinin-based combination therapies (ACTs) have been adopted as the first line of treatment against malaria in nearly all malaria-endemic countries, mainly as a result of Plasmodium falciparum infection, as this species of malaria parasite has developed resistance to most of the available non-artemisinin antimalarial drugs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23121274"}, {"offsetInBeginSection": 84, "offsetInEndSection": 231, "text": "of malaria. Artemisinin-based combination therapy (ACT) is the WHO recommended first-line treatment for Plasmodium falciparum malaria across the en", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27449110"}, {"offsetInBeginSection": 141, "offsetInEndSection": 313, "text": "d in India. By 2007, the first-line treatment for uncomplicated malaria has been revised to recommend artemisinin-based combination therapy (ACT) for all confirmed P. falci", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22818552"}, {"offsetInBeginSection": 276, "offsetInEndSection": 380, "text": "The World Health Organisation (WHO) recommends arthemether combination treatment as a first line choice.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24659706"}, {"offsetInBeginSection": 437, "offsetInEndSection": 589, "text": "The main advance is the positioning of artemisinin derivative- based combinations as first-line, given their rapidity of action and their effectiveness.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30983213"}, {"offsetInBeginSection": 82, "offsetInEndSection": 247, "text": "As recommended by the World Health Organization, the ART-based combination therapies (ACTs) have become the first-line drugs for the treatment of falciparum malaria.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27089770"}, {"offsetInBeginSection": 1526, "offsetInEndSection": 1757, "text": "ost-treatment QTc interval.CONCLUSION: Artenimol-piperaquine displays a satisfying efficacy and tolerance profile as a first-line treatment for children with imported uncomplicated falciparum malaria and only necessitates three onc", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31843017"}, {"offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "BACKGROUND: In sub-Saharan Africa, artemisinin-based combination therapy (ACT) and injectable artesunate are the first-line treatments for uncomplicated and severe Plasmodium falciparum malaria, r", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25217396"}, {"offsetInBeginSection": 2347, "offsetInEndSection": 2674, "text": "Uncomplicated P. falciparum malaria should be treated with an artemisinin combination therapy (Grade 1A). Artemether-lumefantrine (Riamet(\u00ae)) is the drug of choice (Grade 2C) and dihydroartemisinin-piperaquine (Eurartesim(\u00ae)) is an alternative. Quinine or atovaquone-proguanil (Malarone(\u00ae)) can be used if an ACT is not availab", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26880088"}, {"offsetInBeginSection": 1195, "offsetInEndSection": 1322, "text": "The first-line treatment of severe malaria is now intravenous artesunate which is more effective than quinine in endemic areas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30885541"}, {"offsetInBeginSection": 22, "offsetInEndSection": 305, "text": "as recently undergone a rapid decline in Plasmodium falciparum transmission following combined malaria control interventions with artemisinin-based combination therapy (ACT) and integrated vector control. Artesunate-amodiaquine (ASAQ) was implemented as first-line treatment for unco", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22966778"}, {"offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "BACKGROUND: In 2006, the Senegalese National Malaria Control Programme recommended artemisinin-based combination therapy (ACT) with artemether-lumefantrine as the first-line treatment for uncomplicated Plasmodium falciparum malaria.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32228566"}, {"offsetInBeginSection": 2010, "offsetInEndSection": 2075, "text": "For severe malaria, intravenous artesunate is first-line therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35916842"}, {"offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "In the early 2000s, artemisinin-based combination therapy (ACT) was introduced as first-line treatment for uncomplicated Plasmodium falciparum malaria in virtually all endemic countries.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34561157"}, {"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Artemisinin combination therapy (ACT) is the first line to treat uncomplicated Plasmodium falciparum malaria worldwide.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26483118"}, {"offsetInBeginSection": 3197, "offsetInEndSection": 3515, "text": "2. The treatment of choice for severe or complicated malaria in adults and children is intravenous artesunate (Grade 1A). Intravenous artesunate is unlicensed in the EU but is available in many centres. The alternative is intravenous quinine, which should be started immediately if artesunate is not available (Grade 1", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26880088"}, {"offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "BACKGROUND: The artemisinin derivatives are the preferred antimalaria drugs for treating severe Plasmodium falcipa", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35857773"}, {"offsetInBeginSection": 2225, "offsetInEndSection": 2422, "text": "For severe malaria, in the second and third trimester parenteral artesunate is preferred over quinine. In the first trimester, both artesunate and quinine (parenteral) may be considered as options.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23350023"}]}
+{"question_id": "65d1350f1930410b13000038", "question": "Can Rozanolixizumab be used for treatment of multiple sclerosis?", "answer": "No. Rozanolixizumab is approved for myasthenia gravis.", "relevant_passage_ids": ["37059507", "37287352", "37166675", "37602255", "37656420", "37735554", "37962198", "34735735"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Safety and efficacy of rozanolixizumab in patients with generalised myasthenia gravis (MycarinG): a randomised, double-blind, placebo-controlled, adaptive phase 3 study.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37059507"}, {"offsetInBeginSection": 3136, "offsetInEndSection": 3349, "text": "INTERPRETATION: Rozanolixizumab showed clinically meaningful improvements in patient-reported and investigator-assessed outcomes in patients with generalised myasthenia gravis, for both 7 mg/kg and 10 mg/kg doses.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37059507"}, {"offsetInBeginSection": 3508, "offsetInEndSection": 3623, "text": "Rozanolixizumab represents a potential additional treatment option for patients with generalised myasthenia gravis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37059507"}, {"offsetInBeginSection": 816, "offsetInEndSection": 1023, "text": "Additionally, several international clinical trials (e.g., rituximab, inebilizumab, ocrelizumab, bortezomib, and rozanolixizumab) for AE treatments, including anti-NMDAR encephalitis, have been implemented. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37287352"}, {"offsetInBeginSection": 726, "offsetInEndSection": 906, "text": "Post hoc analyses of the MG0002 study, a Phase 2a clinical trial of rozanolixizumab in adults with moderate to severe generalized MG, included correlation and Rasch model analyses.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37166675"}, {"offsetInBeginSection": 1192, "offsetInEndSection": 1379, "text": "Efgartigimod is already approved for the treatment of generalized MG, rozanolixizumab is under review by health authorities, and phase 3 trials of nipocalimab and batoclimab are underway.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37602255"}, {"offsetInBeginSection": 0, "offsetInEndSection": 728, "text": "Rozanolixizumab (rozanolixizumab-noli; RYSTIGGO\u00ae) is a high affinity humanized immunoglobulin G4 monoclonal antibody directed against human neonatal Fc receptor (FcRn). Administered subcutaneously, it is being developed by UCB Pharma for the treatment of autoimmune diseases and received its first approval on 27\u00a0June 2023 in the USA for the treatment of generalized myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor (AChR) or anti-muscle-specific kinase (MuSK) antibody positive. Rozanolixizumab is the first agent to be approved in the USA for both anti-AChR and anti-MuSK antibody-positive gMG. A regulatory assessment of rozanolixizumab for the treatment of gMG is currently underway in the EU and Japan.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37656420"}, {"offsetInBeginSection": 934, "offsetInEndSection": 1126, "text": "This article summarizes the milestones in the development of rozanolixizumab leading to this first approval for the treatment of gMG in adults who are anti-AChR or anti-MuSK antibody positive.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37656420"}]}
+{"question_id": "65f77701c4010b4d78000030", "question": "Are FOLFIRINOX plus Bevacizumab the preferred therapy for left-sided RAS wild type advanced colorectal cancer with aggressive clinical presentation?", "answer": "FOLFIRINOX plus bevacizumab is an option but without superior results in comparison to FOLFOX plus panitumumab for left-sided RAS wild type advanced colorectal cancer patients", "relevant_passage_ids": ["33336844", "33539032", "32107929", "30595807", "25012455", "29873679", "32704062", "34771635", "36729351", "37483589"], "type": "yesno", "snippets": [{"offsetInBeginSection": 500, "offsetInEndSection": 809, "text": "We selected patients with left-sided RAS and BRAF wild-type mCRC treated with first-line FOLFOX-panitumumab or FOLFOXIRI-bevacizumab in five randomized trials: Valentino, TRIBE, TRIBE2, STEAM, and CHARTA. A propensity score-based analysis was performed to compare FOLFOXIRI-bevacizumab with FOLFOX-panitumumab", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33336844"}, {"offsetInBeginSection": 2089, "offsetInEndSection": 2232, "text": "No significant differences were observed, but FOLFOXIRI-bevacizumab achieved numerically superior survival outcomes versus FOLFOX-panitumumab. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33336844"}, {"offsetInBeginSection": 2323, "offsetInEndSection": 2714, "text": "These observations suggest that although doublet chemotherapy plus anti-EGFRs remains the preferred treatment in patients with left-sided RAS/BRAF wild-type mCRC, FOLFOXIRI-bevacizumab is a valuable option able to provide similar, if not better, outcomes at the price of a moderate increase in toxicity and may be adopted based on patients' preference and potential impact on quality of life", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33336844"}, {"offsetInBeginSection": 46, "offsetInEndSection": 165, "text": "nts of RAS wild-type left-sided metastatic colorectal cancer (mCRC) remains controversial, and few studies focus on the", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32704062"}, {"offsetInBeginSection": 115, "offsetInEndSection": 420, "text": "survival of patients with final RAS wild-type (WT) left-sided metastatic colorectal cancer (mCRC) by 38.3 months after treatment with irinotecan, fluorouracil, and leucovorin (FOLFIRI) plus cetuximab and by 28.0 months after treatment with FOLFIRI plus bevacizumab. However, the substantial cost increase ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32107929"}, {"offsetInBeginSection": 1522, "offsetInEndSection": 2088, "text": "Chemotherapy-related adverse events were more frequent in the FOLFOXIRI-bevacizumab group, with specific regard to grade 3 and 4 neutropenia (48% vs. 26%, adjusted p = .001).CONCLUSION: Although randomized comparison is lacking, both FOLFOXIRI-bevacizumab and FOLFOX-panitumumab are valuable treatment options in left-sided RAS/BRAF wild-type mCRC.IMPLICATIONS FOR PRACTICE: A propensity score-based analysis of five trials was performed to compare FOLFOX-panitumumab versus FOLFOXIRI-bevacizumab in left-sided RAS/BRAF wild-type metastatic colorectal cancer (mCRC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33336844"}, {"offsetInBeginSection": 2323, "offsetInEndSection": 2715, "text": "These observations suggest that although doublet chemotherapy plus anti-EGFRs remains the preferred treatment in patients with left-sided RAS/BRAF wild-type mCRC, FOLFOXIRI-bevacizumab is a valuable option able to provide similar, if not better, outcomes at the price of a moderate increase in toxicity and may be adopted based on patients' preference and potential impact on quality of life.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33336844"}, {"offsetInBeginSection": 339, "offsetInEndSection": 704, "text": "No randomized comparison between FOLFOXIRI-bevacizumab versus doublets plus anti-EGFRs is available in left-sided RAS/BRAF wild-type mCRC.MATERIALS AND METHODS: We selected patients with left-sided RAS and BRAF wild-type mCRC treated with first-line FOLFOX-panitumumab or FOLFOXIRI-bevacizumab in five randomized trials: Valentino, TRIBE, TRIBE2, STEAM, and CHARTA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33336844"}, {"offsetInBeginSection": 1702, "offsetInEndSection": 1875, "text": "SION: Although randomized comparison is lacking, both FOLFOXIRI-bevacizumab and FOLFOX-panitumumab are valuable treatment options in left-sided RAS/BRAF wild-type mCRC.IMPLI", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33336844"}, {"offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "A recent subgroup analysis of the TRIBE trial suggested that FOLFOXIRI plus bevacizumab may be a preferred option for the first-line treatment of only right-sided metastatic colorectal cancer (mCRC), regardless of RAS or BRAF status.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30595807"}, {"offsetInBeginSection": 564, "offsetInEndSection": 758, "text": "Chemotherapy regimens were tailored as a doublet drug (FOLFOX/FOLFIRI) with/without targeted therapy (anti-epidermal growth factor receptor/bevacizumab) and triplet-drug combination (FOLFIRINOX)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36729351"}, {"offsetInBeginSection": 234, "offsetInEndSection": 612, "text": "Our subanalysis of a phase II trial of the FOLFOXIRI triplet regimen plus bevacizumab in patients with mCRC who had RAS mutant tumors showed that tumor shrinkage was better and the duration of treatment was longer in patients with left-sided tumors than in those with right-sided tumors, leading to a higher rate of conversion to surgery in mCRC patients with left-sided tumors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30595807"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Considering FOLFOXIRI plus bevacizumab for metastatic colorectal cancer with left-sided tumors.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30595807"}, {"offsetInBeginSection": 0, "offsetInEndSection": 770, "text": "A recent subgroup analysis of the TRIBE trial suggested that FOLFOXIRI plus bevacizumab may be a preferred option for the first-line treatment of only right-sided metastatic colorectal cancer (mCRC), regardless of RAS or BRAF status. Our subanalysis of a phase II trial of the FOLFOXIRI triplet regimen plus bevacizumab in patients with mCRC who had RAS mutant tumors showed that tumor shrinkage was better and the duration of treatment was longer in patients with left-sided tumors than in those with right-sided tumors, leading to a higher rate of conversion to surgery in mCRC patients with left-sided tumors. The early and deep responses to the triplet-regimen in patients with left-sided tumors might facilitate conversion treatment resulting in favorable survival.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30595807"}, {"offsetInBeginSection": 0, "offsetInEndSection": 612, "text": "A recent subgroup analysis of the TRIBE trial suggested that FOLFOXIRI plus bevacizumab may be a preferred option for the first-line treatment of only right-sided metastatic colorectal cancer (mCRC), regardless of RAS or BRAF status. Our subanalysis of a phase II trial of the FOLFOXIRI triplet regimen plus bevacizumab in patients with mCRC who had RAS mutant tumors showed that tumor shrinkage was better and the duration of treatment was longer in patients with left-sided tumors than in those with right-sided tumors, leading to a higher rate of conversion to surgery in mCRC patients with left-sided tumors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30595807"}, {"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "FOLFOXIRI-Bevacizumab or FOLFOX-Panitumumab in Patients with Left-Sided RAS/BRAF Wild-Type Metastatic Colorectal Cancer: A Propensity Score-Based Analysis.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33336844"}, {"offsetInBeginSection": 1385, "offsetInEndSection": 1521, "text": "A statistically nonsignificant difference in favor of FOLFOXIRI-bevacizumab was observed for OS after secondary resection of metastases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33336844"}]}
+{"question_id": "66097092fdcbea915f000010", "question": "Amyloid-\u03b2 is associated with what diseases?", "answer": "Amyloid-\u03b2 is associated with Alzheimer's disease as well as many other neurodegenerative diseases like Lewy body disease, multiple system atrophy, frontotemporal lobar degeneration, Parkinson's disease, and amyotrophic lateral sclerosis, as well as retinal neurodegenerative diseases like Glaucoma and age-related macular degeneration and progressive supranuclear palsy These proteins have also been linked to cardiovascular disease, cancer, traumatic brain injury, and diabetes", "relevant_passage_ids": ["37905874", "37652560", "26614753", "26657517", "32093040", "36687366", "25783987", "38075821", "35558050", "35892582", "29154879", "29298722", "33023198", "32582833", "29080524", "33513738", "36281662", "37556728", "36302506", "37943150", "37489069", "32183293", "32183348", "29574591", "14572915", "32341983"], "type": "list", "snippets": [{"offsetInBeginSection": 49, "offsetInEndSection": 388, "text": " amyloid-beta (A\u03b2) in neurodegenerative diseases beyond Alzheimer's disease (AD). We analyzed A\u03b2 deposition in the temporal cortex and striatum in 116 autopsies, including Lewy body disease (LBD; N\u2009=\u200951), multiple system atrophy (MSA; N\u2009=\u200910), frontotemporal lobar degeneration-TDP-43 (FTLD-TDP; N\u2009=\u200916), and progressive supranuclear palsy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37652560"}, {"offsetInBeginSection": 548, "offsetInEndSection": 985, "text": "Recent studies have indicated associations between aberrant behavior of amyloid-beta and tau proteins and various neurological diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, as well as retinal neurodegenerative diseases like Glaucoma and age-related macular degeneration. Additionally, these proteins have been linked to cardiovascular disease, cancer, traumatic brain injury, and diabetes", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37905874"}, {"offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "The amyloid hypothesis, which proposes that accumulation of the peptide amyloid-\u03b2 at synapses is the key driver of Alzheimer's disease (AD) pathogenesis, has been the dominant idea in the field of Alzheimer's research for nearly 30 years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36687366"}, {"offsetInBeginSection": 188, "offsetInEndSection": 290, "text": "Amyloid-\u03b2 (A\u03b2) is the pathological hallmark of a common neurodegenerative disorder, Alzheimer disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38075821"}, {"offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "The onset of Alzheimer's disease (AD) is associated with the presence of neurofibrillary pathology such as amyloid \u03b2 (A\u03b2) plaque", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35558050"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Amyloid-\u03b2 (A\u03b2)-peptide production or deposition in the neuropathology of Alzheimer's disease (A", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35892582"}, {"offsetInBeginSection": 137, "offsetInEndSection": 224, "text": "Excessive extra cellular deposits of amyloid beta (A\u03b2) are a pathological feature of AD", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29154879"}, {"offsetInBeginSection": 82, "offsetInEndSection": 164, "text": "Accumulation of amyloid-\u03b2 (A\u03b2) in the brain is considered central in AD pathogenes", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29298722"}, {"offsetInBeginSection": 278, "offsetInEndSection": 420, "text": "The cardinal features of AD include extracellular accumulation of amyloid \u03b2 (A\u03b2) and intracellular deposits of hyper-phosphorylated tau (p-tau", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33023198"}, {"offsetInBeginSection": 564, "offsetInEndSection": 787, "text": "a. The accumulation of A\u03b2 and iron in drusen, the hallmark of AMD, and A\u03b2 and p-tau in retinal ganglion cells (RGC), the main retinal cell type implicated in glaucoma, and accompanying inflammation suggest overlapping patho", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33023198"}, {"offsetInBeginSection": 486, "offsetInEndSection": 635, "text": " CSF amyloid beta (A\u03b2)42, total tau, and Mini-Mental State Exam (MMSE) scores in a cohort comprising AD patients (n = 14) and non-demented controls (", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32582833"}, {"offsetInBeginSection": 265, "offsetInEndSection": 498, "text": "Histopathological hallmarks of AD are intracellular neurofibrillary tangles and extracellular formation of senile plaques composed of the amyloid-beta peptide (A\u03b2) in aggregated form along with metal-ions such as copper, iron or zinc", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29080524"}, {"offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "The amyloid-\u03b2 (A\u03b2) peptides are associated with two prominent diseases in the brain, Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33513738"}, {"offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Alzheimer's Disease is a progressive manifestation of aging associated with accumulated Amyloid \u03b2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36281662"}, {"offsetInBeginSection": 149, "offsetInEndSection": 309, "text": "A\u03b242 is the dominant component of cored parenchymal plaques associated with AD, while A\u03b240 is the predominant component of vascular amyloid associated with CAA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33513738"}, {"offsetInBeginSection": 183, "offsetInEndSection": 337, "text": "Amyloids of the amyloid-\u03b2 peptide or the protein \u03b1-synuclein are traditionally considered hallmarks of Alzheimer's and Parkinson's diseases, respectively.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37556728"}, {"offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "It is known that oligomers of amyloid-\u03b2 (A\u03b2) peptide are associated with Alzheimer's disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36302506"}, {"offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with memory decline and cognitive impairment, which is related to hallmark protein aggregates, amyloid-\u03b2 (\u0410\u03b2) plaques and neurofibrillary tangles; the latter are accumulated with hyperphosphorylated Tau protein.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37943150"}, {"offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Amyloid-\u03b2 in Alzheimer's disease - front and centre after all?", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36687366"}, {"offsetInBeginSection": 0, "offsetInEndSection": 502, "text": "Cerebral amyloid angiopathy (CAA) is the most frequent cause of lobar hemorrhages in the brains of elderly individuals. It is characterized by the deposition of amyloidogenic proteins in the vessel wall of leptomeningeal and/or intracerebral blood vessels. Different proteins can cause CAA. Most frequently, the amyloid \u03b2 protein (A\u03b2) is found to be deposited in CAA and indicates a link to Alzheimer's disease, because A\u03b2 is known to be deposited in amyloid plaques characteristic of Alzheimer's disea", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37489069"}, {"offsetInBeginSection": 0, "offsetInEndSection": 378, "text": "Insurmountable evidence has demonstrated a strong association between Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA), along with various other cerebrovascular diseases. One form of CAA, which is the accumulation of amyloid-beta peptides (A\u03b2) along cerebral vessel walls, impairs perivascular drainage pathways and contributes to cerebrovascular dysfunction in AD", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32183293"}, {"offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Cerebral amyloid angiopathy (CAA) is a cerebrovascular disease directly implicated in Alzheimer's disease (AD) pathogenesis through amyloid-\u03b2 (A\u03b2) deposition, which may cause the development and progression of dementi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32183348"}, {"offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Cerebral amyloid angiopathy (CAA) is caused by the deposition of the amyloid \u03b2-protein (A\u03b2) in the wall of cerebral and leptomeningeal blood vessels and is related to Alzheimer's disease (AD", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29574591"}, {"offsetInBeginSection": 134, "offsetInEndSection": 268, "text": "The most common type of CAA is caused by amyloid beta-protein (Abeta), which is particularly associated with Alzheimer's disease (AD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14572915"}, {"offsetInBeginSection": 90, "offsetInEndSection": 217, "text": "Amyloid-\u03b2, a product of amyloid precursor protein, is associated with neuro-inflammation in patients with Alzheimer's diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25783987"}, {"offsetInBeginSection": 298, "offsetInEndSection": 471, "text": "These highly ordered protein aggregates have been, for a long time, mainly associated with human neurodegenerative diseases such as Alzheimer's disease (Amyloid-\u03b2 peptides).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32093040"}, {"offsetInBeginSection": 503, "offsetInEndSection": 641, "text": "This review examines whether amyloid-\u03b2 is associated with other biomarkers indicative of early Alzheimer's disease in normal older people.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26614753"}, {"offsetInBeginSection": 0, "offsetInEndSection": 443, "text": "Several pathophysiological functions of the human \u03b2-amyloid precursor protein (APP) have been recently proposed in different human diseases such as neurodevelopmental and neurodegenerative disorders including rare diseases such as autism, fragile X syndrome, amyotrophic lateral sclerosis, multiple sclerosis, Lesch-Nyhan disease; common and complex disorders such as Alzheimer's disease; metabolic disorders such as diabetes; and also cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32341983"}, {"offsetInBeginSection": 61, "offsetInEndSection": 119, "text": "amyloid-\u03b2 peptides, being a defining feature of Alzheimer'", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26657517"}]}
+{"question_id": "660c0071fdcbea915f00002b", "question": "Which tick genus is the vector for Lyme disease?", "answer": "Ixodes is the tick genus that is known to be a vector for Lyme disease. Specifically, Ixodes scapularis, also known as the blacklegged tick or deer tick, is the primary vector of Lyme disease in the United States and Canada. Other species within the Ixodes genus, such as Ixodes holocyclus in Australia, have also been implicated in the transmission of Lyme disease.", "relevant_passage_ids": ["37042198", "36958955", "36944114"], "type": "factoid", "snippets": [{"offsetInBeginSection": 316, "offsetInEndSection": 330, "text": "Ixodes ricinus", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37042198"}, {"offsetInBeginSection": 132, "offsetInEndSection": 149, "text": "Ixodes scapularis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36958955"}, {"offsetInBeginSection": 53, "offsetInEndSection": 65, "text": "Ixodes ticks", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36944114"}]}
+{"question_id": "660c44f7fdcbea915f000033", "question": "Can lactate levels predict mortality in paediatric sepsis?", "answer": "Yes, lactate can predict mortality in paediatric sepsis.", "relevant_passage_ids": ["34612847", "32861227", "32041465", "28068437", "36377152", "33785937", "23100008", "31315759", "28367008", "29519240", "9255650", "32278589", "38002822", "37962487", "37794545", "26320678", "28220227", "36945991", "21814374", "23818093", "27405903", "36082644", "28072671", "22357468"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1429, "offsetInEndSection": 1862, "text": " In children with sepsis/severe sepsis/septic shock, chronic conditions, oncologic diagnosis, use of vasoactive/inotropic agents, mechanical ventilation, serum lactate, platelet count, fibrinogen, procalcitonin, multi-organ dysfunction syndrome, Pediatric Logistic Organ Dysfunction score, Pediatric Index of Mortality-3, and Pediatric Risk of Mortality score each demonstrated significant and consistent associations with mortality.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34612847"}, {"offsetInBeginSection": 239, "offsetInEndSection": 1486, "text": "parameters.DESIGN: Prospective clinical study of children with sepsis syndrome or septic shock.SETTING: Paediatric intensive care unit in a tertiary referral centre.PATIENTS: 31 children with sepsis syndrome or septic shock.INTERVENTIONS: A tonometer was passed into the stomach via the orogastric route.MEASUREMENTS AND MAIN RESULTS: The following data were recorded at admission, 12, 24 and 48 h: heart rate, mean arterial pressure, arterial pH, base deficit, arterial lactate, gastric intramucosal pH (pHi) and DCO2 (intramucosal carbon dioxide tension minus arterial partial pressure of carbon dioxide). The principal outcome measure was. The secondary outcome measure was the number of organ systems failing at 48 h after admission. There were 10 deaths and 21 survivors. No variable discriminated survival from death at presentation. Blood lactate level was the earliest discriminator of survival. Using univariate logistic regression, lactate discriminated survivors from those who died at 12 and 24 h after admission, but not at 48 h (p = 0.049, 0.044 and 0.062, respectively). The area under the receiver operating characteristic (ROC) curve for lactate was 0.81, 0.88 and 0.89 at 12, 24 and 48 h, respectively. At 12 h after admission, a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9255650"}, {"offsetInBeginSection": 543, "offsetInEndSection": 746, "text": "The highest area under the curve value for the lactate/albumin ratio was detected at the 24th h. Conclusion: Lactate/albumin ratio can be used to predict mortality in children with nosocomial infections.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37962487"}, {"offsetInBeginSection": 2515, "offsetInEndSection": 2718, "text": "The base deficit and heart rate did not identify non-survivors from survivors at any time in the first 48 h.CONCLUSIONS: Blood lactate level was the earliest predictor of outcome in children with sepsis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9255650"}, {"offsetInBeginSection": 845, "offsetInEndSection": 1275, "text": "Compared to CRP and lactate, the area under the ROC curve revealed a good discriminative power of PCT to predict septic shock and mortality, 0.91 (95% CI: 0.83-0.97) and 0.80 (95% CI: 0.69-0.88), respectively.CONCLUSIONS: In contrast to CRP and lactate, the determination of PCT in pediatric intensive care unit admission is a good predictor of mortality and septic shock and can stratify patients according to severity of sepsis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26320678"}, {"offsetInBeginSection": 1245, "offsetInEndSection": 1547, "text": "The lactate level of neonates who could not survive was 5.68\u00b11.22 as compared to who were discharged 4.11\u00b11.14 (p-Value, <0.05).CONCLUSIONS: Higher blood lactate levels and lactate clearance of less than 10% at 6 hours of admission in nursery are significant predictors of mortality in neonatal sepsis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36377152"}, {"offsetInBeginSection": 1108, "offsetInEndSection": 1294, "text": "Although CRP, CRP/albumin ratio, albumin, and lactate levels are all linked to mortality in children, CRP and the CRP/albumin ratio have lower predictive values than albumin and lactate.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38002822"}, {"offsetInBeginSection": 1379, "offsetInEndSection": 1552, "text": "SIONS: Higher blood lactate levels and lactate clearance of less than 10% at 6 hours of admission in nursery are significant predictors of mortality in neonatal sepsis. Earl", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36377152"}, {"offsetInBeginSection": 899, "offsetInEndSection": 1217, "text": "s subsequent lactate levels were significantly higher in nonsurvivors. A lactate value of more than 45 mg/dl (5 mmol/l) at 0-3, 12, and 24 h of PICU admission had an odds ratio for death of 6.7, 12.5, and 8.6 (95% CI: 1.044-42.431, 1.850-84.442, 1.241-61.683) with a positive predictive value (PPV) of 38%, 71%, 64% an", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21814374"}]}
+{"question_id": "65d136f41930410b1300003d", "question": "What is the use of fezolinetant?", "answer": "Fezolinetant is an oral, small molecule, neurokinin 3 receptor (NK3R) antagonist, approved for moderate to severe vasomotor symptoms (VMS) or hot flashes due to menopause.", "relevant_passage_ids": ["36734148", "36470539", "37343519", "37462862", "33724119", "37974591", "31415087", "32102086", "34048742", "37541194", "37808928", "38016166", "38035319"], "type": "summary", "snippets": [{"offsetInBeginSection": 111, "offsetInEndSection": 239, "text": "OBJECTIVE: We aimed to assess efficacy/safety of fezolinetant for treatment of moderate to severe VMS associated with menopause.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36734148"}, {"offsetInBeginSection": 1512, "offsetInEndSection": 1654, "text": "CONCLUSION: Daily fezolinetant 30 and 45 mg were efficacious and well tolerated for treating moderate to severe VMS associated with menopause.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36734148"}, {"offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Fezolinetant is a neurokinin 3 receptor antagonist under investigation for treatment of menopausal symptoms. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37343519"}, {"offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "Fezolinetant (VEOZAH\u2122) is an oral, small molecule, neurokinin 3 receptor (NK3R) antagonist, which is being developed by Astellas Pharma Inc. for the treatment of moderate to severe vasomotor symptoms (VMS) or hot flashes due to menopause.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37462862"}, {"offsetInBeginSection": 165, "offsetInEndSection": 351, "text": "NK3 receptor antagonism has emerged as a novel therapeutic strategy, leading to the recent FDA approval of fezolinetant, a first-in-class nonhormonal treatment for menopausal hot flashes", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37541194"}, {"offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Fezolinetant (VEOZAH\u2122) is an oral, small molecule, neurokinin 3 receptor (NK3R) antagonist, which is being developed by Astellas Pharma Inc. for the treatment of moderate to severe vasomotor symptoms (VMS)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37462862"}, {"offsetInBeginSection": 464, "offsetInEndSection": 589, "text": "Fezolinetant received its first approval in the USA in May 2023 for the treatment of moderate to severe VMS due to menopause.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37462862"}, {"offsetInBeginSection": 1334, "offsetInEndSection": 1596, "text": "Treatment-emergent adverse events were largely mild/moderate; no serious treatment-related treatment-emergent adverse events occurred.CONCLUSIONS: Fezolinetant is a well-tolerated, effective nonhormone therapy that rapidly reduces moderate/severe menopausal VMS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32102086"}, {"offsetInBeginSection": 165, "offsetInEndSection": 352, "text": "NK3 receptor antagonism has emerged as a novel therapeutic strategy, leading to the recent FDA approval of fezolinetant, a first-in-class nonhormonal treatment for menopausal hot flashes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37541194"}, {"offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Fezolinetant is a neurokinin 3 receptor antagonist under investigation for treatment of menopausal symptoms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37343519"}, {"offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Fezolinetant is a neurokinin 3 receptor antagonist under investigation for treatment of menopausal symptoms", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37343519"}, {"offsetInBeginSection": 968, "offsetInEndSection": 1127, "text": "Fezolinetant's oral availability makes it a convenient and accessible option for women seeking relief from VMS, potentially improving their overall well-being.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37808928"}, {"offsetInBeginSection": 2620, "offsetInEndSection": 2768, "text": "Fezolinetant 45 mg once daily was statistically significantly more effective than other non-HTs in reducing the frequency of moderate to severe VMS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38016166"}, {"offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Post-Menopausal Quality of Life Claims: Overlooking the Requirements of Normal Science and Fundamental Measurement in ICER'S Cost-Effectiveness Assessment of Fezolinetant for Moderate to Severe Vasomotor Symptoms.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38035319"}, {"offsetInBeginSection": 1582, "offsetInEndSection": 1844, "text": "The most common fezolinetant-related adverse event was gastrointestinal disorder (n = 6).CONCLUSIONS: Fezolinetant rapidly and significantly reduced moderate/severe VMSs, supporting its potential as an effective nonhormonal treatment option for menopausal women.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31415087"}, {"offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Fezolinetant: A New Nonhormonal Treatment for Vasomotor Symptoms.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37974591"}, {"offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Fezolinetant in the treatment of vasomotor symptoms associated with menopause.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33724119"}, {"offsetInBeginSection": 259, "offsetInEndSection": 403, "text": "The NK3 receptor antagonist fezolinetant is currently in phase 3 development for treatment of moderate to severe VMS associated with menopause. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34048742"}, {"offsetInBeginSection": 277, "offsetInEndSection": 671, "text": "Recently, the FDA approved Veozah (Fezolinetant) as a promising nonhormonal solution for moderate to severe VMS in menopause. Veozah, an innovative neurokinin 3 (NK3) receptor antagonist, targets the disrupted thermoregulation underlying VMS. It modulates neural activity within the thermoregulatory center by crossing the blood-brain barrier, offering relief from hot flashes and night sweats.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37808928"}]}
+{"question_id": "65f7764fc4010b4d7800002f", "question": "Which gene mutations confer acquired resistance to anti-EGFR therapy in advance colorectal cancer?", "answer": "In cetuximab-sensitive patients,  ARID1A, KRAS, BRAF, AKT1, PIK3CA and FGFR1 or ERBB2 mutations are associated to acquired resistance", "relevant_passage_ids": ["31653970", "36117191", "22722830", "25993166", "27341591", "26318427", "24913799", "26416732", "28424201", "23152013", "36007218", "37948593", "37924647", "37628934", "37597246", "37310146", "37038676", "36351210", "31587152", "28133136", "23729478", "20088793", "24676216", "20718710", "29140271", "29700206", "38064878", "23997942", "33204026", "28368335", "25628445", "23404247", "23997940", "37285606", "24158971", "26798432", "31678702", "34315006"], "type": "list", "snippets": [{"offsetInBeginSection": 653, "offsetInEndSection": 813, "text": "In cetuximab-sensitive patients, we found KRAS K117N and A146T mutations in addition to BRAF V600E, AKT1 E17K, PIK3CA E542K, and FGFR1 or ERBB2 amplifications. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31653970"}, {"offsetInBeginSection": 495, "offsetInEndSection": 603, "text": "ARID1A mutations may provide both an acquired and intrinsic mechanism of resistance to anti-EGFR therapies. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36117191"}, {"offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Overcoming the hurdles: surmounting acquired resistance to anti-EGFR therapy in metastatic colorectal cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37948593"}, {"offsetInBeginSection": 139, "offsetInEndSection": 242, "text": "Molecular\u00a0'hyperselection'\u00a0may optimize EGFR inhibition by detecting additional resistance alterations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37924647"}, {"offsetInBeginSection": 3, "offsetInEndSection": 136, "text": " somatic variants are predictors of resistance to anti-EGFR therapy for colorectal cancer (CRC) and affect the outcome of the disease", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37628934"}, {"offsetInBeginSection": 14, "offsetInEndSection": 239, "text": "Activating RAS gene mutations occur in approximately 55% of patients with metastatic colorectal cancer (mCRC) and are associated with poorer clinical outcomes due to epidermal growth factor receptor (EGFR) blockade resistance", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37597246"}, {"offsetInBeginSection": 1954, "offsetInEndSection": 2129, "text": "R pathway is incomplete without KRAS. The activation of PI3K significantly contributes to acquiring resistance to a mixture of MEK inhibitors and anti-EGFR in colorectal cance", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37038676"}, {"offsetInBeginSection": 502, "offsetInEndSection": 616, "text": "mutations may provide both an acquired and intrinsic mechanism of resistance to anti-EGFR therapies. We find that,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36117191"}, {"offsetInBeginSection": 36, "offsetInEndSection": 1193, "text": "Epidermal Growth Factor Receptor (EGFR), such as cetuximab and panitumumab, have evolved to important therapeutic options in metastatic colorectal cancer (CRC). However, almost all patients with clinical response to anti-EGFR therapies show disease progression within a few months and little is known about mechanism and timing of resistance evolution. Here we analyzed plasma DNA from ten patients treated with anti-EGFR therapy by whole genome sequencing (plasma-Seq) and ultra-sensitive deep sequencing of genes associated with resistance to anti-EGFR treatment such as KRAS, BRAF, PIK3CA, and EGFR. Surprisingly, we observed that the development of resistance to anti-EGFR therapies was associated with acquired gains of KRAS in four patients (40%), which occurred either as novel focal amplifications (n = 3) or as high level polysomy of 12p (n = 1). In addition, we observed focal amplifications of other genes recently shown to be involved in acquired resistance to anti-EGFR therapies, such as MET (n = 2) and ERBB2 (n = 1). Overrepresentation of the EGFR gene was associated with a good initial anti-EGFR efficacy. Overall, we identified predictive", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24676216"}, {"offsetInBeginSection": 792, "offsetInEndSection": 960, "text": "acquired resistance to anti-EGFR monoclonal antibodies. However, high-sensitivity techniques should be used to enable the identification of a wide set of gene mutations", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26318427"}, {"offsetInBeginSection": 1793, "offsetInEndSection": 2058, "text": "mutations to further increase the power of patient selection for anti-EGFR therapy. These advances allow us to truly enter a new and exciting era of individualized therapy in oncology. Here we review the molecular basis of EGFR-targeted therapies and the resistance", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20088793"}, {"offsetInBeginSection": 294, "offsetInEndSection": 602, "text": "In addition, we find that patients with ARID1A mutations, at baseline, are associated with worse outcome when treated with cetuximab- but not bevacizumab-containing therapies; thus, this suggests that ARID1A mutations may provide both an acquired and intrinsic mechanism of resistance to anti-EGFR therapies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36117191"}, {"offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "PURPOSE: Acquired resistance to anti-epidermal growth factor receptor (EGFR) inhibitor (EGFRi) therapy in colorectal cancer (CRC) has previously been explained by the model of acquiring new mutations in KRAS/NRAS/EGFR, among other MAPK-pathway members.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36351210"}, {"offsetInBeginSection": 603, "offsetInEndSection": 786, "text": "We find that, ARID1A and EGFR-pathway genetic alterations are mutually exclusive across lung and colorectal cancers, further supporting a functional connection between these pathways.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36117191"}, {"offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "ARID1A mutations confer intrinsic and acquired resistance to cetuximab treatment in colorectal cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36117191"}, {"offsetInBeginSection": 1669, "offsetInEndSection": 2062, "text": "By contrast, commonly acquired resistance alterations in the MAPK pathway do not affect sensitivity to cytotoxic chemotherapy.CONCLUSION: These findings support a model of resistance whereby transcriptomic mechanisms of resistance predominate in the presence of active cytotoxic chemotherapy combined with EGFRi, with a greater predominance of acquired MAPK mutations after single-agent EGFRi.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36351210"}, {"offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Most colorectal (CRC) tumors are dependent on EGFR/KRAS/BRAF/MAPK signaling activation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36117191"}, {"offsetInBeginSection": 742, "offsetInEndSection": 870, "text": "Genomic alterations, such as mutations in KRAS, NRAS, and BRAF, often bypass the EGFR receptor, promoting resistance to therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37948593"}, {"offsetInBeginSection": 1037, "offsetInEndSection": 1197, "text": "It is well established in CRC that mutations in KRAS are predictive of resistance to EGFR pathway inhibition, and may predict for a poorer outcome with therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20718710"}, {"offsetInBeginSection": 505, "offsetInEndSection": 604, "text": "The resistance mechanisms to EGFR-targeted therapies can be categorized as resistant gene mutations", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29140271"}, {"offsetInBeginSection": 1463, "offsetInEndSection": 1770, "text": "Among the above 59 acquired resistance patients, those with PIK3CA or RAS mutations detected in ctDNA showed a pronounced decrease in progression-free survival than patients with no mutation.Conclusions: The PIK3CA mutations may potentially contribute to acquired cetuximab resistance in patients with mCRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28424201"}, {"offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722830"}, {"offsetInBeginSection": 977, "offsetInEndSection": 1202, "text": "Analysis of metastases from patients who developed resistance to cetuximab or panitumumab showed the emergence of KRAS amplification in one sample and acquisition of secondary KRAS mutations in 60% (6 out of 10) of the cases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722830"}, {"offsetInBeginSection": 728, "offsetInEndSection": 976, "text": "Expression of mutant KRAS under the control of its endogenous gene promoter was sufficient to confer cetuximab resistance, but resistant cells remained sensitive to combinatorial inhibition of EGFR and mitogen-activated protein-kinase kinase (MEK).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722830"}, {"offsetInBeginSection": 1069, "offsetInEndSection": 1306, "text": "Biomarkers, including EGFR overexpression, EGFR gene copy number, EGFR and KRAS mutations, and circulating tumor DNA, have been associated with improved clinical efficacy with anti-EGFR mAbs in patients with NSCLC and acquired resistance", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38064878"}, {"offsetInBeginSection": 955, "offsetInEndSection": 1291, "text": "Secondary resistance mutations (n\u2009=\u200916 patients) were observed most frequently in the PI3K pathway (n\u2009=\u20096) and in receptor tyrosine kinases (n\u2009=\u20094), leading to increased upstream signalling.CONCLUSIONS: Genetic alterations in the PI3K and upstream receptor tyrosine kinases were mostly associated with intrinsic and acquired resistance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33204026"}, {"offsetInBeginSection": 289, "offsetInEndSection": 883, "text": "The clinical efficacy of EGFR targeted antibodies is limited by the development of acquired (secondary) resistance, which typically occurs within 3-12 months from the start of therapy. Preclinical models and analyses of clinical samples have uncovered some of the alterations that confer a selective advantage to tumor cells when under the pressure of anti-EGFR therapy. Molecular profiling of clinical specimens confirmed that genetic alterations of genes in the EGFR-RAS-RAF-MEK signaling pathway and of receptor tyrosine kinases are mechanisms of acquired resistance to anti-EGFR antibodies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24913799"}, {"offsetInBeginSection": 679, "offsetInEndSection": 1368, "text": "A further clinical concern is that K-Ras wild type patients who initially respond to EGFR inhibitors eventually develop acquired resistance to these agents and experience tumour progression. Studies from the use of related agents in other disease settings as well as pre-clinical studies provide important insights into mechanisms by which this may occur. While no evidence presently exists for somatic mutations as a basis for acquired resistance to EGFR inhibitors in colon cancer, several studies implicate upregulation and signaling via other Her family members, c-Met, IGFR and Src. Upregulation of the pro-angiogenic factor, VEGF, is also a possible mechanism of acquired resistance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20718704"}, {"offsetInBeginSection": 741, "offsetInEndSection": 994, "text": "LTS: ctDNA identified 12 genes with increased mutation frequency after anti-EGFR therapy, including EGFR (P = .0007), KRAS (P = .0017), LRP1B (P = .0046), ZNF217 (P = .0086), MAP2K1 (P = .018), PIK3CG (P = .018), BRAF (P = .048), and NRAS (P = .048). Ac", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36007218"}, {"offsetInBeginSection": 153, "offsetInEndSection": 319, "text": "In addition, previous studies identified mutations in ERBB2, FGFR1, PDGFRA, BRAF, MAP2K1, PTEN, and PIK3CA as potential mechanisms of resistance to anti-EGFR therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28133136"}, {"offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Acquired resistance to EGFR-targeted therapies in\u00a0colorectal cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24913799"}, {"offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "New findings on primary and acquired resistance to anti-EGFR therapy in metastatic colorectal cancer: do all roads lead to RAS?", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26318427"}, {"offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Numerous inherent and acquired genetic alterations have been demonstrated with resistance to anti-epidermal growth factor receptor (anti-EGFR) therapy in metastatic colorectal cancer (mCRC) patients", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31587152"}, {"offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "Multiple genomic changes caused by clonal evolution induced by therapeutic pressure and corresponding intratumoral heterogeneity have posed great challenges for personalized therapy against metastatic colorectal cancer (mCRC) in the past decade", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29700206"}, {"offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Purpose: Mutations in KRAS are considered to be the main drivers of acquired resistance to epidermal growth factor receptor (EGFR) blockade in patients with metastatic colorectal cancer (mCRC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28424201"}, {"offsetInBeginSection": 536, "offsetInEndSection": 976, "text": "Here we show that molecular alterations (in most instances point mutations) of KRAS are causally associated with the onset of acquired resistance to anti-EGFR treatment in colorectal cancers. Expression of mutant KRAS under the control of its endogenous gene promoter was sufficient to confer cetuximab resistance, but resistant cells remained sensitive to combinatorial inhibition of EGFR and mitogen-activated protein-kinase kinase (MEK).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722830"}, {"offsetInBeginSection": 435, "offsetInEndSection": 976, "text": "The molecular bases of secondary resistance to cetuximab in colorectal cancer are poorly understood. Here we show that molecular alterations (in most instances point mutations) of KRAS are causally associated with the onset of acquired resistance to anti-EGFR treatment in colorectal cancers. Expression of mutant KRAS under the control of its endogenous gene promoter was sufficient to confer cetuximab resistance, but resistant cells remained sensitive to combinatorial inhibition of EGFR and mitogen-activated protein-kinase kinase (MEK).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722830"}, {"offsetInBeginSection": 0, "offsetInEndSection": 653, "text": "Our understanding of the genetic and nongenetic molecular alterations associated with anti-epidermal growth factor receptor (EGFR) therapy resistance in colorectal cancer (CRC) has markedly expanded in recent years. Mutations in RAS genes (KRAS/NRAS exons 2, 3, or 4) predict a lack of clinical benefit when anti-EGFR monoclonal antibodies (mAbs) are added to chemotherapy. Genetic events in additional nodes of the mitogen-activated protein kinase (MAPK)-phosphoinositide 3-kinase (PI3K) pathways that bypass EGFR signaling, such as BRAF or PIK3CA mutations or KRAS, ERBB2, or MET amplifications, also may confer resistance to cetuximab or panitumumab.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25993166"}, {"offsetInBeginSection": 0, "offsetInEndSection": 373, "text": "Our understanding of the genetic and nongenetic molecular alterations associated with anti-epidermal growth factor receptor (EGFR) therapy resistance in colorectal cancer (CRC) has markedly expanded in recent years. Mutations in RAS genes (KRAS/NRAS exons 2, 3, or 4) predict a lack of clinical benefit when anti-EGFR monoclonal antibodies (mAbs) are added to chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25993166"}, {"offsetInBeginSection": 435, "offsetInEndSection": 727, "text": "The molecular bases of secondary resistance to cetuximab in colorectal cancer are poorly understood. Here we show that molecular alterations (in most instances point mutations) of KRAS are causally associated with the onset of acquired resistance to anti-EGFR treatment in colorectal cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722830"}, {"offsetInBeginSection": 316, "offsetInEndSection": 727, "text": "After an initial response, secondary resistance invariably ensues, thereby limiting the clinical benefit of this drug. The molecular bases of secondary resistance to cetuximab in colorectal cancer are poorly understood. Here we show that molecular alterations (in most instances point mutations) of KRAS are causally associated with the onset of acquired resistance to anti-EGFR treatment in colorectal cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722830"}, {"offsetInBeginSection": 536, "offsetInEndSection": 1202, "text": "Here we show that molecular alterations (in most instances point mutations) of KRAS are causally associated with the onset of acquired resistance to anti-EGFR treatment in colorectal cancers. Expression of mutant KRAS under the control of its endogenous gene promoter was sufficient to confer cetuximab resistance, but resistant cells remained sensitive to combinatorial inhibition of EGFR and mitogen-activated protein-kinase kinase (MEK). Analysis of metastases from patients who developed resistance to cetuximab or panitumumab showed the emergence of KRAS amplification in one sample and acquisition of secondary KRAS mutations in 60% (6 out of 10) of the cases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722830"}, {"offsetInBeginSection": 373, "offsetInEndSection": 523, "text": "nce to anti-EGFR therapies act through acquired mutations of KRAS and the EGFR ectodomain. Mutations in cross-talking molecular effectors that partici", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28368335"}, {"offsetInBeginSection": 978, "offsetInEndSection": 1128, "text": "lved in acquired resistance to anti-EGFR therapies, such as MET (n = 2) and ERBB2 (n = 1). Overrepresentation of the EGFR gene was associated with a g", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24676216"}, {"offsetInBeginSection": 1006, "offsetInEndSection": 1156, "text": "dictive markers for matched targeted therapies in CRC, including BRAF V600E and RNF43 mutations. Furthermore, the microsatellite instable hypermutated", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27341591"}, {"offsetInBeginSection": 51, "offsetInEndSection": 208, "text": "in colorectal cancer (CRC) progression and their occurrence is associated with lack of response to anti epidermal growth factor receptor (EGFR) targeted ther", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23404247"}, {"offsetInBeginSection": 34, "offsetInEndSection": 1191, "text": "gene testing prior to using anti-epidermal growth factor receptor(EGFR)antibodies for colorectal cancer patients has been established in past randomized clinical trials. Thus, testing for the 7 most common mutations of KRAS codons 12 and 13 is now recommended as a clinical practice. However, pooled analysis of randomized controlled studies in Western countries in patients treated with cetuximab has suggested that patients with tumors showing the KRAS p. G13D mutation[a glycine(G)to aspartate(D)transition mutation] have longer overall survival and progression-free survival when compared to patients with other KRAS mutations. Furthermore, even among patients whose tumors are wild-type for KRAS codons 12 and 13, response rates are only 13~17% for anti-EGFR antibody monotherapy. These facts suggest that additional activating mutations in the RAS-RAF-MAPK or PI3K-AKT-mTOR pathways may also confer resistance to anti-EGFR antibody therapies. Indeed, recent retrospective studies have shown that mutations in KRAS codon 61 and 146, BRAF, NRAS, and PIK3CA may also predict resistance to anti-EGFR antibodies in colorectal cancer patients. On the other ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23152013"}, {"offsetInBeginSection": 1371, "offsetInEndSection": 1539, "text": "patients with acquired resistance to EGFR blockade. Amplifications and sequence changes in the tyrosine kinase receptor adaptor gene IRS2 were identified in tumours wit", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26416732"}, {"offsetInBeginSection": 13, "offsetInEndSection": 278, "text": "(EGFR)-targeted monoclonal antibodies are effective in a subset of metastatic colorectal cancers. Inevitably, all patients develop resistance, which occurs through emergence of KRAS mutations in approximately 50% of the cases. We show that amplification of the MET ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23729478"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1017, "text": "PURPOSE: Anti-epidermal growth factor receptor (EGFR) antibodies are effective treatments for metastatic colorectal cancer. Improved understanding of acquired resistance mechanisms may facilitate circulating tumor DNA (ctDNA) monitoring, anti-EGFR rechallenge, and combinatorial strategies to delay resistance.METHODS: Patients with treatment-refractory metastatic colorectal cancer (n = 169) enrolled on the CO.26 trial had pre-anti-EGFR tissue whole-exome sequencing (WES) compared with baseline and week 8 ctDNA assessments with the GuardantOMNI assay. Acquired alterations were compared between patients with prior anti-EGFR therapy (n = 66) and those without. Anti-EGFR therapy occurred a median of 111 days before ctDNA assessment.RESULTS: ctDNA identified 12 genes with increased mutation frequency after anti-EGFR therapy, including EGFR (P = .0007), KRAS (P = .0017), LRP1B (P = .0046), ZNF217 (P = .0086), MAP2K1 (P = .018), PIK3CG (P = .018), BRAF (P = .048), and NRAS (P = .048). Acquired mutations appear", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36007218"}, {"offsetInBeginSection": 389, "offsetInEndSection": 553, "text": "In an era of emphasis on refining therapy, the presence of KRAS mutation will predict for resistance and limit exposure to patients who are more likely to benefit. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23997940"}, {"offsetInBeginSection": 335, "offsetInEndSection": 680, "text": "Many biomarkers, including KRAS and NRAS mutations, BRAF mutations, PIK3CA mutations, PTEN loss, AREG and EREG expression, and HER-2 amplification have already been identified to select responders to anti-EGFR agents. Among these alterations KRAS and NRAS mutations are currently recognized as the best predictive factors for primary resistance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26318427"}, {"offsetInBeginSection": 321, "offsetInEndSection": 637, "text": "BRAF V600E somatic mutation and human epidermal growth factor receptor (HER2) amplification/overexpression have been separately implicated in primary resistance to anti-EGFR therapeutic strategies via aberrant activation of the mitogen-activated protein kinase (MAPK) signaling pathway, resulting in poorer outcomes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37285606"}, {"offsetInBeginSection": 0, "offsetInEndSection": 460, "text": "RAS mutation is an established predictive biomarker of resistance to anti-epidermal growth factor receptor(EGFR)therapy in metastatic colorectal cancer. In addition, previous studies identified mutations in ERBB2, FGFR1, PDGFRA, BRAF, MAP2K1, PTEN, and PIK3CA as potential mechanisms of resistance to anti-EGFR therapy. Testing for these mutations might be necessary to determine eligibility for anti-EGFR therapy in patients with metastatic colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28133136"}, {"offsetInBeginSection": 215, "offsetInEndSection": 1351, "text": "Using preclinical models and patients' samples we recently reported that the emergence of KRAS mutations but also KRAS amplification is associated with acquired resistance to the EGFR inhibitors cetuximab or panitumumab. We reasoned that KRAS amplification may also be responsible for primary resistance to these agents. Furthermore, while the prevalence of KRAS mutations has been well established in CRC, little is known about the frequency of KRAS amplification in large CRC series. We performed a screening of 1,039 CRC samples to assess the prevalence of KRAS amplification in this tumor type and further evaluated the role of this genetic alteration on the sensitivity to anti EGFR therapies. We detected KRAS amplification in 7/1,039 (0.67%) and 1/102 evaluable CRC specimens and cell lines, respectively. KRAS amplification was mutually exclusive with KRAS mutations. Tumors or cell lines harboring this genetic lesion are not responsive to anti-EGFR inhibitors. Although KRAS amplification is an infrequent event in CRC, it might be responsible for precluding response to anti-EGFR treatment in a small proportion of patients. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23404247"}, {"offsetInBeginSection": 131, "offsetInEndSection": 389, "text": "The identification of KRAS mutations as markers of resistance to epidermal growth factor receptor (EGFR) inhibitors has paved the way to the interrogation of numerous other markers of resistance to anti-EGFR therapy, such as NRAS, BRAF, and PI3KCA mutations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24158971"}, {"offsetInBeginSection": 247, "offsetInEndSection": 385, "text": "KRAS codon 12 activating mutation is a predominate mechanism of resistance to EGFR inhibitors in around 40% of patients with advanced CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23997942"}, {"offsetInBeginSection": 355, "offsetInEndSection": 960, "text": "However, anti-EGFR therapies have limited usage due to approximately 95% of patients with KRAS mutated mCRC do not response to anti-EGFR treatment. Thus, KRAS mutation is predictive of nonresponse to anti-EGFR therapies but it alone is not a sufficient basis to decide who should not be received such therapies because; approximately fifty percent (40%-60%) of CRC patients with wild-type KRAS mutation also have poor response to anti-EGFR based treatment. This fact leads us to suspect that there must be other molecular determinants of response to anti-EGFR therapies which have not been identified yet.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26798432"}, {"offsetInBeginSection": 200, "offsetInEndSection": 446, "text": "Although the common oncogenic driver mutations identified include KRAS, NRAS, BRAF, and PI3K, recent studies report a vital role played by human epithelial growth factor receptor-2 (HER2) amplification in acquired resistance to anti-EGFR therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31587152"}, {"offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "INTRODUCTION: KRAS and EGFR ectodomain-acquired mutations in patients with metastatic colorectal cancer (mCRC) have been correlated with acquired resistance to anti-EGFR monoclonal anti", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25628445"}, {"offsetInBeginSection": 645, "offsetInEndSection": 971, "text": "1, and 146 and EGFR 492 mutations.RESULTS: Plasma analyses showed newly detectable EGFR and KRAS mutations in 5/62 [8%; 95% confidence interval (CI) 0.02-0.18] and 27/62 (44%; 95% CI 0.3-0.56) samples, respectively. KRAS codon 61 and 146 mutations were predominant (33% and 11%, respectively), and multiple EGFR and/or KRAS mu", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25628445"}, {"offsetInBeginSection": 673, "offsetInEndSection": 1310, "text": "Further research into predictive biomarkers is therefore essential, but has, to date, been conducted with considerable limitations. Whilst molecular heterogeneity has been demonstrated by several studies in mCRC, for incomprehensible reasons, multiple resistant genetic alterations that emerge under the selective pressure of EGFR-targeted therapies are somehow able to influence the biological and clinical behaviour of cancer cells, despite being detectable at extremely low frequencies. Intriguingly, these subclonal events largely seem to converge on RAS/RAF/MAPK pathway in patients treated with EGFR-targeted monoclonal antibodies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31678702"}, {"offsetInBeginSection": 511, "offsetInEndSection": 850, "text": "Multiple genetic alterations driving resistance to anti-EGFR monoclonal antibodies have been described, with significant overlap in primary and acquired resistance mechanisms, in line with a clonal selection process. Some of them have been validated as targets for therapeutic intervention in clinical trials, such as ERBB2 amplifications.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27341591"}, {"offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Recurrent gene mutations and copy number alterations in cancer patients are presumably associated with resistance to targeted therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34315006"}, {"offsetInBeginSection": 494, "offsetInEndSection": 838, "text": "Moreover, we identified the emergent gene mutations (CDK6, EPHA3, ERCC2, MYC, PCMTD1, PIK3CA, PRIM2, RICTOR, and ZNRF3) and copy number alterations (ARAF, BCL2, BRCA2, EGFR, MYC, and SMAD4) that were recurrently observed only in postprogression samples and not in pretreatment or posttreatment samples from patients revealing clinical response.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34315006"}]}
+{"question_id": "66080f4cfdcbea915f000004", "question": "List the methods for pectus excavatum repair?", "answer": "Patients with Pectus Excavatum can be treated both surgically and non surgically with the vacuum bell procedure. The minimally invasive surgical procedure is called the Nuss operation.", "relevant_passage_ids": ["37417215", "36891368", "34815370", "37451288", "35221034", "25754479", "33841932", "20155340", "26982189", "24274344", "38025581", "38016849", "20533731", "18675637", "15318043", "37559617", "24413644", "35722532", "29078501", "19632565", "34847730", "36389300", "31207243", "36881966", "22323132", "25129214", "23275928", "37942345", "37965534", "12062277", "16779689", "17467429", "28757834"], "type": "list", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Treatment of pectus excavatum with vacuum bell during puberty.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37417215"}, {"offsetInBeginSection": 936, "offsetInEndSection": 1115, "text": "This review highlights contemporary management principles of pectus excavatum in the pediatric population, comprising preoperative evaluation, surgical and non-surgical treatment,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36891368"}, {"offsetInBeginSection": 27, "offsetInEndSection": 244, "text": "ectus excavatum is the most common congenital chest wall anomaly, the hallmark of which is the caved-in appearance of the anterior chest. A growing body of literature exists surrounding methods of surgical correction,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36891368"}, {"offsetInBeginSection": 12, "offsetInEndSection": 297, "text": "The purpose of this study was to compare 1-year clinical outcomes between patients who underwent a Nuss operation or vacuum bell therapy and to present vacuum bell therapy as a possible alternative treatment modality for patients who prefer non-surgical correction of pectus excavatum.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34815370"}, {"offsetInBeginSection": 13, "offsetInEndSection": 256, "text": "Pectus excavatum deformities are usually repaired with a minimally invasive approach in which a metal bar is used to correct the chest wall abnormality. We aimed to evaluate long-term outcomes and patient satisfaction after surgical correction", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37451288"}, {"offsetInBeginSection": 21, "offsetInEndSection": 142, "text": "The management of post-operative pain after surgical repair of pectus excavatum with the Ravitch procedure is challenging", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38025581"}, {"offsetInBeginSection": 12, "offsetInEndSection": 187, "text": "Metal allergy following placement of a metal pectus bar for minimally invasive repair of pectus excavatum (MIRPE) is a rare complication with potentially significant morbidity", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38016849"}, {"offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "The minimally invasive repair of pectus excavatum (MIRPE) is widely accepted as a method of pectus excavatum (PE) repair.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37559617"}, {"offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Objectives: Since its introduction, the Nuss minimally invasive procedure for pectus excavatum (PE) repair (MIRPE) has become the method of choice.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35722532"}, {"offsetInBeginSection": 137, "offsetInEndSection": 463, "text": "The standard operative treatment of pectus excavatum has been the Ravitch's technique that requires the exposition of the thorax's anterior region with resection of the costal cartilages affected bilaterally, the performance of a cross sternal osteotomy with the placing of a stabiliser, and the development of muscular flaps.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24413644"}, {"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Minimally invasive surgery (Nuss procedure) is being accepted rapidly as a preferred method for pectus excavatum repair.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20533731"}, {"offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Minimally invasive repair of pectus excavatum or the Nuss procedure has become the standard operation for pectus excavatum repair.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35221034"}, {"offsetInBeginSection": 684, "offsetInEndSection": 932, "text": "Minimally invasive repair of pectus excavatum (MIRPE) was used in 213 patients (42%) during the entire period of time.RESULTS: As for the 295 patients operated on by the open Holcomb and Welch method, the outcome was excellent in 239 (81%) of them.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24274344"}, {"offsetInBeginSection": 136, "offsetInEndSection": 298, "text": "For pectus excavatum, the surgical technique includes conservative sub-perichondral resection of deformed costal cartilages and detachment of the xiphoid process.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19632565"}, {"offsetInBeginSection": 1571, "offsetInEndSection": 1797, "text": "Conclusions: In this pilot study, taulinoplasty technique was as safe as the MIRPE approach and effective for the correction of PE, reducing surgical time, ICU and hospital LOS, and achieving better postoperative pain control.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34847730"}, {"offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Background: Thoracoscopic-assisted Nuss repair is a commonly used method for treating pectus excavatum, which has always been performed under tracheal intubation and general anesthesia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36389300"}, {"offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "BACKGROUND: National data is limited on pectus excavatum, the most common chest wall deformity which is often repaired using the Ravitch and Nuss procedures.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33841932"}, {"offsetInBeginSection": 345, "offsetInEndSection": 536, "text": "The surgical repair of the cleft sternum and pectus excavatum was performed with a modified Ravitch procedure, closure of the defect with stainless steel wires, and insertion of a pectus bar.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31207243"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "The minimally invasive repair of pectus excavatum (MIRPE), or Nuss procedure, is regarded as the gold standard technique for the treatment of symptomatic pectus excavatum.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36881966"}, {"offsetInBeginSection": 317, "offsetInEndSection": 511, "text": "Since it's initial description, numerous surgical techniques have been developed to correct PE, with the Ravtich (open) and Nuss (minimally invasive) procedures being the most commonly employed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22323132"}, {"offsetInBeginSection": 352, "offsetInEndSection": 437, "text": "The Nuss and Ravitch procedures are established methods of surgical correction of PE.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25129214"}, {"offsetInBeginSection": 89, "offsetInEndSection": 235, "text": "There are many surgical methods to correct pectus excavatum such as the Ravitch method, Wada method, Silastic mold method, and the Nuss operation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23275928"}, {"offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "The Nuss procedure for pectus excavatum (PE) is both less invasive and very simple compared to the Ravitch procedure", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37942345"}, {"offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Combined Ravitch and Nuss procedure for pectus excavatum with dyspnea following scoliosis repair.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37965534"}, {"offsetInBeginSection": 0, "offsetInEndSection": 497, "text": "OBJECTIVE: We report our initial 3 years 4 months' single institution experience in 31 consecutive patients with pectus excavatum treated with minimally invasive endoscopic pectus excavatum repair utilizing a modification of the 'Nuss' technique.METHODS: Under general anesthesia, a curved steel bar is individually shaped for each patient to match the ideal chest wall shape and is placed through an endoscopically created retrosternal tunnel between two bilateral midaxillary line 2-cm incisions", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12062277"}, {"offsetInBeginSection": 100, "offsetInEndSection": 529, "text": " Redo open repair (Highly Modified Ravitch Repair, HMRR) or minimally invasive repair of pectus excavatum (MIRPE) are usually performed in indicated cases. This paper focuses on the evaluation of available redo surgical techniques in adult and adolescent patients with recurrent pectus excavatum.METHODS: 126 operative corrections, predominantly in adult patients, were performed by the authors between June 2006 and October 2014", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25754479"}, {"offsetInBeginSection": 168, "offsetInEndSection": 2793, "text": "correction. Whereas extensive and combined deformities of the ventral chest wall are classically corrected using a so-called minimally invasive repair of the pectus excavatum, a modified Ravitch repair, or the minimized Erlangen repair, plastic surgeons are mostly challenged with alloplastic implant corrections of mild funnel chests. The authors have introduced an endoscopic method for placement of customized implants to restore the visible and nonfunctionally disturbing deformation of mild funnel chests when only the sternal plate is involved. This study compared these different plastic surgical and thoracic surgical approaches in a multicenter experience to develop a clinical algorithm and to identify those patients not requiring bony correction but rather alloplastic endoscopic implant correction alone.METHODS: Patients with deformed rib cages and sternal plates were treated with the Erlangen minimally invasive procedure or a modified Ravitch procedure. For deformities involving the sternal bones only, endoscopically assisted minimally invasive implantation of silastic implants was performed.RESULTS: Between 1987 and 2003, 599 patients with a pectus excavatum deformity were treated surgically by the authors' group. Between 1999 and 2003, 515 patients underwent surgery using the Erlangen minimally invasive repair technique at Friedrich-Alexander University-Erlangen. In addition, 84 patients underwent surgery at the Freiburg University Medical Center. In the current series, 79 patients underwent surgery using the modified Ravitch method. The mean patient age was 20.5 years (range, 3-54 years), and the rate of postoperative relapses was 5%. The findings showed that 73% of the patients judged the aesthetic result as excellent to good, and 20% were satisfied. In contrast, only five patients were suitable for soft tissue augmentation only. Two of these patients in the initial period received custom implants presternally via classical transverse skin incisions, whereas three patients were treated with endoscopic customized implant tissue augmentation.CONCLUSION: Whereas with combined deformity of the sternal plate and the rib cage, a modified Ravitch repair yields good results, the endoscopic soft tissue correction with customized implants helps to avoid unsightly scars, allows for safe hemostasis in the dissection pocket, and leads to enhanced patient satisfaction. In the case of major chest wall deformity with orthopedic and functional relevance, a combination of the minimally invasive procedures (e.g., endoscopic correction and Erlangen repair) seems to show both optimized cosmet", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16779689"}, {"offsetInBeginSection": 327, "offsetInEndSection": 970, "text": "Traditionally, repair of the defect was performed with a major open operation, the most common being based on modifications of the Ravitch procedure. In the late 1990's, the operative approach was challenged with a new minimally invasive technique described by Dr. Donald Nuss. This approach utilizes thoracoscopic visualization with small incisions and placement of a temporary metal bar positioned behind the sternum for support it while the costal cartilages remodel. Since introduction, the minimally invasive repair of pectus excavatum (MIRPE) has become accepted in many centers as the procedure of choice for repair of pectus excavatum.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29078501"}, {"offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "OBJECTIVE: Minimally invasive repair of pectus excavatum has been established as the preferred technique for the repair of funnel chest deformity. Original techniques of pectus bar placement have been modified to improve the safety of the ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17467429"}, {"offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "PURPOSE: The Ravitch and minimally invasive Nuss procedures have brought widespread relief to children with pectus excavatum, chest wall deformities, over the last half ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18675637"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1908, "text": "Surgical correction of pectus excavatum in children has gained new momentum since the introduction of the new minimally invasive repair by Nuss. To date, no studies directly evaluate the outcome of the new technique versus that of the conventional technique. From 2000 to 2002, 28 patients underwent pectus excavatum correction in the authors' hospital. Twenty-one were treated by minimally invasive repair of pectus excavatum and seven patients had open correction. Intraoperative and postoperative complications, clinical outcome, and patient satisfaction were evaluated. In the minimally invasive repair of pectus excavatum group, the children were younger (14.4 +/- 2.9 versus 17.8 +/- 3.2 years), had shorter operation times (53 +/- 18 versus 125 +/- 6 minutes), and had less blood loss (minimal versus 380 +/- 175 ml). No intraoperative complications were recorded. In the conventional group, two pleural lacerations occurred. Early postoperative complications in the minimally invasive repair group included two pneumothoraces and one case of pleural effusion. In the conventional group, one pneumothorax and one case of pleural effusion occurred. Late postoperative complications in the Nuss group included one costal erosion, two bar dislocations, one severe wound infection requiring bar removal, one hematothorax, and one case of postpericardiotomy syndrome; in the conventional group, there was one severe wound infection. In both groups, the patients rated their cosmetic results as good to very good. Minimally invasive repair of pectus excavatum is a novel method with clear advantages, such as limited surgical trauma and small scars. The high rate of postoperative complications may decrease with growing experience in the future. In well-selected patients (age, symmetric deformity), the Nuss procedure may become the method of choice. However, there is still a lack of long-term follow-up.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15318043"}, {"offsetInBeginSection": 227, "offsetInEndSection": 574, "text": "ion criteria. The highly modified Ravitch correction (HMRR) and minimally invasive pectus excavatum repair (MIRPE) are by far the most popular methods of correction. MIRPE has been established as the method of choice amongst children. Feasibility of the minimally invasive approach in the funnel chest correction in adult population still remains ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26982189"}, {"offsetInBeginSection": 655, "offsetInEndSection": 1004, "text": "Earlier, open surgical correction in the form of the Ravitch procedure was followed. Currently, in the era of minimally invasive surgery, Nuss technique (pectus bar procedure) is a promising step in chest wall reconstructive surgery for pectus excavatum. Reverse Nuss is a corrective, minimally invasive surgery for pectus carinatum chest deformity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28757834"}, {"offsetInBeginSection": 480, "offsetInEndSection": 1254, "text": "The methods of surgical repair remain controversial. The traditional method, first described by Ravitch, comprises resection of deformed cartilages and correction of the sternum by wedge osteotomy in the upper sternal cortex. Ravitch's methods have been modified using autologous or exogenous materials to fix the lower sternum. Nuss reported a novel method in which neither an anterior wound nor the cutting of cartilage or sternum is required; instead, a convex metal bar is placed behind the sternum. We have reported sternocostal elevation, in which a section of costal cartilage is resected, and all of the cartilage stumps are resutured to the sternum. The secured ribs pull the sternum bilaterally, such that the resultant force causes the sternum to rise anteriorly.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20155340"}]}
+{"question_id": "660d27e3fdcbea915f000039", "question": "Impact of pollution on asthma.", "answer": "Air pollution and climate change have a significant impact on human health and well-being and contribute to the onset and aggravation of allergic rhinitis and asthma among other chronic respiratory diseases. High exposure to indoor allergens (house dust mites, pets, molds, etc), tobacco smoke, and other pollutants, which have an impact on respiratory health. Outdoor air pollution derived from traffic and other human activities not only has a direct negative effect on human health but also enhances the allergenicity of some plants. The effects of indoor air pollution, outdoor air pollution, and subsequent climate change on asthma and allergic rhinitis in children and adults. Air pollution has a negative impact on asthma outcomes in both adult and pediatric populations. The effect of various outdoor and indoor pollutants on asthma. Traffic-related air pollution, nitrogen dioxide and second-hand smoking (SHS) exposures represent significant risk factors for asthma development in children. Exposure to outdoor pollutants can induce asthma symptoms, exacerbations and decreases in lung function. Indoor pollutants such as heating sources and molds can also negatively impact the course of asthma.", "relevant_passage_ids": ["31916265", "32867076"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Air pollution and climate change have a significant impact on human health and well-being and contribute to the onset and aggravation of allergic rhinitis and asthma among other chronic respiratory diseases", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31916265"}, {"offsetInBeginSection": 382, "offsetInEndSection": 533, "text": "high exposure to indoor allergens (house dust mites, pets, molds, etc), tobacco smoke, and other pollutants, which have an impact on respiratory health", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31916265"}, {"offsetInBeginSection": 535, "offsetInEndSection": 709, "text": "Outdoor air pollution derived from traffic and other human activities not only has a direct negative effect on human health but also enhances the allergenicity of some plants", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31916265"}, {"offsetInBeginSection": 924, "offsetInEndSection": 1064, "text": "effects of indoor air pollution, outdoor air pollution, and subsequent climate change on asthma and allergic rhinitis in children and adults", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31916265"}, {"offsetInBeginSection": 166, "offsetInEndSection": 260, "text": "air pollution has a negative impact on asthma outcomes in both adult and pediatric populations", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32867076"}, {"offsetInBeginSection": 330, "offsetInEndSection": 387, "text": "effect of various outdoor and indoor pollutants on asthma", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32867076"}, {"offsetInBeginSection": 514, "offsetInEndSection": 671, "text": "Traffic-related air pollution, nitrogen dioxide and second-hand smoking (SHS) exposures represent significant risk factors for asthma development in children", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32867076"}, {"offsetInBeginSection": 787, "offsetInEndSection": 890, "text": "Exposure to outdoor pollutants can induce asthma symptoms, exacerbations and decreases in lung function", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32867076"}, {"offsetInBeginSection": 1078, "offsetInEndSection": 1177, "text": "indoor pollutants such as heating sources and molds can also negatively impact the course of asthma", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32867076"}]}
+{"question_id": "660c3591fdcbea915f000031", "question": "Do elevated levels of procalcitonin help in diagnosing paediatric sepsis?", "answer": "Yes, PCT can be used to diagnose paediatric sepsis.", "relevant_passage_ids": ["31974673", "32984583", "15524419", "17260130", "38050211", "38034045", "37972690", "37972503", "37892278", "8618197", "27468879", "36093819", "36482951", "26396733", "25379046", "18363001", "34920065", "26351925", "37489147", "29567889", "15451490", "24369589", "33866721", "37593584", "32655314", "27857510", "28911289", "31639728", "29895470", "18250491"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1172, "offsetInEndSection": 1234, "text": "PCT appeared to be superior to MR-proADM in diagnosing sepsis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31974673"}, {"offsetInBeginSection": 1492, "offsetInEndSection": 1593, "text": "CRP and PCT are already included in clinical practice to assess sepsis and estimate disease severity,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31974673"}, {"offsetInBeginSection": 1893, "offsetInEndSection": 1966, "text": "PCT appeared to be superior to MR-proADM in diagnosing paediatric sepsis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31974673"}, {"offsetInBeginSection": 818, "offsetInEndSection": 919, "text": "The CRP, white blood cell, and procalcitonin (PCT) were considerably higher than the non-sepsis group", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38050211"}, {"offsetInBeginSection": 12, "offsetInEndSection": 117, "text": "There is currently no biomarker that can reliably identify sepsis, despite recent scientific advancements", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38034045"}, {"offsetInBeginSection": 113, "offsetInEndSection": 292, "text": "Procalcitonin (PCT) is a promising biomarker for the prediction of infection severity, but further studies have revealed its performance in excluding adverse outcomes of infection", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37972690"}, {"offsetInBeginSection": 970, "offsetInEndSection": 1118, "text": "Children with blood culture positive sepsis had a larger base deficit, -4 vs -1 (p\u00a0<\u00a00.01), and higher procalcitonin, 3.84 vs 0.56\u00a0ng/mL (p\u00a0<\u00a00.01).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37972503"}, {"offsetInBeginSection": 487, "offsetInEndSection": 674, "text": "Among the examined laboratory biomarkers, procalcitonin and neutrophil-to-lymphocyte ratio were the most accurate discriminators between sepsis patients and those with bacterial infection", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37892278"}, {"offsetInBeginSection": 1405, "offsetInEndSection": 2076, "text": "The present results need to be assessed with larger sample size studies.What is Known:\u2022CRP and PCT are already included in clinical practice to assess sepsis and estimate disease severity, although their sensitivity and specificity are lower than desired.\u2022ADM is a protein that has immune and vascular modulation actions, and its blood levels are increased in adult and paediatric sepsis.\u2022ADM is a promising tool for early diagnosis and prognostic assessment in adult sepsis.What is New:\u2022PCT appeared to be superior to MR-proADM in diagnosing paediatric sepsis.\u2022MR-proADM plasma levels could be a useful tool for paediatric sepsis stratification and morbidity prediction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31974673"}, {"offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "BACKGROUND: The biomarker procalcitonin (PCT) is good in detecting sepsis in postoperative pediatric trauma patients, especially those with a high suspicion of sepsis, and formulating a quick treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36093819"}, {"offsetInBeginSection": 1371, "offsetInEndSection": 1494, "text": "ivity when compared to CRP.CONCLUSION: Procalcitonin is a sensitive, independent, and useful biomarker in comparison to CRP", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26396733"}, {"offsetInBeginSection": 322, "offsetInEndSection": 466, "text": "Biomarkers such as C-reactive protein (CRP), procalcitonin (PCT), and serum amyloid A (SAA) can help in the detection of sepsis at early stages.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34920065"}, {"offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Procalcitonin (PCT) and presepsin (PSEP) are useful biomarkers for diagnosing sepsis; however, elevated PCT and PSEP levels may be observed in conditions other than sepsis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28911289"}, {"offsetInBeginSection": 1581, "offsetInEndSection": 1801, "text": "SIONS: Higher serum procalcitonin levels above 30\u2009ng/mL failed to correlate with indicators of sepsis, severity of disease (SOFA and APACHE II scores), and mortality but were associated with positive blood cultures. Lact", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32476970"}, {"offsetInBeginSection": 914, "offsetInEndSection": 1107, "text": "Based on the ROC curve analysis, it was shown that of all the biomarkers tested, only two-IL-6 and procalcitonin-had potential usefulness in the diagnosis of SIRS/sepsis in children with fever.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32655314"}, {"offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "Procalcitonin (PCT) and presepsin (PSEP) are useful biomarkers for diagnosing sepsis; however, elevated PCT and PSEP levels may be observed in conditions other than sepsis. We hypothesised that PCT and PSEP levels could increase after severe traumatic injuries.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28911289"}, {"offsetInBeginSection": 0, "offsetInEndSection": 378, "text": "Procalcitonin (PCT) and presepsin (PSEP) are useful biomarkers for diagnosing sepsis; however, elevated PCT and PSEP levels may be observed in conditions other than sepsis. We hypothesised that PCT and PSEP levels could increase after severe traumatic injuries. Trauma patients with an Injury Severity Score of \u226516 from October 2013 to September 2015 were enrolled in our study.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28911289"}, {"offsetInBeginSection": 0, "offsetInEndSection": 387, "text": "Serum procalcitonin was determined in newborn infants at the time of admission to the pediatrics or obstetrics unit. Increased levels were found in all neonates with bacterial sepsis. Neonates with viral infection, bacterial colonization, or neonatal distress had normal or slightly increased levels. These data suggest that procalcitonin might be of value in diagnosing neonatal sepsis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8618197"}, {"offsetInBeginSection": 202, "offsetInEndSection": 1710, "text": "We performed a prospective longitudinal observational study to evaluate of the role of serum biomarkers (C-reactive protein, procalcitonin, interleukin-6, presepsin) in the early diagnosis of bacteraemia (gram-negative versus gram-positive) in patients with haematological malignancies. We observed 69 febrile episodes in 33 patients (17 male, 16 female; 1.5-18.9 years, mean 7.31 years, median 5 years). Within this sample, there were 22 cases of positive blood cultures, 16 cases of sepsis, 38 cases of fever with no signs or symptoms of sepsis, and two deaths from infectious complications. All markers tested had good negative predictive value (73% - 93%). CRP was characterized by good specificity for registration bacteraemia (96%, 95% CI: 85% - 99%), but other results were inconclusive. We identified comparably balanced sensitivity (64% - 81%) and specificity (61% - 88%) for interleukin-6 and procalcitonin, and we proved their quality to predict positive blood culture and clinical signs of sepsis as well. Patients with gram-negative bacteraemia had significantly elevated levels of PCT and IL-6 in comparison with a group of patients with gram-positive bacteraemia (p = 0.04 for PCT and p = 0.005 for IL-6). Presepsin was characterized by poor specificity (27%, 95% CI: 15% - 43%) and positive predictive value (24%, 95% CI: 12 - 39%) for predicting bacteraemia, and by better sensitivity (84%, 95% CI: 55% - 98%) and specificity (58%, 95% CI: 42% - 73%) for predicting clinical signs of sepsis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27468879"}, {"offsetInBeginSection": 1284, "offsetInEndSection": 1396, "text": " Measurement of procalcitonin concentrations may be useful for early diagnosis of late onset sepsis in neonates.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15524419"}, {"offsetInBeginSection": 1453, "offsetInEndSection": 1674, "text": "Further studies are needed to better understand the application of PCT in the diagnosis of sepsis, differentiating between microbial and non-microbial infection cases and determining the therapeutic approaches for sepsis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28794881"}, {"offsetInBeginSection": 1589, "offsetInEndSection": 1705, "text": " PCT is a highly effective early diagnostic marker of neonatal infection. However, it may not be as reliable as CRP.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25379046"}, {"offsetInBeginSection": 1087, "offsetInEndSection": 1334, "text": " The semi-quantitative PCT test kit is of moderate sensitivity but poor specificity for early diagnosis of neonatal sepsis. A negative PCT test result may help to \"rule out\", while a raised CRP result helps to \"rule in\", the possibility of sepsis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18363001"}]}
+{"question_id": "65cfd7981930410b13000022", "question": "What is the mechanism of action of Zilebesiran?", "answer": "Zilebesiran, an investigational RNA interference therapeutic agent with a prolonged duration of action, inhibits hepatic angiotensinogen synthesis.", "relevant_passage_ids": ["37467498", "37706295", "37897397"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Zilebesiran, an RNA Interference Therapeutic Agent for Hypertension.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37467498"}, {"offsetInBeginSection": 130, "offsetInEndSection": 276, "text": "Zilebesiran, an investigational RNA interference therapeutic agent with a prolonged duration of action, inhibits hepatic angiotensinogen synthesis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37467498"}, {"offsetInBeginSection": 360, "offsetInEndSection": 969, "text": "Dysregulation of the renin-angiotensin system increases BP through its primary effector, Ang II (angiotensin II), which results in tissue remodeling and end-organ damage. Silencing liver angiotensinogen (the sole source of Ang II) has been achieved using novel RNA therapeutics, including the antisense oligonucleotide, IONIS-AGT (angiotensinogen)-LRX, and the small-interfering RNA, zilebesiran. Conjugation to N-acetylgalactosamine enables targeted delivery to hepatocytes, where endosomal storage, slow leakage, and small-interfering RNA recycling (for zilebesiran) result in knockdown over several months.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37706295"}, {"offsetInBeginSection": 735, "offsetInEndSection": 921, "text": "We present an analysis of the published phase I trials using zilebesiran, a siRNA targeting hepatic angiotensinogen, which reduces blood pressure (BP) by up to 20\u2009mmHg, lasting 24\u2009weeks.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37897397"}, {"offsetInBeginSection": 118, "offsetInEndSection": 462, "text": "pertension. Zilebesiran, an investigational RNA interference therapeutic agent with a prolonged duration of action, inhibits hepatic angiotensinogen synthesis.METHODS: In this phase 1 study, patients with hypertension were randomly assigned in a 2:1 ratio to receive either a single ascending subcutaneous dose of zilebesiran (10, 25, 50, 100, ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37467498"}, {"offsetInBeginSection": 130, "offsetInEndSection": 534, "text": "Zilebesiran, an investigational RNA interference therapeutic agent with a prolonged duration of action, inhibits hepatic angiotensinogen synthesis.METHODS: In this phase 1 study, patients with hypertension were randomly assigned in a 2:1 ratio to receive either a single ascending subcutaneous dose of zilebesiran (10, 25, 50, 100, 200, 400, or 800 mg) or placebo and were followed for 24 weeks (Part A).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37467498"}, {"offsetInBeginSection": 129, "offsetInEndSection": 533, "text": " Zilebesiran, an investigational RNA interference therapeutic agent with a prolonged duration of action, inhibits hepatic angiotensinogen synthesis.METHODS: In this phase 1 study, patients with hypertension were randomly assigned in a 2:1 ratio to receive either a single ascending subcutaneous dose of zilebesiran (10, 25, 50, 100, 200, 400, or 800 mg) or placebo and were followed for 24 weeks (Part A)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37467498"}, {"offsetInBeginSection": 129, "offsetInEndSection": 725, "text": " Zilebesiran, an investigational RNA interference therapeutic agent with a prolonged duration of action, inhibits hepatic angiotensinogen synthesis.METHODS: In this phase 1 study, patients with hypertension were randomly assigned in a 2:1 ratio to receive either a single ascending subcutaneous dose of zilebesiran (10, 25, 50, 100, 200, 400, or 800 mg) or placebo and were followed for 24 weeks (Part A). Part B assessed the effect of the 800-mg dose of zilebesiran on blood pressure under low- or high-salt diet conditions, and Part E the effect of that dose when coadministered with irbesartan", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37467498"}, {"offsetInBeginSection": 0, "offsetInEndSection": 533, "text": "BACKGROUND: Angiotensinogen is the sole precursor of angiotensin peptides and has a key role in the pathogenesis of hypertension. Zilebesiran, an investigational RNA interference therapeutic agent with a prolonged duration of action, inhibits hepatic angiotensinogen synthesis.METHODS: In this phase 1 study, patients with hypertension were randomly assigned in a 2:1 ratio to receive either a single ascending subcutaneous dose of zilebesiran (10, 25, 50, 100, 200, 400, or 800 mg) or placebo and were followed for 24 weeks (Part A)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37467498"}, {"offsetInBeginSection": 129, "offsetInEndSection": 276, "text": " Zilebesiran, an investigational RNA interference therapeutic agent with a prolonged duration of action, inhibits hepatic angiotensinogen synthesis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37467498"}]}
+{"question_id": "65f77ac9c4010b4d7800003c", "question": "Why does inflammatory bowel disease predispose to colorectal cancer?", "answer": "Chronic inflammation and alterations in microbiome predispose inflammatory bowel disease to colorectal cancer.  Chronic inflammation is the driver of neoplastic progression, resulting in dysplastic precursor lesions that may arise in multiple areas of the colon through a process of field cancerization. Investigations have demonstrated a potential role for the microbiome in concert with the host immune system in the development of colitis-associated colorectal cancer (CAC).", "relevant_passage_ids": ["34757143", "19596953", "29720903", "34111282", "28506682", "18461651", "15703619", "15663834", "2694348", "21409378", "15194558", "21247378", "22154103", "35432477", "37296943", "30386335", "37627182", "33541800", "29065108", "28852270", "30413188", "29875879", "21669488", "24621115", "21088413", "35416564", "33665583", "35371788", "35261946", "37884500", "21673876", "12950413", "18200660", "9802447", "36059351", "20117342", "27573894", "1511378", "8178948", "33025294", "36768278", "17602977", "36157924", "34744751", "37311872", "10223754", "32268844", "11214128", "12003711", "19317276", "11796261", "16901385", "9559208", "37663937", "37190315", "37002640", "37446747", "38002302", "37290498", "21363920", "19487293", "25592672", "22382701", "25493016", "26596926", "34338892", "24463282", "22122774", "27003989", "10872658", "22632755", "29874428", "36327438", "26674110"], "type": "summary", "snippets": [{"offsetInBeginSection": 160, "offsetInEndSection": 350, "text": "Chronic inflammation is the driver of neoplastic progression, resulting in dysplastic precursor lesions that may arise in multiple areas of the colon through a process of field cancerization", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34757143"}, {"offsetInBeginSection": 433, "offsetInEndSection": 618, "text": "preclinical investigations have demonstrated a potential role for the microbiome in concert with the host immune system in the development of colitis-associated colorectal cancer (CAC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34757143"}, {"offsetInBeginSection": 14, "offsetInEndSection": 175, "text": "inflammatory bowel disease (IBD), particularly ulcerative colitis (UC), have an increased incidence of colorectal carcinoma. The underlying mechanism is unknown,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10872658"}, {"offsetInBeginSection": 573, "offsetInEndSection": 901, "text": "Mounting evidence suggests that the risk of developing colorectal cancer (CRC) is dramatically increased in patients with chronic inflammatory disease. Chronic inflammation in IBD exposes these patients to a number of signals known to have tumorigenic effects including nuclear factor kappa B (NF-\u03baB) activation, proinflammatory", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22632755"}, {"offsetInBeginSection": 715, "offsetInEndSection": 1410, "text": "terial from patients with inflammatory bowel disease (IBD), benign polyps (AD), and colorectal cancer (CRC). The levels of epigenetic DNA modifications and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in examined tissues were determined by means of isotope-dilution automated online two-dimensional ultraperformance liquid chromatography with tandem mass spectrometry (2D-UPLC-MS/MS). The expressions of TET mRNA were measured with RT-qPCR, and the expressions of TET proteins were determined immunohistochemically.Results: IBD was characterized by the highest level of 8-oxodG among all analyzed tissues, as well as by a decrease in 5-hmdC and 5-mdC levels (at a midrange between normal colon ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29875879"}, {"offsetInBeginSection": 993, "offsetInEndSection": 1220, "text": "Therefore, a deeper understanding of the precise mechanisms by which inflammation triggers genetic alterations and disrupts intestinal homeostasis may provide insight into novel therapeutic strategies for the prevention of CAC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35416564"}, {"offsetInBeginSection": 950, "offsetInEndSection": 1074, "text": "These data provided additional mechanism of CAC initiation and supported the \"epigenetic priming model of tumor initiation\".", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33665583"}, {"offsetInBeginSection": 120, "offsetInEndSection": 232, "text": "Colitis-associated colorectal cancer (CAC) is a subtype of CRC associated with inflammatory bowel disease (IBD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35416564"}, {"offsetInBeginSection": 803, "offsetInEndSection": 992, "text": "The discovery of the biological changes that underlie the development of CAC is ongoing; however, current data suggest that chronic inflammation in IBD increases the risk of developing CAC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35416564"}, {"offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "The cumulative impact of chronic inflammation in patients with inflammatory bowel diseases predisposes to the development of inflammatory bowel disease-associated colorectal cancer [IBD-CRC].", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34111282"}, {"offsetInBeginSection": 398, "offsetInEndSection": 699, "text": "Although the etiology and pathogenesis of CAC are incompletely understood, animal models of chronic inflammation and human cohort data indicate that changes in the intestinal environment, including host response dysregulation and gut microbiota perturbations, may contribute to the development of CAC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35416564"}, {"offsetInBeginSection": 700, "offsetInEndSection": 802, "text": "Genomic alterations are a hallmark of CAC, with patterns that are distinct from those in sporadic CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35416564"}, {"offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) predisposes to colorectal cancer (CRC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37296943"}, {"offsetInBeginSection": 233, "offsetInEndSection": 397, "text": "It is well known that individuals with IBD have a 2-3 times higher risk of developing CRC than those who do not, rendering CAC a major cause of death in this group.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35416564"}, {"offsetInBeginSection": 413, "offsetInEndSection": 601, "text": "Indeed, patients with IBD colitis are six times more likely to develop colorectal cancer than the general population and have a higher frequency of multiple synchronous colorectal cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21673876"}, {"offsetInBeginSection": 344, "offsetInEndSection": 581, "text": "Colon cancer risk in inflammatory bowel disease increases with longer duration of colitis, greater anatomic extent of colitis, the presence of primary sclerosing cholangitis, family history of CRC and degree of inflammation of the bowel.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18200660"}, {"offsetInBeginSection": 116, "offsetInEndSection": 319, "text": "Although IBD-associated colorectal cancer (IBD-CRC) accounts for only 1-2% of all cases of colorectal cancer, IBD with colon involvement is among the top three high-risk conditions for colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21673876"}, {"offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "Although colorectal cancer (CRC), complicating ulcerative colitis and Crohn's disease, only accounts for 1-2% of all cases of CRC in the general population, it is considered a serious complication of the disease and accounts for approximately 15% of all deaths in inflammatory bowel disease (IBD) patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12950413"}, {"offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Patients with inflammatory bowel disease (IBD) are subject to increased risks for the development of colorectal cancer (CRC), risks that are attributed to the duration and anatomic extent of disease in patients with ulcerative colitis and Crohn's disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15663834"}, {"offsetInBeginSection": 106, "offsetInEndSection": 299, "text": "Some investigators suggest that patients with extensive colitis have a genetic predisposition to CRC and that long-standing inflammation is not of primary importance in the promotion of cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9802447"}, {"offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Patients with long-standing inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer (CRC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18200660"}, {"offsetInBeginSection": 123, "offsetInEndSection": 343, "text": "Many of the molecular alterations responsible for sporadic colorectal cancer, namely chromosomal instability, microsatellite instability, and hypermethylation, also play a role in colitis-associated colon carcinogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18200660"}, {"offsetInBeginSection": 0, "offsetInEndSection": 357, "text": "BACKGROUND: While ulcerative colitis (UC) and Crohn's disease (CD) are thought to predispose to colorectal cancer (CRC), the association has not been well studied in an older population.AIMS: The objective of our study was to evaluate the association of ulcerative colitis and Crohn's disease and colorectal cancer in a population-based, case-control study.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21409378"}, {"offsetInBeginSection": 315, "offsetInEndSection": 699, "text": "This is supported by the fact that colon cancer risk increases with longer duration of colitis, greater anatomic extent of colitis, the concomitant presence of other inflammatory manifestations such as primary sclerosing cholangitis, and the fact that certain drugs used to treat inflammation, such as 5-aminosalicylates and steroids, may prevent the development of colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15194558"}, {"offsetInBeginSection": 700, "offsetInEndSection": 907, "text": "The major carcinogenic pathways that lead to sporadic colorectal cancer, namely chromosomal instability, microsatellite instability, and hypermethylation, also occur in colitis-associated colorectal cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15194558"}, {"offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Patients with ulcerative colitis and Crohn's disease are at increased risk for developing colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15194558"}, {"offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Patients with inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease, are at increased risk of developing colon cancer, confirming that chronic inflammation predisposes to development of tumors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21247378"}, {"offsetInBeginSection": 504, "offsetInEndSection": 1100, "text": "Cancer risk increases with early onset, duration, and extent of the disease, with development of strictures, intraepithelial neoplasia, and concomitant primary sclerosing cholangitis.In contrast to the sporadic adenoma-carcinoma-sequence, UC-related CRC develops through an inflammation-intraepithelial neoplasia-carcinoma-sequence, in which genetic alterations already occur in the inflamed epithelium before the development of intraepithelial neoplasia.This article summarizes the current state of knowledge regarding UC-related carcinogenesis and its possible impact on prevention and therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37311872"}, {"offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Increased risk of colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients has been attributed to long-standing chronic inflammation, with the contribution of genetic alterations and environmental factors such as the microbiota.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34744751"}, {"offsetInBeginSection": 14, "offsetInEndSection": 366, "text": "The risk of inflammatory bowel disease-associated colorectal cancer (IBD-CRC) is known to increase with primary sclerosing cholangitis (PSC) and a family history of CRC. However, the impact of comorbidities such as liver disease, obesity, diabetes, chronic lung, heart, and renal disease, and psychiatric illness on the risk of IBD-CRC remains unclear.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36059351"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Inflammatory bowel disease (IBD) is a chronic inflammatory gastrointestinal ailment that encompasses Crohn's disease (CD) and ulcerative colitis (UC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35371788"}, {"offsetInBeginSection": 151, "offsetInEndSection": 457, "text": "UC is an idiopathic, chronic inflammatory condition of the colonic mucosa that begins in the rectum and progresses proximally in a continuous way over a portion of the entire colon. Chronic inflammation is linked to cancer, and IBD-related chronic colonic inflammation raises the risk of colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35371788"}, {"offsetInBeginSection": 600, "offsetInEndSection": 747, "text": "When CRC arises in people with IBD, unlike sporadic CRC, the lesions are difficult to identify due to mucosal alterations produced by inflammation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35371788"}, {"offsetInBeginSection": 748, "offsetInEndSection": 852, "text": "The total prevalence of IBD-associated CRC is increasing due to the rapidly increasing frequency of IBD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35371788"}, {"offsetInBeginSection": 0, "offsetInEndSection": 299, "text": "The relation between inflammatory bowel disease (IBD) and colorectal cancer (CRC) is not clearly defined. Some investigators suggest that patients with extensive colitis have a genetic predisposition to CRC and that long-standing inflammation is not of primary importance in the promotion of cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9802447"}, {"offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "BACKGROUND: Few data are available on the incidence, characteristics, treatment, and prognosis of inflammatory bowel disease (IBD)-associated colorectal cancer (CRC) in population-ba", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22467511"}, {"offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "The risk of developing dysplasia leading to colorectal cancer (CRC) is increased in both ulcerative colitis and Crohn's disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24696602"}, {"offsetInBeginSection": 0, "offsetInEndSection": 382, "text": "The cumulative impact of chronic inflammation in patients with inflammatory bowel diseases predisposes to the development of inflammatory bowel disease-associated colorectal cancer [IBD-CRC]. Inflammation can induce mutagenesis, and the relapsing-remitting nature of this inflammation, together with epithelial regeneration, may exert selective pressure accelerating carcinogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34111282"}, {"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Colorectal cancers (CRC) are known to be related to inflammatory conditions, and inflammatory bowel diseases increase the relative risk for developing CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27573894"}, {"offsetInBeginSection": 129, "offsetInEndSection": 496, "text": "Although most of the molecular alterations reported in sporadic CRC have also been observed in colitis-associated CRC, they do not occur at the same timing and frequency, indicating a different pathophysiology. In particular, recent work highlighted the importance of chronic mucosal inflammation as a key factor favouring colorectal carcinogenesis in these patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20117342"}, {"offsetInBeginSection": 333, "offsetInEndSection": 457, "text": "Chronic inflammation is linked to cancer, and IBD-related chronic colonic inflammation raises the risk of colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35371788"}, {"offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "BACKGROUND: Inflammatory bowel disease (IBD) and colorectal cancer might share a common cause and, therefore, relatives of patients with IBD could be at increased risk of this malign", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11214128"}, {"offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Colorectal cancer (CRC) is a complication in both patients with longstanding ulcerative colitis and those with Crohn's disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12003711"}, {"offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Colitis-associated colorectal cancer (CAC) is defined as a specific cluster of colorectal cancers that develop as a result of prolonged colitis in patients with inflammatory bowel disease (IBD)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37663937"}, {"offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Patients affected by inflammatory bowel disease (IBD) have a two-fold higher risk of developing colorectal cancer (CRC) than the general population", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37190315"}, {"offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Risk of colorectal neoplasia according to histologic disease activity in patients with inflammatory bowel disease and colonic post-inflammatory polyps.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37002640"}, {"offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Colorectal cancer is a known complication of chronic inflammation of the colon (\"colitis-associated colon cancer\")", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38002302"}, {"offsetInBeginSection": 88, "offsetInEndSection": 215, "text": "Inflammatory bowel disease, a risk factor for CRC, is associated with higher levels of proinflammatory cytokines and bile acids", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37290498"}, {"offsetInBeginSection": 216, "offsetInEndSection": 624, "text": "Moreover, it appears that colon cancers that do not develop as a complication of inflammatory bowel disease are also driven by inflammation, because it has been shown that regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) lowers the mortality from sporadic colon cancer and results in regression of adenomas in familial adenomatous polyposis (FAP) patients, who inherit a mutation in the Apc gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21247378"}, {"offsetInBeginSection": 1601, "offsetInEndSection": 1735, "text": "Our findings argue that senescence acts as a tumor suppressor mechanism that is abrogated during the transition from LGD to HGD in UC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21363920"}, {"offsetInBeginSection": 1443, "offsetInEndSection": 1600, "text": "These results suggest that dysplasia arises in a preneoplastic field of chronic inflammation, which leads to telomere shortening, DNA damage, and senescence.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21363920"}, {"offsetInBeginSection": 1220, "offsetInEndSection": 1445, "text": "Proinflammatory cytokines, such as TNF\u03b1, IL-6 and IL-1\u03b2, or transcription factors that are required for signaling by these cytokines, including NF-\u03baB and STATs, are indeed emerging as potential targets for anticancer therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21247378"}, {"offsetInBeginSection": 580, "offsetInEndSection": 1025, "text": "Continuing colonic inflammation has been shown to be important in the development of colorectal cancer and therefore anti-inflammatory agents have been considered potential chemopreventive agents. As present no agents have been shown to have indisputable chemopreventive activity in IBD but 5-ASAs and thiopurine analogues by reducing inflammation are likely to have some chemopreventive activity and will often be indicated for disease control.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22122774"}, {"offsetInBeginSection": 580, "offsetInEndSection": 1168, "text": "Continuing colonic inflammation has been shown to be important in the development of colorectal cancer and therefore anti-inflammatory agents have been considered potential chemopreventive agents. As present no agents have been shown to have indisputable chemopreventive activity in IBD but 5-ASAs and thiopurine analogues by reducing inflammation are likely to have some chemopreventive activity and will often be indicated for disease control. More studies are needed using agents such as aspirin and calcium which have been shown to be chemopreventive in sporadic colorectal neoplasia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22122774"}, {"offsetInBeginSection": 0, "offsetInEndSection": 556, "text": "PURPOSE OF REVIEW: Patients with inflammatory bowel disease, either Crohn disease or ulcerative colitis, are at an increased risk for developing colorectal carcinoma.RECENT FINDINGS: Surveillance colonoscopy, although never formally evaluated in a prospective controlled trial, is performed in an effort to reduce this risk. Novel methods of detecting dysplasia are constantly being evaluated, including chromoendoscopy and biomarkers of carcinoma, in an attempt to stratify patients who are at a higher risk of developing high-grade dysplasia or carcinoma", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15703619"}, {"offsetInBeginSection": 144, "offsetInEndSection": 753, "text": "Until recently, understanding of pathogenesis in inflammatory bowel disease-associated colorectal cancer was restricted to the demonstration of chromosomic/microsatellite instabilities and aneuploidy. The advance of high-throughput sequencing technologies has highlighted the complexity of the pathobiology and revealed recurrently mutated genes involved in the RTK/RAS, PI3K, WNT, and TGF\u03b2 pathways, leading to potentially new targetable mutations. Moreover, alterations of mitochondrial DNA and the dysregulation of non-coding sequences have also been described, as well as several epigenetic modifications.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32268844"}, {"offsetInBeginSection": 237, "offsetInEndSection": 606, "text": " However, despite adoption of colonoscopic surveillance programs by many clinicians, we have noted a pattern of continued referrals for inflammatory bowel disease-associated malignancy. This study was undertaken in an effort to characterize this cohort of patients.METHODS: We reviewed the operative records of a large metropolitan colorectal practice from 1983 to 1995", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10223754"}, {"offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "Inflammatory bowel diseases are characterised by inflammation that compromises the integrity of the epithelial barrier. The intestinal epithelium is not only a static barrier but has evolved complex mechanisms to control and regulate bacterial interactions with the mucosal surface.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27003989"}, {"offsetInBeginSection": 217, "offsetInEndSection": 468, "text": "Continuing colonic inflammation has been shown to be important in the development of colorectal cancer and therefore anti-inflammatory agents such as the 5-aminosalicylates and immunomodulators have been considered as potential chemopreventive agents.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24463282"}, {"offsetInBeginSection": 1970, "offsetInEndSection": 2120, "text": "anding inflammatory bowel disease. The tumors are often mucinous, multiple, and located in the left colon. Despite increasing acceptance of surveillan", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10223754"}, {"offsetInBeginSection": 93, "offsetInEndSection": 243, "text": "tal cancer (CRC), principally resulting from the pro-neoplastic effects of chronic intestinal inflammation. Epidemiologic studies continue to highligh", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29720903"}, {"offsetInBeginSection": 170, "offsetInEndSection": 331, "text": "to chronic inflammation in the intestine. Patients with IBD had a higher risk of developing colorectal carcinoma (CRC), of which the subset was classified as col", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30413188"}, {"offsetInBeginSection": 67, "offsetInEndSection": 308, "text": "times more frequently in patients with inflammatory bowel diseases (IBD) than in healthy population. CRC in IBD patients is more aggressive and needs total colectomy, which leads to permanent disability That is why canceroprevention is one o", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29874428"}, {"offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "INTRODUCTION: Patients with inflammatory bowel diseases (IBDs) of the colon are at an increased risk of colorectal", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36327438"}, {"offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Patients with long-standing ulcerative colitis and Crohn's disease have an increased risk of developing colorectal cancer and patients with small intestinal Crohn's disease are at increased risk of small bowel adenocarcinoma. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19596953"}, {"offsetInBeginSection": 0, "offsetInEndSection": 669, "text": "Ulcerative colitis and colonic Crohn's disease (together known as inflammatory bowel disease or IBD) are both associated with increased risk for colorectal cancer. Although it is customary to emphasize differences in the biology of IBD-associated and sporadic colon cancer, we believe these are far outweighed by the similarities. These similarities suggest that they might have similar pathogenic mechanisms. Because the normal colon is arguably in a continual state of low-grade inflammation in response to its microbial flora, it is reasonable to speculate that both IBD-associated and sporadic colon cancer might be the consequence of bacteria-induced inflammation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11796261"}, {"offsetInBeginSection": 0, "offsetInEndSection": 496, "text": "Patients with chronic colitis (ulcerative colitis or colonic Crohn's disease) have an increased risk of colorectal cancer (CRC). Although most of the molecular alterations reported in sporadic CRC have also been observed in colitis-associated CRC, they do not occur at the same timing and frequency, indicating a different pathophysiology. In particular, recent work highlighted the importance of chronic mucosal inflammation as a key factor favouring colorectal carcinogenesis in these patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20117342"}, {"offsetInBeginSection": 0, "offsetInEndSection": 407, "text": "Increased risk of colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients has been attributed to long-standing chronic inflammation, with the contribution of genetic alterations and environmental factors such as the microbiota. Moreover, accumulating data indicate that IBD-associated CRC (IBD-CRC) may initiate and develop through a pathway of tumorigenesis distinct from that of sporadic CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34744751"}, {"offsetInBeginSection": 0, "offsetInEndSection": 340, "text": "BACKGROUND: Inflammatory bowel disease (IBD) and colorectal cancer might share a common cause and, therefore, relatives of patients with IBD could be at increased risk of this malignant disease. We aimed to assess cancer rates among first-degree relatives of patients with IBD to try to determine whether an association between the two dise", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11214128"}, {"offsetInBeginSection": 0, "offsetInEndSection": 660, "text": "Patients with inflammatory bowel disease (IBD) face an increased lifetime risk of developing colorectal cancer (CRC). Although CRC in IBD only accounts for 1-2% of all cases of CRC in the general population, it is responsible for approximately 15% of the mortality of patients with Crohn's disease (CD) and ulcerative colitis (UC). Independent factors associated with increased risk include long disease duration, extensive colonic involvement, young age at onset of IBD, severity of inflammation, primary sclerosing cholangitis, backwash ileitis and a family history of CRC. Many of these factors emphasise the role of inflammation as an underlying mechanism.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19317276"}, {"offsetInBeginSection": 0, "offsetInEndSection": 444, "text": "BACKGROUND: Inflammatory bowel disease (IBD; including ulcerative colitis and Crohn's disease) is associated with an increased risk for colorectal cancer (CRC). Chronic mucosal inflammation is a key factor in the onset of carcinogenesis in IBD patients. Although most gene alterations that cause sporadic CRCs also occur in patients with IBD-associated CRC, some gene sequences and mutation frequencies differ between sporadic CRCs and IBD-asso", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26674110"}]}
+{"question_id": "66088ffafdcbea915f00000f", "question": "In what part of the body would a periprosthetic infection occur?", "answer": "A periprosthetic infection would occur in close to a joint or  structure in close relation to an implant.", "relevant_passage_ids": ["37380142", "29559232", "19756495", "35106346", "36200815", "21821313", "24921460", "34142445", "36683646", "37887186", "29351538", "23898349", "32238194", "31955984"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 327, "text": "BACKGROUND: The aim of the present study was to compare causative bacteria and their antibiotic resistance profiles in patients developing a periprosthetic joint infection (PJI) based on preoperative prophylactic antibiotic regimens in primary total hip (THA) and primary total and unicompartmental knee arthroplasty (TKA/UKA).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37380142"}, {"offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "OBJECTIVE: Endoprosthetic replacement surgery of hip and knee joints is widely performed, but always carries the risk of developing periprosthetic infection (PPI).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34142445"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Periprosthetic joint infection (PJI) is a potentially catastrophic complication of total joint arthroplasty of the lower extremity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35106346"}, {"offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "BACKGROUND: Periprosthetic joint infection (PJI) is a catastrophic complication that can occur following total knee arthroplasty (TKA).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36683646"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Periprosthetic joint infection (PJI) is a relatively frequent and devastating complication following prosthetic joint implantation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30374532"}, {"offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Periprosthetic joint infections are a devastating complication after arthroplasty and are associated with substantial patient morbidity. More than 25% of revisions are attributed to these infections, which are expected to increase.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26135702"}, {"offsetInBeginSection": 119, "offsetInEndSection": 403, "text": "While periprosthetic joint infection (PJI) affects a small percentage of patients, with an estimated incidence of 1-9% following primary total joint replacement, this postoperative complication necessitates a lengthy hospitalisation, extended antibiotic treatment and further surgery.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37887186"}, {"offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Periprosthetic infection is a foreign-body-associated infection that is characterised by delayed osteomyelitis of bone tissue surrounding artificial joint replacement.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19756495"}, {"offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "PURPOSE OF THE STUDY A very serious complication following joint replacement surgery is periprosthetic joint infection that can be caused by a urinary tract infection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29351538"}, {"offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Periprosthetic infection (PJI) is the most serious joint replacement complication, occurring in 0.8-1.9% of knee arthroplasties and 0.3-1.7% of hip arthroplasties.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23898349"}, {"offsetInBeginSection": 0, "offsetInEndSection": 470, "text": "BACKGROUND: Periprosthetic joint infection is a major complication of total joint replacement surgery and is associated with significant morbidity, mortality and financial burden. Surgical body suits (space suits), originally designed to reduce the incidence of infection, have paradoxically been implicated in increased periprosthetic joint infection rates recently. Air exhausted from space suits may contribute to this increased rate of periprosthetic joint infection", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29559232"}, {"offsetInBeginSection": 0, "offsetInEndSection": 366, "text": "BACKGROUND: Periprosthetic joint infection is a major complication of total joint replacement surgery and is associated with significant morbidity, mortality and financial burden. Surgical body suits (space suits), originally designed to reduce the incidence of infection, have paradoxically been implicated in increased periprosthetic joint infection rates recently", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29559232"}, {"offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "The incidences of periprosthetic fracture and periprosthetic joint infection after total hip arthroplasty are expected to increase exponentially over the coming decades. Epidemiologic data suggest that many periprosthetic fractures after THA occur concurrently with a loose femoral implant.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36200815"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1210, "text": "Prosthetic joint infection is a devastating complication of arthroplasty. Previous epidemiological studies have assessed factors associated with arthroplasty infections but have not assessed the impact of comorbidity on infection at different arthroplasty locations. We used a case-control design to investigate risk factors for prosthetic joint infection with reference to the anatomical site. During an eight-year period at a single hospital, 63 patients developed a prosthetic joint infection (36 hips, 27 knees). Cases of prosthetic hip or knee joint infection were matched 1:2 to controls. The results suggest that factors associated with arthroplasty infections differ with anatomical location. Following knee arthroplasty, wound discharge was associated with an increased risk of prosthetic joint infection whereas the presence of a drain tube reduced the risk. By contrast, increased body mass index, increased drain tube loss and superficial incisional surgical site infections (SSIs) were associated with prosthetic hip infection. When analysed as a combined cohort, systemic steroid use, increased SSI drain tube losses, wound discharge, and superficial incisional SSIs were predictors of infection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21821313"}, {"offsetInBeginSection": 430, "offsetInEndSection": 638, "text": "These findings were unique to periprosthetic joint infections (PJI) of the knee and were never observed for PJIs of other lower extremity joints (hip and ankle) or upper extremity joints (shoulder and elbow).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24921460"}, {"offsetInBeginSection": 0, "offsetInEndSection": 565, "text": "BACKGROUND: Periprosthetic joint infections (PJIs) are a major source of morbidity and mortality for patients undergoing total joint arthroplasty (TJA). Staphylococcus aureus (S. aureus) colonization is an independent, modifiable risk factor for periprosthetic joint infections. Post-operative infections are reported to be ten times greater in S. aureus carriers than in non-carriers in developed countries though recorded data is lacking for the developing world. This study aims to determine the prevalence of S. aureus colonization in patients awaiting TJA in S", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32238194"}, {"offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Prosthetic joint infection is a devastating complication of arthroplasty.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21821313"}]}
+{"question_id": "65f86b3ac4010b4d78000058", "question": "What is the estimated impact of social determinants of health on health outcomes?", "answer": "The impact of social determinants of health on health outcomes has been extensively studied and it is estimated that these factors play a significant role in shaping health outcomes. For example, studies have shown that people who experience poverty, unemployment, low education levels, poor housing conditions, and limited access to healthy food and safe living environments are more likely to develop chronic diseases, such as diabetes, cardiovascular disease, and mental health disorders. Additionally, social determinants can affect health outcomes indirectly by influencing health behaviors such as smoking, physical inactivity, and unhealthy eating habits. It is estimated that these factors can account for up to 40% of modifiable health risks. Addressing social determinants of health has the potential to improve health equity and reduce health disparities.", "relevant_passage_ids": ["37501568", "33614572", "37131177", "24532079", "33639878", "29480769", "36987604", "37843837", "37001969", "27696682", "37022779", "30815107", "33181043", "34478162", "35590354", "31133069", "20171001"], "type": "factoid", "snippets": [{"offsetInBeginSection": 658, "offsetInEndSection": 751, "text": "social determinants contribute directly and indirectly (through lifestyle) to life expectancy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37501568"}, {"offsetInBeginSection": 2230, "offsetInEndSection": 2302, "text": "community SDOH play an important role in diabetes control and management", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33614572"}, {"offsetInBeginSection": 2026, "offsetInEndSection": 2506, "text": "Children exposed to socioeconomic deprivation (SDOH pattern 3) showed the worst health profiles, manifesting more internalizing (\u03b2\u2009=\u20090.75; 95% CI, 0.14-1.37) and externalizing (\u03b2\u2009=\u20091.43; 95% CI, 0.83-2.02) mental health problems, lower cognitive performance, and adverse physical health.Conclusions: This study shows that an unbiased quantitative analysis of multidimensional SDOH can permit the determination of how SDOH patterns are associated with child developmental outcomes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37843837"}, {"offsetInBeginSection": 299, "offsetInEndSection": 609, "text": "This study examined the cumulative impact of social determinants of health on mortality in U.S. adults with CKD and diabetes.METHODS: We analyzed data from National Health and Nutrition Examination Surveys (2005-2014) for 1376 adults age 20 and older (representing 7,579,967\u2009U.S. adults) with CKD and diabetes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33639878"}, {"offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "The cumulative impact of social determinants of health factors on mortality in adults with diabetes and chronic kidney disease.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33639878"}, {"offsetInBeginSection": 632, "offsetInEndSection": 752, "text": "The findings confirm that social determinants contribute directly and indirectly (through lifestyle) to life expectancy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37501568"}, {"offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "OBJECTIVE: Interventions to tackle the social determinants of health can improve outcomes during pregnancy and early childhood, leading to better health across the l", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37001969"}, {"offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "There is substantial evidence across different healthcare contexts that social determinants of health are strongly associated with morbidity and mortality in the United States.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27696682"}, {"offsetInBeginSection": 1153, "offsetInEndSection": 1488, "text": "SDH also have a significant impact on SLE outcomes, with worse disease and psychosocial outcomes associated with lower income level, lower educational attainment, disadvantaged neighbourhoods, lack of health insurance or public health insurance in the USA, travel burden to nearest provider, anti-Black racism and lower social support.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36987604"}, {"offsetInBeginSection": 771, "offsetInEndSection": 1152, "text": "We found that adverse SDH conditions may lead to more severe SLE with increased morbidity and mortality, and that SDH affect SLE management by dictating the most feasible monitoring and treatment plan for each individual patient based on his or her specific life circumstances (for example, based on health insurance status, distance to nearest provider and/or drug affordability).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36987604"}, {"offsetInBeginSection": 140, "offsetInEndSection": 297, "text": "However, a growing body of research indicates that social determinants of health (SDH) also have substantial impact on the disparities that characterize SLE.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36987604"}, {"offsetInBeginSection": 585, "offsetInEndSection": 770, "text": "We reviewed the impact of key SDH on SLE presentation, management and outcomes, including income, education, neighbourhood factors, healthcare access, discrimination and social support.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36987604"}, {"offsetInBeginSection": 1410, "offsetInEndSection": 1588, "text": "Certain potentially positive factors like family and community resilience remain poorly studied.CONCLUSIONS: SDoHs are associated with higher rates of and worse outcomes in SSPD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37022779"}, {"offsetInBeginSection": 298, "offsetInEndSection": 584, "text": "According to the World Health Organization, SDH are defined as 'the conditions in which people are born, grow, work, live, and age', account for 30-55% of health outcomes, and adversely impact health outcomes among those of low socioeconomic status and stigmatized racial/ethnic groups.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36987604"}, {"offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "BACKGROUND: Social determinants of health (SDoHs) are receiving growing attention and are particularly relevant to persons with schizophrenia-spectrum psychotic disorders (SSPDs), considering their heightened risk of comorbidities, cognitive and functional decline, and early mortality.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37022779"}, {"offsetInBeginSection": 0, "offsetInEndSection": 368, "text": "Since the World Health Organization launched its commission on the social determinants of health (SDOH) over a decade ago, a large body of research has proven that social determinants-defined as the conditions in which people are born, grow, live, work, and age-are significant drivers of disease risk and susceptibility within clinical care and public health systems.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33181043"}, {"offsetInBeginSection": 173, "offsetInEndSection": 394, "text": "Although social determinants of health have been found to affect the mental health of a population, less information is available regarding the impact of social determinants on physical health, especially among offenders.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29480769"}, {"offsetInBeginSection": 11, "offsetInEndSection": 175, "text": "Interventions to tackle the social determinants of health can improve outcomes during pregnancy and early childhood, leading to better health across the life course", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37001969"}, {"offsetInBeginSection": 1203, "offsetInEndSection": 1595, "text": "Based on the studies reviewed, social determinants have an impact on glycemic control, LDL, and blood pressure to varying degrees. The impact on cost and quality of life was not often measured, but when quality of life was investigated, it did show significance. More research is needed to better characterize the direct impact of social determinants of health on health outcomes in diabetes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24532079"}, {"offsetInBeginSection": 1203, "offsetInEndSection": 1465, "text": "Based on the studies reviewed, social determinants have an impact on glycemic control, LDL, and blood pressure to varying degrees. The impact on cost and quality of life was not often measured, but when quality of life was investigated, it did show significance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24532079"}, {"offsetInBeginSection": 1117, "offsetInEndSection": 1558, "text": "Two social determinants factors in particular were consistently related to the health of offenders, a history of childhood abuse, and the use of social assistance. Research limitations/implications The study is limited to the use of self-report data. Additionally, the measures of social determinants of health were indicators taken from assessments that provided only rough estimates of the constructs rather than from established measures.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29480769"}, {"offsetInBeginSection": 0, "offsetInEndSection": 299, "text": "BACKGROUND: Social determinants of health (SDOHs) cluster together and can have deleterious impacts on health outcomes. Individually, SDOHs increase the risk of cancer mortality, but their cumulative burden is not well understood. The authors sought to determine the combined effect of SDOH on cance", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34478162"}, {"offsetInBeginSection": 0, "offsetInEndSection": 343, "text": "Social determinants of health (SDH) such as education and socioeconomic status are strongly associated with health and health outcomes. Incorporating SDH variables into clinical data sets could therefore improve the accuracy of predictive analytics, but individual-level SDH are rarely available and must be inferred from community-level data.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30815107"}, {"offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "BACKGROUND: Social determinants of health (SDoH) are known to have a large impact on health outcomes, but their effects are difficult to make visible. They are part of complex systems of variables largely indirect effects on multiple levels, constituting so-called wick", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35590354"}, {"offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "BACKGROUND: Low socioeconomic status (SES) is often associated with excess morbidity and premature mortality. Such health disparities claim a steep economic cost: Possibly-preventable poor health outcomes harm societal welfare, impair the domestic product, and increase health care e", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31133069"}, {"offsetInBeginSection": 1415, "offsetInEndSection": 1604, "text": "Race/ethnicity and neighborhood SES had substantial and independent influences on life expectancy, underscoring the importance of monitoring health outcomes simultaneously by these factors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20171001"}, {"offsetInBeginSection": 1605, "offsetInEndSection": 1771, "text": "African-American males living in the poorest 20% of California neighborhoods had life expectancy comparable to that reported for males living in developing countries.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20171001"}]}
+{"question_id": "660c49f4fdcbea915f000034", "question": "Should corticosteroids be considered as adjunctive therapy in paediatric sepsis management?", "answer": "No, there is uncertainty regarding the use of corticosteroids as adjunctive therapy.", "relevant_passage_ids": ["35307800", "20228689", "23537672", "17914311", "36741650", "17530137", "2661496", "31808551"], "type": "yesno", "snippets": [{"offsetInBeginSection": 940, "offsetInEndSection": 1195, "text": "Controversy remains regarding resuscitation fluid volume and type, antibiotic choices depending upon infectious risks in the patient's community, and adjunctive therapies such as vitamin C, corticosteroids, intravenous immunoglobulin, and methylene blue. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35307800"}, {"offsetInBeginSection": 658, "offsetInEndSection": 1067, "text": "Although it may be prudent to provide stress-dose steroids to children with septic shock who are clinically at risk for adrenal insufficiency (chronic or recent steroid use, purpura fulminans, etomidate or ketoconazole administration, hypothalamic, pituitary, adrenal disease), the safety and efficacy of stress-dose steroids as general adjunctive therapy for pediatric septic shock have not been established.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17914311"}, {"offsetInBeginSection": 1451, "offsetInEndSection": 1645, "text": "Accordingly, pediatric critical care researchers have a responsibility to generate pediatric-specific evidence-based medicine for adjunctive corticosteroid therapy for severe sepsis in children.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17914311"}, {"offsetInBeginSection": 1497, "offsetInEndSection": 1812, "text": "Similarly there was no difference in mean ventilator days between the corticosteroid and no corticosteroid groups, 8.3 days vs. 7.7 days, respectively, p = .38.CONCLUSIONS: Children with severe sepsis who received adjunctive corticosteroid therapy exhibited similar illness severity compared with those who did not.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20228689"}, {"offsetInBeginSection": 607, "offsetInEndSection": 1017, "text": "Within this cohort, 193 children received corticosteroids during their septic episode and 284 did not.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: Baseline summary characteristics demonstrated that children receiving or not receiving corticosteroids had similar demographics and disease severity as indicated by age, gender, mean Pediatric Risk of Mortality scores, and mean number of organ dysfunctions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20228689"}, {"offsetInBeginSection": 1606, "offsetInEndSection": 1820, "text": "Adjunctive therapy with stress dose of corticosteroid is indicated in selected populations.CONCLUSIONS: Septic shock hemodynamics is a changing process that requires frequent assessment and therapeutic adjustments.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17530137"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1873, "text": "OBJECTIVE: To assess whether corticosteroids, used as adjunctive therapy for pediatric severe sepsis, is associated with improved outcomes.DESIGN: Retrospective cohort study examining the clinical database derived from the RESOLVE (REsearching severe Sepsis and Organ dysfunction in children: a gLobal perspective, F1K-MC-EVBP) trial of activated protein C for pediatric severe sepsis.SETTING: A total of 104 pediatric centers in 18 countries from which data were originally gathered.SUBJECTS: Children with severe sepsis (n = 477), requiring both vasoactive-inotropic infusions and mechanical ventilation. Within this cohort, 193 children received corticosteroids during their septic episode and 284 did not.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: Baseline summary characteristics demonstrated that children receiving or not receiving corticosteroids had similar demographics and disease severity as indicated by age, gender, mean Pediatric Risk of Mortality scores, and mean number of organ dysfunctions. Use of adjunctive corticosteroids increased during the F1K-MC-EVBP trial. Indications for corticosteroid prescription were therapeutic (89%, mostly shock) and prophylactic (13%). All cause 28-day mortality among children receiving and not receiving corticosteroids was 15.1% and 18.8%, respectively, p = .30. There was no difference in mean vasoactive-inotropic infusion days between the corticosteroid and no corticosteroid groups, 4.5 days vs. 4.3 days, respectively, p = .59. Similarly there was no difference in mean ventilator days between the corticosteroid and no corticosteroid groups, 8.3 days vs. 7.7 days, respectively, p = .38.CONCLUSIONS: Children with severe sepsis who received adjunctive corticosteroid therapy exhibited similar illness severity compared with those who did not. No definitive improvement in outcomes can be attributable to", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20228689"}]}
+{"question_id": "65cfdc561930410b13000026", "question": "JYNNEOS vaccine is protective against which diseases?", "answer": "Jynneos is smallpox and monkeypox vaccine.", "relevant_passage_ids": ["36626099", "36752829", "36720271", "36326768", "37498796", "37440743", "37475115", "36344361", "36301741", "36146497", "37199451", "36580416", "37339074", "36115792", "37200229", "37921836", "37590262", "36480479", "36201401", "37846528", "36480476", "37102477", "36228673"], "type": "list", "snippets": [{"offsetInBeginSection": 897, "offsetInEndSection": 1029, "text": "Monkeypox may be treated with tecovirimat, cidofovir, or brincidofovir, and prevention with the vaccination JYNNEOS is recommended. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36626099"}, {"offsetInBeginSection": 117, "offsetInEndSection": 335, "text": "This case highlights magnetic resonance (MR) neurography findings in an individual who developed Parsonage-Turner syndrome (PTS) 5 days after monkeypox symptom onset and 12 days after receiving the JYNNEOS vaccination.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36752829"}, {"offsetInBeginSection": 153, "offsetInEndSection": 332, "text": "The smallpox and mpox vaccine (JYNNEOS; Modified Vaccinia Ankara-Bavarian Nordic; MVA-BN), provided as a two-dose regimen, is currently the primary vaccine utilized against mpox. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36720271"}, {"offsetInBeginSection": 1804, "offsetInEndSection": 1946, "text": "Smallpox vaccines (JYNNEOS [Bavarian Nordic] and ACAM2000 [Emergent Product Development Gaithersburg Inc]) provide immunity against monkeypox.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36326768"}, {"offsetInBeginSection": 0, "offsetInEndSection": 317, "text": "In August 2022, the Food and Drug Administration authorized JYNNEOS vaccine (modified vaccinia Ankara vaccine, Bavarian Nordic), a 2-dose series used for the prevention of Monkeypox virus infection, to be administered via a dose-sparing intradermal route, in addition to the previously authorized subcutaneous route. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37498796"}, {"offsetInBeginSection": 643, "offsetInEndSection": 784, "text": " Jynneos (smallpox and mpox vaccine, live, nonreplicating) is a live, attenuated vaccine that is safe for patients who are immunocompromised.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37440743"}, {"offsetInBeginSection": 153, "offsetInEndSection": 325, "text": "Licensed and approved for mpox, the JYNNEOS vaccine has fewer side-effects than previous smallpox vaccines and has shown immunogenicity against monkeypox in animal models. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37475115"}, {"offsetInBeginSection": 417, "offsetInEndSection": 582, "text": "HODS: We collected mixed-methods data from a convenience sample of adults presenting for JYNNEOS vaccination at three DC Health mpox vaccine clinics during August-Oc", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37921836"}, {"offsetInBeginSection": 17, "offsetInEndSection": 123, "text": "JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic) to prevent monkeypox commenced shortly", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36301741"}, {"offsetInBeginSection": 414, "offsetInEndSection": 703, "text": "(3). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic), administered subcutaneously as a 2-dose (0.5 mL per dose) series with doses administered 4 weeks apart, was approved by the Food and Drug Administration (FDA) in 2019 to prevent smallpox and monkeypox infection (4).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36201401"}, {"offsetInBeginSection": 357, "offsetInEndSection": 647, "text": "* JYNNEOS vaccine is licensed by the Food and Drug Administration (FDA) as a 0.5-mL 2-dose series administered subcutaneously 28 days apart to prevent smallpox and monkeypox infections (2) and has been found to provide protection against monkeypox infection during the current outbreak (3).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36301741"}, {"offsetInBeginSection": 123, "offsetInEndSection": 312, "text": "JYNNEOS, a Modified Vaccinia Ankara (MVA)-based live, non-replicating vaccine, was recently approved for monkeypox prevention for adults at high risk of MPXV infection in the United States.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36344361"}, {"offsetInBeginSection": 1939, "offsetInEndSection": 2083, "text": "The findings suggest that JYNNEOS vaccine was effective in preventing mpox disease, and a two-dose series appeared to provide better protection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37199451"}, {"offsetInBeginSection": 239, "offsetInEndSection": 506, "text": "JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic) was approved by the Food and Drug Administration (FDA) in 2019 for the prevention of smallpox and mpox via subcutaneous injection as a 2-dose series (0.5 mL per dose, administered 4 weeks apart) (2).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37200229"}, {"offsetInBeginSection": 679, "offsetInEndSection": 889, "text": "New York State Department of Health (NYSDOH) conducted a case-control study to estimate JYNNEOS VE against diagnosed mpox in New York residents outside of NYC, using data from systematic surveillance reporting.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37339074"}, {"offsetInBeginSection": 644, "offsetInEndSection": 784, "text": "Jynneos (smallpox and mpox vaccine, live, nonreplicating) is a live, attenuated vaccine that is safe for patients who are immunocompromised.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37440743"}, {"offsetInBeginSection": 1308, "offsetInEndSection": 1460, "text": " Currently recommended JYNNEOS vaccination among all adults at risk for mpox should be encouraged, irrespective of childhood smallpox vaccination status", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37590262"}, {"offsetInBeginSection": 359, "offsetInEndSection": 647, "text": "JYNNEOS vaccine is licensed by the Food and Drug Administration (FDA) as a 0.5-mL 2-dose series administered subcutaneously 28 days apart to prevent smallpox and monkeypox infections (2) and has been found to provide protection against monkeypox infection during the current outbreak (3).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36301741"}, {"offsetInBeginSection": 1475, "offsetInEndSection": 1598, "text": "Smallpox immunizations like JYNNEOS and ACAM2000 are also used as prophylactic measures in the case of the monkeypox virus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37102477"}, {"offsetInBeginSection": 415, "offsetInEndSection": 597, "text": "JYNNEOS vaccine was approved by the Food and Drug Administration (FDA) in 2019 as a 2-dose series (0.5 mL per dose, administered subcutaneously) to prevent smallpox and mpox disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36580416"}, {"offsetInBeginSection": 141, "offsetInEndSection": 312, "text": "l pathogen. Licensed and approved for mpox, the JYNNEOS vaccine has fewer side-effects than previous smallpox vaccines and has shown immunogenicity against monkeypox in an", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37475115"}, {"offsetInBeginSection": 214, "offsetInEndSection": 426, "text": "JYNNEOS is a live, nonreplicating viral vaccine licensed for the prevention of smallpox and mpox in adults aged \u226518 years, administered as a 0.5-mL 2-dose series given 28 days apart by subcutaneous injection (2).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36480476"}, {"offsetInBeginSection": 224, "offsetInEndSection": 719, "text": "JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic), administered subcutaneously as a 2-dose (0.5 mL per dose) series (with doses administered 4 weeks apart), was approved by the Food and Drug Administration (FDA) in 2019 to prevent smallpox and mpox disease (2); an FDA Emergency Use Authorization issued on August 9, 2022, authorized intradermal administration of 0.1 mL per dose, increasing the number of persons who could be vaccinated with the available vaccine supply\u2020 (3).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36480479"}, {"offsetInBeginSection": 688, "offsetInEndSection": 853, "text": "ACAM2000 (a live-attenuated replicating vaccine) and JYNNEOS (a live-attenuated, nonreplicating vaccine) are two US FDA-approved vaccines that can prevent monkeypox.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36146497"}, {"offsetInBeginSection": 419, "offsetInEndSection": 703, "text": "JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic), administered subcutaneously as a 2-dose (0.5 mL per dose) series with doses administered 4 weeks apart, was approved by the Food and Drug Administration (FDA) in 2019 to prevent smallpox and monkeypox infection (4).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36201401"}, {"offsetInBeginSection": 224, "offsetInEndSection": 713, "text": "JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic), administered subcutaneously as a 2-dose (0.5 mL per dose) series (with doses administered 4 weeks apart), was approved by the Food and Drug Administration (FDA) in 2019 to prevent smallpox and mpox disease (2); an FDA Emergency Use Authorization issued on August 9, 2022, authorized intradermal administration of 0.1 mL per dose, increasing the number of persons who could be vaccinated with the available vaccine supply", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36480479"}, {"offsetInBeginSection": 1246, "offsetInEndSection": 1404, "text": "Although Imvamune (JYNNEOS), a vaccine against monkeypox, is authorized in the United States, there are currently no established routine vaccination programs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36228673"}, {"offsetInBeginSection": 1952, "offsetInEndSection": 2134, "text": "This report provides additional data suggesting JYNNEOS vaccine provides protection against mpox, irrespective of whether the vaccine is administered intradermally or subcutaneously.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36480479"}, {"offsetInBeginSection": 1952, "offsetInEndSection": 2196, "text": "This report provides additional data suggesting JYNNEOS vaccine provides protection against mpox, irrespective of whether the vaccine is administered intradermally or subcutaneously. The degree and durability of such protection remains unclear.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36480479"}, {"offsetInBeginSection": 2200, "offsetInEndSection": 2319, "text": "This early finding suggests that a single dose of JYNNEOS vaccine provides some protection against monkeypox infection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36201401"}, {"offsetInBeginSection": 237, "offsetInEndSection": 648, "text": "To date, more than 27,000 cases have been reported across all 50 states, the District of Columbia (DC), and Puerto Rico.* JYNNEOS vaccine is licensed by the Food and Drug Administration (FDA) as a 0.5-mL 2-dose series administered subcutaneously 28 days apart to prevent smallpox and monkeypox infections (2) and has been found to provide protection against monkeypox infection during the current outbreak (3). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36301741"}, {"offsetInBeginSection": 2200, "offsetInEndSection": 2489, "text": "This early finding suggests that a single dose of JYNNEOS vaccine provides some protection against monkeypox infection. The degree and durability of such protection is unknown, and it is recommended that people who are eligible for monkeypox vaccination receive the complete 2-dose series.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36201401"}, {"offsetInBeginSection": 415, "offsetInEndSection": 1198, "text": "JYNNEOS vaccine was approved by the Food and Drug Administration (FDA) in 2019 as a 2-dose series (0.5 mL per dose, administered subcutaneously) to prevent smallpox and mpox disease.\u2020 On August 9, 2022, FDA issued an emergency use authorization to allow administration of JYNNEOS vaccine by intradermal injection (0.1 mL per dose) (2). A previous report on U.S. mpox cases during July 31-September 3, 2022, suggested that 1 dose of vaccine offers some protection against mpox (3). This report describes demographic and clinical characteristics of cases occurring \u226514 days after receipt of 1 dose of JYNNEOS vaccine and compares them with characteristics of cases among unvaccinated persons with mpox and with the vaccine-eligible vaccinated population in participating jurisdictions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36580416"}, {"offsetInBeginSection": 602, "offsetInEndSection": 752, "text": "ed by the Food and Drug Administration (FDA) in 2019 to prevent smallpox and monkeypox infection (4). U.S. distribution of JYNNEOS vaccine as postexpo", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36201401"}, {"offsetInBeginSection": 90, "offsetInEndSection": 240, "text": "ealth emergency by the World Health Organization in July 2022. The smallpox and mpox vaccine (JYNNEOS; Modified Vaccinia Ankara-Bavarian Nordic; MVA-B", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36720271"}, {"offsetInBeginSection": 157, "offsetInEndSection": 241, "text": "smallpox and mpox vaccine (JYNNEOS; Modified Vaccinia Ankara-Bavarian Nordic; MVA-BN", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36720271"}, {"offsetInBeginSection": 337, "offsetInEndSection": 634, "text": "Jynneos\u00ae in the U.S. (Imvamune\u00ae in Canada or Imvanex\u00ae in the Europe) and ACAM2000\u00ae (Acambis, Inc.) initially developed in the smallpox eradication program, can provide protective immunity to monkeypox, and their production and availability are rapidly scaled up in the response to the emerging thr", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36115792"}, {"offsetInBeginSection": 1330, "offsetInEndSection": 1460, "text": " JYNNEOS vaccination among all adults at risk for mpox should be encouraged, irrespective of childhood smallpox vaccination status", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37590262"}, {"offsetInBeginSection": 674, "offsetInEndSection": 805, "text": "Fenway Health administered its first dose of the Jynneos vaccine under the Emergency Use Authorization for protection against mpox.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37846528"}, {"offsetInBeginSection": 1635, "offsetInEndSection": 1813, "text": "MPXV vaccination with JYNNEOS may help ameliorate the disease and economic burden associated with monkeypox and combat potential outbreaks in areas with active virus circulation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36344361"}, {"offsetInBeginSection": 1449, "offsetInEndSection": 1634, "text": "Taken together, our data demonstrates that JYNNEOS vaccination triggers potent OPXV neutralizing antibody responses in a cohort of healthcare workers in DRC, a monkeypox-endemic region.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36344361"}, {"offsetInBeginSection": 153, "offsetInEndSection": 331, "text": "The smallpox and mpox vaccine (JYNNEOS; Modified Vaccinia Ankara-Bavarian Nordic; MVA-BN), provided as a two-dose regimen, is currently the primary vaccine utilized against mpox.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36720271"}]}
+{"question_id": "65f7798dc4010b4d78000038", "question": "What is the optimal antiemetic treatment for FOLFIRINOX chemotherapy?", "answer": "A three-drug combination of 5-hydroxytryptamine-3 receptor antagonists (5HT3RA), dexamethasone (DEX), and neurokinin 1 receptor antagonists (NK1RA) for the prevention of chemotherapy-induced nausea and vomit during FOLFORINOX therapy", "relevant_passage_ids": ["37884842", "34486707", "33023657", "34131576", "36033477", "30333194", "22316362", "3967569", "28191518", "30019968", "20413062"], "type": "factoid", "snippets": [{"offsetInBeginSection": 1255, "offsetInEndSection": 1408, "text": "CINV induced by mFFX was poorly controlled even with prophylactic antiemetic therapy using 5HT3RA, DEX, and NK1RA, and was found to persist beyond 5\u00a0days", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37884842"}, {"offsetInBeginSection": 9, "offsetInEndSection": 1039, "text": "Modified FOLFIRINOX (mFFX), a standard chemotherapy regimen for advanced pancreatic cancer (APC), is expected to be associated with a higher risk of chemotherapy-induced nausea and vomiting (CINV). Herein, we conducted a retrospective cohort study to evaluate the efficacy and safety of a three-drug combination of 5-hydroxytryptamine-3 receptor antagonists (5HT3RA), dexamethasone (DEX), and neurokinin 1 receptor antagonists (NK1RA) for the prevention of CINV during mFFX therapy.METHODS: This study enrolled patients with APC who received mFFX as initial therapy with a combination of 5HT3RA, DEX, and NK1RA as antiemetic prophylaxis. The primary endpoint was the complete response (CR) rate during cycle 1, which was defined as no emetic episodes and no rescue medication use during the overall period (0-120\u00a0h). Safety was also evaluated with a focus on hyperglycemia, which is a concern in patients with APC.RESULTS: Seventy patients were eligible for this retrospective analysis. The CR rate during the overall period was 5", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37884842"}, {"offsetInBeginSection": 1160, "offsetInEndSection": 1409, "text": "Hyperglycemia occurred in 37.1% of patients, and 34.3% were grade 3 hyperglycemia.CONCLUSIONS: CINV induced by mFFX was poorly controlled even with prophylactic antiemetic therapy using 5HT3RA, DEX, and NK1RA, and was found to persist beyond 5\u00a0days.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37884842"}, {"offsetInBeginSection": 207, "offsetInEndSection": 646, "text": "Herein, we conducted a retrospective cohort study to evaluate the efficacy and safety of a three-drug combination of 5-hydroxytryptamine-3 receptor antagonists (5HT3RA), dexamethasone (DEX), and neurokinin 1 receptor antagonists (NK1RA) for the prevention of CINV during mFFX therapy.METHODS: This study enrolled patients with APC who received mFFX as initial therapy with a combination of 5HT3RA, DEX, and NK1RA as antiemetic prophylaxis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37884842"}, {"offsetInBeginSection": 1811, "offsetInEndSection": 2152, "text": "During the acute and delayed phases, the CR rate was 72.5% and 74.8% with Folfoxiri plus Bevacizumab, as well as 75.2% and 74.6% with Folfirinox.CONCLUSIONS: This study has shown the therapeutic benefits of NEPA in the management and prophylaxis of CINV events, both in naive patients and patients previously treated with 5HT3-RA and NK1-RA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34486707"}, {"offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Efficacy and safety of 5HT3RA, DEX, and NK1RA for the prevention of FOLFIRINOX-induced nausea and vomiting in patients with pancreatic cancer: a retrospective cohort study.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37884842"}, {"offsetInBeginSection": 2384, "offsetInEndSection": 2873, "text": "Finally, chemotherapy delays (p = 0.000009) and chemotherapy dose reductions (p = 0.0000006) were less frequently observed in primary NK1-RA users.Conclusion: In patients affected by gastrointestinal malignancies, a primary CINV prophylaxis with NK1-RA, 5HT3-RA, and dexamethasone might be appropriate, particularly in those situations at higher risk of emesis and in which it is important to avoid dose delays and/or dose reductions, keeping a proper dose intensity of chemotherapy drugs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36033477"}, {"offsetInBeginSection": 1248, "offsetInEndSection": 1414, "text": "SIONS: CINV induced by mFFX was poorly controlled even with prophylactic antiemetic therapy using 5HT3RA, DEX, and NK1RA, and was found to persist beyond 5\u00a0days. Enha", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37884842"}, {"offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "NEPA (netupitant/palonosetron) for the antiemetic prophylaxis of nausea and vomiting induced by chemotherapy (CINV) with Folfirinox and Folfoxiri even during the COVID-19 pandemic: a real-life study.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34486707"}, {"offsetInBeginSection": 393, "offsetInEndSection": 481, "text": "s documenting CINV. All participants received a 5-hydroxytryptamine-3 receptor antagonis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33023657"}]}
+{"question_id": "65f857b0c4010b4d7800004f", "question": "Please list the symptoms of Havana syndrome", "answer": "In 2016 diplomatic personnel serving in Havana, Cuba, began reporting audible sensory phenomena paired with onset of complex and persistent neurological symptoms consistent with brain injury. Vestibular, cognitive, hearing, sleep, and visual symptoms,", "relevant_passage_ids": ["35962646", "34873135", "37965360", "35505689", "31770686", "30828629", "32655474", "29450484"], "type": "list", "snippets": [{"offsetInBeginSection": 132, "offsetInEndSection": 345, "text": "have experienced an abrupt onset of unusual clinical symptoms including, tinnitus, visual problems, vertigo, and cognitive difficulties, after they encountered strange sounds; this has been called \"Havana syndrome", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35962646"}, {"offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Clinical and Psychological Factors Associated With Return to Work Among United States Diplomats Who Sustained a Work-Related Injury While on Assignment in Havana, Cuba.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34873135"}, {"offsetInBeginSection": 1, "offsetInEndSection": 205, "text": "ntroduction: In 2016 diplomatic personnel serving in Havana, Cuba, began reporting audible sensory phenomena paired with onset of complex and persistent neurological symptoms consistent with brain injury.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37965360"}, {"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Diplomats representing the USA have reported with unusual neurologic symptoms and MRI changes after being posted in Havana, Cuba between late 2016 and 2018", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35505689"}, {"offsetInBeginSection": 578, "offsetInEndSection": 902, "text": "Given similarities in presentation with mild traumatic brain injury (mTBI), we used the latter as a clinically relevant means of evaluating if the neuropsychological profiles observed in Havana Syndrome Havana Syndrome might be explained at least in part by a dysregulation of neurotransmission, neuro-inflammation, or both.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37965360"}, {"offsetInBeginSection": 29, "offsetInEndSection": 161, "text": "tic personnel serving in Havana, Cuba, began reporting audible sensory phenomena paired with onset of complex and persistent neurolo", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37965360"}, {"offsetInBeginSection": 849, "offsetInEndSection": 1067, "text": "In conclusion, Havana syndrome is\u00a0a nonspecific neurological illness with an\u00a0unidentified causative factor(s), an acute phase of auditory-vestibular symptoms and a chronic phase of nonspecific neurobehavioral symptoms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35962646"}, {"offsetInBeginSection": 0, "offsetInEndSection": 352, "text": "Since 2016, numerous American and Canadian diplomats and secret (intelligence) agents in Cuba, China, and other places in the world have experienced an abrupt onset of unusual clinical symptoms including, tinnitus, visual problems, vertigo, and cognitive difficulties, after they encountered strange sounds; this has been called \"Havana syndrome\" (HS).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35962646"}, {"offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Introduction: In 2016 diplomatic personnel serving in Havana, Cuba, began reporting audible sensory phenomena paired with onset of complex and persistent neurological symptoms consistent with brain injury.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37965360"}, {"offsetInBeginSection": 0, "offsetInEndSection": 496, "text": "Importance: From late 2016 through August 2017, US government personnel serving on diplomatic assignment in Havana, Cuba, reported neurological symptoms associated with exposure to auditory and sensory phenomena.Objective: To describe the neurological manifestations that followed exposure to an unknown energy source associated with auditory and sensory phenomena.Design, Setting, and Participants: Preliminary results from a retrospective case series of US government personnel in Havana, Cuba.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29450484"}, {"offsetInBeginSection": 2439, "offsetInEndSection": 2931, "text": "Of those, 7 began graduated return to work with restrictions in place, home exercise programs, and higher-level work-focused cognitive rehabilitation.Conclusions and Relevance: In this preliminary report of a retrospective case series, persistent cognitive, vestibular, and oculomotor dysfunction, as well as sleep impairment and headaches, were observed among US government personnel in Havana, Cuba, associated with reports of directional audible and/or sensory phenomena of unclear origin.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29450484"}, {"offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Introduction: In 2016 diplomatic personnel serving in Havana, Cuba, began reporting audible sensory phenomena paired with onset of complex and persistent neurological symptoms consistent with", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37965360"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "In late 2016, diplomats in Havana, Cuba, began presenting with a unique symptom complex after perceiving a strange noise and/or feeling a pressure field in their domicile.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32655474"}, {"offsetInBeginSection": 8, "offsetInEndSection": 191, "text": "tion: In 2016 diplomatic personnel serving in Havana, Cuba, began reporting audible sensory phenomena paired with onset of complex and persistent neurological symptoms consistent with", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37965360"}, {"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Between 2016 and 2017, several U.S. Diplomats in Havana, Cuba, experienced perplexing vestibular and neurological symptoms attributed to an unknown source.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31770686"}, {"offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Diplomats representing the USA have reported with unusual neurologic symptoms and MRI changes after being posted in Havana, Cuba between late 2016 and 2018.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35505689"}, {"offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "BACKGROUND: In the Autumn of 2016, diplomatic personnel residing in Havana began to present with symptoms of dizziness, ear pain, and tinnitus that emerged after perception of high frequency noise and/or a pressure sensation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30828629"}, {"offsetInBeginSection": 734, "offsetInEndSection": 1067, "text": "While these studies provided a\u00a0constellation of signs and symptoms for HS, none provided a good level of\u00a0evidence. In conclusion, Havana syndrome is\u00a0a nonspecific neurological illness with an\u00a0unidentified causative factor(s), an acute phase of auditory-vestibular symptoms and a chronic phase of nonspecific neurobehavioral symptoms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35962646"}, {"offsetInBeginSection": 646, "offsetInEndSection": 1067, "text": "Only five original studies and 18 non-original articles were considered to be relevant. While these studies provided a\u00a0constellation of signs and symptoms for HS, none provided a good level of\u00a0evidence. In conclusion, Havana syndrome is\u00a0a nonspecific neurological illness with an\u00a0unidentified causative factor(s), an acute phase of auditory-vestibular symptoms and a chronic phase of nonspecific neurobehavioral symptoms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35962646"}, {"offsetInBeginSection": 0, "offsetInEndSection": 600, "text": "Since 2016, numerous American and Canadian diplomats and secret (intelligence) agents in Cuba, China, and other places in the world have experienced an abrupt onset of unusual clinical symptoms including, tinnitus, visual problems, vertigo, and cognitive difficulties, after they encountered strange sounds; this has been called \"Havana syndrome\" (HS). MEDLINE, Scopus, and Ovid databases from 2016 until 24 September 2021 were systematically searched for the related published manuscripts. The\u00a0following search strategy was implemented: \"Havana syndrome\" OR \"Neurological Symptoms and US Diplomats\".", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35962646"}, {"offsetInBeginSection": 849, "offsetInEndSection": 1170, "text": "In conclusion, Havana syndrome is\u00a0a nonspecific neurological illness with an\u00a0unidentified causative factor(s), an acute phase of auditory-vestibular symptoms and a chronic phase of nonspecific neurobehavioral symptoms. This syndrome should be considered and investigated as a health concern, and not as a political issue.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35962646"}, {"offsetInBeginSection": 0, "offsetInEndSection": 490, "text": "Since 2016, numerous American and Canadian diplomats and secret (intelligence) agents in Cuba, China, and other places in the world have experienced an abrupt onset of unusual clinical symptoms including, tinnitus, visual problems, vertigo, and cognitive difficulties, after they encountered strange sounds; this has been called \"Havana syndrome\" (HS). MEDLINE, Scopus, and Ovid databases from 2016 until 24 September 2021 were systematically searched for the related published manuscripts.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35962646"}, {"offsetInBeginSection": 204, "offsetInEndSection": 1066, "text": " tinnitus, visual problems, vertigo, and cognitive difficulties, after they encountered strange sounds; this has been called \"Havana syndrome\" (HS). MEDLINE, Scopus, and Ovid databases from 2016 until 24 September 2021 were systematically searched for the related published manuscripts. The\u00a0following search strategy was implemented: \"Havana syndrome\" OR \"Neurological Symptoms and US Diplomats\". The primary search yielded 120 publications. Only five original studies and 18 non-original articles were considered to be relevant. While these studies provided a\u00a0constellation of signs and symptoms for HS, none provided a good level of\u00a0evidence. In conclusion, Havana syndrome is\u00a0a nonspecific neurological illness with an\u00a0unidentified causative factor(s), an acute phase of auditory-vestibular symptoms and a chronic phase of nonspecific neurobehavioral symptoms", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35962646"}]}
+{"question_id": "660c0a85fdcbea915f000030", "question": "What are common complications of prematurity for babies?", "answer": "Common complications of prematurity for babies include respiratory distress syndrome (RDS), hyperbilirubinemia, gastroesophageal reflux (GERD), intraventricular hemorrhage (periventricular leukomalacia), retinopathy of prematurity (ROP), and necrotizing enterocolitis (NEC). Additionally, preterm infants are at higher risk for developmental delays, sensory processing difficulties, and other long-term health issues.", "relevant_passage_ids": ["36829980"], "type": "list", "snippets": [{"offsetInBeginSection": 1188, "offsetInEndSection": 1338, "text": "respiratory distress, bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, necrotizing enterocolitis, neonatal sepsis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36829980"}]}
+{"question_id": "65d145651930410b13000042", "question": "What disease was studied in the ANGEL-ASPECT trial?", "answer": "ANGEL-ASPECT studied large infarcts. It is a multicentre, prospective, randomised, open-label, blinded End-point trial to evaluate whether best medical management (BMM) combined with endovascular therapy improves neurological functional outcomes as compared with BMM alone in acute LVO patients with Alberta Stroke Program Early CT Score (ASPECTS) of 3-5 on non-contrast CT or infarct core volume range of 70-100\u2009mL (defined as rCBF <30% on CT perfusion or ADC <620 on MRI) up to 24 hours from symptom onset or last seen well.", "relevant_passage_ids": ["36762852", "36137599", "37156088", "38010691"], "type": "summary", "snippets": [{"offsetInBeginSection": 2150, "offsetInEndSection": 2514, "text": "CONCLUSIONS: In a trial conducted in China, patients with large cerebral infarctions had better outcomes with endovascular therapy administered within 24 hours than with medical management alone but had more intracranial hemorrhages. (Funded by Covidien Healthcare International Trading [Shanghai] and others; ANGEL-ASPECT ClinicalTrials.gov number, NCT04551664.).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36762852"}, {"offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Endovascular therapy in acute anterior circulation large vessel occlusive patients with a large infarct core (ANGEL-ASPECT): protocol of a multicentre randomised trial.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36137599"}, {"offsetInBeginSection": 294, "offsetInEndSection": 801, "text": "DESIGN: ANGEL-ASPECT is a multicentre, prospective, randomised, open-label, blinded End-point trial to evaluate whether best medical management (BMM) combined with endovascular therapy improves neurological functional outcomes as compared with BMM alone in acute LVO patients with Alberta Stroke Program Early CT Score (ASPECTS) of 3-5 on non-contrast CT or infarct core volume range of 70-100\u2009mL (defined as rCBF <30% on CT perfusion or ADC <620 on MRI) up to 24 hours from symptom onset or last seen well.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36137599"}, {"offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "OBJECTIVES: Recently published results of the ANGEL-ASPECT and SELECT2 trials suggest that stroke patients presenting with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) benefit from mechanical thrombectomy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37156088"}, {"offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Alberta Stroke Program Early Computed Tomography Score, Infarct Core Volume, and Endovascular Therapy Outcomes in Patients With Large Infarct: A Secondary Analysis of the ANGEL-ASPECT Trial.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38010691"}, {"offsetInBeginSection": 422, "offsetInEndSection": 703, "text": "This prespecified secondary analysis of subgroups of the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core (ANGEL-ASPECT) RCT included patients from 46 stroke centers across China between October 2, 2020, and May 18, 2022.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38010691"}, {"offsetInBeginSection": 302, "offsetInEndSection": 801, "text": "ANGEL-ASPECT is a multicentre, prospective, randomised, open-label, blinded End-point trial to evaluate whether best medical management (BMM) combined with endovascular therapy improves neurological functional outcomes as compared with BMM alone in acute LVO patients with Alberta Stroke Program Early CT Score (ASPECTS) of 3-5 on non-contrast CT or infarct core volume range of 70-100\u2009mL (defined as rCBF <30% on CT perfusion or ADC <620 on MRI) up to 24 hours from symptom onset or last seen well.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36137599"}, {"offsetInBeginSection": 0, "offsetInEndSection": 884, "text": "BACKGROUND: The benefit of stroke thrombectomy for large infarct core still lacks robust randomised controlled studies.AIM: To demonstrate the design of a clinical trial on endovascular therapy for acute anterior circulation large vessel occlusion (LVO) patients with large infarct core volume.DESIGN: ANGEL-ASPECT is a multicentre, prospective, randomised, open-label, blinded End-point trial to evaluate whether best medical management (BMM) combined with endovascular therapy improves neurological functional outcomes as compared with BMM alone in acute LVO patients with Alberta Stroke Program Early CT Score (ASPECTS) of 3-5 on non-contrast CT or infarct core volume range of 70-100\u2009mL (defined as rCBF <30% on CT perfusion or ADC <620 on MRI) up to 24 hours from symptom onset or last seen well.STUDY OUTCOMES: The primary efficacy outcome is 90 (\u00b17) days modified Rankin Scale.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36137599"}, {"offsetInBeginSection": 885, "offsetInEndSection": 1222, "text": "Symptomatic intracranial haemorrhage within 48 hours from randomisation is the primary safety outcome.DISCUSSION: The ANGEL-ASPECT trial will screen patients with large infarct core (ASPECTS 3-5 or 70-100\u2009mL) through image evaluation criteria within 24 hours and explore the efficacy and safety of endovascular therapy compared with BMM.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36137599"}, {"offsetInBeginSection": 298, "offsetInEndSection": 804, "text": "GN: ANGEL-ASPECT is a multicentre, prospective, randomised, open-label, blinded End-point trial to evaluate whether best medical management (BMM) combined with endovascular therapy improves neurological functional outcomes as compared with BMM alone in acute LVO patients with Alberta Stroke Program Early CT Score (ASPECTS) of 3-5 on non-contrast CT or infarct core volume range of 70-100\u2009mL (defined as rCBF <30% on CT perfusion or ADC <620 on MRI) up to 24 hours from symptom onset or last seen well.STU", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36137599"}, {"offsetInBeginSection": 298, "offsetInEndSection": 990, "text": "GN: ANGEL-ASPECT is a multicentre, prospective, randomised, open-label, blinded End-point trial to evaluate whether best medical management (BMM) combined with endovascular therapy improves neurological functional outcomes as compared with BMM alone in acute LVO patients with Alberta Stroke Program Early CT Score (ASPECTS) of 3-5 on non-contrast CT or infarct core volume range of 70-100\u2009mL (defined as rCBF <30% on CT perfusion or ADC <620 on MRI) up to 24 hours from symptom onset or last seen well.STUDY OUTCOMES: The primary efficacy outcome is 90 (\u00b17) days modified Rankin Scale. Symptomatic intracranial haemorrhage within 48 hours from randomisation is the primary safety outcome.DIS", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36137599"}, {"offsetInBeginSection": 298, "offsetInEndSection": 887, "text": "GN: ANGEL-ASPECT is a multicentre, prospective, randomised, open-label, blinded End-point trial to evaluate whether best medical management (BMM) combined with endovascular therapy improves neurological functional outcomes as compared with BMM alone in acute LVO patients with Alberta Stroke Program Early CT Score (ASPECTS) of 3-5 on non-contrast CT or infarct core volume range of 70-100\u2009mL (defined as rCBF <30% on CT perfusion or ADC <620 on MRI) up to 24 hours from symptom onset or last seen well.STUDY OUTCOMES: The primary efficacy outcome is 90 (\u00b17) days modified Rankin Scale. Sy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36137599"}, {"offsetInBeginSection": 121, "offsetInEndSection": 802, "text": "M: To demonstrate the design of a clinical trial on endovascular therapy for acute anterior circulation large vessel occlusion (LVO) patients with large infarct core volume.DESIGN: ANGEL-ASPECT is a multicentre, prospective, randomised, open-label, blinded End-point trial to evaluate whether best medical management (BMM) combined with endovascular therapy improves neurological functional outcomes as compared with BMM alone in acute LVO patients with Alberta Stroke Program Early CT Score (ASPECTS) of 3-5 on non-contrast CT or infarct core volume range of 70-100\u2009mL (defined as rCBF <30% on CT perfusion or ADC <620 on MRI) up to 24 hours from symptom onset or last seen well.S", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36137599"}, {"offsetInBeginSection": 391, "offsetInEndSection": 843, "text": "gn, Setting, and Participants: This prespecified secondary analysis of subgroups of the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core (ANGEL-ASPECT) RCT included patients from 46 stroke centers across China between October 2, 2020, and May 18, 2022. Participants were enrolled within 24 hours of symptom onset and had ASPECTS of 3 to 5 or 0 to 2 and infarct core volume of 70 to 100 mL. Pa", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38010691"}, {"offsetInBeginSection": 391, "offsetInEndSection": 1027, "text": "gn, Setting, and Participants: This prespecified secondary analysis of subgroups of the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core (ANGEL-ASPECT) RCT included patients from 46 stroke centers across China between October 2, 2020, and May 18, 2022. Participants were enrolled within 24 hours of symptom onset and had ASPECTS of 3 to 5 or 0 to 2 and infarct core volume of 70 to 100 mL. Patients were divided into 3 groups: ASPECTS of 3 to 5 with infarct core volume less than 70 mL, ASPECTS of 3 to 5 with infarct core volume of 70 mL or greater, and ASPECTS of 0 to 2.Int", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38010691"}]}
+{"question_id": "65f773cdc4010b4d78000026", "question": "Why is the clinical benefit of EGFR inhibitors different in right and left colorectal cancer?", "answer": "Tumors in the proximal colon (right side) and distal colon (left side) exhibit different molecular characteristics and histology. In the right-sided tumors, mutations in the DNA mismatch repair pathway are commonly observed; and these tumors generally have a flat histology. In the left-sided tumors, chromosomal instability pathway-related mutations, such as KRAS, APC, PIK3CA, p53 mutations are observed and these tumors demonstrate polypoid-like morphology. The analysis of the immune microenvironment showed that immune infiltration was more common in RCC than LCC.  This suggests that the molecular mechanisms of RCC and LCC differed.", "relevant_passage_ids": ["34026368", "30116425", "29796712", "23572025", "34188197", "31519572", "28794806", "25979833", "32428838"], "type": "summary", "snippets": [{"offsetInBeginSection": 293, "offsetInEndSection": 754, "text": "Tumors in the proximal colon (right side) and distal colon (left side) exhibit different molecular characteristics and histology. In the right-sided tumors, mutations in the DNA mismatch repair pathway are commonly observed; and these tumors generally have a flat histology. In the left-sided tumors, chromosomal instability pathway-related mutations, such as KRAS, APC, PIK3CA, p53 mutations are observed and these tumors demonstrate polypoid-like morphology. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30116425"}, {"offsetInBeginSection": 1279, "offsetInEndSection": 1878, "text": " The analysis of the immune microenvironment showed that immune infiltration was more common in RCC than LCC. The results of differential gene analysis showed that there were 360 differentially expressed genes, with 142 upregulated genes in LCC and 218 upregulated genes in RCC. The mutation frequency of RCC was generally higher than that of LCC. BRAF and KRAS gene mutations were the dominant genes mutations in RCC, and they had a strong mutual exclusion with APC, while APC gene mutation was the dominant gene mutation in LCC. This suggests that the molecular mechanisms of RCC and LCC differed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34026368"}, {"offsetInBeginSection": 465, "offsetInEndSection": 592, "text": "the fact that we do not understand why left-sided but not right-sided tumors have improved outcomes following anti-EGFR therapy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28794806"}, {"offsetInBeginSection": 114, "offsetInEndSection": 297, "text": "i-EGFR antibody therapy. Left-sided colon cancer is more sensitive to anti-EGFR antibodies than right-sided, although the mechanism is unclear. The aim of this study was to determine ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31519572"}, {"offsetInBeginSection": 0, "offsetInEndSection": 447, "text": "INTRODUCTION: EGF/EGFR interactions are important mechanisms behind colorectal tumour development and growth. Recently a single nucleotide polymorphism in the EGF gene has been identified (EGF A61G). It may be a potential predictor for survival of patients receiving EGFR-inhibitor cetuximab treatment, but the clinical importance and the functional influence on EGF gene expression levels in colorectal cancer (CRC) patients have not yet been fur", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17851837"}, {"offsetInBeginSection": 339, "offsetInEndSection": 498, "text": "targets for mCRC. The aim of this study was to clarify the prognostic value of NF-\u03baB, HIF-1\u03b1, IL-8, and TGF-\u03b2 expression in patients with left-sided mCRC recei", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36808300"}, {"offsetInBeginSection": 1521, "offsetInEndSection": 1648, "text": "3CA mutations, including BRAFnon-V600E, which may contribute to the difference in the anti-EGFR efficacy between the right- and", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32428838"}]}
+{"question_id": "660712a1fdcbea915f000003", "question": "Can Connexin hemi channels be used for drug delivery?", "answer": "yes,  pore forming channels such as connexin can potentiially be used as a drug delivery system.", "relevant_passage_ids": ["30472182", "29861876", "35263989"], "type": "yesno", "snippets": [{"offsetInBeginSection": 763, "offsetInEndSection": 920, "text": "he permeability of Cx43 channels to small molecules and macromolecules makes them highly attractive targets for delivering drugs directly into the cytoplasm.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30472182"}, {"offsetInBeginSection": 921, "offsetInEndSection": 1011, "text": "Cancer cells overexpressing Cx43 may be more permeable and sensitive to chemotherapeutics.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30472182"}, {"offsetInBeginSection": 1213, "offsetInEndSection": 1434, "text": "n this context, certain channels lead to transitory plasma membrane permeability changes, such as pannexin, connexin hemmichannels, TRPV1-4 and P2\u00d77, which allow for the non-selective passage of molecules up to 1,000 Da. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29861876"}, {"offsetInBeginSection": 1428, "offsetInEndSection": 1679, "text": "Collectively, these results reveal that polymeric macromolecules can be delivered to cells via gap junctions, suggesting that the gap junction route may be useful for the delivery of polymeric therapeutic molecules, such as nucleic acids and peptides.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35263989"}, {"offsetInBeginSection": 176, "offsetInEndSection": 422, "text": "Gap junction channels, composed of connexin proteins, provide a mechanism for direct transfer of small molecules across membranes, and recent evidence suggests that the transfer of larger, polymer-like molecules such as microRNAs may be possible.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35263989"}, {"offsetInBeginSection": 762, "offsetInEndSection": 920, "text": "The permeability of Cx43 channels to small molecules and macromolecules makes them highly attractive targets for delivering drugs directly into the cytoplasm.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30472182"}]}
+{"question_id": "660c02e1fdcbea915f00002c", "question": "Pasteurization kills Mycobacterium tuberculosis from infected cattle.", "answer": "Yes, Mycobacterium bovis is eliminated by pasteurization.", "relevant_passage_ids": ["10835092", "9039448", "7579326"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1231, "offsetInEndSection": 1434, "text": "M. bovis infection was recognised as a major public health problem when this organism was transmitted to man via milk from infected cows. The introduction of pasteurization helped eliminate this problem.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7579326"}, {"offsetInBeginSection": 1038, "offsetInEndSection": 1330, "text": "cut-off in the animal to human chain of infection at two points; the animal source and the ingestion of (now pasteurized) milk. This would suggest that disease in humans is now due to reactivation of previous foci of infection which were acquired when milk pasteurization was not compulsory. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9039448"}, {"offsetInBeginSection": 1181, "offsetInEndSection": 1570, "text": "M bovis patients were also even more likely to be Hispanic (90.2%), to present with extrapulmonary disease (95.1%), and to be older than 12 months (96.8%).CONCLUSION: These data demonstrate the dramatic impact of this underappreciated cause of zoonotic TB on US children at the Mexican border and underscore the need for cross-collaboration to enforce existing Mexican pasteurization laws.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10835092"}]}
+{"question_id": "65cfd3961930410b1300001f", "question": "TAK-994 is developed for which disease?", "answer": "TAK-994 is an oral orexin receptor 2-selective agonist that was developed and tested for narcolepsy type 1.", "relevant_passage_ids": ["37494485", "37001988"], "type": "factoid", "snippets": [{"offsetInBeginSection": 93, "offsetInEndSection": 255, "text": "METHODS: We conducted a phase 2, randomized, placebo-controlled trial of TAK-994, an oral orexin receptor 2-selective agonist, in patients with narcolepsy type 1.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37494485"}, {"offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "TAK-994, a Novel Orally Available Brain-Penetrant Orexin 2 Receptor-Selective Agonist, Suppresses Fragmentation of Wakefulness and Cataplexy-Like Episodes in Mouse Models of Narcolepsy.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37001988"}, {"offsetInBeginSection": 2127, "offsetInEndSection": 2277, "text": "These findings indicate that TAK-994 is an orally available brain-penetrant OX2R-selective agonist with potential to improve narcolepsy-like symptoms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37001988"}, {"offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "BACKGROUND: Narcolepsy type 1 is caused by severe loss or lack of brain orexin neuropeptides.METHODS: We conducted a phase 2, randomized, placebo-controlled trial of TAK-994, an oral orexin receptor 2-selective agonist, in patients with narcolepsy type 1.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37494485"}]}
+{"question_id": "66099b20fdcbea915f000021", "question": "Is high blood pressure a clinical biomarker of response to Bevacizumab in advanced colorectal cancer patients?", "answer": "Bevacizumab-induced hypertension during the first-line treatment of mCRC is an independent prognostic factor, also adopting a time-dependency correction.  In TRIBE and TRIBE-2 study populations (N = 1175), patients experiencing \u2265 G2 HTN during first-line bevacizumab administration showed longer Progression free survival  (median: 14.7 versus 10.3 months, p < 0.001) and Overall survival (median: 31.7 versus 24.2 months, p < 0.001).", "relevant_passage_ids": ["35016085", "23254964", "21304526", "27843607", "21807768", "22033274", "27109438", "22531628", "28303751", "30396388", "24283603", "25536596", "33231381", "18842611", "19470921", "21627340", "20924372", "21409384", "24153157", "26269767", "36723787", "19921473", "29969436"], "type": "yesno", "snippets": [{"offsetInBeginSection": 2166, "offsetInEndSection": 2309, "text": "Bevacizumab-induced HTN during the first-line treatment of mCRC is an independent prognostic factor, also adopting a time-dependency correction", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35016085"}, {"offsetInBeginSection": 1485, "offsetInEndSection": 1727, "text": "In TRIBE and TRIBE-2 study populations (N\u00a0=\u00a01175), patients experiencing\u00a0\u2265\u00a0G2 HTN during first-line bevacizumab administration showed longer PFS (median: 14.7 versus 10.3\u00a0months, p\u00a0<\u00a00.001) and OS (median: 31.7 versus 24.2\u00a0months, p\u00a0<\u00a00.001).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35016085"}, {"offsetInBeginSection": 12, "offsetInEndSection": 105, "text": "In patients treated with bevacizumab, hypertension may be a biomarker of therapeutic efficacy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33231381"}, {"offsetInBeginSection": 418, "offsetInEndSection": 594, "text": "Here, we have explored potential associations between circulating levels of vasoactive peptides and tumor response during bevacizumab-containing treatment of colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28303751"}, {"offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "An observational study of bevacizumab-induced hypertension as a clinical biomarker of antitumor activity.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21807768"}, {"offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Hypertension and overall survival in metastatic colorectal cancer patients treated with bevacizumab-containing chemotherapy.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21304526"}, {"offsetInBeginSection": 1239, "offsetInEndSection": 1309, "text": "Bevacizumab decreased tumor interstitial fluid pressure and blood flow", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19470921"}, {"offsetInBeginSection": 345, "offsetInEndSection": 486, "text": "remains unclear. We aimed to evaluate the effect of bevacizumab-induced hypertension in terms of prognosis in patients with colorectal cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27109438"}, {"offsetInBeginSection": 153, "offsetInEndSection": 406, "text": "ab commonly cause hypertension (HTN) and proteinuria (PTN), which may be biomarkers of response and clinical outcome.STUDY: We conducted a retrospective analysis of patients with histologically proven metastatic colorectal cancer (mCRC) treated with eit", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24153157"}, {"offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "BACKGROUND: In patients treated with bevacizumab, hypertension may be a biomarker of therapeutic efficacy. However, it is not c", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33231381"}, {"offsetInBeginSection": 1779, "offsetInEndSection": 2062, "text": "pressure. Randomized prospective studies are necessary to provide data that will be useful for the development of specific guidelines for the management of bevacizumab-related hypertension. In the meantime, treatment of anti-VEGF-induced hypertension should follow current guidelines", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21627340"}, {"offsetInBeginSection": 1050, "offsetInEndSection": 1444, "text": "Very early hypertension (within 42 days, according to the ESH criteria) but not hypertension (occurring at any time during treatment period) was predictive of response (p = .0011 and p = .26, respectively).CONCLUSIONS: Our preliminary results indicate that home-based measurement and grading according to the ESH criteria represents a reliable method to detect bevacizumab-induced hypertension.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21807768"}, {"offsetInBeginSection": 882, "offsetInEndSection": 1231, "text": "There was no correlation between the development of hypertension and radiological response rate (P=0.642), progression-free survival (P=0.644) or overall survival (P=0.480) in those who developed hypertension compared with those who did not.CONCLUSION: Bevacizumab-induced hypertension did not predict radiological response or survival in our study.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22531628"}, {"offsetInBeginSection": 159, "offsetInEndSection": 578, "text": "This study aimed to describe the incidence of bevacizumab-induced hypertension and factors associated with its development, then to retrospectively assess its relation with activity.PATIENTS AND METHODS: One hundred nineteen patients with advanced or metastatic non-small cell lung cancer, colorectal cancer, or ovarian cancer receiving bevacizumab (2.5 mg/kg per week) and chemotherapy were eligible for this analysis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21807768"}, {"offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "BACKGROUND: Retrospective series suggest that bevacizumab-induced hypertension (HTN) is a prognostic and potentially predictive biomarker of efficacy of the antiangiogenic drug in the upfront treatment of metastatic colorectal cancer (mCRC) patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35016085"}, {"offsetInBeginSection": 1935, "offsetInEndSection": 2310, "text": "Moreover, in patients with pre-existing HTN, no difference in terms of PFS and OS was observed compared with the subgroup of patients who never experienced\u00a0\u2265G2 HTN (HR 1.01, p\u00a0=\u00a00.86 and HR 1.02, p\u00a0=\u00a00.78 respectively.CONCLUSIONS: Bevacizumab-induced HTN during the first-line treatment of mCRC is an independent prognostic factor, also adopting a time-dependency correction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35016085"}, {"offsetInBeginSection": 1009, "offsetInEndSection": 1121, "text": "Bevacizumab-related HTN may represent a biomarker for clinical benefit in metastatic colorectal cancer patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23254964"}, {"offsetInBeginSection": 1648, "offsetInEndSection": 1831, "text": "sion (15.1 vs. 8.3\u00a0months, P\u00a0=\u00a00.04).CONCLUSIONS: Our data suggest that bevacizumab-related arterial hypertension may represent a predictive factor of response and prolonged PFS in pa", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21409384"}, {"offsetInBeginSection": 1215, "offsetInEndSection": 1420, "text": "-analysis, respectively. Bevacizumab-related hypertension was associated with increased ORR (RR= 1.63; 95% CI 1.26-2.12; p=0.0002), improved PFS (HR=0.68; 95% CI 0.58-0.79; p<0.00001) and OS (HR=0.52; 95% ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25536596"}, {"offsetInBeginSection": 1239, "offsetInEndSection": 1530, "text": " estimated for ORR.RESULTS: The occurrence of bevacizumab-induced hypertension in patients was highly associated with improvements in PFS (HR = 0.57, 95% CI: 0.46-0.72; P <0.001), OS (HR = 0.50; 95% CI: 0.37-0.68; P <0.001), and ORR (RR = 1.57, 95% CI: 1.07-2.30, P <0.05), as compared to pa", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24283603"}, {"offsetInBeginSection": 818, "offsetInEndSection": 1008, "text": "HTN was associated with better OS in HTN-positive versus HTN-negative patients (median not reached vs. 36.8 months, p = 0.029) and better PFS (29.9 vs. 17.2 months, p = 0.024, respectively).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23254964"}, {"offsetInBeginSection": 181, "offsetInEndSection": 399, "text": "l outcomes. Hypertension (HTN) is a common complication of the treatment with bevacizumab and, owing to its close relation with antiangiogenic mechanism, may represent a clinical biomarker to predict the efficacy of th", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27843607"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Hypertension as a predictive biomarker in bevacizumab treatment for colorectal cancer patients.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23254964"}, {"offsetInBeginSection": 1576, "offsetInEndSection": 1938, "text": "In the group that developed bevacizumab-related HTN, the median OS was 33\u2005months (25.7-40.3), and in the group that did not, it was 21\u2005months (16.5-25.5) with no significant statistical difference between the two groups (p 0.114).CONCLUSIONS: In this subset of patients, HTN G2-3 was predictive of response to treatment with bevacizumab and of PFS but not of OS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27843607"}, {"offsetInBeginSection": 1152, "offsetInEndSection": 1490, "text": "Median overall survival was not reached in patients with hypertension while it was 15.1 months in the remaining cases (P = 0.11).CONCLUSIONS: Our data indicate that bevacizumab-induced hypertension may represent an interesting prognostic factor for clinical outcome in advanced colorectal cancer patients receiving first-line bevacizumab.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18842611"}, {"offsetInBeginSection": 1522, "offsetInEndSection": 1881, "text": "Kaplan-Meier analysis showed a statistically significant improvement in median PFS for patients with induced arterial hypertension (15.1 vs. 8.3\u00a0months, P\u00a0=\u00a00.04).CONCLUSIONS: Our data suggest that bevacizumab-related arterial hypertension may represent a predictive factor of response and prolonged PFS in patients with mCRC receiving first-line bevacizumab.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21409384"}, {"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Bevacizumab treatment is associated with an increased risk of hypertension (HTN), a potential marker for effectiveness.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23254964"}, {"offsetInBeginSection": 618, "offsetInEndSection": 970, "text": "Furthermore, the proportion of patients who required intervention with antihypertensive drugs during bevacizumab treatment was significantly higher in group A than in group B (36% vs 4%; P<0.01).CONCLUSION: This study suggests that a temporary blood pressure drop after bevacizumab administration could be a predictive marker for bevacizumab treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22033274"}, {"offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "BACKGROUND: Arterial hypertension occurring during antiangiogenic therapy has been correlated with the biological inhibition of the vascular endothelial growth factor-related pathway and may represent a possible clinical marker for treatme", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18842611"}, {"offsetInBeginSection": 240, "offsetInEndSection": 486, "text": "t efficacy. The aim of our study was to retrospectively assess if grades 2-3 hypertension were associated with response to bevacizumab, progression-free survival (PFS) and survival in metastatic colorectal cancer patients treated with first-line ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18842611"}, {"offsetInBeginSection": 1241, "offsetInEndSection": 1437, "text": "onths in the remaining cases (P = 0.11).CONCLUSIONS: Our data indicate that bevacizumab-induced hypertension may represent an interesting prognostic factor for clinical outcome in advanced colorec", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18842611"}, {"offsetInBeginSection": 936, "offsetInEndSection": 1148, "text": "ssion-free survival (PFS) was 10 months. Patients with any grade hypertension while on bevacizumab had an adjusted hazard ratio for death of 0.32 (p = 0.03) and adjusted risk of progression of 51% (p = 0.02) comp", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19921473"}, {"offsetInBeginSection": 1531, "offsetInEndSection": 1644, "text": "ients without hypertension.CONCLUSIONS: Bevacizumab-induced hypertension may represent a prognostic factor in pat", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24283603"}, {"offsetInBeginSection": 121, "offsetInEndSection": 311, "text": " It may be a marker of VEGF signalling pathway inhibition and therefore represent a cancer biomarker in metastatic colorectal cancer (mCRC) patients treated with chemotherapy and bevacizumab", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21304526"}, {"offsetInBeginSection": 1631, "offsetInEndSection": 1755, "text": "Bevacizumab-induced hypertension may represent a biomarker for clinical benefit in cancer patients treated with bevacizumab.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27109438"}, {"offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "BACKGROUND: In patients treated with bevacizumab, hypertension may be a biomarker of therapeutic efficacy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33231381"}, {"offsetInBeginSection": 1529, "offsetInEndSection": 1651, "text": "SION: These results suggest that plasma VEGF-Axxxb levels could be an effective biomarker of response to Bevacizumab. Thes", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26269767"}, {"offsetInBeginSection": 257, "offsetInEndSection": 361, "text": "However, the relationship between bevacizumab-induced hypertension and clinical outcome remains unclear.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27109438"}, {"offsetInBeginSection": 138, "offsetInEndSection": 305, "text": " However, blood pressure measurement as a surrogate response biomarker has methodological limitations, and predictive biomarkers of angiogenesis inhibitors are lacking", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28303751"}, {"offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "BACKGROUND: Bevacizumab has become standard of care as first-line treatment of metastatic colorectal cancer (mCRC), after proving increased response rates and improvement in surviv", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27843607"}, {"offsetInBeginSection": 1633, "offsetInEndSection": 1726, "text": "rogression to a first-line treatment with bevacizumab. The development of hypertension during", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36723787"}, {"offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Association between bevacizumab-related hypertension and response to treatment in patients with metastatic colorectal cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27843607"}, {"offsetInBeginSection": 1446, "offsetInEndSection": 1652, "text": "There was no statistically significant difference between-study heterogeneity.CONCLUSION: These analyses suggest that hypertension may be a potential biomarker for efficacy of bevacizumab treatment in mCRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25536596"}, {"offsetInBeginSection": 353, "offsetInEndSection": 606, "text": "The aim of this meta-analysis was to dissect the association between hypertension and efficacy of bevacizumab treatment in mCRC.METHODS: We searched PubMed, EMBASE, Chinese Biomedical Database (CBM), and Wan Fang Digital Journals before September, 2013.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25536596"}, {"offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Hypertension as a predictive biomarker for efficacy of bevacizumab treatment in metastatic colorectal cancer: a meta-analysis.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25536596"}, {"offsetInBeginSection": 1421, "offsetInEndSection": 1755, "text": "Patients who developed hypertension during treatment with bevacizumab for colorectal cancer and non-small cell lung cancer had significantly prolonged overall survival when compared with normotensive patients. Bevacizumab-induced hypertension may represent a biomarker for clinical benefit in cancer patients treated with bevacizumab.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27109438"}, {"offsetInBeginSection": 183, "offsetInEndSection": 793, "text": "Therefore, we investigated the relationships between increased blood pressure and bevacizumab administration, patient characteristics, and laboratory data. Between April 2007 and January 2018, factor analysis was retrospectively conducted by monitoring increases in blood pressure, the status of bevacizumab administration, patient characteristics, and laboratory data before the first administration in Japanese patients with colorectal cancer who satisfied the criteria for this study. Sixty-seven patients were included, 34 of whom (50.7%) had an increase in blood pressure after bevacizumab administration.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30396388"}, {"offsetInBeginSection": 183, "offsetInEndSection": 670, "text": "Therefore, we investigated the relationships between increased blood pressure and bevacizumab administration, patient characteristics, and laboratory data. Between April 2007 and January 2018, factor analysis was retrospectively conducted by monitoring increases in blood pressure, the status of bevacizumab administration, patient characteristics, and laboratory data before the first administration in Japanese patients with colorectal cancer who satisfied the criteria for this study.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30396388"}, {"offsetInBeginSection": 339, "offsetInEndSection": 793, "text": "Between April 2007 and January 2018, factor analysis was retrospectively conducted by monitoring increases in blood pressure, the status of bevacizumab administration, patient characteristics, and laboratory data before the first administration in Japanese patients with colorectal cancer who satisfied the criteria for this study. Sixty-seven patients were included, 34 of whom (50.7%) had an increase in blood pressure after bevacizumab administration.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30396388"}, {"offsetInBeginSection": 133, "offsetInEndSection": 308, "text": "THODS: Blood pressure data at 0, 90, and 180 min after a total of 162 bevacizumab administrations in 81 advanced colorectal cancer patients were retrospectively investigated.R", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22033274"}, {"offsetInBeginSection": 339, "offsetInEndSection": 670, "text": "Between April 2007 and January 2018, factor analysis was retrospectively conducted by monitoring increases in blood pressure, the status of bevacizumab administration, patient characteristics, and laboratory data before the first administration in Japanese patients with colorectal cancer who satisfied the criteria for this study.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30396388"}, {"offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "BACKGROUND: Hypertension is a common early adverse event of anti-angiogenic treatment of cancer and may associate with treatment response. However, blood pressure measurement as a surrogate response biomarker has methodological limitations, and predicti", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28303751"}, {"offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "Bevacizumab treatment is associated with an increased risk of hypertension (HTN), a potential marker for effectiveness. We aimed to assess whether grades 2-3 HTN during bevacizumab treatment was associated with increased overall survival (OS) or progression-free survival (PFS). One ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23254964"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1697, "text": "PURPOSE: Bevacizumab has demonstrated survival benefit in patients with metastatic colorectal cancer (mCRC) when combined with chemotherapy. However, no validated predictors currently exist for its efficacy. Hypertension has been evaluated as a surrogate marker for efficacy of bevacizumab, although analyses, to date, have yielded conflicting results. The aim of this meta-analysis was to dissect the association between hypertension and efficacy of bevacizumab treatment in mCRC.METHODS: We searched PubMed, EMBASE, Chinese Biomedical Database (CBM), and Wan Fang Digital Journals before September, 2013. The primary clinical outcomes included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Relative risk (RR) or summary hazard ratio (HR) were calculated using a fixed-effects or random-effects model, depending on the heterogeneity of the included studies. Studies meeting our search criteria were assessed.RESULTS: Nine studies were considered eligible, with 1674 mCRC patients included. Six (308 patients, 104 with hypertension), 8 (1661 patients, 431 with hypertension) and 5 (1512 patients, 408 with hypertension) studies were eligible for the ORR, PFS and OS meta-analysis, respectively. Bevacizumab-related hypertension was associated with increased ORR (RR= 1.63; 95% CI 1.26-2.12; p=0.0002), improved PFS (HR=0.68; 95% CI 0.58-0.79; p<0.00001) and OS (HR=0.52; 95% CI 0.42-0.66; p<0.00001). There was no statistically significant difference between-study heterogeneity.CONCLUSION: These analyses suggest that hypertension may be a potential biomarker for efficacy of bevacizumab treatment in mCRC. Additional large prospective trials are requ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25536596"}, {"offsetInBeginSection": 181, "offsetInEndSection": 668, "text": "l outcomes. Hypertension (HTN) is a common complication of the treatment with bevacizumab and, owing to its close relation with antiangiogenic mechanism, may represent a clinical biomarker to predict the efficacy of the treatment. The aim of this study was to retrospectively evaluate if HTN grades 2 to 3 were correlated with response to treatment with bevacizumab in first line, as well as with improved progression-free survival (PFS) and overall survival (OS), in a series of patient", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27843607"}, {"offsetInBeginSection": 230, "offsetInEndSection": 1292, "text": "identified. The development of bevacizumab-induced arterial hypertension has recently been suggested as a potential predictive biomarker.METHODS: Blood pressure was recorded during the BOXER study, a phase II study of capecitabine, oxaliplatin (CAPOX) plus bevacizumab as peri-operative treatment in 45 patients with poor-risk colorectal liver-only metastases unsuitable for upfront resection. In this analysis, the development of bevacizumab-induced hypertension was correlated with clinical outcomes.RESULTS: Fifteen percent of patients developed \u2265grade 1 hypertension while receiving neoadjuvant chemotherapy, and 4% developed grade 3 hypertension. There was no correlation between the development of hypertension and radiological response rate (P=0.642), progression-free survival (P=0.644) or overall survival (P=0.480) in those who developed hypertension compared with those who did not.CONCLUSION: Bevacizumab-induced hypertension did not predict radiological response or survival in our study. The results highlight a number of important issues regarding", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22531628"}, {"offsetInBeginSection": 0, "offsetInEndSection": 2228, "text": "BACKGROUND: Hypertension is a common early adverse event of anti-angiogenic treatment of cancer and may associate with treatment response. However, blood pressure measurement as a surrogate response biomarker has methodological limitations, and predictive biomarkers of angiogenesis inhibitors are lacking. In disease associated with hypertension, vasoactive peptides have been linked to cardiovascular pressure load. Here, we have explored potential associations between circulating levels of vasoactive peptides and tumor response during bevacizumab-containing treatment of colorectal cancer.MATERIAL AND METHODS: Metastatic colorectal cancer (mCRC) patients with available best objective response (ORR) and time to tumor progression (TTP) data were included from a randomized clinical trial investigating maintenance therapy after first line chemotherapy plus bevacizumab. Midregional-pro-adrenomedullin (MR-proADM), midregional-pro-atrial-natriuretic-peptide (MR-proANP), and C-terminal-prepro-vasopressin (Copeptin) vasoactive peptide concentrations were measured in plasma at baseline and after 6 weeks of chemotherapy and bevacizumab treatment (n\u2009=\u200997). We determined associations among clinical outcome (ORR and TTP), peptide levels, and hypertension (NCI-CTCAE 4.0 criteria), using Spearman's test, multiple linear regression, and Mann-Whitney's test.RESULTS: Increasing levels of vasoactive peptides from baseline and after six weeks of treatment were associated with improved treatment outcome (MR-proADM: ORR, p\u2009=\u2009.0003; TTP, p\u2009=\u2009.05; MR-proANP: ORR, p\u2009=\u2009.05; TTP, p\u2009=\u2009.03; Copeptin: ORR, p\u2009=\u2009.10; TTP, p\u2009=\u2009.02). Patients with increasing levels of all three peptides (n\u2009=\u200928) versus increasing levels of one or two peptides (n\u2009=\u200959) showed a median TTP of 284 and 225 d, respectively (p\u2009=\u2009.02).CONCLUSIONS: Our results suggest that increasing systemic levels of vasoactive peptides associate with improved tumor response and TTP in mCRC patients treated with a bevacizumab-containing regimen. These findings support the proposed link between the tumor vasculature and the cardiovascular system of the host. This should motivate further studies that investigate the potential role of vasoactive peptides as a novel cl", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28303751"}, {"offsetInBeginSection": 102, "offsetInEndSection": 1554, "text": "giogenesis. Antiangiogenic agents such as bevacizumab commonly cause hypertension (HTN) and proteinuria (PTN), which may be biomarkers of response and clinical outcome.STUDY: We conducted a retrospective analysis of patients with histologically proven metastatic colorectal cancer (mCRC) treated with either bevacizumab or a tyrosine kinase inhibitor in combination with chemotherapy at The Christie Hospital from January 2006 to September 2009.RESULTS: Of 90 patients evaluated, 50 were eligible. Seventeen (34%), 4 (8%), and 3 (6%) patients developed Common Toxicity Criteria (v 3.0) grades 1, 2, and 3 HTN, respectively. Response rates were 42% for patients with grades 0 to 1 HTN compared with 86% for patients with \u2265grade 2 HTN (P=0.043). Median overall survival was 21.6 months for patients with grades 0 to 1 HTN and 25.2 months for patients with \u2265grade 2 HTN (P=0.270). Twelve patients (24%) developed grade 1 PTN and 4 patients (8%) developed \u2265grade 2 PTN. Median overall survival was 23.9 months for patients with grades 0 to 1 PTN and 4.2 months for those with \u2265grade 2 PTN (P=0.028).CONCLUSIONS: To our knowledge, this is the first study to demonstrate the utility of PTN as a surrogate marker of outcome in antiangiogenic therapy for metastatic colorectal cancer. Although HTN is predictive of a significantly higher response rate, the development of PTN during treatment with bevacizumab or tyrosine kinase inhibitor portends poorer survi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24153157"}, {"offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "We tested the hypothesis that bevacizumab-induced hypertension may be a useful predictor for objective response rate, progression-free and overall survival in patients with metastatic colorectal cancer via a comprehensive meta-analysis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29969436"}, {"offsetInBeginSection": 0, "offsetInEndSection": 355, "text": "BACKGROUND: Bevacizumab is commonly used in combination with chemotherapy in the treatment of metastatic colorectal cancer, but to date, despite extensive research, no predictive or prognostic biomarkers for bevacizumab have been identified. The development of bevacizumab-induced arterial hypertension has recently been suggested as a potential predictiv", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22531628"}, {"offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "BACKGROUND: Hypertension (HTN) is a common toxicity of anti-VEGF (vascular endothelial growth factor) antibody treatment. It may be a marker of VEGF signalling pathway inhibition and therefore represent a cancer biomarker in metastatic colorectal cancer (mCRC) patients treated with chemotherapy and ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21304526"}, {"offsetInBeginSection": 949, "offsetInEndSection": 1285, "text": "th HTN (30 vs 20%; P=0.025). Hypertension was associated with improved progression-free survival (10.5 vs 5.3 months; P=0.008) and overall survival (25.8 vs 11.7 months; P<0.001), and development of HTN within 3 months had an independent, prognostic influence in a multivariate landmark survival analysis together with other known mCRC ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21304526"}]}
+{"question_id": "66088cccfdcbea915f00000b", "question": "What is the significance of Acute pancreatitis-induced splanchnic vein thrombosis", "answer": "Deep Venous Thrombosis in Acute Pancreatitis Is Associated with High Mortality.", "relevant_passage_ids": ["35867193", "37210302", "37933195", "33180323", "26513113", "29720864", "33887991", "35433812", "34815653", "31954635", "37461391", "37377583", "37282658", "25466845", "22081920", "32898006", "31159864", "26451142"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Deep Venous Thrombosis in Acute Pancreatitis Is Associated with High Mortality", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35867193"}, {"offsetInBeginSection": 10, "offsetInEndSection": 127, "text": ": Splanchnic vein thrombosis (SVT) is a well-recognised though little-studied complication in acute pancreatitis (AP)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37210302"}, {"offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Acute pancreatitis-induced splanchnic vein thrombosis (APISVT) is an important sequela complication of acute pancreatitis, which may cause poor prognosis, such as severe gastrointestinal hemorrhage, bowel ischemic necrosis and liver failure.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37933195"}, {"offsetInBeginSection": 12, "offsetInEndSection": 160, "text": "Splanchnic vein thrombosis (SVT) is an uncommon but potentially life-threatening disease usually related to different underlying clinical conditions", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33180323"}, {"offsetInBeginSection": 11, "offsetInEndSection": 98, "text": "Splanchnic vein thrombosis (SVT) is a potentially severe complication of pancreatitis. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26513113"}, {"offsetInBeginSection": 12, "offsetInEndSection": 110, "text": "Splanchnic vein thrombosis (SVT) is a major complication of moderate and severe acute pancreatitis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37377583"}, {"offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Splanchnic vein thrombosis (SVT) is a serious vascular complication that can occur in patients with acute pancreatitis. We assessed the incidence of SVT and its relationship with acute pancreatitis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33887991"}, {"offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "OBJECTIVE: Splanchnic vein thrombosis (SVT) is a potentially severe complication of pancreatitis. The ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26513113"}, {"offsetInBeginSection": 1234, "offsetInEndSection": 1495, "text": "One patient developed liver failure associated with progressive PV thrombosis and one patient died.CONCLUSIONS: Splanchnic vein thrombosis is a relatively common observation in severe AP and is associated with pancreatic necrosis and peripancreatic collections.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22081920"}, {"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Splanchnic vein thrombosis (SVT) is a serious vascular complication that can occur in patients with acute pancreatitis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33887991"}, {"offsetInBeginSection": 136, "offsetInEndSection": 288, "text": " mortality. A consequence of severe acute pancreatitis is thrombus in the splanchnic veins. These thrombi can potentially lead to bowel ischemia or hepa", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31954635"}, {"offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "OBJECTIVE: Splanchnic vein thrombosis (SVT) is a potentially severe complication of pancreatitis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26513113"}, {"offsetInBeginSection": 12, "offsetInEndSection": 121, "text": "Splanchnic venous thrombosis (SVT) is a relevant complication in patients with acute necrotizing pancreatitis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32898006"}, {"offsetInBeginSection": 0, "offsetInEndSection": 339, "text": "Acute pancreatitis-induced splanchnic vein thrombosis (APISVT) is an important sequela complication of acute pancreatitis, which may cause poor prognosis, such as severe gastrointestinal hemorrhage, bowel ischemic necrosis and liver failure. However, its mechanism remains uncertain, and there is not a general consensus on the management.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37933195"}, {"offsetInBeginSection": 0, "offsetInEndSection": 553, "text": "Acute pancreatitis-induced splanchnic vein thrombosis (APISVT) is an important sequela complication of acute pancreatitis, which may cause poor prognosis, such as severe gastrointestinal hemorrhage, bowel ischemic necrosis and liver failure. However, its mechanism remains uncertain, and there is not a general consensus on the management. In this study, we reviewed the latest academic publications in APISVT, and discussed its pathogenesis, clinical presentation, adverse outcome and treatment, especially focused on the role of anticoagulant therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37933195"}, {"offsetInBeginSection": 437, "offsetInEndSection": 827, "text": "Splanchnic vein thrombosis in acute pancreatitis is most commonly associated with the severe form of the disease and pancreatic necrosis. This report describes a case of splanchnic vein thrombosis as a complication of necrotizing acute pancreatitis in a pediatric patient. Splanchnic vein thrombosis was incidentally detected on contrast-enhanced computed tomography to assess the pancreas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35433812"}, {"offsetInBeginSection": 437, "offsetInEndSection": 574, "text": "Splanchnic vein thrombosis in acute pancreatitis is most commonly associated with the severe form of the disease and pancreatic necrosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35433812"}, {"offsetInBeginSection": 437, "offsetInEndSection": 709, "text": "Splanchnic vein thrombosis in acute pancreatitis is most commonly associated with the severe form of the disease and pancreatic necrosis. This report describes a case of splanchnic vein thrombosis as a complication of necrotizing acute pancreatitis in a pediatric patient.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35433812"}, {"offsetInBeginSection": 0, "offsetInEndSection": 352, "text": "BACKGROUND: Splanchnic vein thrombosis is a well-recognized local vascular complication of acute pancreatitis (AP), estimated to occur in approximately 15% of patients. While splanchnic vein recanalization occurs spontaneously in approximately one third of patients, severe complications such as bowel ischemia and liver failure have also been reported", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34815653"}, {"offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "BACKGROUND: Splanchnic vein thrombosis is a well-recognized local vascular complication of acute pancreatitis (AP), estimated to occur in approximately 15% of patients", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34815653"}, {"offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "BACKGROUND: Splanchnic venous thrombosis (SVT) is a common vascular complication of acute pancreatiti", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29720864"}, {"offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Splanchnic vein thrombosis (SVT) is not rare in patients with acute pancreatitis. It remains unclear about whether anticoagulation should be given for ac", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37461391"}, {"offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Splanchnic vein thrombosis (SVT) may be negatively associated with the prognosis of pancreatitis. We p", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26451142"}, {"offsetInBeginSection": 0, "offsetInEndSection": 411, "text": "BACKGROUND: Acute pancreatitis (AP) is one of the most common digestive emergencies, and vascular complication is one of the primary reasons for death, with splanchnic venous thrombosis being the most common. Although extra-splanchnic venous thrombosis is rare, it carries the risk of life-threatening secondary pulmonary embolism.CASE PRESENTATION: We have, herein, reported a case of AP complicated by rare br", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37282658"}, {"offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "BACKGROUND: Splanchnic vein thrombosis is a well-recognized local vascular complication of acute pancreatitis (AP), estimated to occur in approximately 15% of patients. While splanchnic vein recanalization occurs spontaneously in approximately one third of patients, severe complications such as bowel ischemia and liver failure have also be", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34815653"}, {"offsetInBeginSection": 1396, "offsetInEndSection": 1612, "text": "the two parameters and SVT. Regarding the clinical outcomes, patients with SVT showed higher mortality, longer hospital and intensive care unit duration, higher rates of a variety of complications and more utilizatio", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25466845"}, {"offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "BACKGROUND: Vascular complications of acute pancreatitis are common. Splanchnic thrombosis accounts for 11% of these complications, whereas extrasplanchnic thrombosis remains a rare entity. These complications are associated with high morbidity an", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31159864"}]}
+{"question_id": "660d6cc3fdcbea915f00003d", "question": "Is gout a very common inflammatory arthritis, which is caused by hyperbilirubinemia?", "answer": "No, gout is not caused by hyperbilirubinemia. Gout is an inflammatory arthritis caused by the deposition of monosodium urate (MSU) crystals. Hyperbilirubinemia refers to an elevated level of bilirubin in the blood and is not a known cause of gout. Gout is primarily associated with elevated levels of uric acid in the blood, which leads to the formation of MSU crystals in the joints and tissues.", "relevant_passage_ids": ["32541923", "34802900"], "type": "yesno", "snippets": [{"offsetInBeginSection": 495, "offsetInEndSection": 508, "text": "hyperuricemia", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34802900"}, {"offsetInBeginSection": 625, "offsetInEndSection": 701, "text": "effect of various dietary approaches on hyperuricemia among people with gout", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34802900"}, {"offsetInBeginSection": 746, "offsetInEndSection": 813, "text": "dietary factors appear to have a small effect on serum urate levels", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34802900"}, {"offsetInBeginSection": 1077, "offsetInEndSection": 1131, "text": "Urate-lowering therapy remains the mainstay of therapy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34802900"}, {"offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "Gout is the most common inflammatory arthritis and occurs when hyperuricaemia, sustained elevation of serum urate levels resulting in supersaturation of body tissues with urate, leads to the formation and deposition of monosodium urate crystals in and around the joints", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32541923"}]}
+{"question_id": "65cfce461930410b1300001a", "question": "What receptors are targeted by Retatrutide?", "answer": "Retatrutide is an agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucagon receptors", "relevant_passage_ids": ["37366315", "37086147", "37385280", "37947489"], "type": "list", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "BACKGROUND: Retatrutide (LY3437943) is an agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucagon receptors. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37366315"}, {"offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Is retatrutide (LY3437943), a GLP-1, GIP, and glucagon receptor agonist a step forward in the treatment of diabetes and obesity?", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37086147"}, {"offsetInBeginSection": 282, "offsetInEndSection": 581, "text": "AREAS COVERED: A multiple-ascending dose phase 1b clinical trial of a new drug retatrutide (LY3437943), which in addition to stimulating Glucagon-like peptide 1 (GLP-1) and Glucose-dependent insulinotropic polypeptide (GIP) receptors, stimulates glucagon receptors, in subjects with type 2 diabetes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37086147"}, {"offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37385280"}, {"offsetInBeginSection": 156, "offsetInEndSection": 397, "text": "Retatrutide, a single peptide with agonist activity at the glucose-dependent insulinotropic polypeptide (GIP), GLP-1, and glucagon receptors, showed clinically meaningful glucose-lowering and bodyweight-lowering efficacy in a phase 1 study. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37385280"}, {"offsetInBeginSection": 4779, "offsetInEndSection": 5037, "text": "INTERPRETATION: In people with type 2 diabetes, retatrutide showed clinically meaningful improvements in glycaemic control and robust reductions in bodyweight, with a safety profile consistent with GLP-1 receptor agonists and GIP and GLP-1 receptor agonists.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37385280"}, {"offsetInBeginSection": 117, "offsetInEndSection": 331, "text": "Retatrutide stimulates Glucagon-like peptide 1 (GLP-1), Glucose-dependent insulinotropic polypeptide (GIP) receptors, and glucagon receptors, and is being developed for the treatment of obesity and type 2 diabetes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37947489"}, {"offsetInBeginSection": 135, "offsetInEndSection": 384, "text": "g glycaemic targets. Retatrutide, a single peptide with agonist activity at the glucose-dependent insulinotropic polypeptide (GIP), GLP-1, and glucagon receptors, showed clinically meaningful glucose-lowering and bodyweight-lowering efficacy in a ph", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37385280"}, {"offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "BACKGROUND: Retatrutide (LY3437943) is an agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucagon receptors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37366315"}, {"offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "BACKGROUND: Retatrutide (LY3437943) is an agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucago", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37366315"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "BACKGROUND: Retatrutide (LY3437943) is an agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucagon receptors", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37366315"}, {"offsetInBeginSection": 155, "offsetInEndSection": 395, "text": " Retatrutide, a single peptide with agonist activity at the glucose-dependent insulinotropic polypeptide (GIP), GLP-1, and glucagon receptors, showed clinically meaningful glucose-lowering and bodyweight-lowering efficacy in a phase 1 study", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37385280"}, {"offsetInBeginSection": 284, "offsetInEndSection": 582, "text": "EAS COVERED: A multiple-ascending dose phase 1b clinical trial of a new drug retatrutide (LY3437943), which in addition to stimulating Glucagon-like peptide 1 (GLP-1) and Glucose-dependent insulinotropic polypeptide (GIP) receptors, stimulates glucagon receptors, in subjects with type 2 diabetes. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37086147"}, {"offsetInBeginSection": 144, "offsetInEndSection": 384, "text": "ic targets. Retatrutide, a single peptide with agonist activity at the glucose-dependent insulinotropic polypeptide (GIP), GLP-1, and glucagon receptors, showed clinically meaningful glucose-lowering and bodyweight-lowering efficacy in a ph", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37385280"}, {"offsetInBeginSection": 116, "offsetInEndSection": 425, "text": " Retatrutide stimulates Glucagon-like peptide 1 (GLP-1), Glucose-dependent insulinotropic polypeptide (GIP) receptors, and glucagon receptors, and is being developed for the treatment of obesity and type 2 diabetes.AREAS COVERED: A phase 2 clinical trial of retatrutide (LY3437943) in the treatment of obesity", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37947489"}, {"offsetInBeginSection": 284, "offsetInEndSection": 817, "text": "EAS COVERED: A multiple-ascending dose phase 1b clinical trial of a new drug retatrutide (LY3437943), which in addition to stimulating Glucagon-like peptide 1 (GLP-1) and Glucose-dependent insulinotropic polypeptide (GIP) receptors, stimulates glucagon receptors, in subjects with type 2 diabetes. Retatrutide was relatively safe and pharmacokinetics support once-weekly dosing.EXPERT OPINION: The role of stimulating glucagon receptors in the treatment of type 2 diabetes and/or obesity is poorly defined and needs to be clarified. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37086147"}, {"offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "BACKGROUND: Retatrutide (LY3437943) is an agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucagon receptors. Its dose-response relationships with respect to side effects, safety, and efficacy for the treatment of obesity are not known.METHODS: We condu", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37366315"}]}
+{"question_id": "65f77919c4010b4d78000036", "question": "What is the mechanism by which the microbiota module the effectiveness of chemotherapy?", "answer": "The gut microbiota influences both local and systemic inflammation. Inflammation contributes to development, progression, and treatment of cancer. \n In preclinical models, disruption of the microbiota impairs the response of subcutaneous tumors to CpG-oligonucleotide immunotherapy and platinum chemotherapy.", "relevant_passage_ids": ["24264989", "28270698", "36212852", "32602287", "31533218", "34722328", "31293523", "36103048", "30263059", "37593337", "38013112", "31344431", "37029611", "37707749", "28303904", "35933808", "34568308", "33317795", "35008915", "31316514", "37757978", "31634731", "35277453", "36309208", "33147357", "37233715", "29473096", "34572850"], "type": "summary", "snippets": [{"offsetInBeginSection": 275, "offsetInEndSection": 412, "text": "disruption of the microbiota impairs the response of subcutaneous tumors to CpG-oligonucleotide immunotherapy and platinum chemotherapy. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24264989"}, {"offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "The gut microbiota influences both local and systemic inflammation. Inflammation contributes to development, progression, and treatment of cancer,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24264989"}, {"offsetInBeginSection": 562, "offsetInEndSection": 850, "text": "Chemotherapy effectiveness, for example, appears to be strongly influenced by the presence of some microorganisms capable of modulating the pharmacokinetics and pharmacodynamics of the compounds used, thus varying the real response and therefore the efficacy of the oncological treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37593337"}, {"offsetInBeginSection": 998, "offsetInEndSection": 1298, "text": "This finding has or could have considerable relevance as it is possible that our ability to modulate and modify the microbial structure before, during, and after treatment could influence all the clinical parameters related to pharmacological treatments and, eventually, the prognosis of the disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37593337"}, {"offsetInBeginSection": 364, "offsetInEndSection": 659, "text": "Intriguingly, gut microbiota can mediate the biotransformation of drugs, thereby altering their bioavailability, bioactivity, or toxicity.AIM OF REVIEW: The review aims to elaborate on the role of gut microbiota and microbial metabolites in the efficacy and adverse effects of chemotherapeutics.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38013112"}, {"offsetInBeginSection": 509, "offsetInEndSection": 700, "text": "Targeting the gut microbiota influences the efficacy and toxicity of CPT11 chemotherapy through three key mechanisms: microbial ecocline, catalysis of microbial enzymes, and immunoregulation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34722328"}, {"offsetInBeginSection": 140, "offsetInEndSection": 281, "text": "Also, many bacterial groups are now directly or indirectly associated with the capability of stimulating or inhibiting carcinogenic pathways.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37593337"}, {"offsetInBeginSection": 701, "offsetInEndSection": 966, "text": "This review summarizes and explores how the gut microbiota participates in CPT11 metabolism and mediates host immune dynamics to affect the toxicity and efficacy of CPT11 chemotherapy, thus introducing a new concept that is called \"microbiota-host-irinotecan axis\".", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34722328"}, {"offsetInBeginSection": 421, "offsetInEndSection": 561, "text": "We have recently begun to understand how oncological therapies and the microbiota are closely interconnected and could influence each other.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37593337"}, {"offsetInBeginSection": 282, "offsetInEndSection": 420, "text": "However, little is known about the importance and impact of microbiota patterns related to the efficacy and toxicity of cancer treatments.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37593337"}, {"offsetInBeginSection": 765, "offsetInEndSection": 965, "text": "Examination of various clinical and experimental drugs by EM reveales that the gut microbiota affects drug efficacy through three pathways: immunological effects, bioaccumulation, and drug metabolism.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37029611"}, {"offsetInBeginSection": 529, "offsetInEndSection": 743, "text": "The presence of bacteria within the tumor environment can also impact the responses to cancer therapies; changing the chemical structure of chemotherapeutic drugs, affecting their activity, and local concentration.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31344431"}, {"offsetInBeginSection": 260, "offsetInEndSection": 480, "text": "Intestinal microbiome has been shown to participate in the resistance to a wide range of anticancer treatments by direct interaction with the treatment or by indirectly stimulating host response through immunomodulation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31533218"}, {"offsetInBeginSection": 770, "offsetInEndSection": 942, "text": "Furthermore, some of the taxa that are depleted in subjects with HIV have proved to modulate the anti-tumor efficacy of various chemotherapies and immunotherapeutic agents.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31316514"}, {"offsetInBeginSection": 194, "offsetInEndSection": 332, "text": "Current evidence suggests that alterations in the composition of the microbiota may affect efficacy and toxicity of anti-cancer therapies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33317795"}, {"offsetInBeginSection": 1864, "offsetInEndSection": 2183, "text": "This study provides the first evidence of the neuroprotective effects of fibre via dietary intake in alleviating the neuroimmune changes seen in response to systemically administered 5-FU, indicating that the microbiota-gut-brain axis is a targetable mediator to reduce the neurotoxic effects of chemotherapy treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37757978"}, {"offsetInBeginSection": 456, "offsetInEndSection": 743, "text": "Gut microbiota can modulate the metabolism of drugs in a number of ways. The presence of bacteria within the tumor environment can also impact the responses to cancer therapies; changing the chemical structure of chemotherapeutic drugs, affecting their activity, and local concentration.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31344431"}, {"offsetInBeginSection": 796, "offsetInEndSection": 1025, "text": "The gut microbiota modulate these agents through key mechanisms, structured as the 'TIMER' mechanistic framework: Translocation, Immunomodulation, Metabolism, Enzymatic degradation, and Reduced diversity and ecological variation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28270698"}, {"offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "Gut microbiota is involved in gastrointestinal carcinogenesis. Also, it modulates the activity, efficacy and toxicity of several chemotherapy agents, such as gemcitabine, cyclophosphamide, irinotecan, cisplatin and 5-Fluorouracil, and target therapy, such as tyrosine kinase inhibitors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31634731"}, {"offsetInBeginSection": 291, "offsetInEndSection": 632, "text": "Gut microbiota shapes the efficiency of drugs through several key mechanisms: metabolism, immunomodulation, translocation, enzymatic degradation, reduction of diversity, and ecological variability. Therefore, gut microbiota have emerged as a novel target to enhance the efficacy and reduce the toxicity and adverse effects of cancer therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31293523"}, {"offsetInBeginSection": 0, "offsetInEndSection": 445, "text": "Accumulating evidence supports not only the functional role of the gut microbiome in cancer development and progression but also its role in defining the efficacy and toxicity of chemotherapeutic agents (5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, methotrexate) and immunotherapeutic compounds (anti-programmed death-ligand 1/anti-programmed cell death protein 1 and anti-cytotoxic T-lymphocyte-associated antigen 4).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36309208"}, {"offsetInBeginSection": 350, "offsetInEndSection": 538, "text": "Several high-impact studies have repeatedly shown that the presence, composition and level of diversity of the gut flora directly impact cancer treatment outcome in both mice and patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33147357"}, {"offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Over the last decade, mounting evidence has revealed the key roles of gut microbiota in modulating the efficacy and toxicity of anticancer drugs, via mechanisms such as immunomodulation and microbial enzymatic degradation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35933808"}, {"offsetInBeginSection": 212, "offsetInEndSection": 331, "text": "Microbial drug metabolism has a profound impact on drug absorption, bioavailability, stability, efficacy, and toxicity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37233715"}, {"offsetInBeginSection": 427, "offsetInEndSection": 591, "text": "Studies have shown that gut microbiota can regulate the tumour microenvironment and affect the efficacy and toxicity of chemotherapy through a variety of mechanisms", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36103048"}, {"offsetInBeginSection": 723, "offsetInEndSection": 1033, "text": "In this Review, we discuss the evidence for the ability of the microbiota to modulate chemotherapy, radiotherapy and immunotherapy with a focus on the microbial species involved, their mechanism of action and the possibility of targeting the microbiota to improve anticancer efficacy while preventing toxicity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28303904"}, {"offsetInBeginSection": 442, "offsetInEndSection": 578, "text": "The composition of fecal microbiota, the activation of NF-kB pathway in cancer tissues and the serum metabolomics were further analyzed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29473096"}, {"offsetInBeginSection": 301, "offsetInEndSection": 466, "text": "The microbiota modulates the host response to chemotherapy via numerous mechanisms, including immunomodulation, xenometabolism and alteration of community structure.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30263059"}, {"offsetInBeginSection": 464, "offsetInEndSection": 795, "text": "This thinking is based on evidence from human, animal and in vitro studies that gut bacteria are intimately linked to the pharmacological effects of chemotherapies (5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, methotrexate) and novel targeted immunotherapies such as anti-PD-L1 and anti-CLTA-4 therapies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28270698"}, {"offsetInBeginSection": 427, "offsetInEndSection": 873, "text": "Studies have shown that gut microbiota can regulate the tumour microenvironment and affect the efficacy and toxicity of chemotherapy through a variety of mechanisms. This paper focuses on the specific mechanism that gut microbiota uses to influence chemotherapy and the potential therapeutic effect of supplementing with probiotics, to provide an important basis for individualised treatment strategies to be used when treating malignant tumours.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36103048"}, {"offsetInBeginSection": 0, "offsetInEndSection": 471, "text": "This review presents up-to-date information on the effects of microbiota on the individual chemotherapy sensitivity in cancer treatment. Recent studies have shown that a fine balance between the intestinal microbiota and the immune system is crucial for maintaining an efficacy of cancer chemotherapy. A number of antitumor drugs have complex mechanisms of action involving not only direct effects but also the activity of the intestinal microbiota and the immune system.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32602287"}, {"offsetInBeginSection": 427, "offsetInEndSection": 592, "text": "Studies have shown that gut microbiota can regulate the tumour microenvironment and affect the efficacy and toxicity of chemotherapy through a variety of mechanisms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36103048"}, {"offsetInBeginSection": 282, "offsetInEndSection": 850, "text": "However, little is known about the importance and impact of microbiota patterns related to the efficacy and toxicity of cancer treatments. We have recently begun to understand how oncological therapies and the microbiota are closely interconnected and could influence each other. Chemotherapy effectiveness, for example, appears to be strongly influenced by the presence of some microorganisms capable of modulating the pharmacokinetics and pharmacodynamics of the compounds used, thus varying the real response and therefore the efficacy of the oncological treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37593337"}, {"offsetInBeginSection": 323, "offsetInEndSection": 525, "text": "microbiota have an effect on tumor treatment. The microbiota directly promote, eliminate, and coordinate the efficacy of chemotherapy drugs and the toxicity of adjuvant drugs, and enhance the ability of", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34568308"}, {"offsetInBeginSection": 0, "offsetInEndSection": 928, "text": "Over the last decade, mounting evidence has revealed the key roles of gut microbiota in modulating the efficacy and toxicity of anticancer drugs, via mechanisms such as immunomodulation and microbial enzymatic degradation. As such, human microbiota presents as an exciting prospect for developing biomarkers for predicting treatment outcomes and interventional approaches for improving therapeutic effects. In this review, we analyze the current knowledge of the interplays among gut microorganisms, host responses and anticancer therapies (including cytotoxic chemotherapy and targeted therapy), with an emphasis on the immunomodulation function of microbiota which facilitates the efficacy of immune checkpoint inhibitors. Moreover, we propose several microbiota-modulating strategies including fecal microbiota transplantation and probiotics, which can be pursued to optimize the use and development of anticancer treatments.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35933808"}, {"offsetInBeginSection": 332, "offsetInEndSection": 743, "text": "An ever-growing body of evidence implicates the potential link between the microbiome and the efficacy of cancer therapies. Gut microbiota can modulate the metabolism of drugs in a number of ways. The presence of bacteria within the tumor environment can also impact the responses to cancer therapies; changing the chemical structure of chemotherapeutic drugs, affecting their activity, and local concentration.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31344431"}, {"offsetInBeginSection": 768, "offsetInEndSection": 1150, "text": "New evidence suggests that gut microbiota can change cancer cell characteristics by impacting the mechanisms involved in cancer plasticity. Interestingly, gut microbiota can also influence the therapeutic efficacy of anticancer drugs by modulating the mechanisms involved in cancer cell plasticity. The gut microbiota has been shown to reduce the toxicity of certain clinical drugs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37707749"}, {"offsetInBeginSection": 0, "offsetInEndSection": 624, "text": "The gut microbiota exists in a dynamic balance between symbiosis and pathogenesis and can influence almost any aspect of host physiology. Growing evidence suggests that the gut microbiota not only plays a key role in carcinogenesis but also influences the efficacy and toxicity of anticancer therapy. The microbiota modulates the host response to chemotherapy via numerous mechanisms, including immunomodulation, xenometabolism and alteration of community structure. Furthermore, exploitation of the microbiota offers opportunities for the personalisation of chemotherapeutic regimens and the development of novel therapies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30263059"}, {"offsetInBeginSection": 225, "offsetInEndSection": 582, "text": "Gut microbiota play a role in host metabolism, and the positive and negative alterations of these microbiota have an effect on tumor treatment. The microbiota directly promote, eliminate, and coordinate the efficacy of chemotherapy drugs and the toxicity of adjuvant drugs, and enhance the ability of patients to respond to tumors in adjuvant immunotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34568308"}, {"offsetInBeginSection": 735, "offsetInEndSection": 1024, "text": "Herein, we review the mechanistic insights of gut microbial interactions with chemotherapy and ICIs, particularly focusing on the interplay between gut bacteria and the pharmacokinetics (eg, metabolism, enzymatic degradation) or pharmacodynamics (eg, immunomodulation) of cancer treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35277453"}, {"offsetInBeginSection": 612, "offsetInEndSection": 893, "text": "Gut microbiota can regulate the metabolism of drugs in several ways. The presence of bacteria in the tumor environment can also affect the response to cancer therapy by altering the chemical structure of chemotherapeutic agents and affecting their activity and local concentration.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36212852"}, {"offsetInBeginSection": 348, "offsetInEndSection": 609, "text": "Recent studies suggest that the gut microbiota has the ability to affect the host response to chemotherapeutic agents by enhancing drug efficacy, promoting chemoresistance and mediating chemotherapy-induced toxicity and side effects via a variety of mechanisms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34572850"}, {"offsetInBeginSection": 0, "offsetInEndSection": 612, "text": "Accumulating evidence supports not only the functional role of the gut microbiome in cancer development and progression but also its role in defining the efficacy and toxicity of chemotherapeutic agents (5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, methotrexate) and immunotherapeutic compounds (anti-programmed death-ligand 1/anti-programmed cell death protein 1 and anti-cytotoxic T-lymphocyte-associated antigen 4). This evidence is supported in numerous in\u00a0vitro, animal, and clinical studies that highlight the importance of microbial mechanisms in defining therapeutic responses.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36309208"}, {"offsetInBeginSection": 698, "offsetInEndSection": 914, "text": "In addition to involvement in drug metabolism and immune surveillance, the production of microbiota-derived metabolites might represent the link between gut/intratumoral bacteria and response to anticancer therapies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35008915"}]}
+{"question_id": "660a8fc4fdcbea915f000027", "question": "What is Tagraxofusp?", "answer": "Tagraxofusp (or SL-401) is a recombinant molecule composed of human interleukin-3 that binds CD123 on neoplastic cells fused to a truncated diphtheria toxin (DT). It is a  is a first-in-class drug targeting CD123 approved for treatment of blastic plasmacytoid dendritic cell neoplasm.", "relevant_passage_ids": ["36951152", "37846131", "38052038", "30859413", "31465247", "32460559", "32606740", "31942876", "32336420", "31437130", "31018069", "37156483", "37105563", "31548341", "36467820", "31547472", "33113953"], "type": "summary", "snippets": [{"offsetInBeginSection": 477, "offsetInEndSection": 562, "text": "tagraxofusp, a CD123-targeting drug consisting of the ligand for CD123, interleukin 3", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36951152"}, {"offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Tagraxofusp (or SL-401) is a recombinant molecule composed of human interleukin-3 that binds CD123 on neoplastic cells fused to a truncated diphtheria toxin (DT). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37846131"}, {"offsetInBeginSection": 104, "offsetInEndSection": 309, "text": "Tagraxofusp (TAG), recombinant interleukin-3 fused to a truncated diphtheria toxin payload, is a first-in-class drug targeting CD123 approved for treatment of blastic plasmacytoid dendritic cell neoplasm. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38052038"}, {"offsetInBeginSection": 104, "offsetInEndSection": 307, "text": "Tagraxofusp (TAG), recombinant interleukin-3 fused to a truncated diphtheria toxin payload, is a first-in-class drug targeting CD123 approved for treatment of blastic plasmacytoid dendritic cell neoplasm", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38052038"}, {"offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Tagraxofusp (or SL-401) is a recombinant molecule composed of human interleukin-3 that binds CD123 on neoplastic cells fused to a truncated diphtheria toxin (DT)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37846131"}, {"offsetInBeginSection": 938, "offsetInEndSection": 1150, "text": "Recent advances in molecular biology and genetics have led to the development of targeted agents, such as tagraxofusp (a recombinant fusion protein targeting CD123), anti-CD123 CAR-T cells, XmAb14045, and IMGN632", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37105563"}, {"offsetInBeginSection": 200, "offsetInEndSection": 251, "text": "Tagraxofusp, is a targeted therapy for BPDCN. Here,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36467820"}, {"offsetInBeginSection": 252, "offsetInEndSection": 395, "text": "Tagraxofusp (or SL-401) is a recombinant cytotoxin which consists of human interleukin-3 fused to a truncated diphtheria toxin. It is currently", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32606740"}, {"offsetInBeginSection": 179, "offsetInEndSection": 372, "text": "(BPDCN). Tagraxofusp (SL-401) is a CD123-targeted therapy consisting of interleukin-3 fused to a truncated diphtheria toxin payload. Factors influencing response to tagraxofusp other than CD123", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31437130"}, {"offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Tagraxofusp-erzs (Elzonris, Stemline) is a cytotoxin that targets CD123-expressing cells. On December 21, 2018, FDA approved tagraxofusp-erzs for the treatment of blastic plasmacytoid dendritic cell neoplasms (BPDCN)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31548341"}, {"offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Tagraxofusp, a CD123-targeted immunotoxin, is the first FDA-approved treatment for patients 2 years and older", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32336420"}, {"offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "Tagraxofusp (tagraxofusp-erzs) [Elzonris\u2122] is an intravenously administered CD123-directed cytotoxin (composed of human interleukin-3 and a truncated diphtheria toxin payload) that was developed by Stemline Therapeutics, Inc. for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30859413"}, {"offsetInBeginSection": 232, "offsetInEndSection": 599, "text": "Tagraxofusp (SL-401) is a CD123-directed cytotoxin consisting of human interleukin-3 fused to truncated diphtheria toxin.METHODS: In this open-label, multicohort study, we assigned 47 patients with untreated or relapsed BPDCN to receive an intravenous infusion of tagraxofusp at a dose of 7 \u03bcg or 12 \u03bcg per kilogram of body weight on days 1 to 5 of each 21-day cycle.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31018069"}, {"offsetInBeginSection": 104, "offsetInEndSection": 308, "text": "Tagraxofusp (TAG), recombinant interleukin-3 fused to a truncated diphtheria toxin payload, is a first-in-class drug targeting CD123 approved for treatment of blastic plasmacytoid dendritic cell neoplasm.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38052038"}, {"offsetInBeginSection": 252, "offsetInEndSection": 379, "text": "Tagraxofusp (or SL-401) is a recombinant cytotoxin which consists of human interleukin-3 fused to a truncated diphtheria toxin.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32606740"}, {"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Tagraxofusp is a toxin-cytokine fusion protein consisting of engineered diphtheria toxin (DT) and interleukin-3 (IL-3).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31942876"}, {"offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Tagraxofusp (or SL-401) is a recombinant molecule composed of human interleukin-3 that binds CD123 on neoplastic cells fused to a truncated diphtheria toxin (DT).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37846131"}, {"offsetInBeginSection": 107, "offsetInEndSection": 439, "text": "Tagraxofusp is an intravenously administered CD123-directed cytotoxin consisting of the fusion of interleukin-3 with a truncated diphtheria toxin payload and was recently approved by the Food and Drug Administration for the treatment of adults and children aged 2 and older with blastic plasmacytoid dendritic cell neoplasm (BPDCN).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31465247"}, {"offsetInBeginSection": 187, "offsetInEndSection": 310, "text": " Tagraxofusp (SL-401) is a CD123-targeted therapy consisting of interleukin-3 fused to a truncated diphtheria toxin payload", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31437130"}, {"offsetInBeginSection": 220, "offsetInEndSection": 341, "text": " or CD123). Tagraxofusp (SL-401) is a CD123-directed cytotoxin consisting of human interleukin-3 fused to truncated dipht", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31018069"}, {"offsetInBeginSection": 1178, "offsetInEndSection": 1420, "text": " Tagraxofusp (SL-401), a recombinant fusion protein containing interleukin-3 fused to truncated diphtheria toxin, was the first approved CD123-targeted therapy for BPDCN based on a phase I/II clinical trial showing a 90% overall response rate", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37156483"}, {"offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "Tagraxofusp (tagraxofusp-erzs) [Elzonris\u2122] is an intravenously administered CD123-directed cytotoxin (composed of human interleukin-3 and a truncated diphtheria toxin payload) that was developed by Stemline Therapeutics, Inc. for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30859413"}, {"offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "Tagraxofusp-erzs (Elzonris, Stemline) is a cytotoxin that targets CD123-expressing cells. On December 21, 2018, FDA approved tagraxofusp-erzs for the treatment of blastic plasmacytoid dendritic cell neoplasms (BPDCN) in adult and pediatric patients 2 years and older.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31548341"}, {"offsetInBeginSection": 251, "offsetInEndSection": 546, "text": " Tagraxofusp (or SL-401) is a recombinant cytotoxin which consists of human interleukin-3 fused to a truncated diphtheria toxin. It is currently the only novel therapy with a prospective evaluation of efficacy and safety in the treatment of BPDCN and is also the only one to achieve FDA approval", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32606740"}, {"offsetInBeginSection": 271, "offsetInEndSection": 544, "text": "luding BPDCN. Tagraxofusp-ezrs (tagraxofusp from herein) is an agent that consists of interleukin-3 fused to a truncated diphtheria toxin, targeting CD123. The Food and Drug Administration recently approved tagraxofusp as therapy for BPDCN for adults and children aged 2\u00a0ye", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32460559"}, {"offsetInBeginSection": 188, "offsetInEndSection": 311, "text": "Tagraxofusp (SL-401) is a CD123-targeted therapy consisting of interleukin-3 fused to a truncated diphtheria toxin payload.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31437130"}, {"offsetInBeginSection": 231, "offsetInEndSection": 352, "text": " Tagraxofusp (SL-401) is a CD123-directed cytotoxin consisting of human interleukin-3 fused to truncated diphtheria toxin", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31018069"}, {"offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Tagraxofusp, a CD123-targeted immunotoxin, is the first FDA-approved treatment for patients 2 years and older with blastic plasmacytoid dendritic cell neoplasm (BPDCN).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32336420"}, {"offsetInBeginSection": 467, "offsetInEndSection": 651, "text": "Recently, tagraxofusp, a CD123-targeting drug consisting of the ligand for CD123, interleukin 3, conjugated to a truncated diphtheria toxin payload was approved for treatment of BPDCN.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36951152"}, {"offsetInBeginSection": 285, "offsetInEndSection": 426, "text": "Tagraxofusp-ezrs (tagraxofusp from herein) is an agent that consists of interleukin-3 fused to a truncated diphtheria toxin, targeting CD123.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32460559"}, {"offsetInBeginSection": 626, "offsetInEndSection": 861, "text": "Tagraxofusp (SL401, Stemline Therapeutics), a recombinant protein composed of a truncated diphtheria toxin payload fused to IL-3, was approved for use in patients with BPDCN in December of 2018 and showed some clinical activity in AML.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31547472"}, {"offsetInBeginSection": 0, "offsetInEndSection": 352, "text": "Tagraxofusp, a CD123-targeted immunotoxin, is the first FDA-approved treatment for patients 2 years and older with blastic plasmacytoid dendritic cell neoplasm (BPDCN). It has been shown to be safe and effective in treatment-na\u00efve and previously treated adult patients, with high rates of successful bridging to hematopoietic stem cell transplantation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32336420"}, {"offsetInBeginSection": 0, "offsetInEndSection": 418, "text": "Tagraxofusp, a CD123-targeted immunotoxin, is the first FDA-approved treatment for patients 2 years and older with blastic plasmacytoid dendritic cell neoplasm (BPDCN). It has been shown to be safe and effective in treatment-na\u00efve and previously treated adult patients, with high rates of successful bridging to hematopoietic stem cell transplantation. The pediatric experience is more limited but demonstrates safety.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32336420"}, {"offsetInBeginSection": 467, "offsetInEndSection": 756, "text": "Recently, tagraxofusp, a CD123-targeting drug consisting of the ligand for CD123, interleukin 3, conjugated to a truncated diphtheria toxin payload was approved for treatment of BPDCN. This was the first agent specifically approved for BPDCN and the first CD123 targeted agent in oncology.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36951152"}, {"offsetInBeginSection": 252, "offsetInEndSection": 445, "text": "Tagraxofusp (or SL-401) is a recombinant cytotoxin which consists of human interleukin-3 fused to a truncated diphtheria toxin. It is currently the only novel therapy with a prospective evaluat", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32606740"}, {"offsetInBeginSection": 0, "offsetInEndSection": 465, "text": "Tagraxofusp (tagraxofusp-erzs) [Elzonris\u2122] is an intravenously administered CD123-directed cytotoxin (composed of human interleukin-3 and a truncated diphtheria toxin payload) that was developed by Stemline Therapeutics, Inc. for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN). In December 2018, tagraxofusp received its first global approval in the USA for the treatment of BPDCN in adults and in paediatric patients aged 2\u00a0years and older. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30859413"}, {"offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Tagraxofusp is a toxin-cytokine fusion protein consisting of engineered diphtheria toxin (DT) and interleukin-3 (IL-3). The IL-3 domain binds to the cluster of differentiation 123 (CD123) and translocates DT into the cytosol, which leads to cell death.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31942876"}, {"offsetInBeginSection": 631, "offsetInEndSection": 789, "text": " Tagraxofusp, an anti-CD123 antibody conjugated to a diphtheria toxin, has been approved for use in patients with blastic plasmacytoid dendritic cell neoplasm", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33113953"}]}
+{"question_id": "660d6f0cfdcbea915f00003e", "question": "What is the epidemiology of breast cancer in men?", "answer": "The epidemiology of breast cancer in men is similar to that of female breast cancer. However, male breast cancer accounts for less than 1% of all cancers in men and less than 1% of all breast cancers. Despite its rarity, the incidence of male breast cancer has been increasing over the past 25 years. The major risk factors for the development of male breast cancer include advancing age, hormonal imbalance, radiation exposure, and a family history of breast cancer. BRCA2 gene mutations are the most common genetic risk factor for male breast cancer. Male breast cancer is often diagnosed at a later stage than female breast cancer, with higher-grade tumors and lower estrogen receptor positivity. The incidence of lobular breast cancer is rare in men, but Paget's disease and papillary carcinoma occur more frequently in men than in women. Localized breast cancer is the most common stage at diagnosis for both men", "relevant_passage_ids": ["34458944", "31471487", "32952827"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Male breast cancer (MBC) is rare, accounting for less than 1% of all breast cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34458944"}, {"offsetInBeginSection": 126, "offsetInEndSection": 306, "text": "Risk factors include increased longevity, obesity, testicular diseases and tumours, and germline mutations of BRCA2. BRCA2 carriers have 80 times the risk of the general population", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34458944"}, {"offsetInBeginSection": 308, "offsetInEndSection": 384, "text": "Men generally present with breast cancer at an older age compared with women", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34458944"}, {"offsetInBeginSection": 418, "offsetInEndSection": 560, "text": "grade 2, hormone receptor positive, HER2 negative, and no special type carcinoma although in situ and invasive papillary carcinomas are common", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34458944"}, {"offsetInBeginSection": 0, "offsetInEndSection": 39, "text": "Breast cancer occurs in about 1% of men", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31471487"}, {"offsetInBeginSection": 780, "offsetInEndSection": 843, "text": "The most common histological type was invasive ductal carcinoma", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32952827"}]}
+{"question_id": "65cfdaae1930410b13000025", "question": "What disease can be treatment with Bulevirtide?", "answer": "Bulevirtide can be used for chronic hepatitis D virus infection.", "relevant_passage_ids": ["36648369", "36396025", "36377139", "37360907", "37473778", "37345876", "32926353", "34268531", "35942695", "36113537", "33999515", "36004554", "37025462", "38041549", "37943548", "37929228", "37880598", "37593170", "36196680", "35329913", "36931396", "35122369", "34799189", "35973578", "38037956", "36192563", "34155804"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "The entry inhibitor bulevirtide (BLV) is a new treatment option for patients with chronic hepatitis D virus (HDV) infection and compensated liver disease. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36648369"}, {"offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Kinetics and predictive value of HBcrAg, HBV RNA and anti-HBc during bulevirtide treatment of chronic HDV-infected patients.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36648369"}, {"offsetInBeginSection": 601, "offsetInEndSection": 781, "text": "Bulevirtide, an entry inhibitor, was conditionally approved in July 2020 in the European Union for adult patients with chronic hepatitis delta (CHD) and compensated liver disease. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36396025"}, {"offsetInBeginSection": 1397, "offsetInEndSection": 1585, "text": "To our knowledge, this is the first reported case of a pembrolizumab-induced exacerbation of hepatitis D and a successful management by application of bulevirtide in the context of cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36377139"}, {"offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Background & Aims: Bulevirtide (BLV) is a novel antiviral drug licensed for the treatment of chronic hepatitis D.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37360907"}, {"offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Long-term follow-up of patients discontinuing bulevirtide treatment upon long-term HDV-RNA suppression.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37360907"}, {"offsetInBeginSection": 920, "offsetInEndSection": 1203, "text": "Pegylated interferon (off-label use) has long been the only available treatment, although bulevirtide is conditionally approved in some European countries. There are many potential treatments in development, but as yet, there are few effective and safe therapies for HDV infection. I", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37473778"}, {"offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "A Phase 3, Randomized Trial of Bulevirtide in Chronic Hepatitis D.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37345876"}, {"offsetInBeginSection": 135, "offsetInEndSection": 190, "text": "Bulevirtide inhibits the entry of HDV into hepatocytes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37345876"}, {"offsetInBeginSection": 2259, "offsetInEndSection": 2387, "text": "CONCLUSIONS: After 48 weeks of bulevirtide treatment, HDV RNA and ALT levels were reduced in patients with chronic hepatitis D. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37345876"}, {"offsetInBeginSection": 256, "offsetInEndSection": 480, "text": "The approval of bulevirtide has shed some light for patients with Chronic Hepatitis D, although important gaps regarding its use in therapy as well as about the epidemiology and diagnosis of the disease need to be addressed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38041549"}, {"offsetInBeginSection": 2425, "offsetInEndSection": 2562, "text": "Bulevirtide was recently approved for HDV in Europe, whereas pegylated interferon alfa is the only treatment available in most countries.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37943548"}, {"offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Broad-spectrum activity of bulevirtide against clinical isolates of HDV and recombinant pan-genotypic combinations of HBV/HDV.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37929228"}, {"offsetInBeginSection": 11, "offsetInEndSection": 208, "text": "To compare the effectiveness of seven major interventions [Bulevirtide (BLV), Interferon (IFN), Nucleoside analogs (NAs), BLV\u2009+\u2009IFN, BLV\u2009+\u2009NAs, IFN\u2009+\u2009NAs, and Placebo] to treat chronic hepatitis D.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37880598"}, {"offsetInBeginSection": 961, "offsetInEndSection": 1248, "text": "The discovery of the entry inhibitor bulevirtide has represented a breakthrough in HDV treatment, by demonstrating high rates of viral suppression in phase II and III trials, results which have been confirmed in real-world settings and in patients with compensated advanced liver disease", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37593170"}, {"offsetInBeginSection": 19, "offsetInEndSection": 112, "text": "Bulevirtide (BLV) is a novel antiviral drug licensed for the treatment of chronic hepatitis D", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37360907"}, {"offsetInBeginSection": 71, "offsetInEndSection": 142, "text": "hepatitis. Bulevirtide (BLV, Hepcludex\u00ae ) is an HDV/HBV entry inhibitor", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33999515"}, {"offsetInBeginSection": 779, "offsetInEndSection": 1013, "text": "therapy for both infections. In July 2020 bulevirtide was authorized for use in the E.U. following a positive opinion by the European Medicines Agency (EMA) for the treatment of chronic HDV infection in HDV RNA-positive adult patients", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34268531"}, {"offsetInBeginSection": 1069, "offsetInEndSection": 1760, "text": "bulevirtide (BLV, Hepcludex\u00ae ), which was recently approved in Europe at a dose of 2\u00a0mg in sub-cutaneous injection per day, is indicated for the treatment of CHD in adult patients with compensated liver disease and positive HDV viremia. BLV can be administrated in monotherapy or in combination with PEG-IFN\u03b1. Nucleos(t)ide analogues can be used in combination for underlying HBV infection. The optimal treatment duration has not yet been determined and treatment should be continued if a clinical benefit is observed. There are other promising therapies such as IFN lambda (IFN\u03bb) (immunomodulator), lonafarnib (prenylation inhibitor) and nucleic acid polymers (Inhibitors of HBsAg release).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34155804"}, {"offsetInBeginSection": 672, "offsetInEndSection": 1301, "text": "Recently, Bulevirtide (BLV), a first-in-class HBV-HDV entry inhibitor blocking Na+ -taurocholate co-transporting polypeptide (NTCP), has provided very promising efficacy data in Phase II and Phase III (interim analysis) trials as well as in preliminary real-life reports. In July 2020, BLV has granted conditional approval by EMA for treatment of compensated CHD, at the dose of 2\u00a0mg/day by self-administered subcutaneous injections. In Phase II and Phase III trials, BLV was evaluated at different doses (2 vs. 10\u2009mg/day) for 24 or 48\u2009weeks, either in monotherapy or in combination with PegIFN. Administration of BLV monotherapy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35942695"}, {"offsetInBeginSection": 0, "offsetInEndSection": 39, "text": "Bulevirtide for HBV and HDV infections.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34268531"}, {"offsetInBeginSection": 0, "offsetInEndSection": 583, "text": "BACKGROUND: Coinfection with hepatitis D virus (HDV) accelerates the progression of liver disease associated with chronic hepatitis B. Bulevirtide inhibits the entry of HDV into hepatocytes.METHODS: In this ongoing phase 3 trial, patients with chronic hepatitis D, with or without compensated cirrhosis, were randomly assigned, in a 1:1:1 ratio, to receive bulevirtide subcutaneously at 2 mg per day (2-mg group) or 10 mg per day (10-mg group) for 144 weeks or to receive no treatment for 48 weeks followed by bulevirtide subcutaneously at 10 mg per day for 96 weeks (control group).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37345876"}, {"offsetInBeginSection": 196, "offsetInEndSection": 366, "text": "Bulevirtide was recently approved in the European Union (EU) for the treatment of chronic HDV infection in HDV RNA positive adult patients with compensated liver disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32926353"}, {"offsetInBeginSection": 816, "offsetInEndSection": 1073, "text": "A new treatment has been approved, Bulevirtide (Hepcludex\u00ae) an HDV/HBV entry inhibitor, for any patient with chronic hepatitis Delta infection (CHD) with active replication (except in decompensated cirrhosis), at a dose of 2mg/day by subcutaneous injection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34799189"}, {"offsetInBeginSection": 601, "offsetInEndSection": 780, "text": "Bulevirtide, an entry inhibitor, was conditionally approved in July 2020 in the European Union for adult patients with chronic hepatitis delta (CHD) and compensated liver disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36396025"}, {"offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Bulevirtide, an entry inhibitor for the hepatitis B virus (HBV) and hepatitis D virus (HDV), is currently available on the European market", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38037956"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Bulevirtide has been recently conditionally approved by the European Medicines Agency for the treatment of Chronic Hepatitis Delta,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36931396"}, {"offsetInBeginSection": 256, "offsetInEndSection": 341, "text": "The approval of bulevirtide has shed some light for patients with Chronic Hepatitis D", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38041549"}, {"offsetInBeginSection": 858, "offsetInEndSection": 1075, "text": "Despite the severity of HDV, there are few treatment options. Pegylated interferon (off-label use) has long been the only available treatment, although bulevirtide is conditionally approved in some European countries.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37473778"}, {"offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Bulevirtide has been recently conditionally approved by the European Medicines Agency for the treatment of Chronic Hepatitis Delta, but the ideal duration of therapy is unknown.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36931396"}, {"offsetInBeginSection": 98, "offsetInEndSection": 303, "text": " In July 2020, bulevirtide was conditionally approved for the treatment of hepatitis D, the most severe form of viral hepatitis, which frequently causes end-stage liver disease and hepatocellular carcinoma", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37025462"}, {"offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "BACKGROUND: Bulevirtide is a first-in-class peptidic entry inhibitor for hepatitis B virus (HBV) and hepatitis D virus infection", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36113537"}, {"offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "Background & Aims: Bulevirtide is a first-in-class entry inhibitor of hepatitis B surface antigen. In July 2020, bulevirtide was conditionally approved for the treatment of hepatitis D, the most severe form of viral hepatitis, which frequently causes end-stage liver disease and hepato", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37025462"}, {"offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "BACKGROUND: Bulevirtide is a first-in-class peptidic entry inhibitor for hepatitis B virus (HBV) and hepatitis D viru", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36113537"}, {"offsetInBeginSection": 982, "offsetInEndSection": 1259, "text": "Pegylated interferon was the mainstay of treatment for HDV infection until bulevirtide, a viral entry inhibitor, was recently approved by the European Union (EMA) and FDA in America, while multiple novel therapies are already in clinical trials as part of the HBV cure program.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36192563"}, {"offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Bulevirtide monotherapy for 48 weeks in patients with HDV-related compensated cirrhosis and clinically significant portal hypertension.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35973578"}, {"offsetInBeginSection": 63, "offsetInEndSection": 186, "text": "In this new era, the virus entry inhibitor bulevirtide has received conditional approval as a treatment for compensated CHD", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36196680"}, {"offsetInBeginSection": 459, "offsetInEndSection": 667, "text": "Recently, bulevirtide, a first in its class HDV entry inhibitor, has received conditional authorization of use from the European Medicines Agency (EMA) and was also submitted for approval in the United States", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35122369"}, {"offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "The entry inhibitor bulevirtide (BLV) is a new treatment option for patients with chronic hepatitis D virus (HDV) infection and compensated liver disease", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36648369"}, {"offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Bulevirtide (Hepcludex\u00ae), a first-in-class entry inhibitor, is being developed by MYR GmbH for the treatment of chronic hepatitis delta virus (HDV) and chronic hepatitis B virus (HBV) infections.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32926353"}, {"offsetInBeginSection": 196, "offsetInEndSection": 487, "text": "Bulevirtide was recently approved in the European Union (EU) for the treatment of chronic HDV infection in HDV RNA positive adult patients with compensated liver disease. This article summarizes the milestones in the development of bulevirtide leading to this first approval for chronic HDV.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32926353"}, {"offsetInBeginSection": 808, "offsetInEndSection": 1180, "text": "In July 2020 bulevirtide was authorized for use in the E.U. following a positive opinion by the European Medicines Agency (EMA) for the treatment of chronic HDV infection in HDV RNA-positive adult patients with compensated liver disease. In this paper we have examined the studies that led to this approval as well as studies examining the drug's efficacy in treating HBV.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34268531"}, {"offsetInBeginSection": 98, "offsetInEndSection": 488, "text": " In July 2020, bulevirtide was conditionally approved for the treatment of hepatitis D, the most severe form of viral hepatitis, which frequently causes end-stage liver disease and hepatocellular carcinoma. Herein, we report the first data from a large multicenter real-world cohort of patients with hepatitis D treated with bulevirtide at a daily dose of 2\u00a0mg without additional interferon", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37025462"}, {"offsetInBeginSection": 0, "offsetInEndSection": 366, "text": "Bulevirtide (Hepcludex\u00ae), a first-in-class entry inhibitor, is being developed by MYR GmbH for the treatment of chronic hepatitis delta virus (HDV) and chronic hepatitis B virus (HBV) infections. Bulevirtide was recently approved in the European Union (EU) for the treatment of chronic HDV infection in HDV RNA positive adult patients with compensated liver disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32926353"}, {"offsetInBeginSection": 0, "offsetInEndSection": 488, "text": "Background & Aims: Bulevirtide is a first-in-class entry inhibitor of hepatitis B surface antigen. In July 2020, bulevirtide was conditionally approved for the treatment of hepatitis D, the most severe form of viral hepatitis, which frequently causes end-stage liver disease and hepatocellular carcinoma. Herein, we report the first data from a large multicenter real-world cohort of patients with hepatitis D treated with bulevirtide at a daily dose of 2\u00a0mg without additional interferon", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37025462"}, {"offsetInBeginSection": 0, "offsetInEndSection": 487, "text": "Bulevirtide (Hepcludex\u00ae), a first-in-class entry inhibitor, is being developed by MYR GmbH for the treatment of chronic hepatitis delta virus (HDV) and chronic hepatitis B virus (HBV) infections. Bulevirtide was recently approved in the European Union (EU) for the treatment of chronic HDV infection in HDV RNA positive adult patients with compensated liver disease. This article summarizes the milestones in the development of bulevirtide leading to this first approval for chronic HDV.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32926353"}, {"offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "Background & Aims: Bulevirtide is a first-in-class entry inhibitor of hepatitis B surface antigen. In July 2020, bulevirtide was conditionally approved for the treatment of hepatitis D, the most severe form of viral hepatitis, which frequently causes end-stage liver disease and hepatocellular carcinoma", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37025462"}, {"offsetInBeginSection": 573, "offsetInEndSection": 1264, "text": "HBV mono-infected patients. Bulevirtide, an entry inhibitor, was conditionally approved in July 2020 in the European Union for adult patients with chronic hepatitis delta (CHD) and compensated liver disease. There are several drugs in development, including lonafarnib and interferon lambda, with different modes of action. In this review, we detail our current fundamental knowledge of HDV lifecycle and review antiviral treatments under development against this virus, outlining their respective mechanisms-of-action. Finally, we describe the antiviral effect these compounds are showing in ongoing clinical trials, discussing their promise and potential pitfalls for managing HDV infected", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36396025"}, {"offsetInBeginSection": 1069, "offsetInEndSection": 1698, "text": "bulevirtide (BLV, Hepcludex\u00ae ), which was recently approved in Europe at a dose of 2\u00a0mg in sub-cutaneous injection per day, is indicated for the treatment of CHD in adult patients with compensated liver disease and positive HDV viremia. BLV can be administrated in monotherapy or in combination with PEG-IFN\u03b1. Nucleos(t)ide analogues can be used in combination for underlying HBV infection. The optimal treatment duration has not yet been determined and treatment should be continued if a clinical benefit is observed. There are other promising therapies such as IFN lambda (IFN\u03bb) (immunomodulator), lonafarnib (prenylation inhib", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34155804"}, {"offsetInBeginSection": 851, "offsetInEndSection": 1072, "text": "Bulevirtide (Hepcludex\u00ae) an HDV/HBV entry inhibitor, for any patient with chronic hepatitis Delta infection (CHD) with active replication (except in decompensated cirrhosis), at a dose of 2mg/day by subcutaneous injection", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34799189"}, {"offsetInBeginSection": 643, "offsetInEndSection": 772, "text": "In recent years, new therapeutic approaches have been studied, and EMA has approved a new drug (bulevirtide) for Delta hepatitis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35329913"}, {"offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "In July 2020, the entry inhibitor bulevirtide was approved in the European Union for the treatment of chronic hepatitis delta virus (HDV) infection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36004554"}]}
+{"question_id": "65f7785dc4010b4d78000033", "question": "Which initial chemotherapy regimen is the most appropriate in Total Neoadjuvant Therapy (TNT) for locally advanced rectal cancer patients?", "answer": "Neoadjuvant mFOLFOXIRI regimens improved pCR rate and survival outcome, reduced the rate of distant metastasis and anastomotic fistula when comparing with propensity-score matched controls of mFOLFOX6 neoadjuvant chemotherapy.", "relevant_passage_ids": ["37174033", "34963563", "37479897", "37198556", "35304396", "37553666", "31054549", "31150315", "37697712", "33169626", "30381141", "21851185", "33419188", "37429749"], "type": "factoid", "snippets": [{"offsetInBeginSection": 1243, "offsetInEndSection": 1449, "text": "A plethora of potential chemotherapy schedules are available around the radiotherapy component, which include preoperative induction or consolidation with a range of options (FOLFOXIRI, FOLFOX, or CAPEOX,) ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37174033"}, {"offsetInBeginSection": 1606, "offsetInEndSection": 1832, "text": "Neoadjuvant mFOLFOXIRI regimens improved pCR rate and survival outcome, reduced the rate of distant metastasis and anastomotic fistula when comparing with propensity-score matched controls of mFOLFOX6 neoadjuvant chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34963563"}, {"offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "PURPOSE: Total neoadjuvant therapy (TNT) with pre-operative chemotherapy and chemoradiotherapy results in improved survival and is becoming the new standard of care in locally advanced rectal cancer (LARC). We describe our experience with TNT consisting of induction chemotherapy followed by chemoradiotherapy using full dose 5FU without oxa", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37479897"}, {"offsetInBeginSection": 500, "offsetInEndSection": 846, "text": "Therefore, the aim of this trial was to investigate whether preoperative short-course radiotherapy followed by chemotherapy with four cycles of CAPOX can double the pCR rate compared to a standard schedule of long-course preoperative CRT in patients with LARC.METHODS: This is a multi-centre, prospective, open label, randomised controlled trial.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37553666"}, {"offsetInBeginSection": 247, "offsetInEndSection": 791, "text": "The present study will be an open-label, single-arm, single-center trial to develop a new protocol.METHODS: Thirty LARC patients at high risk of distant metastasis will receive CRT consisting of long-course radiation, concurrent with tegafur/uracil, oral leucovorin, irinotecan (TEGAFIRI), followed by mFOLFOX-6 or CAPOX before undergoing surgery.DISCUSSION: Since previous findings showed a high percentage of grade 3-4 adverse events with the TEGAFIRI regimen for CRT and TNT, the primary outcome of this study will be safety and feasibility.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37198556"}, {"offsetInBeginSection": 986, "offsetInEndSection": 1299, "text": "ion or intersphincteric resection). Patients will be randomised to either arm A consisting of CRT (50.4\u2009Gy with capecitabine) followed by consolidation chemotherapy (six cycles of CapeOx), or arm B consisting of induction chemotherapy (three cycles of CapeOx plus bevacizumab) followed by CRT and consolidation ch", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35304396"}, {"offsetInBeginSection": 1345, "offsetInEndSection": 1440, "text": "ery or its omission. Neoadjuvant FOLFIRINOX has established efficacy, with a significant increa", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37697712"}, {"offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "INTRODUCTION: Administration of chemotherapeutic regimens such as FOLFOX or CAPEOX with chemoradiation in the neoadjuvant setting, termed total neoadjuvant treatment (TNT), was introduced in recent years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33169626"}, {"offsetInBeginSection": 1268, "offsetInEndSection": 1478, "text": "The regimen of TNT: 3 cycles of induction CAPOX (oxaliplatin plus capecitabine) were followed by pelvic radiotherapy and concurrent CAPOX, then 3 cycles of consolidation CAPOX were delivered after radiotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31054549"}, {"offsetInBeginSection": 237, "offsetInEndSection": 658, "text": "ious study. The aim of this study was to evaluate the efficacy in terms of pathologic complete response to pre-operative therapy.MATERIAL AND METHODS: A Phase II study was designed and clinical stage T3-T4 and/ or N \u2265 1 patients were treated with concomitant boost radiotherapy (55 Gy/5 weeks) plus concurrent chemotherapy (Tom-Ox). The primary endpoint was the assessment of efficacy in terms of clinical and pathologic ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21851185"}, {"offsetInBeginSection": 817, "offsetInEndSection": 925, "text": "be included. Evaluation of the tumoral response will be performed after six courses of high-dose FOLFIRINOX ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37697712"}]}
+{"question_id": "66088d66fdcbea915f00000c", "question": "In what part of the cell would a SNARE Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) be found", "answer": "Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (R-SNAREs) mainly promoted the assembly of the SNARE complex to drive the final membrane fusion step of membrane transport", "relevant_passage_ids": ["37465385", "36750663", "37027300", "35972760", "11001046", "28203732", "10557242", "10908612", "29696021", "26359495", "36608162", "25501368", "20589833", "19617396", "12805548", "16536742", "30194295", "26101353", "11427709", "26339030", "27301672"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (R-SNAREs) mainly promoted the assembly of the SNARE complex to drive the final membrane fusion step of membrane transport", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37465385"}, {"offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "The dynamic assembly of the Synaptic-soluble N-ethylmaleimide-sensitive factor Attachment REceptor (SNARE) complex is crucial to understand membrane fusion. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36750663"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "The AAA+ NSF complex is responsible for SNARE complex disassembly both before and after membrane fusion.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37027300"}, {"offsetInBeginSection": 3, "offsetInEndSection": 164, "text": "have examined the role of the R-soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) synaptobrevin-2/vesicle-associated membrane protein", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12517971"}, {"offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins of the syntaxin, SNAP-25, and VAMP families mediate intracellular membrane fusion through the formation of helical bundles that span opposing membranes. Soluble SNARE domains", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11427709"}, {"offsetInBeginSection": 210, "offsetInEndSection": 412, "text": "soluble proteins [N-ethylmaleimide-sensitive fusion protein (NSF) and soluble NSF attachment proteins (SNAPs)] and integral membrane proteins [vesicle and target SNAP receptors (v- and t-SNAREs)]. Three", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12773094"}, {"offsetInBeginSection": 1224, "offsetInEndSection": 1401, "text": "These data suggest that Vti1a-beta does not function in exocytosis but in a separate SNARE complex in a membrane fusion step during recycling or biogenesis of synaptic vesicles.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10908612"}, {"offsetInBeginSection": 531, "offsetInEndSection": 1214, "text": "Thus, we aimed to investigate the localization and relative concentrations of neuronal SNARE proteins syntaxin-1, synaptosomal nerve-associated protein 25 (SNAP-25), vesicle-associated membrane protein 2 (VAMP-2) (synaptobrevin-2) and calcium sensor synaptotagmin 1 in perisynaptic astrocytic processes compared to nerve terminals and dendrites.METHODS: We used quantitative immunogold electron microscopy of the rat hippocampus to investigate the localization and concentration of neuronal SNARE proteins.RESULTS: As expected, analysis of the immunogold data revealed a lower labeling density of SNARE proteins in the perisynaptic astrocytic processes than in presynaptic terminals.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36608162"}, {"offsetInBeginSection": 172, "offsetInEndSection": 359, "text": "The pairing of vesicle v-SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) with target membrane t-SNAREs has a central role in intracellular membrane fusion.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11001046"}, {"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Specific soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) proteins are required for different membrane transport steps.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10908612"}, {"offsetInBeginSection": 113, "offsetInEndSection": 333, "text": "This process is mediated by the formation of functional soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes between the plasma membrane t-SNARE complex and the vesicle v-SNARE or VAMP.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25501368"}, {"offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Syntaxin 16 (Syx16) is member of the soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) family of molecules that functions in membrane fusion in eukaryotic cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20589833"}, {"offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "The specificity of vesicle-mediated transport is largely regulated by the membrane-specific distribution of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19617396"}, {"offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "SNARE proteins (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) mediate membrane interactions and are conventionally divided into Q-SNAREs and R-SNAREs according to the possession of a glutamine or arginine residue at the core of their SNARE domain.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16536742"}, {"offsetInBeginSection": 0, "offsetInEndSection": 325, "text": "Protein cargo is trafficked between the organelles of the endomembrane system inside transport vesicles, a process mediated by integral membrane proteins called SNAREs (soluble N-ethylmaleimide sensitive factor attachment protein receptors) that reside on the surface of the vesicle (v-SNAREs) and target membrane (t-SNAREs).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10557242"}, {"offsetInBeginSection": 0, "offsetInEndSection": 404, "text": "SNAREs constitute the core machinery of intracellular membrane fusion, but vesicular SNAREs localize to specific compartments via largely unknown mechanisms. Here, we identified an interaction between VAMP7 and SNAP-47 using a proteomics approach. We found that SNAP-47 mainly localized to cytoplasm, the endoplasmic reticulum (ER), and ERGIC and could also shuttle between the cytoplasm and the nucleus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26359495"}, {"offsetInBeginSection": 0, "offsetInEndSection": 995, "text": "Yeast Bet1p participates in vesicular transport from the endoplasmic reticulum to the Golgi apparatus and functions as a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) associated with ER-derived vesicles. A mammalian protein (rbet1) homologous to Bet1p was recently identified, and it was concluded that rbet1 is associated with the Golgi apparatus based on the subcellular localization of transiently expressed epitope-tagged rbet1. In the present study using rabbit antibodies raised against the cytoplasmic domain of rbet1, we found that the majority of rbet1 is not associated with the Golgi apparatus as marked by the Golgi mannosidase II in normal rat kidney cells. Rather, rbet1 is predominantly associated with vesicular spotty structures that concentrate in the peri-Golgi region but are also present throughout the cytoplasm. These structures colocalize with the KDEL receptor and ERGIC-53, which are known to be enriched in the intermediate compartment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9382863"}, {"offsetInBeginSection": 269, "offsetInEndSection": 459, "text": "Here, cells expressing the interacting domains of v- and t-SNAREs on the cell surface were found to fuse spontaneously, demonstrating that SNAREs are sufficient to fuse biological membranes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12805548"}, {"offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Neuronal soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) catalyze synaptic vesicle fusion with presynaptic membranes through the formation of SNARE complexes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30194295"}, {"offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) that reside in the target membranes and transport vesicles assemble into specific SNARE complexes to drive membrane fusion.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26101353"}, {"offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are membrane-associated trafficking proteins that confer identity to lipid membranes and facilitate membrane fusion.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35972760"}, {"offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Formation of complexes between soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) proteins on opposing membranes is the minimal requirement for intracellular membrane fusion.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28203732"}, {"offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Redistribution of soluble N-ethylmaleimide-sensitive-factor attachment protein receptors in mouse sperm membranes prior to the acrosome reaction.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28203732"}, {"offsetInBeginSection": 0, "offsetInEndSection": 362, "text": "Syntaxin 16 (Syx16) is member of the soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) family of molecules that functions in membrane fusion in eukaryotic cells. A rather ubiquitously expressed, tail-anchored membrane protein localized mainly at the trans-Golgi network (TGN), it mediates primarily retrograde endosomal-TGN transport.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20589833"}, {"offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Intracellular membrane fusion is mediated in most cases by membrane-bridging complexes of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27301672"}]}
+{"question_id": "660c0895fdcbea915f00002f", "question": "Relevance of tumoral microbiome.", "answer": "The tumoral microbiome (TM) has been linked to cancer prognosis and is garnering progressively greater consideration as an essential facet of the tumor microenvironment that regulates tumor proliferation and affects cancer prognosis. The TM plays an important role in the formation of the tumor microenvironment, regulation of local immunity, and modification of tumor cell biology, and directly affects the efficacy of drug treatment for tumors. Recent studies have begun to highlight the diverse and tumor-specific microbiomes across multiple cancer types. New evidence suggests that microbes are also present in many tumors, though the scope of how they affect tumor biology and clinical outcomes is in its early stages. In cancer patients, the clinical response to checkpoint-based immunotherapy is associated with the composition and functional quality of the host microbiome. Our study suggests novel microbiome-specific/derived biomarkers for checkpoint immunotherapy response prediction and prognosis in lung cancer.", "relevant_passage_ids": ["37997816", "34506740"], "type": "summary", "snippets": [{"offsetInBeginSection": 737, "offsetInEndSection": 863, "text": "molecular pathogenic mechanisms shared throughout microbial niches that contribute to the initiation and progression of cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34506740"}, {"offsetInBeginSection": 944, "offsetInEndSection": 1022, "text": "how the microbiome may causally impact cancer and its treatment responsiveness", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34506740"}, {"offsetInBeginSection": 1028, "offsetInEndSection": 1161, "text": "how microorganisms or their secreted bioactive metabolites may be potentially harnessed and targeted as precision cancer therapeutics", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34506740"}, {"offsetInBeginSection": 1600, "offsetInEndSection": 1727, "text": "Different pre\u2011clinical and clinical models are available for studying cancer development downstream of gut microbiome dysbiosis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37997816"}, {"offsetInBeginSection": 1138, "offsetInEndSection": 1364, "text": "Dysbiosis of the gut microbiota can alter the metabolite profile, whilst increasing the levels of toxins, such as Bacteroides\u00a0fragilis toxin and colibactin and cytolethal distending toxin, which are responsible for oncogenesis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37997816"}, {"offsetInBeginSection": 1412, "offsetInEndSection": 1519, "text": "impact of gut microbiome dysbiosis on the progression of different types of cancers associated with obesity", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37997816"}, {"offsetInBeginSection": 787, "offsetInEndSection": 910, "text": "relationship between the gut microbiome and obesity\u2011associated malignancies, including colorectal, gastric and liver cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37997816"}, {"offsetInBeginSection": 1056, "offsetInEndSection": 1136, "text": "obesity\u2011associated microbiome alterations can lead to cancer and its progression", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37997816"}]}
+{"question_id": "65cf6ae91930410b13000007", "question": "What disease is treated with Teplizumab?", "answer": "Teplizumab is a CD3-directed monoclonal antibody that was approved for type 1 diabetes (T1D) and was shown to delay the onset of Stage 3 T1D in adults and pediatric patients 8 years of age and older with Stage 2 T1D, based on results of a clinical trial in high-risk relatives of individuals with T1D.", "relevant_passage_ids": ["37502867", "37256143", "37296593", "35533645", "36741943", "36896700", "36877454", "22968521", "33302842", "20095914", "23086558", "24517093", "23835333", "37158990", "37861217", "37607392", "37004543", "37878676", "37937833", "37883211", "37867976", "32789003", "26364507", "34936848"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Teplizumab has been approved for the delay of the onset of type 1 diabetes and may modulate new onset disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37502867"}, {"offsetInBeginSection": 650, "offsetInEndSection": 802, "text": "An anti-CD3 antibody, teplizumab, was recently shown to delay clinical progression to T1D in high-risk individuals including adults and older children. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37256143"}, {"offsetInBeginSection": 440, "offsetInEndSection": 781, "text": "Within the National Clinical Trial (NCT) database, a vast majority of over 3000 trials to treat T1D are devoted to insulin therapy. This review focuses on non-insulin pharmacological therapies. Many investigational new drugs fall under the category of immunomodulators, such as the recently FDA-approved CD-3 monoclonal antibody teplizumab. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37296593"}, {"offsetInBeginSection": 1103, "offsetInEndSection": 1307, "text": "Furthermore, regarding the timing of intervention, teplizumab was the first immunomodulatory agent to demonstrate a significant delay in disease progression in high-risk individuals before clinical onset.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35533645"}, {"offsetInBeginSection": 0, "offsetInEndSection": 466, "text": "Context: Participants with stage 1 or 2 type 1 diabetes (T1D) qualify for prevention trials, but factors involved in screening for such trials are largely unknown.Objective: To identify factors associated with screening for T1D prevention trials.Methods: This study included TrialNet Pathway to Prevention participants who were eligible for a prevention trial: oral insulin (TN-07, TN-20), teplizumab (TN-10), abatacept (TN-18), and oral hydroxychloroquine (TN-22). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36741943"}, {"offsetInBeginSection": 496, "offsetInEndSection": 762, "text": "We focus on phase 2 clinical trials with promising results, thus avoiding the exhausted list of every new therapy for T1DM.EXPERT OPINION: Teplizumab has demonstrated potential as a preventative agent for individuals at risk prior to the onset of overt dysglycemia. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36896700"}, {"offsetInBeginSection": 0, "offsetInEndSection": 434, "text": "Teplizumab (teplizumab-mzwv; TZIELD\u2122) is a CD3-directed monoclonal antibody (humanized IgG1\u03ba) that is being developed by Provention Bio, Inc. for the treatment of type 1 diabetes (T1D). In November 2022, teplizumab was approved in the USA to delay the onset of Stage 3 T1D in adults and pediatric patients 8 years of age and older with Stage 2 T1D, based on results of a clinical trial in high-risk relatives of individuals with T1D. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36877454"}, {"offsetInBeginSection": 1080, "offsetInEndSection": 1127, "text": "Teplizumab marks a turning point in T1D therapy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37937833"}, {"offsetInBeginSection": 125, "offsetInEndSection": 266, "text": "Teplizumab, an anti-CD3 monoclonal, delays T1D onset in patients at risk, but additional therapies are needed to prevent the disease entirely", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37883211"}, {"offsetInBeginSection": 978, "offsetInEndSection": 1138, "text": "We identified IgG2 responses to three species that were associated with time to T1D diagnosis and with teplizumab treatment responses that delayed disease onset", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37878676"}, {"offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Teplizumab has been approved for the delay of the onset of type 1 diabetes and may modulate new onset disease", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37502867"}, {"offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Treatment of new onset type 1 diabetes with teplizumab: successes and pitfalls in development.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24517093"}, {"offsetInBeginSection": 1651, "offsetInEndSection": 1907, "text": "Initial studies indicated that teplizumab is well tolerated, with a self-limiting rash as the most commonly reported adverse effect.CONCLUSIONS: Teplizumab is an anti-CD3 human monoclonal antibody with promising activity in treatment of patients with T1DM.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22968521"}, {"offsetInBeginSection": 518, "offsetInEndSection": 981, "text": "One of the most promising agents, teplizumab , is an FcR-nonbinding anti-CD3 monoclonal antibody that has been tested in Phase II - III clinical trials and was shown to preserve the C-peptide levels and reduce the need for exogenous insulin.AREAS COVERED: In this review, we discuss the recent update on clinical data obtained from trials of teplizumab in type 1 diabetes, the drug's postulated mechanism of action and the identification of responders to therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24517093"}, {"offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "BACKGROUND: Teplizumab, a humanized monoclonal antibody to CD3 on T cells, is approved by the Food and Drug Administration to delay the onset of clinical type 1 diabetes (stage 3) in patients 8 years of age or older with preclinical (stage 2) disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37861217"}, {"offsetInBeginSection": 147, "offsetInEndSection": 501, "text": "Teplizumab is a humanized anti- CD3 monoclonal antibody, which may have beneficial effects for T1DM patients.OBJECTIVE: The aim of the study was to assess the safety and efficacy of teplizumab in T1DM patients.METHODS: We searched electronic databases using related keywords for randomized clinical trials assessing the safety and efficacy of teplizumab.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33302842"}, {"offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Teplizumab Therapy to Delay the Onset of Type 1 Diabetes.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37158990"}, {"offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Teplizumab (teplizumab-mzwv; TZIELD\u2122) is a CD3-directed monoclonal antibody (humanized IgG1\u03ba) that is being developed by Provention Bio, Inc. for the treatment of type 1 diabetes (T1D).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36877454"}, {"offsetInBeginSection": 1004, "offsetInEndSection": 1198, "text": "Teplizumab, a monoclonal antibody (manufactured by Provention Bio and marketed as Tzield), was recently approved by the Food and Drug Administration as the first preventative treatment for T1DM.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37158990"}, {"offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "BACKGROUND: Teplizumab, a humanized monoclonal antibody to CD3 on T cells, is approved by the Food and Drug Administration to delay the onset of clinical type 1 diabetes (stage 3) in patients 8 years of age or older with preclinical (stage", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37861217"}, {"offsetInBeginSection": 426, "offsetInEndSection": 511, "text": " Teplizumab is a novel drug recently approved by the US FDA for the treatment of T1DM", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37004543"}, {"offsetInBeginSection": 1146, "offsetInEndSection": 1290, "text": "We conclude that teplizumab treatment preserves insulin production and reduces the use of exogenous insulin in some patients with new-onset T1D.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23835333"}, {"offsetInBeginSection": 1010, "offsetInEndSection": 1162, "text": "mmune attack and remission of the disease. The immunosuppressants (teplizumab, rituximab and abatacept) show promise in slowing the T1DM progressions fo", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26364507"}, {"offsetInBeginSection": 0, "offsetInEndSection": 500, "text": "IMPORTANCE OF THE FIELD: Type 1 diabetes mellitus (T1D) is a T-cell mediated autoimmune disease with selective destruction of beta cells. Immunological interventions are directed at arresting the loss of beta-cell function with the promise that this will make it easier for patients to control their glucose levels.AREAS COVERED IN THIS REVIEW: This review provides a summary of the preclinical and clinical research published between 1992 and 2009 using teplizumab and other anti-CD3 antibodies to a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20095914"}, {"offsetInBeginSection": 0, "offsetInEndSection": 439, "text": "Despite the clear evidence that type 1 diabetes (T1D) begins well before hyperglycemia is evident, there are no clinically available disease-modifying therapies for early-stage disease. However, following the exciting results of the Teplizumab Prevention Study, the first study to demonstrate that overt T1D can be delayed with immunotherapy, there is renewed optimism that in the future, T1D will be treated before hyperglycemia develops.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32789003"}, {"offsetInBeginSection": 0, "offsetInEndSection": 834, "text": "INTRODUCTION: Immunotherapies for type 1 diabetes mellitus (T1D) have been the focus of intense research over the past few decades. Nevertheless, the results of clinical trials have not matched expectations. However, thanks to the recent and promising results on T1D prevention, among all the different immune-intervention strategies, clinical evidence on anti-CD3 monoclonal antibodies (mAb) deserves particular attention and in-depth evaluation.In this narrative review, we introduce the role of T-cells and their co-receptor CD3 in the pathogenesis of T1D and examine the potential of anti-CD3 mAbs as a treatment for preventing or curing T1D. We discuss pre-clinical studies and phase II/III clinical trials testing the anti-CD3 mAb teplizumab in subjects at T1D high risk, and testing teplizumab and otelixizumab in T1D recent on", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34936848"}, {"offsetInBeginSection": 97, "offsetInEndSection": 271, "text": "treatment with the T cell-specific anti-CD3 antibody teplizumab delayed disease onset in participants at high risk for type 1 diabetes (T1D) in the TrialNet 10 (TN-10) trial.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37878676"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Biologic treatment of type 1 diabetes (T1D) with agents including anti-CD3 (otelixizumab and teplizumab)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29925930"}, {"offsetInBeginSection": 1757, "offsetInEndSection": 2061, "text": "SIONS: Two 12-day courses of teplizumab in children and adolescents with newly diagnosed type 1 diabetes showed benefit with respect to the primary end point of preservation of \u03b2-cell function, but no significant differences between the groups were observed with respect to the secondary end points. (Fun", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37861217"}, {"offsetInBeginSection": 427, "offsetInEndSection": 512, "text": "Teplizumab is a novel drug recently approved by the US FDA for the treatment of T1DM.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37004543"}, {"offsetInBeginSection": 0, "offsetInEndSection": 620, "text": "BACKGROUND: Teplizumab, a humanized monoclonal antibody to CD3 on T cells, is approved by the Food and Drug Administration to delay the onset of clinical type 1 diabetes (stage 3) in patients 8 years of age or older with preclinical (stage 2) disease. Whether treatment with intravenous teplizumab in patients with newly diagnosed type 1 diabetes can prevent disease progression is unknown.METHODS: In this phase 3, randomized, placebo-controlled trial, we assessed \u03b2-cell preservation, clinical end points, and safety in children and adolescents who were assigned to receive teplizumab or placebo for two 12-day courses", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37861217"}, {"offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Teplizumab: A Disease-Modifying Therapy for Type 1 Diabetes That Preserves \u03b2-Cell Function.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37607392"}, {"offsetInBeginSection": 0, "offsetInEndSection": 389, "text": "BACKGROUND: Teplizumab, a humanized monoclonal antibody to CD3 on T cells, is approved by the Food and Drug Administration to delay the onset of clinical type 1 diabetes (stage 3) in patients 8 years of age or older with preclinical (stage 2) disease. Whether treatment with intravenous teplizumab in patients with newly diagnosed type 1 diabetes can prevent disease progression is unknown", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37861217"}, {"offsetInBeginSection": 0, "offsetInEndSection": 356, "text": "BACKGROUND: Type one diabetes mellitus (T1DM) is an autoimmune disease characterized by gradual destruction of beta cells in islets of Langerhans. Teplizumab is a humanized anti- CD3 monoclonal antibody, which may have beneficial effects for T1DM patients.OBJECTIVE: The aim of the study was to assess the safety and efficacy of teplizumab in T1DM patients", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33302842"}, {"offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "BACKGROUND: Type one diabetes mellitus (T1DM) is an autoimmune disease characterized by gradual destruction of beta cells in islets of Langerhans. Teplizumab is a humanized anti- CD3 monoclonal antibody, which may have beneficial effects for T1DM patients", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33302842"}, {"offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "BACKGROUND: Teplizumab, a humanized monoclonal antibody to CD3 on T cells, is approved by the Food and Drug Administration to delay the onset of clinical type 1 diabetes (stage 3) in patients 8 years of age or older with preclinical (stage 2) disease", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37861217"}, {"offsetInBeginSection": 115, "offsetInEndSection": 502, "text": " We tested whether treatment with teplizumab (a Fc receptor non-binding anti-CD3 monoclonal antibody), after the new-onset period, affects the decline in C-peptide production in individuals with type 1 diabetes.METHODS: In a randomised placebo-controlled trial we treated 58 participants with type 1 diabetes for 4-12\u00a0months with teplizumab or placebo at four academic centres in the USA", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23086558"}, {"offsetInBeginSection": 426, "offsetInEndSection": 671, "text": " Teplizumab is a novel drug recently approved by the US FDA for the treatment of T1DM. This drug reduces abnormal glucose tolerance who are at high risk for developing T1DM and have antibodies suggesting an immunological attack on their pancreas", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37004543"}]}
+{"question_id": "65f7778fc4010b4d78000031", "question": "Is Trifluridine/Tipiracil a preferential treatment over Regorafenib in elderly colorectal cancer patients?", "answer": "Although no difference in overall survival was found between the two drugs in adjusted analysis using propensity score, regorafenib showed favorable survival in patients aged <65 years, whereas trifluridine/tipiracil was favored in patients aged \u226565 years in the subgroup analysis", "relevant_passage_ids": ["34406678", "28894015", "30344762", "27670892", "32912821", "27900102", "36990929", "34718946", "33952483", "35289802", "27487107", "32653227", "30350179", "29452346", "34199694", "33597364"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1664, "offsetInEndSection": 1778, "text": "Patients treated with FTD/TPI had better tumor response and disease control than patients treated with regorafenib", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34406678"}, {"offsetInBeginSection": 2180, "offsetInEndSection": 2460, "text": "Although no difference in overall survival was found between the two drugs in adjusted analysis using propensity score, regorafenib showed favorable survival in patients aged <65 years, whereas trifluridine/tipiracil was favored in patients aged \u226565 years in the subgroup analysis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28894015"}, {"offsetInBeginSection": 1194, "offsetInEndSection": 1372, "text": "Regorafenib showed favorable survival in patients aged <65 years (HR, 1.29; 95% CI, 0.98-1.69), whereas TFTD was favored in patients aged \u226565 years (HR, 0.78; 95% CI, 0.59-1.03).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28894015"}, {"offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Trifluridine/tipiracil (FTD/TPI) and regorafenib in older patients with metastatic colorectal cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36990929"}, {"offsetInBeginSection": 12, "offsetInEndSection": 151, "text": "Regorafenib and trifluridine/tipiracil are standard third-line chemotherapies for colorectal cancer patients, but their efficacy is limited", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34718946"}, {"offsetInBeginSection": 10, "offsetInEndSection": 1487, "text": "project aimed to better understand practice patterns, identify drivers for treatment goals, and determine third- and fourth-line treatment choices for patients with metastatic colorectal cancer (mCRC). The survey was developed by an expert panel of gastrointestinal oncologists. Questions concerned general practice patterns, and treatment decisions for three hypothetical patient case scenarios. Participants had to routinely manage patients with mCRC. We present results from 629 participants who provided input on patient treatment scenarios (data cutoff: 17/01/2020). Prolonging overall survival (OS; 51%) was the main aim in first line. In third line, quality of life (QOL) was the primary goal (34%). Forty-three percent also cited efficacy-focused goals; 18% and 13% noted prolonging OS and improving progression-free survival as main aims, respectively. For fit and active patients, 89% of respondents considered trifluridine-tipiracil an appropriate third-line treatment; regorafenib (31%) or clinical trial enrollment (29%) were the fourth-line options. For patients with comorbidities and limited caregiver support, trifluridine-tipiracil was the preferred third-line treatment (70%). For KRAS-mutated patients with comorbidities and adverse events who received prior oxaliplatin, 90% considered oxaliplatin rechallenge an unsuitable third-line treatment, mainly due to the risk of cumulative toxicity (75%). In the third/fourth-line settings, trifluridine-tipiracil", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34199694"}, {"offsetInBeginSection": 1194, "offsetInEndSection": 1480, "text": "Regorafenib showed favorable survival in patients aged <65 years (HR, 1.29; 95% CI, 0.98-1.69), whereas TFTD was favored in patients aged \u226565 years (HR, 0.78; 95% CI, 0.59-1.03).CONCLUSION: No significant difference in OS between regorafenib and TFTD was observed in patients with mCRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28894015"}, {"offsetInBeginSection": 1893, "offsetInEndSection": 2281, "text": "IONS FOR PRACTICE: In this retrospective cohort study, patients with refractory metastatic colorectal cancer treated with trifluridine/tipiracil (FTD/TPI) were significantly less likely than those treated with regorafenib to have dose modifications and more likely to have higher real-world objective response rate (rwORR) and real-world disease control rate (rwDCR) while treated. Patien", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34406678"}, {"offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "Although the effectiveness of trifluridine/tipiracil(TFTD)with bevacizumab for unresectable colorectal cancer that was refractory to previous standard chemotherapy was reported, its effectiveness as a first-line treatment, especially for elderly frail patients, is unclear.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33597364"}, {"offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Colorectal cancer is a disease of older patients, but few guidelines directly address age in their recommendations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36990929"}, {"offsetInBeginSection": 0, "offsetInEndSection": 329, "text": "Regorafenib and trifluridine/tipiracil combination tablet regimens are standard third-line or later treatments for advanced and recurrent colorectal cancer with no significant difference in efficacy. The present study aimed to compare the cost-effectiveness of using regorafenib vs. the trifluridine/tipiracil combination tablet.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27900102"}, {"offsetInBeginSection": 327, "offsetInEndSection": 453, "text": "oral agents for third-line treatment in older patients with refractory metastatic colorectal cancer, regorafenib, and trifluri", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36990929"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1477, "text": "Background: The optimal chemotherapeutic regimen for use beyond the second line for patients with metastatic colorectal cancer (mCRC) remains unclear.Materials and methods: We systematically searched the Cochrane Database of Systematic Reviews, EMBASE and Medline for records published between January 2002 and May 2017, and cancer congress databases for records published between January 2014 and June 2017. Eligible studies evaluated the efficacy, safety and patient-reported outcomes of monotherapies or combination therapies at any dose and number of treatment cycles for use beyond the second line in patients with mCRC. Studies were assessed for design and quality, and a qualitative data synthesis was conducted to understand the impact of treatment on overall survival and other relevant cancer-related outcomes.Results: The search yielded 938 references of which 68 were included for qualitative synthesis. There was limited evidence to support rechallenge with chemotherapy, targeted therapy or both. Compared with placebo, an overall survival benefit for trifluridine/tipiracil (also known as TAS-102) or regorafenib has been shown for patients previously treated with conventional chemotherapy and targeted therapy. There was no evidence to suggest a difference in efficacy between these treatments. Patient choice and quality of life at this stage of treatment should also be considered when choosing an appropriate therapy.Conclusions: These findings support the ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29452346"}, {"offsetInBeginSection": 715, "offsetInEndSection": 927, "text": "The safety profile of each agent can help guide selection. Patients with metastatic colorectal cancer require an individualized treatment strategy that incorporates their age, comorbidities, and prior treatments.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35289802"}]}
+{"question_id": "66088bbafdcbea915f00000a", "question": "What is the function of Diphthamide?", "answer": "Diphthamide is a post-translationally modified histidine residue of eukaryotic TRANSLATION ELONGATION FACTOR2 (eEF2),", "relevant_passage_ids": ["36802593", "37246715", "35781884", "35817801", "30335802", "30060184", "15485916", "28357244", "16648478", "25352115", "30204891", "31463593", "33057331", "18765564", "35482014", "8473309", "16901746", "26261303", "18373493", "20873788", "1353910", "22188241", "22869748"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Diphthamide, a post-translationally modified histidine residue of eukaryotic TRANSLATION ELONGATION FACTOR2 (eEF2), ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35817801"}, {"offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Diphthamide biosynthesis protein 1 (DPH1) is biochemically involved in the first step of diphthamide biosynthesis, a post-translational modification of eukaryotic elongation factor 2 (EEF2). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35781884"}, {"offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Diphthamide (DPH), a conserved amino acid modification on eukaryotic translation elongation factor eEF2, is synthesized via a complex, multi-enzyme pathway.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37246715"}, {"offsetInBeginSection": 150, "offsetInEndSection": 283, "text": "It catalyzes the ADP-ribosylation of a post-translationally modified histidine (diphthamide) on eukaryotic elongation factor 2 (eEF2)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36802593"}, {"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Diphthamide (DPH), a conserved amino acid modification on eukaryotic translation elongation factor eEF2, is synthesized via a complex, multi-enzyme pathway", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37246715"}, {"offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Diphthamide, a posttranslational modification of translation elongation factor 2 that is conserved in all eukaryotes and archaebacteria and is the target of diphtheria", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15485916"}, {"offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Diphthamide, the target of diphtheria toxin, is a post-translationally modified histidine residue found in archaeal and eukaryotic translation", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31463593"}, {"offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Diphthamide is a modified histidine residue which is uniquely present in archaeal and eukaryotic elongation factor 2 (EF-2), an essential GTPase responsible for catalyzing the coordinated translocation of tRNA and mRNA through the ribosome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30060184"}, {"offsetInBeginSection": 292, "offsetInEndSection": 523, "text": "Diphthamide is not only essential for normal physiology (such as ensuring fidelity of mRNA translation), but is also exploited by bacterial ADP-ribosylating toxins (e.g., diphtheria toxin) as their molecular target in pathogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33057331"}, {"offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "Diphthamide is a conserved modification in archaeal and eukaryal translation elongation factor 2 (EF2). Its name refers to the target function for diphtheria toxin, the disease-causing agent that, through ADP ribosylation of diphthamide, causes irreversible inactivation of EF2 and cell death.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25352115"}, {"offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "The translation elongation factor 2 in eukaryotes (eEF-2) contains a unique posttranslationally modified histidine residue, termed diphthamide, which serves as the only target for diphtheria toxin and Pseudomonas aeruginosa exotoxin A.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16648478"}, {"offsetInBeginSection": 0, "offsetInEndSection": 545, "text": "The histidine residue at position 715 of elongation factor 2 (EF-2) is posttranslationally modified in a series of enzymatic reactions to 2-[3-carboxyamido-3-(trimethylammonio)-propyl]histidine, which has been given the trivial name diphthamide. The diphthamide residue of EF-2 is the target site for ADP ribosylation by diphtheria toxin and Pseudomonas exotoxin A. ADP-ribosylated EF-2 does not function in protein synthesis. EF-2 that has not been posttranslationally modified at histidine 715 is resistant to ADP ribosylation by these toxins.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1353910"}, {"offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "The intracellular target of diphtheria toxin is a modified histidine residue, diphthamide, in the translation elongation factor, eEF2 (also known as EFT1). This enigmatic modification occurs in all eukaryotes and is produced in yeast by the action of five gene products, DPH1 to DPH5.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18765564"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Diphthamide is a highly conserved modification of archaeal and eukaryal translation elongation factor 2 (EF2) and yet why cells need EF2 to contain diphthamide is unclear.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28357244"}, {"offsetInBeginSection": 152, "offsetInEndSection": 265, "text": "Diphthamide is a unique site of ADP-ribosylation by diphtheria toxin (DT), which is responsible for cell killing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16901746"}, {"offsetInBeginSection": 1562, "offsetInEndSection": 1665, "text": "This finding suggests a role of diphthamide in modulating NF-\u03baB, death receptor, or apoptosis pathways.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26261303"}, {"offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Diphthamide, the target of diphtheria toxin, is a unique posttranslational modification on eukaryotic and archaeal translation elongation factor 2 (EF2).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20873788"}, {"offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Diphthamide, a post-translationally modified histidine residue of eukaryotic TRANSLATION ELONGATION FACTOR2 (eEF2), is the human host cell-sensitizing target of diphtheria toxin.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35817801"}, {"offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "Diphthamide is a unique post-translationally modified histidine residue (His715 in all mammals) found only in eukaryotic elongation factor-2 (eEF-2). The biosynthesis of diphthamide represents one of the most complex modifications, executed by protein factors conserved from yeast to humans.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33057331"}, {"offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "eEF2 (eukaryotic elongation factor 2) contains a post-translationally modified histidine residue, known as diphthamide, which is the specific ADP-ribosylation target of diphtheria toxin, cholix toxin and Pseudomonas aeruginosa exotoxin A.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18373493"}, {"offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "Diphthamide, a posttranslational modification of translation elongation factor 2 that is conserved in all eukaryotes and archaebacteria and is the target of diphtheria toxin, is formed in yeast by the actions of five proteins, Dph1 to -5, and a still unidentified amidating enzyme.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15485916"}, {"offsetInBeginSection": 9, "offsetInEndSection": 137, "text": "Diphthamide is a post-translationally modified histidine essential for messenger RNA translation and ribosomal protein synthesis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35482014"}, {"offsetInBeginSection": 211, "offsetInEndSection": 431, "text": "Diphthamide is the target for diphtheria toxin and related lethal ADP ribosylases, which collectively kill cells by inactivating the essential translocase function of EF2 during mRNA translation and protein biosynthesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30335802"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Diphthamide, the target of diphtheria toxin, is a post-translationally modified histidine residue that is found in archaeal and eukaryotic translation elongation factor 2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22188241"}, {"offsetInBeginSection": 369, "offsetInEndSection": 685, "text": "Recent studies have suggested that diphthamide has specific functions for the cellular stress response and active proliferation. In this review, we summarize the history and findings of diphthamide obtained to date and discuss the possibility of a specific function for diphthamide in regulating protein translation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30204891"}, {"offsetInBeginSection": 272, "offsetInEndSection": 685, "text": "On the other hand, the physiological function of this rare modification in vivo remains unknown. Recent studies have suggested that diphthamide has specific functions for the cellular stress response and active proliferation. In this review, we summarize the history and findings of diphthamide obtained to date and discuss the possibility of a specific function for diphthamide in regulating protein translation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30204891"}, {"offsetInBeginSection": 369, "offsetInEndSection": 497, "text": "Recent studies have suggested that diphthamide has specific functions for the cellular stress response and active proliferation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30204891"}, {"offsetInBeginSection": 272, "offsetInEndSection": 497, "text": "On the other hand, the physiological function of this rare modification in vivo remains unknown. Recent studies have suggested that diphthamide has specific functions for the cellular stress response and active proliferation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30204891"}, {"offsetInBeginSection": 0, "offsetInEndSection": 483, "text": "Diphthamide is a conserved modification in archaeal and eukaryal translation elongation factor 2 (EF2). Its name refers to the target function for diphtheria toxin, the disease-causing agent that, through ADP ribosylation of diphthamide, causes irreversible inactivation of EF2 and cell death. Although this clearly emphasizes a pathobiological role for diphthamide, its physiological function is unclear, and precisely why cells need EF2 to contain diphthamide is hardly understood.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25352115"}, {"offsetInBeginSection": 121, "offsetInEndSection": 497, "text": "eEF2 is an essential factor in protein translation, and the diphthamide modification has been a famous target of the diphtheria toxin for a long time. On the other hand, the physiological function of this rare modification in vivo remains unknown. Recent studies have suggested that diphthamide has specific functions for the cellular stress response and active proliferation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30204891"}, {"offsetInBeginSection": 0, "offsetInEndSection": 368, "text": "The protein translation elongation factor eEF2 undergoes a unique posttranslational modification called diphthamidation. eEF2 is an essential factor in protein translation, and the diphthamide modification has been a famous target of the diphtheria toxin for a long time. On the other hand, the physiological function of this rare modification in vivo remains unknown.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30204891"}, {"offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Diphthamide is a conserved modification in archaeal and eukaryal translation elongation factor 2 (EF2). Its name refers to the target function for diphtheria toxin, the disease-causing agent that, through ADP ribosylation of diphthamide, causes irreversible inactivation of EF2 and cell death. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25352115"}, {"offsetInBeginSection": 151, "offsetInEndSection": 282, "text": "Diphthamide, an unique post-translationally modified histidine residue, is both required for and the site of this ADP-ribosylation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8473309"}, {"offsetInBeginSection": 0, "offsetInEndSection": 523, "text": "Diphthamide is a unique post-translationally modified histidine residue (His715 in all mammals) found only in eukaryotic elongation factor-2 (eEF-2). The biosynthesis of diphthamide represents one of the most complex modifications, executed by protein factors conserved from yeast to humans. Diphthamide is not only essential for normal physiology (such as ensuring fidelity of mRNA translation), but is also exploited by bacterial ADP-ribosylating toxins (e.g., diphtheria toxin) as their molecular target in pathogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33057331"}, {"offsetInBeginSection": 1017, "offsetInEndSection": 1202, "text": "We confirmed that the diphthamide modification is essential for eEF2 to prevent -1 frameshifting during translation and show that the Gly(717)-to-Arg mutation cannot rescue this defect.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22869748"}]}
+{"question_id": "660d6a97fdcbea915f00003c", "question": "Without immunization, rabies is a lethal disease.", "answer": "Rabies lethality is close to 100% without immunization.", "relevant_passage_ids": ["35931921", "36343866", "37728394"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Rabies is a lethal zoonotic disease mainly transmitted to humans by dog bites", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35931921"}, {"offsetInBeginSection": 12, "offsetInEndSection": 89, "text": "Rabies is an acute lethal infectious disease caused by a lyssavirus infection", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36343866"}, {"offsetInBeginSection": 0, "offsetInEndSection": 38, "text": "Rabies, a lethal zoonotic encephalitis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37728394"}]}
+{"question_id": "65cfaf7e1930410b13000016", "question": "What is the target of Divarasib?", "answer": "Divarasib is a KRAS G12C inhibitor.", "relevant_passage_ids": ["37611121", "37774359", "38052910"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Single-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37611121"}, {"offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "BACKGROUND: Divarasib (GDC-6036) is a covalent KRAS G12C inhibitor that was designed to have high potency and selectivity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37611121"}, {"offsetInBeginSection": 1706, "offsetInEndSection": 1854, "text": "CONCLUSIONS: Treatment with divarasib resulted in durable clinical responses across KRAS G12C-positive tumors, with mostly low-grade adverse events.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37611121"}, {"offsetInBeginSection": 437, "offsetInEndSection": 700, "text": "Here, we describe the identification and characterization of GDC-1971 (formerly RLY-1971), a SHP2 inhibitor currently in clinical trials in combination with KRAS G12C inhibitor divarasib (GDC-6036) for the treatment of solid tumors driven by a KRAS G12C mutation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37774359"}, {"offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38052910"}, {"offsetInBeginSection": 105, "offsetInEndSection": 220, "text": "Divarasib, a KRAS G12C inhibitor, has shown modest activity as a single agent in KRAS G12C-positive CRC at 400\u2009mg. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38052910"}, {"offsetInBeginSection": 1404, "offsetInEndSection": 1577, "text": "The manageable safety profile and encouraging antitumor activity of divarasib plus cetuximab support the further investigation of this combination in KRAS G12C-positive CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38052910"}, {"offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "BACKGROUND: Divarasib (GDC-6036) is a covalent KRAS G12C inhibitor that was designed to have high potency and selectivity.METHODS:", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37611121"}, {"offsetInBeginSection": 53, "offsetInEndSection": 211, "text": "cancer (CRC) and is associated with poor prognosis. Divarasib, a KRAS G12C inhibitor, has shown modest activity as a single agent in KRAS G12C-positive CRC at", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38052910"}, {"offsetInBeginSection": 0, "offsetInEndSection": 331, "text": "BACKGROUND: Divarasib (GDC-6036) is a covalent KRAS G12C inhibitor that was designed to have high potency and selectivity.METHODS: In a phase 1 study, we evaluated divarasib administered orally once daily (at doses ranging from 50 to 400 mg) in patients who had advanced or metastatic solid tumors that harbor a KRAS G12C mutation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37611121"}, {"offsetInBeginSection": 105, "offsetInEndSection": 396, "text": "Divarasib, a KRAS G12C inhibitor, has shown modest activity as a single agent in KRAS G12C-positive CRC at 400\u2009mg. Epidermal growth factor receptor has been recognized as a major upstream activator of RAS-MAPK signaling, a proposed key mechanism of resistance to KRAS G12C inhibition in CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38052910"}, {"offsetInBeginSection": 1509, "offsetInEndSection": 1854, "text": "Serial assessment of circulating tumor DNA showed declines in KRAS G12C variant allele frequency associated with response and identified genomic alterations that may confer resistance to divarasib.CONCLUSIONS: Treatment with divarasib resulted in durable clinical responses across KRAS G12C-positive tumors, with mostly low-grade adverse events.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37611121"}, {"offsetInBeginSection": 124, "offsetInEndSection": 506, "text": "THODS: In a phase 1 study, we evaluated divarasib administered orally once daily (at doses ranging from 50 to 400 mg) in patients who had advanced or metastatic solid tumors that harbor a KRAS G12C mutation. The primary objective was an assessment of safety; pharmacokinetics, investigator-evaluated antitumor activity, and biomarkers of response and resistance were also assessed.R", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37611121"}, {"offsetInBeginSection": 0, "offsetInEndSection": 330, "text": "BACKGROUND: Divarasib (GDC-6036) is a covalent KRAS G12C inhibitor that was designed to have high potency and selectivity.METHODS: In a phase 1 study, we evaluated divarasib administered orally once daily (at doses ranging from 50 to 400 mg) in patients who had advanced or metastatic solid tumors that harbor a KRAS G12C mutation", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37611121"}, {"offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "BACKGROUND: Divarasib (GDC-6036) is a covalent KRAS G12C inhibitor that was designed to have high potency and ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37611121"}]}
+{"question_id": "65f77a71c4010b4d7800003b", "question": "What is the appropriate treatment in HER2Neu amplificated refractory advanced colorectal cancer patients?", "answer": "Tucatinib plus trastuzumab had clinically meaningful anti-tumour activity and favourable tolerability", "relevant_passage_ids": ["37142372", "35238866", "35649212", "32988996", "33203645", "29387480", "29330210", "30513002", "30952821", "33005299", "33961795", "35941028", "36550683", "35228040", "33194604", "30857956", "27108243", "32229076", "37284365", "27332557", "30100092", "30294606", "34214965"], "type": "factoid", "snippets": [{"offsetInBeginSection": 3128, "offsetInEndSection": 3463, "text": "Tucatinib plus trastuzumab had clinically meaningful anti-tumour activity and favourable tolerability. This treatment is the first US Food and Drug Administration-approved anti-HER2 regimen for metastatic colorectal cancer and is an important new treatment option for chemotherapy-refractory HER2-positive metastatic colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37142372"}, {"offsetInBeginSection": 2339, "offsetInEndSection": 2741, "text": "Five patients (6%) had adjudicated interstitial lung disease or pneumonitis (two grade 2; one grade 3; two grade 5, the only treatment-related deaths).INTERPRETATION: Trastuzumab deruxtecan showed promising and durable activity in HER2-positive metastatic colorectal cancer refractory to standard treatment, with a safety profile consistent with that reported in previous trastuzumab deruxtecan trials.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33961795"}, {"offsetInBeginSection": 1529, "offsetInEndSection": 1880, "text": "Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC.CONCLUSION: Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36550683"}, {"offsetInBeginSection": 3049, "offsetInEndSection": 3230, "text": "All deaths in treated patients were due to disease progression.INTERPRETATION: Tucatinib plus trastuzumab had clinically meaningful anti-tumour activity and favourable tolerability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37142372"}, {"offsetInBeginSection": 0, "offsetInEndSection": 645, "text": "PURPOSE: We compared overall survival (OS) in patients with human epidermal growth factor receptor 2 (HER2)-amplified, treatment-refractory metastatic colorectal cancer (mCRC) receiving pertuzumab plus trastuzumab (PER-HER) in the phase IIa MyPathway multibasket study (ClinicalTrials.gov identifier: NCT02091141) with OS in those receiving routine clinical care in an electronic health record-derived external control arm.METHODS: A noninterventional study was conducted using patient-level data from MyPathway participants receiving PER-HER and real-world patients with HER2-amplified treatment-refractory mCRC receiving routine clinical care.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35649212"}, {"offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33961795"}, {"offsetInBeginSection": 615, "offsetInEndSection": 790, "text": "For patients with HER2-positive mCRC, who have developed resistance to trastuzumab and lapatinib, pyrotinib is a promising new candidate, which can be used as salvage therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33194604"}, {"offsetInBeginSection": 2230, "offsetInEndSection": 2436, "text": "no treatment-related deaths.INTERPRETATION: Dual HER2-targeted therapy with pertuzumab plus trastuzumab is well tolerated and could represent a therapeutic opportunity for patients with heavily pretreated, ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30857956"}, {"offsetInBeginSection": 1615, "offsetInEndSection": 1850, "text": "patients who received one or more doses of trastuzumab deruxtecan. This ongoing trial is registered with ClinicalTrials.gov, number NCT03384940.FINDINGS: Between Feb 23, 2018, and July 3, 2019, 78 patients were enrolled in the study (5", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33961795"}, {"offsetInBeginSection": 2362, "offsetInEndSection": 2517, "text": "ated serious adverse events.INTERPRETATION: The combination of trastuzumab and lapatinib is active and well tolerated in treatment-refractory patients with", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27108243"}, {"offsetInBeginSection": 1342, "offsetInEndSection": 1652, "text": "Five (31.3%) patients reported grade 3 TEAEs, and no death was reported.CONCLUSIONS: Trastuzumab in combination with pyrotinib demonstrated encouraging antitumor activity that translated to prolonged survival benefit in HER2 positive refractory or mCRC patients who are RAS wild-type with acceptable tolerance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35941028"}, {"offsetInBeginSection": 74, "offsetInEndSection": 555, "text": "We assessed the activity of tucatinib plus trastuzumab in patients with chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer.METHODS: MOUNTAINEER is a global, open-label, phase 2 study that enrolled patients aged 18 years and older with chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer at 34 sites (clinics and hospitals) in five countries (Belgium, France, Italy, Spain, and the USA).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37142372"}, {"offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "BACKGROUND: HER2 is an actionable target in metastatic colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37142372"}, {"offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37142372"}, {"offsetInBeginSection": 530, "offsetInEndSection": 590, "text": "She had an excellent response to fam-trastuzumab deruxtecan.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37284365"}, {"offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "BACKGROUND: HER2 amplification is detected in 3% of patients with colorectal cancer (CRC), making tumors in the metastatic setting vulnerable to double pharmacological HE", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30952821"}, {"offsetInBeginSection": 843, "offsetInEndSection": 1046, "text": "To date, recently published and presented early phase data provide promising evidence suggesting anti-HER2 therapy may have a potentially beneficial role in the treatment of HER2-positive metastatic CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30100092"}, {"offsetInBeginSection": 151, "offsetInEndSection": 347, "text": "Pyrotinib, a novel irreversible HER2/epidermal growth factor receptor (EGFR) dual tyrosine kinase inhibitor, can efficiently inhibit the proliferation of HER2-positive cancer cells in many tumors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33194604"}, {"offsetInBeginSection": 953, "offsetInEndSection": 1234, "text": "AS wild-type, anti-EGFR resistant tumors). Dual HER2 blockade with monoclonal antibodies (mAbs) (trastuzumab and pertuzumab) or the combination of mAbs with tyrosine kinase inhibitors (trastuzumab and lapatinib) induces durable tumor responses in about one-third of HER2-positive C", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30513002"}, {"offsetInBeginSection": 442, "offsetInEndSection": 624, "text": "Furthermore, several studies such as HERACLES-A, MyPathway and the DESTINY-CRC01 trials have shown significant clinical benefit of HER2 blockade in patients with HER2 amplified mCRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35228040"}, {"offsetInBeginSection": 431, "offsetInEndSection": 699, "text": "The HERACLES trial at four Italian academic cancer centers has confirmed the effectiveness of dual blockage of HER2 with trastuzumab plus lapatinib in patients with heavily pretreated HER2-positive mCRC, refractory to the anti-EGFR antibodies cetuximab or panitumumab.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30294606"}, {"offsetInBeginSection": 230, "offsetInEndSection": 531, "text": "The aim of HERACLES-B trial is to assess the efficacy of the combination of pertuzumab and trastuzumab-emtansine (T-DM1) in this setting.METHODS: HERACLES-B was a single-arm, phase II trial, in patients with histologically confirmed RAS/BRAF wild-type and HER2+ mCRC refractory to standard treatments.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32988996"}, {"offsetInBeginSection": 2219, "offsetInEndSection": 2519, "text": "There were no treatment-related deaths.INTERPRETATION: Dual HER2-targeted therapy with pertuzumab plus trastuzumab is well tolerated and could represent a therapeutic opportunity for patients with heavily pretreated, HER2-amplified metastatic colorectal cancer.FUNDING: F Hoffmann-La Roche/Genentech.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30857956"}, {"offsetInBeginSection": 453, "offsetInEndSection": 772, "text": "Presented are three cases of HER2 amplified colorectal cancer that developed acquired refractoriness to trastuzumab pertuzumab with subsequent clinical benefit to lapatinib plus trastuzumab, highlighting the potential for HER2 tyrosine kinase inhibition plus trastuzumab in overcoming trastuzumab/pertuzumab resistance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29330210"}, {"offsetInBeginSection": 14, "offsetInEndSection": 95, "text": "tastatic colorectal cancer (mCRC), HER2 (ERBB2) gene amplification is implicated ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33203645"}, {"offsetInBeginSection": 1172, "offsetInEndSection": 1442, "text": "tance to anti-EGFR MABs. HER2/ERBB2 amplification is a further driver of resistance to anti-EGFR MABs in mCRC. The phase II study of HER2 Amplification for Colo-Rectal Cancer Enhanced Stratification (HERACLES) discovers that a dual HER2-targeted therapy may be an option", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27332557"}, {"offsetInBeginSection": 221, "offsetInEndSection": 399, "text": "nt failure. Compared to dual anti-HER2 treatments, which have been shown to be effective in HER2-positive metastatic CRC patients, single-agent anti-HER2 therapy is rarely used t", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33005299"}, {"offsetInBeginSection": 348, "offsetInEndSection": 790, "text": "We report a case of a 40-year-old woman with both HER2- and EGFR-amplified metastatic colon cancer, who developed refractory disease resistant to multiline therapies (including trastuzumab with lapatinib) but achieved a remarkable response after pyrotinib treatment. For patients with HER2-positive mCRC, who have developed resistance to trastuzumab and lapatinib, pyrotinib is a promising new candidate, which can be used as salvage therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33194604"}, {"offsetInBeginSection": 0, "offsetInEndSection": 624, "text": "Despite recent advances in the treatment of metastatic colorectal cancer (mCRC), 5\u00a0years survival rates remain low. Chemotherapy remains as the mainstay of treatment with only few available targeted therapies. Human epidermal growth factor receptor 2 (HER2) amplification occurs in approximately 5% of metastatic colorectal cancer and it has been studied as a mechanism of resistance for anti-epidermal growth factor receptor (EGFR) therapy. Furthermore, several studies such as HERACLES-A, MyPathway and the DESTINY-CRC01 trials have shown significant clinical benefit of HER2 blockade in patients with HER2 amplified mCRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35228040"}, {"offsetInBeginSection": 0, "offsetInEndSection": 745, "text": "Importance: Amplification of ERBB2 (formerly referred to as HER2) is present in nearly 3% of patients with metastatic colorectal cancer overall and 5% of patients with KRAS and NRAS wild-type tumors. Despite the availability of several ERBB2-targeted therapeutic options for patients with ERBB2-positive breast and gastric/gastroesophageal tumors, to date, there are currently no approved therapies for patients with ERBB2-positive metastatic colorectal cancer, although ERBB2-targeted therapies are recommended in National Comprehensive Cancer Network guidelines. Recent evidence indicates that anti-ERBB2 therapeutic strategies are active in patients with ERBB2-positive metastatic colorectal cancer and could potentially represent a new stand", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35238866"}, {"offsetInBeginSection": 298, "offsetInEndSection": 505, "text": "cer (mCRC). Both HER2 Amplification for Colorectal Cancer Enhanced Stratification (HERACLES) cohort A and My Pathway clinical trials provided clinical evidence that anti-HER2 therapies could be active in the", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29387480"}, {"offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Dual HER2-targeted therapy has been associated with clinical responses and prolonged progression-free survival and overall survival in RAS-wild type HER2-amplified colorectal cancer (CRC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34214965"}, {"offsetInBeginSection": 538, "offsetInEndSection": 681, "text": "Dual HER2 inhibition with trastuzumab plus lapatinib or pertuzumab has shown promising preliminary anti-tumoral efficacy in RAS wild-type mCRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32229076"}]}
+{"question_id": "66088f67fdcbea915f00000e", "question": "What is a basket trial?", "answer": "The phase II basket trial in oncology is a novel design that enables the simultaneous assessment of treatment effects of one anti-cancer targeted agent in multiple cancer types.", "relevant_passage_ids": ["35993875", "36163614", "28098411", "35537102", "32380518", "32779393", "29984488", "31608505", "37934000", "37120858", "26970120", "37919834", "32769873", "38033501", "33942894", "36849940", "32031692", "35100726", "25993165", "36625301", "30696689", "36636028", "25176973", "27716293", "35917296", "35358718", "36988397"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Basket trials are increasingly used for the simultaneous evaluation of a new treatment in various patient subgroups under one overarching protocol. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35993875"}, {"offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "The phase II basket trial in oncology is a novel design that enables the simultaneous assessment of treatment effects of one anti-cancer targeted agent in multiple cancer types.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36163614"}, {"offsetInBeginSection": 0, "offsetInEndSection": 435, "text": "Background: Basket trials are increasingly used in oncology drug development for early signal detection, accelerated tumor-agnostic approvals, and prioritization of promising tumor types in selected patients with the same mutation or biomarker. Participants are grouped into so-called baskets according to tumor type, allowing investigators to identify tumors with promising responses to treatment for further study. However, it remain", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38033501"}, {"offsetInBeginSection": 89, "offsetInEndSection": 241, "text": "A basket trial is a type of clinical trial for which eligibility is based on the presence of a specific genomic alteration, irrespective of cancer type.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32779393"}, {"offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "BACKGROUND: A basket trial is a type of clinical trial in which eligibility is based on the presence of specific molecular characteristics across subpopulations with different cancer types.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36849940"}, {"offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Basket trials are a novel clinical trial design in which a single intervention is investigated in multiple patient subgroups, or \"baskets.\"", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37120858"}, {"offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "A basket trial aims to expedite the drug development process by evaluating a new therapy in multiple populations within the same clinical trial.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37919834"}, {"offsetInBeginSection": 242, "offsetInEndSection": 376, "text": "Additionally, basket trials are often used to evaluate the response rate of an investigational therapy across several types of cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32779393"}, {"offsetInBeginSection": 397, "offsetInEndSection": 536, "text": "Basket trials, one type of master protocol, emerged as a tool for evaluating biomarker-targeted therapies among multiple tumor histologies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35537102"}, {"offsetInBeginSection": 575, "offsetInEndSection": 747, "text": "Basket trials have been devised to ascertain the extent to which a treatment strategy offers benefit to various patient subpopulations defined by a common molecular target.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35100726"}, {"offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Basket clinical trials are a new category of early clinical trials in which a treatment is evaluated in a population of patients with tumors of various histologic types and primary sites selected for containing specific genomic abnormalities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26970120"}, {"offsetInBeginSection": 782, "offsetInEndSection": 989, "text": "In contrast, basket studies generally enroll patients with different tumor types based on the presence of a specific mutation or biomarker regardless of histology; these trials may include expansion cohorts.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30696689"}, {"offsetInBeginSection": 753, "offsetInEndSection": 942, "text": "The design of basket trials involves screening patients for specific molecular alterations or biomarkers and enrolling them in the trial to receive the targeted therapy under investigation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37934000"}, {"offsetInBeginSection": 562, "offsetInEndSection": 781, "text": "Basket trial designs offer the possibility to include multiple molecularly defined subpopulations, often across histology or tumor types, but included in one cohesive design to evaluate the targeted therapy in question.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25993165"}, {"offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Basket trials are an innovative precision medicine clinical trial design evaluating a single targeted therapy across multiple diseases that share a common characteristic.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36636028"}, {"offsetInBeginSection": 534, "offsetInEndSection": 703, "text": "Basket trials are often viewed as parallel phase II trials within the same entity, designed on the basis of a common denominator, which can be a molecular alteration(s).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25176973"}, {"offsetInBeginSection": 0, "offsetInEndSection": 859, "text": "Basket trials simultaneously evaluate the effect of one or more drugs on a defined biomarker, genetic alteration, or molecular target in a variety of disease subtypes, often called strata. A conventional approach for analyzing such trials is an independent analysis of each of the strata. This analysis is inefficient as it lacks the power to detect the effect of drugs in each stratum. To address these issues, various designs for basket trials have been proposed, centering on designs using Bayesian hierarchical models. In this article, we propose a novel Bayesian basket trial design that incorporates predictive sample size determination, early termination for inefficacy and efficacy, and the borrowing of information across strata. The borrowing of information is based on the similarity between the posterior distributions of the response probability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31608505"}, {"offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "BACKGROUND: A basket trial is a type of clinical trial in which eligibility is based on the presence of specific molecular characteristics across subpopulations with different c", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36849940"}, {"offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Basket trials evaluate a single drug targeting a single genetic variant in multiple cancer cohorts.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36625301"}, {"offsetInBeginSection": 361, "offsetInEndSection": 606, "text": "One type of master protocol is the basket trial, in which a targeted therapy is evaluated for multiple diseases that share common molecular alterations or risk factors that may help predict whether the patients will respond to the given therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32031692"}, {"offsetInBeginSection": 122, "offsetInEndSection": 347, "text": "Baskets trials are used in oncology to study interventions that are developed to target a specific feature (often genetic alteration or immune phenotype) that is observed across multiple tissue types and/or tumor histologies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35917296"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Basket trials have emerged as a new class of efficient approaches in oncology to evaluate a new treatment in several patient subgroups simultaneously.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32380518"}, {"offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "A basket trial investigates the effects of one drug on multiple tumor indications.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35358718"}, {"offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "For multiple rare diseases as defined by a common biomarker signature, or a disease with multiple disease subtypes of low frequency, it is often possible to provide confirmatory evidence for these disease or subtypes (baskets) as a combined group.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36988397"}, {"offsetInBeginSection": 452, "offsetInEndSection": 688, "text": "Therefore, we have designed a organ-agnostic basket study, which covers a variety of solid cancers harboring HER2 amplification, in 1 study protocol.METHODS/DESIGN: This trial is a multicenter, single-arm, basket phase 2 study in Japan.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32769873"}, {"offsetInBeginSection": 402, "offsetInEndSection": 1008, "text": "Basket trials comprise a class of experimental designs used to study solid malignancies that are devised to evaluate the effectiveness of a therapeutic strategy among patients defined by the presence of a particular drug target (often a genetic mutation) rather than a particular tumor histology. Acknowledging the potential for differential effectiveness on the basis of traditional criteria for cancer subtyping, evaluations of treatment effectiveness are conducted with respect to the \"baskets\" which collectively represent a partition of the targeted patient population consisting of discrete subtypes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29984488"}, {"offsetInBeginSection": 227, "offsetInEndSection": 698, "text": "Thus, precision medicine challenges conventional paradigms of clinical translational which have relied on estimates of population-averaged effects to guide clinical practice. Basket trials comprise a class of experimental designs used to study solid malignancies that are devised to evaluate the effectiveness of a therapeutic strategy among patients defined by the presence of a particular drug target (often a genetic mutation) rather than a particular tumor histology.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29984488"}, {"offsetInBeginSection": 227, "offsetInEndSection": 1008, "text": "Thus, precision medicine challenges conventional paradigms of clinical translational which have relied on estimates of population-averaged effects to guide clinical practice. Basket trials comprise a class of experimental designs used to study solid malignancies that are devised to evaluate the effectiveness of a therapeutic strategy among patients defined by the presence of a particular drug target (often a genetic mutation) rather than a particular tumor histology. Acknowledging the potential for differential effectiveness on the basis of traditional criteria for cancer subtyping, evaluations of treatment effectiveness are conducted with respect to the \"baskets\" which collectively represent a partition of the targeted patient population consisting of discrete subtypes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29984488"}, {"offsetInBeginSection": 96, "offsetInEndSection": 736, "text": " Basket- and integrated protocol designs are two of these new strategies and have been applied in a handful oncologic trials. We have taken the concept outside the realm of oncology and report about a first-in-human integrated protocol design that facilitates the transition from phase Ia in healthy volunteers to phase Ib in patients with rare complement-mediated disorders driven by the classical pathway.RESULTS: We have been conducting a prospective, double-blind, randomized, placebo-controlled first-in-human study with TNT009, which is a humanized monoclonal antibody directed against the C1s subunit of human complement component C1", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27716293"}, {"offsetInBeginSection": 406, "offsetInEndSection": 556, "text": "t trials is emerging, whereby the drug is tested simultaneously in different baskets, that is, subgroups of different tumor types. Investigators desir", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28098411"}, {"offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "The phase II basket trial in oncology is a novel design that enables the simultaneous assessment of treatment effects of one anti-cancer targeted agent in multiple cancer types. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36163614"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1208, "text": "Basket trials simultaneously evaluate the effect of one or more drugs on a defined biomarker, genetic alteration, or molecular target in a variety of disease subtypes, often called strata. A conventional approach for analyzing such trials is an independent analysis of each of the strata. This analysis is inefficient as it lacks the power to detect the effect of drugs in each stratum. To address these issues, various designs for basket trials have been proposed, centering on designs using Bayesian hierarchical models. In this article, we propose a novel Bayesian basket trial design that incorporates predictive sample size determination, early termination for inefficacy and efficacy, and the borrowing of information across strata. The borrowing of information is based on the similarity between the posterior distributions of the response probability. In general, Bayesian hierarchical models have many distributional assumptions along with multiple parameters. By contrast, our method has prior distributions for response probability and two parameters for similarity of distributions. The proposed design is easier to implement and less computationally demanding than other Bayesian basket designs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31608505"}, {"offsetInBeginSection": 0, "offsetInEndSection": 734, "text": "Basket trials have become a virulent topic in medical and statistical research during the last decade. The core idea of them is to treat patients, who express the same genetic predisposition-either personally or their disease-with the same treatment irrespective of the location of the disease. The location of the disease defines each basket and the pathway of the treatment uses the common genetic predisposition among the baskets. This opens the opportunity to share information among baskets, which can consequently increase the information of the basket-wise response with respect to the investigated treatment. This further allows dynamic decisions regarding futility and efficacy of individual baskets during the ongoing trial.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33942894"}, {"offsetInBeginSection": 402, "offsetInEndSection": 699, "text": "Basket trials comprise a class of experimental designs used to study solid malignancies that are devised to evaluate the effectiveness of a therapeutic strategy among patients defined by the presence of a particular drug target (often a genetic mutation) rather than a particular tumor histology. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29984488"}, {"offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Basket trials simultaneously evaluate the effect of one or more drugs on a defined biomarker, genetic alteration, or molecular target in a variety of disease subtypes, often called strata.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31608505"}, {"offsetInBeginSection": 402, "offsetInEndSection": 698, "text": "Basket trials comprise a class of experimental designs used to study solid malignancies that are devised to evaluate the effectiveness of a therapeutic strategy among patients defined by the presence of a particular drug target (often a genetic mutation) rather than a particular tumor histology.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29984488"}, {"offsetInBeginSection": 89, "offsetInEndSection": 376, "text": "A basket trial is a type of clinical trial for which eligibility is based on the presence of a specific genomic alteration, irrespective of cancer type. Additionally, basket trials are often used to evaluate the response rate of an investigational therapy across several types of cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32779393"}]}
+{"question_id": "660d2d6afdcbea915f00003b", "question": "What are atypical symptoms of gluten allergy?", "answer": "Atypical symptoms of gluten allergy, such as celiac disease, can include peripheral neuropathy, cerebellar ataxia, laryngospasm, enamel defects, aphthous stomatitis, neuromuscular symptoms, skin rash, insomnia, abnormal taste, impaired memory, and concentration, among others. These symptoms may not be the typical gastrointestinal manifestations commonly associated with gluten-related disorders like diarrhea, weight loss, and abdominal pain. It is important to consider a wide range of symptoms when diagnosing gluten allergies to ensure proper treatment and management.", "relevant_passage_ids": ["37546121", "33573512"], "type": "list", "snippets": [{"offsetInBeginSection": 225, "offsetInEndSection": 355, "text": "atypical presentations can pose diagnostic challenges, particularly when hematological abnormalities are the primary manifestation", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37546121"}, {"offsetInBeginSection": 425, "offsetInEndSection": 557, "text": "paraesthesia, numbness in her hands and feet, marked thinness, extreme thrombocytosis, severe anemia, and mild electrolyte imbalance", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37546121"}, {"offsetInBeginSection": 915, "offsetInEndSection": 1039, "text": "CD as a potential cause for atypical hematological manifestations, such as extreme thrombocytosis secondary to severe anemia", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37546121"}, {"offsetInBeginSection": 462, "offsetInEndSection": 476, "text": "stunted growth", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33573512"}, {"offsetInBeginSection": 481, "offsetInEndSection": 492, "text": "underweight", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33573512"}, {"offsetInBeginSection": 494, "offsetInEndSection": 580, "text": "Irritability, anaemia, rickets, dermatitis herpetiformis, alopecia and intussusception", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33573512"}]}
+{"question_id": "65d136081930410b1300003a", "question": "Is transdermal glyceryl trinitrate effective for stroke?", "answer": "No. Transdermal glyceryl trinitrate is not effective for stroke treatment.", "relevant_passage_ids": ["37290930", "37564156", "30738649"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1690, "offsetInEndSection": 1942, "text": "CONCLUSIONS: In patients who had an ischaemic stroke, ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital trials.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37290930"}, {"offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Background: The Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke Trial-2 (RIGHT-2) reported no overall treatment difference between glyceryl trinitrate (GTN) and sham at day 90. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37564156"}, {"offsetInBeginSection": 1452, "offsetInEndSection": 1595, "text": "Conclusion: At 1\u2009year post randomisation, dependency did not differ between GTN and sham treatment in either the target population or overall. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37564156"}, {"offsetInBeginSection": 2858, "offsetInEndSection": 2995, "text": "INTERPRETATION: Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patients with presumed stroke. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30738649"}]}
+{"question_id": "65f7794dc4010b4d78000037", "question": "What is the mechanism by which the microbiota modulates the effectiveness of immunotherapy?", "answer": "The microbiota may affect tumor immunity by regulating the host immune system and tumor microenvironment. Some bacteria help fight tumors by activating immunity, while some bacteria mediate immunosuppression to help cancer cells escape from the immune system.", "relevant_passage_ids": ["34485534", "35488243", "34003768", "30939293", "32580024", "37828613", "33845122", "31911189", "34360802", "33369247", "33600603", "37307905", "38082435", "36253536", "36343977", "31736775", "29425062", "29494275", "37364479", "36149765", "33783613", "34490119", "31533218", "33488618", "32010123", "31014119", "35663831", "31663125", "34512356", "34277834", "38035338", "32425919", "34444834", "35892821", "33375686", "36588712", "33145316", "31634731", "33435800", "35847121", "36798129", "35757563", "33515779", "36309208", "31109338", "34162429"], "type": "summary", "snippets": [{"offsetInBeginSection": 481, "offsetInEndSection": 740, "text": "The microbiota may affect tumor immunity by regulating the host immune system and tumor microenvironment. Some bacteria help fight tumors by activating immunity, while some bacteria mediate immunosuppression to help cancer cells escape from the immune system.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34485534"}]}
+{"question_id": "660a912dfdcbea915f000028", "question": "What is the results of diphthamide deficiency?", "answer": "Diphthamide deficiency syndrome is a novel human developmental disorder and ribosomopathy. It is s an autosomal recessive disorder associated with developmental delay, abnormal head circumference (microcephaly or macrocephaly), short stature, and congenital heart disease", "relevant_passage_ids": ["33704902", "35781884", "32576952", "30312900", "35482014", "22869748", "26261303", "37675463", "16648478", "34507998", "24895408", "30335802", "29410513"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "Variants of the diphthamide biosynthesis I (DPH1, OMIM*603527) are associated with developmental delay, short stature, and sparse hair syndrome (DEDSSH/DPH1 syndrome) (OMIM# 616901). Another name is Loucks-Innes syndrome. DPH1 syndrome is an ultrarare and severe neurodevelopmental disorder. L", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33704902"}, {"offsetInBeginSection": 2109, "offsetInEndSection": 2389, "text": "These findings indicate that diphthamide deficiency differentially regulates hepatocellular carcinogenesis, which inhibits pericentral hepatocyte-derived tumors and promotes periportal progenitor-associated liver tumors. \u00a9 2022 The Pathological Society of Great Britain and Irelan", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35781884"}, {"offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Diphthamide-deficiency syndrome: a novel human developmental disorder and ribosomopathy.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32576952"}, {"offsetInBeginSection": 430, "offsetInEndSection": 628, "text": "he human DPH1 syndrome is an autosomal recessive disorder associated with developmental delay, abnormal head circumference (microcephaly or macrocephaly), short stature, and congenital heart disease", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32576952"}, {"offsetInBeginSection": 0, "offsetInEndSection": 311, "text": "PURPOSE: Diphthamide is a post-translationally modified histidine essential for messenger RNA translation and ribosomal protein synthesis. We present evidence for DPH5 as a novel cause of embryonic lethality and profound neurodevelopmental delays (NDDs).METHODS: Molecular testing was performed using exome or g", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35482014"}, {"offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Diphthamide affects selenoprotein expression: Diphthamide deficiency reduces selenocysteine incorporation, decreases selenite sensitivity and pre-disposes to oxidative stress.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30312900"}, {"offsetInBeginSection": 1246, "offsetInEndSection": 1591, "text": "In silico modeling of the variants showed altered DPH5 structure and disruption of its interaction with eEF2.CONCLUSION: We provide strong clinical, biochemical, and functional evidence for DPH5 as a novel cause of embryonic lethality or profound NDDs with multisystem involvement and expand diphthamide-deficiency syndromes and ribosomopathies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35482014"}, {"offsetInBeginSection": 365, "offsetInEndSection": 564, "text": "Additional phenotypes resulting from diphthamide\u00a0deficiency include altered tRNA-synthetase and selenoprotein transcript levels, hypersensitivity to oxidative stress and increased selenite tolerance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30312900"}, {"offsetInBeginSection": 1608, "offsetInEndSection": 1791, "text": "These findings define \"diphthamide-deficiency syndrome\" as a special ribosomopathy due to reduced functionality of components of the cellular machinery for eEF2-diphthamide synthesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32576952"}, {"offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "The autosomal-recessive diphthamide deficiency syndrome presents as intellectual disability with developmental abnormalities, seizures, craniofacial and additional morphological phenotypes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37675463"}, {"offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Loss of diphthamide pre-activates NF-\u03baB and death receptor pathways and renders MCF7 cells hypersensitive to tumor necrosis factor", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26261303"}, {"offsetInBeginSection": 2109, "offsetInEndSection": 2329, "text": "These findings indicate that diphthamide deficiency differentially regulates hepatocellular carcinogenesis, which inhibits pericentral hepatocyte-derived tumors and promotes periportal progenitor-associated liver tumors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35781884"}, {"offsetInBeginSection": 803, "offsetInEndSection": 1016, "text": "Moreover, eEF2(G717R/G717R)/OVCA1(-/-) double mutant mice displayed the milder phenotypes of the eEF2(G717R/G717R) mice, suggesting that the embryonic lethality of OVCA1(-/-) mice is due to diphthamide deficiency.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22869748"}, {"offsetInBeginSection": 206, "offsetInEndSection": 564, "text": "We have analyzed the phenotypes of diphthamide deficient cells and found that diphthamide\u00a0deficiency reduces selenocysteine incorporation into selenoproteins. Additional phenotypes resulting from diphthamide\u00a0deficiency include altered tRNA-synthetase and selenoprotein transcript levels, hypersensitivity to oxidative stress and increased selenite tolerance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30312900"}, {"offsetInBeginSection": 206, "offsetInEndSection": 694, "text": "We have analyzed the phenotypes of diphthamide deficient cells and found that diphthamide\u00a0deficiency reduces selenocysteine incorporation into selenoproteins. Additional phenotypes resulting from diphthamide\u00a0deficiency include altered tRNA-synthetase and selenoprotein transcript levels, hypersensitivity to oxidative stress and increased selenite tolerance. Diphthamide-eEF2 occupies the aminoacyl-tRNA translocation site at which UGA either stalls translation or decodes selenocysteine.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30312900"}, {"offsetInBeginSection": 365, "offsetInEndSection": 694, "text": "Additional phenotypes resulting from diphthamide\u00a0deficiency include altered tRNA-synthetase and selenoprotein transcript levels, hypersensitivity to oxidative stress and increased selenite tolerance. Diphthamide-eEF2 occupies the aminoacyl-tRNA translocation site at which UGA either stalls translation or decodes selenocysteine.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30312900"}, {"offsetInBeginSection": 118, "offsetInEndSection": 564, "text": "Nevertheless, cells lacking diphthamide can carry out protein synthesis and are viable. We have analyzed the phenotypes of diphthamide deficient cells and found that diphthamide\u00a0deficiency reduces selenocysteine incorporation into selenoproteins. Additional phenotypes resulting from diphthamide\u00a0deficiency include altered tRNA-synthetase and selenoprotein transcript levels, hypersensitivity to oxidative stress and increased selenite tolerance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30312900"}, {"offsetInBeginSection": 490, "offsetInEndSection": 929, "text": "Diphthamide deficiency in yeast suppresses the translation of TORC1-activating proteins Vam6 and Rtc1. Interestingly, TORC1 signaling also promotes diphthamide biosynthesis, suggesting that diphthamide forms a positive feedback loop to promote translation under nutrient-rich conditions. Our results provide an explanation for why diphthamide is evolutionarily conserved and why diphthamide deletion can cause severe developmental defects.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34507998"}, {"offsetInBeginSection": 365, "offsetInEndSection": 945, "text": "Additional phenotypes resulting from diphthamide\u00a0deficiency include altered tRNA-synthetase and selenoprotein transcript levels, hypersensitivity to oxidative stress and increased selenite tolerance. Diphthamide-eEF2 occupies the aminoacyl-tRNA translocation site at which UGA either stalls translation or decodes selenocysteine. Its position is in close proximity and mutually exclusive to the ribosomal binding site of release/recycling factor ABCE1, which harbors a redox-sensitive Fe-S cluster and, like diphthamide, is present in eukaryotes and archaea but not in eubacteria.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30312900"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1367, "text": "The autosomal-recessive diphthamide deficiency syndrome presents as intellectual disability with developmental abnormalities, seizures, craniofacial and additional morphological phenotypes. It is caused by reduced activity of proteins that synthesize diphthamide on human translation elongation factor 2. Diphthamide synthesis requires seven proteins (DPH1-DPH7), with clinical deficiency described for DPH1, DPH2 and DPH5. A limited set of variant alleles from syndromic patients has been functionally analyzed, but databases (gnomAD) list additional so far uncharacterized variants in human DPH1 and DPH2. Because DPH enzymes are conserved among eukaryotes, their functionality can be assessed in yeast and mammalian cells. Our experimental assessment of known and uncharacterized DPH1 and DPH2 missense alleles showed that six variants are tolerated despite inter-species conservation. Ten additional human DPH1 (G113R, A114T, H132P, H132R, S136R, C137F, L138P, Y152C, S221P, H240R) and two DPH2 (H105P, C341Y) variants showed reduced functionality and hence are deficiency-susceptibility alleles. Some variants locate close to the active enzyme center and may affect catalysis, while others may impact on enzyme activation. In sum, our study has identified functionally compromised alleles of DPH1 and DPH2 genes that likely cause diphthamide deficiency syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37675463"}, {"offsetInBeginSection": 236, "offsetInEndSection": 1560, "text": "Diphthamide biosynthesis is carried out by five highly conserved proteins, Dph1 to Dph5, and an as-yet-unidentified amidating enzyme. The evolutionary conservation of the complex diphthamide biosynthesis pathway throughout eukaryotes implies a key role for diphthamide in normal cellular physiology. Of the proteins required for diphthamide synthesis, Dph3 is the smallest, containing only 82 residues. In addition to having a role in diphthamide biosynthesis, Dph3 is also involved in modulating the functions of the Elongator complex in yeast. To explore the physiological roles of Dph3 and to begin to investigate the function of diphthamide, we generated dph3 knockout mice and showed that dph3+/- mice are phenotypically normal, whereas dph3-/- mice, which lack the diphthamide modification on eEF-2, are embryonic lethal. Loss of both dph3 alleles causes a general delay in embryonic development accompanied by lack of allantois fusion to the chorion and increased degeneration and necrosis in neural tubes and is not compatible with life beyond embryonic day 11.5. The dph3-/- placentas also developed abnormally, showing a thinner labyrinth lacking embryonic erythrocytes and blood vessels. These results attest to the physiological importance of Dph3 in development. The biological roles of Dph3 are also discussed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16648478"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1290, "text": "PURPOSE: Diphthamide is a post-translationally modified histidine essential for messenger RNA translation and ribosomal protein synthesis. We present evidence for DPH5 as a novel cause of embryonic lethality and profound neurodevelopmental delays (NDDs).METHODS: Molecular testing was performed using exome or genome sequencing. A targeted Dph5 knockin mouse (C57BL/6Ncrl-Dph5em1Mbp/Mmucd) was created for a DPH5 p.His260Arg homozygous variant identified in 1 family. Adenosine diphosphate-ribosylation assays in DPH5-knockout human and yeast cells and in silico modeling were performed for the identified DPH5 potential pathogenic variants.RESULTS: DPH5 variants p.His260Arg (homozygous), p.Asn110Ser and p.Arg207Ter (heterozygous), and p.Asn174LysfsTer10 (homozygous) were identified in 3 unrelated families with distinct overlapping craniofacial features, profound NDDs, multisystem abnormalities, and miscarriages. Dph5 p.His260Arg homozygous knockin was embryonically lethal with only 1 subviable mouse exhibiting impaired growth, craniofacial dysmorphology, and multisystem dysfunction recapitulating the human phenotype. Adenosine diphosphate-ribosylation assays showed absent to decreased function in DPH5-knockout human and yeast cells. In silico modeling of the variants showed al", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35482014"}, {"offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Biallelic mutations of the gene encoding diphthamide biosynthesis 1 (DPH1, NM_001383.3) cause developmental delay, dysmorphic features, sparse hair, and short stature (MIM *603527).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29410513"}, {"offsetInBeginSection": 0, "offsetInEndSection": 401, "text": "OVCA1/DPH1 (OVCA1) encodes a component of the diphthamide biosynthesis pathway and is located on chromosome 17p13.3. Deletions in this region are associated with Miller-Dieker syndrome (MDS). Ovca1/Dph1 (Ovca1)-null mice exhibit multiple developmental defects, including cleft palate, growth restriction and perinatal lethality, suggesting a role in the craniofacial abnormalities associated with MDS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24895408"}]}
+{"question_id": "660c06b8fdcbea915f00002e", "question": "What is the cause of Sydenham's chorea?", "answer": "Sydenham's chorea is caused by an autoimmune response after a group A beta-hemolytic streptococcal (GABHS) infection.", "relevant_passage_ids": ["34353207", "31474378", "29287833", "30345135"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Sydenham's chorea is an autoimmune chorea emerging after a group A beta-hemolytic streptococcal (GABHS) infection, i.e. a rheumatic chorea with or without the presence of carditis or arthritis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34353207"}, {"offsetInBeginSection": 975, "offsetInEndSection": 1188, "text": "He was subsequently diagnosed with chorea by the neurology team. The cause of chorea was later determined to be SC, and the patient's throat swab came back positive for group A-beta hemolytic strep (GAS) infection", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31474378"}, {"offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Sydenham's chorea (SC) is an immune-mediated hyperkinetic movement disorder, developing after group A Beta-hemolytic streptococcal (GABHS) infection", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29287833"}, {"offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Immune-mediated central nervous system manifestations of group A \u03b2-hemolytic Streptococcus (GABHS) infection include Sydenham's chorea", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30345135"}]}
+{"question_id": "65d375011930410b1300004a", "question": "What are active ingredients of Xultophy pill?", "answer": "Xultophy is a fixed ratio combination of basal insulin degludec and glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide.", "relevant_passage_ids": ["36467033", "30740861", "28799414", "30335259", "30006093", "28063135", "28250698"], "type": "list", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Introduction: IDegLira (brand name Xultophy) is a novel fixed ratio combination of insulin degludec and liraglutide for type 2 diabetes (T2D) patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36467033"}, {"offsetInBeginSection": 0, "offsetInEndSection": 421, "text": "AIM: To evaluate the long-term cost-effectiveness of fixed-ratio combination insulin degludec/liraglutide (IDegLira) versus comparator regimens for type 2 diabetes in Spain, based on real-world evidence.MATERIALS AND METHODS: Clinical data were taken from the European Xultophy Treatment Retrospective Audit (EXTRA) real-world evidence study in which patients failing to meet glycaemic targets were switched to IDegLira. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30740861"}, {"offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "The Clinical Use of a Fixed-Dose Combination of Insulin Degludec and Liraglutide (Xultophy 100/3.6) for the Treatment of Type 2 Diabetes.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28799414"}, {"offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "[Basal insulin degludec - liraglutide fixed ratio combination (Xultophy\u00ae)].", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30335259"}, {"offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Xultophy\u00ae (IDegLira) is a fixed ratio combination of basal insulin degludec and glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30335259"}, {"offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Xultophy\u00ae (IDegLira) is a fixed ratio combination of basal insulin degludec and glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30335259"}, {"offsetInBeginSection": 0, "offsetInEndSection": 582, "text": "BACKGROUND: Patients with uncontrolled type 2 diabetes mellitus (T2DM) are a priority group for intensified therapy without weight gain and with low risk of hypoglycaemia.OBJECTIVE: This study evaluates the cost effectiveness of insulin degludec plus liraglutide (IDegLira, Xultophy\u00ae) compared with six potential intensification treatment options for patients with T2DM that is uncontrolled with basal insulin.METHODS: The Swedish Institute for Health Economics (IHE) Cohort Model of Type 2 Diabetes was used with Swedish input data, a 40-year time frame and a societal perspective.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28063135"}, {"offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "AIMS: Xultophy is the first fixed co-formulation pen containing insulin degludec and the glucagon-like peptide-1 (GLP-1) analogue liraglutide, authorized for type 2 diabetes patients since 2014.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30006093"}, {"offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Insulin degludec/liraglutide (Xultophy 100/3.6) for type-2 diabetes; rucaparib (Rubraca) for the treatment of deleterious BRCA mutation-associated ovarian cancer; and nusinersen (Spinraza) for the treatment of spinal muscular atrophy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28250698"}, {"offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "AIMS: Xultophy is the first fixed co-formulation pen containing insulin degludec and the glucagon-like peptide-1 (GLP-1) analogue liraglutide, authorized for type 2 diabetes patients since 2014", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30006093"}, {"offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "AIMS: Xultophy is the first fixed co-formulation pen containing insulin degludec and the glucagon-like peptide-1 (GLP-1) analogue liraglutide, authorized for type 2 diabetes patients since 2014. The aim was to review the clinical effectiveness of Xultophy across two hospitals in Wales", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30006093"}, {"offsetInBeginSection": 0, "offsetInEndSection": 395, "text": "AIMS: Xultophy is the first fixed co-formulation pen containing insulin degludec and the glucagon-like peptide-1 (GLP-1) analogue liraglutide, authorized for type 2 diabetes patients since 2014. The aim was to review the clinical effectiveness of Xultophy across two hospitals in Wales.METHODS: Retrospective review of patients commenced on Xultophy between April 2016 and January 2018 was taken", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30006093"}, {"offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "AIMS: Xultophy is the first fixed co-formulation pen containing insulin degludec and the glucagon-like peptide-1 (GLP-1) analogue liraglutide, authorized for type 2 diabetes patients since", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30006093"}]}
+{"question_id": "65f775e8c4010b4d7800002d", "question": "Should UGT1A1 alteration be routinely determined in colorectal cancer patients?", "answer": "An examination of more UGT1A loci, except for UGT1A1*6 and UGT1A1*28, was not helpful to improve the predictive value of irinotecan-based toxicity and efficacy.", "relevant_passage_ids": ["28637434", "19125128", "32829105", "30583998", "19125129", "25817555", "18594531", "21287524", "26692528", "19450125", "27072236", "35356222", "26098842", "25545261", "37932443", "37802427", "37257181", "36308049", "36239106", "36183220", "34860573", "37470120", "33125947", "30585257", "30550693", "35822291", "33090402", "18437170", "25981652", "23840132", "15280927", "34327766", "23236239", "26830078", "22559977", "17184208", "32264830", "26811156", "28474802", "28502040", "30538568", "33619631", "32357899", "25782327", "19770637", "16551870", "24439671", "24642571", "25285015", "16641252", "33877904", "19859999", "26591441", "23686699", "16965601", "24033692", "23386248", "16982469", "17090741", "21486535", "17510208"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1879, "offsetInEndSection": 2039, "text": "An examination of more UGT1A loci, except for UGT1A1*6 and UGT1A1*28, was not helpful to improve the predictive value of irinotecan-based toxicity and efficacy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28637434"}, {"offsetInBeginSection": 178, "offsetInEndSection": 297, "text": "However, severe adverse effects due to irinotecan have been observed even in patients who do not harbor UGT1A1*28 or *6", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36308049"}, {"offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Efficacy and safety of high doses of irinotecan in patients with metastatic colorectal cancer treated with the FOLFIRI regimen based on the UGT1A1 genotype: A systematic review.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36183220"}, {"offsetInBeginSection": 475, "offsetInEndSection": 619, "text": "UGT1A1 gene polymorphism as a predictor of toxicity and treatment efficacy in patients who received irinotecan for metastatic colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19770637"}, {"offsetInBeginSection": 166, "offsetInEndSection": 301, "text": "UGT1A1(*)28 and (*)6 polymorphisms and irinotecan toxicity in Thai patients with metastatic colorectal cancer. 44 metastatic colorectal", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26830078"}, {"offsetInBeginSection": 288, "offsetInEndSection": 450, "text": "UGT1A1 genetic polymorphisms and the occurrences of irinotecan-induced neutropenia in 25 patients of colorectal cancer at our hospital. Analysis of UGT1A1 genetic", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25981652"}, {"offsetInBeginSection": 54, "offsetInEndSection": 159, "text": "e1A1 (UGT1A1) and thymidylate synthetase (TS) gene polymorphisms on irinotecan in metastatic colorectal c", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23236239"}, {"offsetInBeginSection": 1294, "offsetInEndSection": 1412, "text": "heterozygosity for UGT1A1*6 and *28, dose reduction of irinotecan is strongly recommended. Genotyping tests for UGT1A1", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26591441"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1873, "text": "Personalized/individualized/tailored therapy for each patient is an important goal for improving the outcome of patients with colorectal adenocarcinoma and includes the intention to maximize efficacy and minimize toxicity of chemotherapeutic agents. Numerous barriers must be overcome to reach this goal because outcome is affected by an unholy trinity of tumor characteristics that include somatic alterations at the DNA, RNA, and protein level; patient characteristics that include germline genetic differences such as polymorphisms in enzymes affecting the metabolism of chemotherapeutic agents; and environmental exposures and factors that include diet and physical activity. At present, evaluation of epidermal growth factor receptor (EGFR) expression by immunohistochemistry in colorectal adenocarcinoma is generally required for treatment with one of the monoclonal antibody therapies directed against that target, despite the absence of evidence for predictive value of the assay, whereas EGFR fluorescent in situ hybridization (FISH) may be predictive. In addition, the Food and Drug Administration of the United States now requires a 'black box' warning on the packaging of irinotecan for evaluation of germline polymorphism in UGT1A1, the gene mutated in Gilbert's syndrome, for potential reduction of drug dosage in patients with the UGT1A1*28 polymorphism. Numerous other potential markers have been identified but have not yet reached levels of evidence that support their routine usage. For example, KRAS gene mutation appears to preclude improved survival after therapy with monoclonal antibody therapy directed at EGFR, and extensive DNA methylation is associated with lack of efficacy of 5-fluorouracil (5-FU)-based chemotherapy. Additional markers will come into routine usage as reports of research studies continue to appear in the literature. Clinical", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18437170"}, {"offsetInBeginSection": 2697, "offsetInEndSection": 3092, "text": "Given the large number of colorectal cancer cases diagnosed each year, a randomized controlled trial of the effects of irinotecan dose modifications in patients with colorectal cancer based on their UGT1A1 genotype is feasible and could clarify the tradeoffs between possible reductions in severe neutropenia and improved tumor response and/or survival in patients with various UGT1A1 genotypes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19125129"}, {"offsetInBeginSection": 0, "offsetInEndSection": 659, "text": "SUMMARY OF RECOMMENDATIONS: The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group found that the evidence is currently insufficient to recommend for or against the routine use of UGT1A1 genotyping in patients with metastatic colorectal cancer who are to be treated with irinotecan, with the intent of modifying the dose as a way to avoid adverse drug reactions (severe neutropenia).RATIONALE: The EGAPP Working Group (EWG) found no intervention trials showing that targeted dosing of irinotecan based on UGT1A1 genotyping could reduce the rates of two specific adverse drug events, severe (Grade 3-4) neutropenia or diarrhea.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19125128"}, {"offsetInBeginSection": 944, "offsetInEndSection": 1141, "text": "Patients homozygous for the *28 allele are 3.5 times more likely to develop severe neutropenia compared with individuals with the wild genotype (risk ratio 3.51; 95% confidence interval 2.03-6.07).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19125129"}, {"offsetInBeginSection": 1813, "offsetInEndSection": 2056, "text": "Although the quality of evidence on clinical utility is inadequate, two of three reviewed studies (and one published since our initial selection of studies for review) found that individuals homozygous for the *28 allele had improved survival.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19125129"}, {"offsetInBeginSection": 983, "offsetInEndSection": 1304, "text": "An additional finding was the suggestion that reducing irinotecan dose may result in patient harms due to diminished effectiveness of treatment in highest risk individuals (*28/*28 homozygotes), and that a higher dose might be warranted among individuals at lower risk of adverse drug events (*1/*1 and *1/*28 genotypes).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19125128"}, {"offsetInBeginSection": 102, "offsetInEndSection": 547, "text": "We developed a pyrosequencing method to detect allele frequency and genotype of UGT1A1 polymorphisms (UGT1A1*28 and UGT1A1*6) in Thai colorectal cancer patients.METHOD: A pyrosequencing method was designed to determine UGT1A1 genetic polymorphisms including UGT1A1*28 (A[TA]7TAA) and UGT1A1*6 (211G>A) in 91 Thai colorectal cancers.RESULT: Genotyping by the pyrosequencing technique was 100% concordant with capillary electrophoresis sequencing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25545261"}, {"offsetInBeginSection": 1612, "offsetInEndSection": 1915, "text": "This study is the first to use the UGT1A1 genotype to stratify patients into groups based on their risk of diarrhea, and to provide a complete assessment of chemotherapy-related diarrhea (CRD), including records of diarrhea duration, grading the severity of diarrhea, and evaluating concomitant symptoms", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32357899"}, {"offsetInBeginSection": 172, "offsetInEndSection": 680, "text": "This study is a multicenter, randomised clinical trial comparing the clinical outcomes and adverse events (AEs) in metastatic colorectal cancer (mCRC) patients treated with bevacizumab plus FOLFIRI with or without UGT1A1 genotyping and irinotecan dose escalation as the first-line therapy.METHODS: The control group received conventional biweekly FOLFIRI plus bevacizumab without UGT1A1 genotyping, whereas the study group received the same regimen with irinotecan dose escalation based on UGT1A1 genotyping.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32829105"}, {"offsetInBeginSection": 1142, "offsetInEndSection": 1381, "text": "The proposed clinical utility of UGT1A1 genotyping would be derived from a reduction in drug-related adverse reactions (benefits) while at the same time avoiding declines in tumor response rate and increases in morbidity/mortality (harms).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19125129"}, {"offsetInBeginSection": 460, "offsetInEndSection": 614, "text": "For patients showing homozygosity for UGT1A1*28, *6 or compound heterozygosity for UGT1A1*6 and *28, dose reduction of irinotecan is strongly recommended.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30550693"}, {"offsetInBeginSection": 154, "offsetInEndSection": 421, "text": "As the US FDA-approved label of irinotecan (CPT-11, Camptosar) has been recently revised to include UGT1A1 genotype among potential risk factors for toxicity, it is expected that UGT1A1 genotyping will be increasingly used in patients undergoing irinotecan treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17184208"}, {"offsetInBeginSection": 386, "offsetInEndSection": 535, "text": "perbilirubinemia presenting with severe jaundice. UGT1A1 genotyping was used before therapy to ascertain whether genotype-adjusted dosages of irinote", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24642571"}, {"offsetInBeginSection": 284, "offsetInEndSection": 793, "text": " The aim of this study was to determine whether the presence of the variant allele UGT1A1*28, harbouring seven TA repetitions, (TA)7, in the homozygous state, is associated with precancerous colonic lesions and/or with specific colorectal cancer characteristics.MATERIAL AND METHODS: All patients treated for colorectal cancer in a tertiary care centre, between January 2009 and December 2013, who had routine UGT1A1 genotyping for irinotecan dose-adjustment were included. Data were retrospectively collected", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30583998"}, {"offsetInBeginSection": 284, "offsetInEndSection": 756, "text": " The aim of this study was to determine whether the presence of the variant allele UGT1A1*28, harbouring seven TA repetitions, (TA)7, in the homozygous state, is associated with precancerous colonic lesions and/or with specific colorectal cancer characteristics.MATERIAL AND METHODS: All patients treated for colorectal cancer in a tertiary care centre, between January 2009 and December 2013, who had routine UGT1A1 genotyping for irinotecan dose-adjustment were included", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30583998"}, {"offsetInBeginSection": 0, "offsetInEndSection": 385, "text": "The aim of this study was to investigate the associations between UDP-glucuronosyltransferase (UGT) 1A1 polymorphisms and irinotecan-induced toxicities in Chinese advanced colorectal cancer patients. The genotypes of UGT1A1 6 and UGT1A1 28 were analyzed by PCR amplification and Sanger sequencing in 276 advanced colorectal cancer patients receiving irinotecan-containing chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23686699"}, {"offsetInBeginSection": 256, "offsetInEndSection": 423, "text": "We retrospectively investigated UGT1A1 genetic polymorphisms and the occurrences of irinotecan-induced neutropenia in 25 patients of colorectal cancer at our hospital.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25981652"}, {"offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "The aim of this study was to investigate the associations between UDP-glucuronosyltransferase (UGT) 1A1 polymorphisms and irinotecan-induced toxicities in Chinese advanced colorectal cancer patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23686699"}, {"offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Clinical implications of UGT1A1*28 genotype testing in colorectal cancer patients.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21287524"}, {"offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Correlation of UGT1A1(*)28 and (*)6 polymorphisms with irinotecan-induced neutropenia in Thai colorectal cancer patients.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26830078"}, {"offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "UGT1A1 6/28 polymorphisms could predict irinotecan-induced severe neutropenia not diarrhea in Chinese colorectal cancer patients.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23686699"}, {"offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "This evidence-based review addresses the question of whether testing for UGT1A1 mutations in patients with metastatic colorectal cancer treated ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19125129"}, {"offsetInBeginSection": 24, "offsetInEndSection": 159, "text": "a new UGT1A and DPYD polymorphism panel to better predict irinotecan-induced toxicity and the clinical response in Chinese patients wit", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28637434"}, {"offsetInBeginSection": 293, "offsetInEndSection": 382, "text": "UGT1A1 gene promoter polymorphism in the toxicity profile, in the response rate and in th", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15280927"}, {"offsetInBeginSection": 192, "offsetInEndSection": 614, "text": "Recent pharmacogenetic studies on irinotecan have revealed the impact of UGT1A1 polymorphisms on severe adverse effects. The concurrence of UGT1A1*28 and UGT1A1*6, even when heterozygous, markedly alters the disposition of irinotecan, potentially increasing toxicity. For patients showing homozygosity for UGT1A1*28, *6 or compound heterozygosity for UGT1A1*6 and *28, dose reduction of irinotecan is strongly recommended.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30550693"}, {"offsetInBeginSection": 1062, "offsetInEndSection": 1369, "text": "In addition, the Food and Drug Administration of the United States now requires a 'black box' warning on the packaging of irinotecan for evaluation of germline polymorphism in UGT1A1, the gene mutated in Gilbert's syndrome, for potential reduction of drug dosage in patients with the UGT1A1*28 polymorphism.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18437170"}, {"offsetInBeginSection": 308, "offsetInEndSection": 640, "text": "Recent FDA approval of genetic testing for mutations in the UGT1A1 gene that predict adverse reactions to irinotecan is ushering in a new era that will increasingly rely on genotyping to individualize treatment decisions for patients with cancer as well as for patients at high risk who may be candidates for chemoprevention agents.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16982469"}, {"offsetInBeginSection": 1148, "offsetInEndSection": 1601, "text": "s for UGT1A1*28.CONCLUSION: At least part of the interpatient variability of irinotecan toxicity can be explained by the UGT1A1*28 polymorphism. Patients who are homozygous for the UGT1A1*28 allele have an increased risk of developing severe neutropenia when receiving irinotecan, especially the 300-350- mg/m2 regimen. A molecular assay is now available to identify the at-risk subgroup and should be used by health care professionals to help guide iri", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17090741"}, {"offsetInBeginSection": 1260, "offsetInEndSection": 1536, "text": "ile neutropenic event avoided.CONCLUSIONS: UGT1A1 genotype screening before irinotecan treatment is a cost-efficient strategy for the hospital. Systematic genotyping prior to chemotherapy, and administration of CSF in patients homozygotes for the *28 allele allow to avoid 91 ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21486535"}, {"offsetInBeginSection": 512, "offsetInEndSection": 626, "text": " DPD deficiency. An assay is available for genotypic testing of the enzyme UGT1A1, which is predictive of toxicity", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16641252"}]}
+{"question_id": "66088b42fdcbea915f000009", "question": "Please list sources of orthobiologics", "answer": "Orthobiologics  are derived from patient's own tissues, such as blood, bone marrow, and adipose tissue to prepare platelet-rich plasma (PRP), bone marrow concentrate, Stem cells and adipose tissue concentrate.", "relevant_passage_ids": ["36410877", "38090881", "36410882", "35668394", "36428501", "33410651", "37130369", "34293441", "30466724", "32399133", "33708344", "22894643", "36410885", "35867717", "31034242", "34937114", "29803299", "34106093", "31380488"], "type": "list", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Basic Science of Autologous Orthobiologics: Part 1. Platelet-Rich Plasma.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36410877"}, {"offsetInBeginSection": 175, "offsetInEndSection": 441, "text": "These cellular therapies are often referred to as orthobiologics and are derived from patient's own tissues, such as blood, bone marrow, and adipose tissue to prepare platelet-rich plasma (PRP), bone marrow concentrate, and adipose tissue concentrate, respectively. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36410877"}, {"offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "The use of orthobiologics such as platelet-rich plasma, bone marrow aspirate, and stem cells has been proposed as a biologic augmentation for treatment of various conditions of cartilage, tendon, and bone.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38090881"}, {"offsetInBeginSection": 66, "offsetInEndSection": 267, "text": "Orthobiologics continue to be studied for their ability to improve muscle healing. To date, the basic science research for treating muscle injuries with platelet-rich plasma or stem cell remains novel.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36410882"}, {"offsetInBeginSection": 815, "offsetInEndSection": 1800, "text": "Promising and established treatment modalities include hyaluronic acid (HA); platelet-rich plasma (PRP) and platelet rich concentrates (PRC); bone marrow aspirate (BMA) comprising mesenchymal stromal cells (MSCs alternatively termed medicinal signaling cells and frequently, misleadingly labelled \"mesenchymal stem cells\"); MSC harvested from adipose, umbilical, or placental sources; factors including vascular endothelial growth factors (VEGF), basic fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF\u03b2), bone morphogenic protein (BMP), and matrix metalloproteinases (MMPs); prolotherapy; pulsed electromagnetic field therapy; microfracture and other marrow-stimulation techniques; biologic resurfacing using acellular dermal allografts, allograft Achilles tendons, allograft lateral menisci, fascia lata autografts, and porcine xenografts; osteochondral autograft or allograft); and autologous chondrocyte implantation (ACI).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34293441"}, {"offsetInBeginSection": 175, "offsetInEndSection": 449, "text": "These cellular therapies are often referred to as orthobiologics and are derived from patient's own tissues, like blood, bone marrow, and adipose tissue to prepare platelet-rich plasma (PRP), bone marrow concentrate (BMC), and adipose tissue concentrate (ATC), respectively.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36410885"}, {"offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Orthobiologic agents, including platelet-rich plasma, connective tissue progenitor cells derived from bone marrow, adipose, and other tissues, and purified cytokines and small peptides, have tremendous potential to target deficiencies in soft-tissue healing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37130369"}, {"offsetInBeginSection": 0, "offsetInEndSection": 611, "text": "INTRODUCTION: Investigations are rapidly increasing into products referred to as orthobiologics and their utility in the nonsurgical and surgical treatment of diverse orthopaedic pathology.METHODS: Members (599) of the American Orthopaedic Society for Sports Medicine were sent a survey that assessed their usage, motivation for use, and perceived efficacy of the following orthobiologics: leukocyte-rich platelet-rich plasma, leukocyte-poor platelet-rich plasma (PRP-LP), bone marrow aspirate concentrate, amniotic membrane products, adipose-derived mesenchymal stromal cells, and umbilical cord-derived cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33410651"}, {"offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "The use of orthobiologics such as platelet-rich plasma, bone marrow aspirate, and stem cells has been proposed as a biologic augmentation for treatment of various conditions of cartilage, tendon, and bone", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38090881"}, {"offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "BACKGROUND: Platelet-rich plasma (PRP) and bone marrow concentrate (BMC) are orthobiologic therapies with numerous growth factors and other bioactive molecules.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31034242"}, {"offsetInBeginSection": 0, "offsetInEndSection": 572, "text": "Autologous biological cellular preparations have materialized as a growing area of medical advancement in interventional (orthopedic) practices and surgical interventions to provide an optimal tissue healing environment, particularly in tissues where standard healing is disrupted and repair and ultimately restoration of function is at risk. These cellular therapies are often referred to as orthobiologics and are derived from patient's own tissues to prepare point of care platelet-rich plasma (PRP), bone marrow concentrate (BMC), and adipose tissue concentrate (ATC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36428501"}, {"offsetInBeginSection": 343, "offsetInEndSection": 572, "text": "These cellular therapies are often referred to as orthobiologics and are derived from patient's own tissues to prepare point of care platelet-rich plasma (PRP), bone marrow concentrate (BMC), and adipose tissue concentrate (ATC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36428501"}, {"offsetInBeginSection": 371, "offsetInEndSection": 508, "text": "Platelet-rich plasma (PRP) is an orthobiologic that has recently gained popularity as an adjuvant treatment for musculoskeletal injuries.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22894643"}, {"offsetInBeginSection": 0, "offsetInEndSection": 395, "text": "Orthobiologics are a group of biological materials and substrates that promote bone, ligament, muscle, and tendon healing. These substances include bone autograft, bone allograft, demineralized bone matrix, bone graft substitutes, bone marrow aspirate concentrate, platelet-rich plasma, bone morphogenetic proteins, platelet-derived growth factor, parathyroid hormone, and vitamin D and calcium.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30466724"}, {"offsetInBeginSection": 0, "offsetInEndSection": 499, "text": "Orthobiologics are a group of biological materials and substrates that promote bone, ligament, muscle, and tendon healing. These substances include bone autograft, bone allograft, demineralized bone matrix, bone graft substitutes, bone marrow aspirate concentrate, platelet-rich plasma, bone morphogenetic proteins, platelet-derived growth factor, parathyroid hormone, and vitamin D and calcium. Properties of orthobiologics in bone healing include osteoconduction, osteoinduction, and osteogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30466724"}, {"offsetInBeginSection": 61, "offsetInEndSection": 126, "text": "orthobiologic treatments, such as platelet-rich plasma, bone marr", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35668394"}, {"offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "BACKGROUND: Platelet-rich plasma (PRP) and bone marrow concentrate (BMC) are orthobiologic therapies with numerous growth factors and other bioactiv", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31034242"}, {"offsetInBeginSection": 788, "offsetInEndSection": 907, "text": "Bone marrow (BM) aspirate (BMA) and concentrate are well-known orthobiologics used to treat musculoskeletal conditions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32399133"}, {"offsetInBeginSection": 351, "offsetInEndSection": 473, "text": "Platelet-rich plasma, stem cells, and autologous conditioned serum are the most commonly used orthobiologics in the horse.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29803299"}, {"offsetInBeginSection": 95, "offsetInEndSection": 164, "text": "Bone marrow aspirate concentrate is a key orthobiologic tissue source", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34106093"}, {"offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "\u27a4: Orthobiologics encompass numerous substances that are naturally found in the human body including platelet-rich plasma (PRP), isolated growth factors, and cell therapy approaches to theoretically optimize and improve the healing of cartilage, fractures, and injured muscles, tendons, and ligamen", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35867717"}, {"offsetInBeginSection": 367, "offsetInEndSection": 560, "text": "Various orthobiologic materials are available for use, including autologous and allogeneic bone graft, bone marrow aspirate (BMA), demineralized bone matrix (DBM), ceramics, and growth factors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31380488"}, {"offsetInBeginSection": 0, "offsetInEndSection": 399, "text": "The use of orthobiologics as a novel therapy for the treatment of numerous musculoskeletal disorders has increased considerably over the past decade. Currently, there are multiple alternatives available as suitable treatments; however, the use of autologous blood-derived products such as platelet-rich plasma (PRP), bone marrow aspirate (BMA) and BMA concentrate (BMAC), specifically, is expanding.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33708344"}, {"offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Orthobiologics, including platelet-rich plasma, prolotherapy, and mesenchymal stem cells, are seeing increasing use in the treatment of osteoarthritis (OA), muscle injury, and tendinopathy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34937114"}]}
+{"question_id": "65f84eadc4010b4d7800004c", "question": "Are advanced directives an expression of the patient's wishes for future care in case they become cognitively impaired or find themselves in critical condition?", "answer": "Yes. Advance care directives are important for documenting treatment preferences in patient care planning.", "relevant_passage_ids": ["37450641", "37444658", "37382889", "17039293", "3985517", "10402612", "35268299", "28943360", "28152998", "31961841", "35441880", "33958958", "35477323", "22951247", "10029787", "1635870", "24571002"], "type": "yesno", "snippets": [{"offsetInBeginSection": 20, "offsetInEndSection": 211, "text": "older patients with advance directives such as a living will, or durable power of attorney for healthcare, are more likely to receive care consistent with their preferences at the end of life", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37444658"}, {"offsetInBeginSection": 875, "offsetInEndSection": 988, "text": "Advance care directives are an important mechanism for documenting treatment preferences in patient care planning", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37382889"}, {"offsetInBeginSection": 12, "offsetInEndSection": 137, "text": "Advance directives documentation can increase the likelihood that patient's wishes are respected if they become incapacitated", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37450641"}, {"offsetInBeginSection": 338, "offsetInEndSection": 562, "text": "Advance directives (ADs) allow everyone to give their preferences in advance regarding life sustaining treatments, continuation, and withdrawal or withholding of treatments in case one is not able to speak their mind anymore", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35268299"}, {"offsetInBeginSection": 9, "offsetInEndSection": 162, "text": "Documenting patients' advance care planning (ACP) wishes is essential to providing value-aligned care, as is having this documentation readily accessible", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28943360"}, {"offsetInBeginSection": 12, "offsetInEndSection": 126, "text": "Advance directives (AD) imply the promise of determining future medical treatment in case of decisional incapacity", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28152998"}, {"offsetInBeginSection": 374, "offsetInEndSection": 698, "text": "advance directives and the appointment of an enduring power of attorney for people of all ages. A person's rights to self-determination in health care, including decision making about their wishes for future care in the event they lose cognitive capacity, should not be overlooked against the backdrop of increasing pressure", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22951247"}, {"offsetInBeginSection": 625, "offsetInEndSection": 791, "text": "Based on these principal views, concrete preferences on how to be treated under defined medical circumstances can be discussed and documented in an advance directive.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35441880"}, {"offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "An Advance Medical Directive (AMD) is a document in which competent patients express their wishes regarding their preferred choice of future medical plans in the event they become incompetent.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33958958"}, {"offsetInBeginSection": 104, "offsetInEndSection": 285, "text": "Advance directives (ADs) are documents that express an individual's wishes regarding their medical care if they are incapacitated and may appoint someone to make decisions for them.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35477323"}, {"offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Advance directives are designed to establish a person's preferences for treatment if the person becomes incompetent in the future or unable to communicate those preferences to treatment providers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10402612"}, {"offsetInBeginSection": 223, "offsetInEndSection": 420, "text": "An advance directive (AD), a living will, or a durable power of attorney for health care contains statements made by competent people directing their medical care if they should become incompetent.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1635870"}, {"offsetInBeginSection": 0, "offsetInEndSection": 405, "text": "BACKGROUND: Advance care planning (ACP) is an ongoing process of communication involving patients, family members, and caregivers on one side and healthcare providers on the other to establish values, goals, and preferences for future care, along with discussions concerning end-of-life care options. Advance directives promote patient autonomy and provide written documentation of a patient's wishes for ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31961841"}, {"offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Advance directives are specific competent consumers' wishes about future medical plans in the event that they become incompetent.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24571002"}, {"offsetInBeginSection": 548, "offsetInEndSection": 701, "text": "An advance directive consists of oral and written instructions about a person's future medical care in the event he or she becomes unable to communicate.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10029787"}, {"offsetInBeginSection": 180, "offsetInEndSection": 1003, "text": "Although the complexity and unpredictability of health care circumstances make it impossible to guarantee complete control over therapeutic measures to be used when survival is in question, physicians should offer their patients the opportunity to reflect on their values and wishes and to express them explicitly. The ideal advanced directive should clearly state the author's intentions; contain clear documentation regarding authorship; be flexible, allowing family and caregivers to respond appropriately to changing circumstances; be available when needed; and be supported by legal powers that grant patients the right of enforcement and grant health care providers protection from liability. Advanced directives can be set as instruction directives or proxy directives, each form having advantages and disadvantages.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3985517"}, {"offsetInBeginSection": 180, "offsetInEndSection": 878, "text": "Although the complexity and unpredictability of health care circumstances make it impossible to guarantee complete control over therapeutic measures to be used when survival is in question, physicians should offer their patients the opportunity to reflect on their values and wishes and to express them explicitly. The ideal advanced directive should clearly state the author's intentions; contain clear documentation regarding authorship; be flexible, allowing family and caregivers to respond appropriately to changing circumstances; be available when needed; and be supported by legal powers that grant patients the right of enforcement and grant health care providers protection from liability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3985517"}, {"offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "Advance directives allow competent persons to extend their right of self-determination into the future, by recording choices that are intended to influence their future care should they become unable to make choices. They are considered tools to facilitate end-of-life decision making.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17039293"}]}
+{"question_id": "65cf69541930410b13000006", "question": "Which drugs were tested in the CodeBreaK 300 clinical trial?", "answer": "Phase III CodeBreaK 300 showed EGFR inhibitor panitumumab plus KRAS G12C inhibitor sotorasib resulted in longer progression-free survival than standard treatment in Refractory Colorectal Cancer with Mutated KRAS G12C.", "relevant_passage_ids": ["37870968", "37921413"], "type": "list", "snippets": [{"offsetInBeginSection": 2215, "offsetInEndSection": 2665, "text": "CONCLUSIONS: In this phase 3 trial of a KRAS G12C inhibitor plus an EGFR inhibitor in patients with chemorefractory metastatic colorectal cancer, both doses of sotorasib in combination with panitumumab resulted in longer progression-free survival than standard treatment. Toxic effects were as expected for either agent alone and resulted in few discontinuations of treatment. (Funded by Amgen; CodeBreaK 300 ClinicalTrials.gov number, NCT05198934.).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37870968"}, {"offsetInBeginSection": 135, "offsetInEndSection": 316, "text": "Findings from the phase III CodeBreaK 300 trial indicate that adding the EGFR inhibitor panitumumab to sotorasib bests standard care for chemorefractory KRASG12C colorectal cancer. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37921413"}]}
+{"question_id": "65f779edc4010b4d78000039", "question": "Is surgical resection an appropriate treatment over immunotherapy in MSI-H locally advanced rectal cancer patients?", "answer": "Immunotherapy with organ preservation are the preferred treatment over surgical resection in locally advanced rectal cancer patients with MSI-H", "relevant_passage_ids": ["35371084", "36030556", "36400657", "36139613", "35958603", "35340166", "37441082", "35352512", "36949951", "37637243", "37435212", "36896306", "36791752", "36569918", "36615039", "38022667", "37039887"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1713, "offsetInEndSection": 1807, "text": "Our team also proposes a new organ-preservation strategy for patients with MSI-H/dMMR low LARC", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35371084"}, {"offsetInBeginSection": 168, "offsetInEndSection": 357, "text": "patients with high microsatellite instability/deficient mismatch repair (MSI-H/dMMR) LACRC receive little benefit from neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant chemotherapy (nCT)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35371084"}, {"offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Patients with locally advanced colorectal cancer (LACRC) have a high risk of recurrence and metastasis, although neoadjuvant therapy may provide some benefit", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35371084"}, {"offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "The emergence of immunotherapy has revolutionized the traditional treatment paradigm of colorectal cancer (CRC)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37637243"}, {"offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Locally advanced rectal cancer with dMMR/MSI-H may be excused from surgery after neoadjuvant anti-PD-1 monotherapy: a multiple-center, cohort study.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37441082"}, {"offsetInBeginSection": 1488, "offsetInEndSection": 1702, "text": "Preoperative PD-1 blockade immunotherapy in dMMR/MSI-H gastrointestinal malignancies can achieve a high CR, especially in patients with duodenal or low rectal cancer, and can achieve high organ function protection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36896306"}, {"offsetInBeginSection": 390, "offsetInEndSection": 654, "text": "Patients with locally advanced rectal cancer with MSI-H/dMMR tumors receiving neoadjuvant ICI (nICI) treatment (n=13) and matched patients receiving neoadjuvant chemoradiotherapy (nCRT; n=13) were included to compare clinical response and histopathologic features.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36791752"}, {"offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Neoadjuvant chemoradiotherapy combined with immunotherapy for locally advanced rectal cancer: A new era for anal preservation.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36569918"}, {"offsetInBeginSection": 99, "offsetInEndSection": 434, "text": "bility-high (MSI-H) rectal cancer, clinical complete response (cCR) could be achieved after anti-programmed cell death protein 1 (anti-PD-1) immunotherapy. However, no data are available concerning the safety of omitting surgery and adopting immunotherapy as a curative-intent treatment for these patients.METHODS: We retrospectively c", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36030556"}, {"offsetInBeginSection": 0, "offsetInEndSection": 493, "text": "Objective: Examine patients with locally advanced rectal cancer (LARC) with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) who received neoadjuvant immunotherapy (nIT), and compare the outcomes of those who chose a watch-and-wait (WW) approach after achieving clinical complete response (cCR) or near-cCR with those who underwent surgery and were confirmed as pathological complete response (pCR).Methods: LARC patients with dMMR/MSI-H who received nIT were retros", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37441082"}, {"offsetInBeginSection": 0, "offsetInEndSection": 378, "text": "Background: Immunotherapy is the first-line treatment in patients with advanced microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) colorectal cancer (CRC). Although immune checkpoint inhibitors (ICIs) for locally advanced rectal cancer (LARC) are not yet a standard, the results are very encouraging and raise the question of whether patients with clini", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37435212"}, {"offsetInBeginSection": 232, "offsetInEndSection": 505, "text": "(MSI-H) colorectal cancer patients who benefit from the efficacy of immune checkpoint inhibitors are expected to further improve the efficacy of traditional neoadjuvant therapy based on radiotherapy and chemotherapy. In this paper, the current status of immunotherapy (with", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35340166"}, {"offsetInBeginSection": 0, "offsetInEndSection": 459, "text": "Although recent trials started the use of neoadjuvant immunotherapy (NIT) in instability-high (MSI-H) or mismatch repair deficient (dMMR) early-stage or locally advanced colorectal cancer (LACRC), little data on the treatment strategy of NIT has been shown, and whether the tirelizumab mono-immune checkpoint inhibitor (ICI) can be used as NIT for patients with LACRC has not been reported as yet. In this study we report on a locally advanced ascending colon", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36615039"}, {"offsetInBeginSection": 654, "offsetInEndSection": 985, "text": "Recently, some efforts have been made to translate ICIs in earlier stages of CRC, including localized rectal cancer, with breakthrough efficacy and an organ preservation rate of mono-immunotherapy in dMMR/MSI-H patients and promising anti-tumor activity of immunotherapy plus neoadjuvant (chemo)radiotherapy in pMMR/MSI-L subjects.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36139613"}, {"offsetInBeginSection": 2173, "offsetInEndSection": 2453, "text": "tive period was 10.3% (3/29).Conclusions: Neoadjuvant monoimmunotherapy with PD-1\u00a0inhibitor has favorable ORR and pCR rate, and relatively low incidences of irAEs and srAEs for patients with dMMR/MSI-H LACRC, suggesting that this nIT regimen of single-agent PD-1 inhibitor is sign", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35958603"}, {"offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Neoadjuvant immunotherapy for dMMR/MSI-H locally advanced rectal cancer: The future new standard approach?", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36400657"}, {"offsetInBeginSection": 254, "offsetInEndSection": 404, "text": " However, no data are available concerning the safety of omitting surgery and adopting immunotherapy as a curative-intent treatment for these patients", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36030556"}, {"offsetInBeginSection": 1400, "offsetInEndSection": 1592, "text": "00% and 100%, respectively.CONCLUSIONS: For patients with dMMR/MSI-H locally advanced rectal cancer who achieved cCR during anti-PD-1 immunotherapy, adopting immunotherapy as curative-intent t", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36030556"}, {"offsetInBeginSection": 1433, "offsetInEndSection": 1637, "text": "SIONS: For patients with dMMR/MSI-H locally advanced rectal cancer who achieved cCR during anti-PD-1 immunotherapy, adopting immunotherapy as curative-intent treatment might be an alternative option. Long", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36030556"}, {"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Neoadjuvant Immunotherapy for MSI-H/dMMR Locally Advanced Colorectal Cancer: New Strategies and Unveiled Opportunities.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35371084"}, {"offsetInBeginSection": 0, "offsetInEndSection": 335, "text": "Objective: Examine patients with locally advanced rectal cancer (LARC) with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) who received neoadjuvant immunotherapy (nIT), and compare the outcomes of those who chose a watch-and-wait (WW) approach after achieving clinical complete response (cCR) or near-cCR w", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37441082"}, {"offsetInBeginSection": 0, "offsetInEndSection": 493, "text": "Background: Immunotherapy is the first-line treatment in patients with advanced microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) colorectal cancer (CRC). Although immune checkpoint inhibitors (ICIs) for locally advanced rectal cancer (LARC) are not yet a standard, the results are very encouraging and raise the question of whether patients with clinical complete response (cCR) could receive nonoperative management (NOM). However, different patterns of response ha", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37435212"}, {"offsetInBeginSection": 959, "offsetInEndSection": 1337, "text": "r for the pembrolizumab group (16.5 vs. 8.2\u00a0months). In a\u00a0small series of patients with MSI-H/dMMR rectal cancers treatment with dostarlimab resulted in complete remission in all patients with no regrowth during an admittedly short follow-up. A\u00a0series of patients with locally advanced MSI-H/dMMR colon cancers showed a\u00a0treatment response in nearly all patients with 67% experie", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37039887"}, {"offsetInBeginSection": 0, "offsetInEndSection": 459, "text": "For colorectal cancer (CRC), surgical resection remains essential for achieving good prognoses. Unfortunately, numerous patients with locally advanced CRC and metastatic CRC failed to meet surgical indications or achieve pathological complete response after surgery. Perioperative therapy has been proven to effectively lower tumor staging and reduce recurrence and metastasis. Immune checkpoint inhibitors (ICIs) have shown unprecedented prolongation of surv", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38022667"}, {"offsetInBeginSection": 531, "offsetInEndSection": 877, "text": "According to mismatch repair protein expression, MSI-H/dMMR and non-MSI-H/pMMR statuses were defined in colorectal cancer (CRC) patients. Due to the special features of biologics in MSI-H/dMMR CRC patients, this subgroup of patients achieved little treatment efficacy from chemoradiotherapy but benefited from immune checkpoint inhibitors (ICIs).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36949951"}]}
+{"question_id": "66081d61fdcbea915f000007", "question": "Is One-carbon (1C)  metabolism associated with folate?", "answer": "One-carbon (1C) metabolism, mediated by the folate cofactor, supports multiple physiological processes. These include biosynthesis (purines and thymidine), amino acid homeostasis (glycine, serine, and methionine), epigenetic maintenance, and redox defense.", "relevant_passage_ids": ["36822494", "37665322", "35508111", "19033438", "29483189", "19812215", "34298902", "28813411", "27641100", "33212887", "33326752", "33616629", "27211901", "33707653", "33829277", "37801048", "37764675", "30412672", "32879053", "22962226", "23138010", "26700149", "32632125", "18804690", "17963270", "30813413", "37960352", "34114759", "25710200", "32961717", "31737034", "26207201", "37864660", "36816414", "37958324", "37202066", "37858220", "37797585", "26373967", "28707064", "38000545"], "type": "yesno", "snippets": [{"offsetInBeginSection": 12, "offsetInEndSection": 132, "text": "Folate (FA) is an essential cofactor in the one-carbon (1C) metabolic pathway and participates in amino acid metabolism,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36822494"}, {"offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "One-carbon/folate (1C) metabolism supplies methyl groups required for DNA and histone methylation, and is involved in the maintenance of self-renewal in stem cells. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37665322"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "The folic acid cycle mediates the transfer of one-carbon (1C) units to support nucleotide biosynthesis. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35508111"}, {"offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "Adequate maternal dietary levels of one-carbon metabolites, such as folic acid and choline, play an important role in the closure of the neural tube in utero; however, the impact of deficiencies in one-carbon (1C) metabolism on offspring neurological function after birth remain undefined", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37801048"}, {"offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "One-carbon metabolism (1C-metabolism), also called folate metabolism because the carbon group is attached to folate-derived tetrahydrofolate,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33616629"}, {"offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "One-carbon (1C) metabolism consists of an integrated series of metabolic pathways that include the folate", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25710200"}, {"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "One-carbon (1C) metabolism, mediated by the folate cofactor, supports multiple physiological processes. These include biosynthesis (purines and thymidine),", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27641100"}, {"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "One-carbon (1C) metabolism comprises a series of interlinking metabolic pathways that include the methionine and folate", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30412672"}, {"offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Mammalian folate-dependent one-carbon (1C) metabolism provides the building blocks essential during development via amino acid", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33829277"}, {"offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Folate-mediated one carbon (1C) metabolism supports a series of processes that are essential for the", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33707653"}, {"offsetInBeginSection": 4, "offsetInEndSection": 106, "text": "folate-driven one-carbon (1C) cycle is a fundamental metabolic hub in cells that enables the synthesis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28813411"}, {"offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "One-carbon (1C) units for purine and thymidine synthesis can be generated from serine by cytosolic or mitochondrial folate", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27211901"}, {"offsetInBeginSection": 210, "offsetInEndSection": 355, "text": "ficiency on markers of one carbon (1C) metabolism in the blood, and response to a methionine load in clinically healthy young women.SUBJECTS/METH", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26373967"}, {"offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "One-carbon (1C) metabolism is a universal folate-dependent pathway essential for de novo purine and thymidylate synthesis, amino acid interconversion, universal methyl-donor production, and regeneration of redox cofactors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29483189"}, {"offsetInBeginSection": 0, "offsetInEndSection": 38, "text": "Folate-mediated one-carbon metabolism.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18804690"}, {"offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "One-carbon metabolism (1C-metabolism), also called folate metabolism because the carbon group is attached to folate-derived tetrahydrofolate, is crucial in metabolism.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33616629"}, {"offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "One-carbon (1C) metabolism, mediated by the folate cofactor, supports multiple physiological processes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27641100"}, {"offsetInBeginSection": 223, "offsetInEndSection": 641, "text": "Homozygous deletion of the 1C pathway gene Mthfd1l encoding methylenetetrahydrofolate dehydrogenase (NADP+-dependent) 1-like, which catalyzes mitochondrial formate production from 10-formyltetrahydrofolate, results in 100% penetrant embryonic neural tube defects (NTDs), underscoring the central role of mitochondrially derived formate in embryonic development and providing a mechanistic link between folate and NTDs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29483189"}, {"offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "One-carbon (1C) metabolism is a metabolic network that is centered on folate, a B vitamin; it integrates nutritional signals with biosynthesis, redox homeostasis, and epigenetics.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33212887"}, {"offsetInBeginSection": 507, "offsetInEndSection": 661, "text": "Folate-mediated one-carbon metabolism (OCM) is essential for de novo nucleotide biosynthesis, methionine biosynthesis, and cellular methylation reactions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17963270"}, {"offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Vitamins B9 (folate) and B12 act as methyl donors in the one-carbon metabolism which influences epigenetic mechanisms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30813413"}, {"offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "One-carbon (1C) metabolism encompasses folate-mediated 1C transfer reactions and related processes, including nucleotide and amino acid biosynthesis, antioxidant regeneration, and epigenetic regulation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32879053"}, {"offsetInBeginSection": 189, "offsetInEndSection": 353, "text": "While folate plays a pivotal role in the one-carbon cycle, which is essential for DNA synthesis, repair, and methylation, concerns arise about its excessive intake.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37960352"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "One-carbon (1C) metabolism plays a key role in biological functions linked to the folate cycle.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34298902"}, {"offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "BACKGROUND: Folate (FA) is an essential cofactor in the one-carbon (1C) metabolic pathway and participates in amino acid metabolism, purine and thymidylate synthesis, and DNA methylation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36822494"}, {"offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Mammalian folate-dependent one-carbon (1C) metabolism provides the building blocks essential during development via amino acid interconversion, methyl-donor production, regeneration of redox factors, and de novo purine and thymidylate synthesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33829277"}, {"offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "One-carbon (1C) metabolism is a metabolic network that is centered on folate, a B vitamin; it integrates nutritional signals with biosynthesis, redox homeostasis, and epigenetics. This metabolic pathway also reduces levels of homocysteine, a non-protein amino acid.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33212887"}, {"offsetInBeginSection": 0, "offsetInEndSection": 454, "text": "One-carbon (1C) metabolism comprises a series of interlinking metabolic pathways that include the methionine and folate cycles that are central to cellular function, providing 1C units (methyl groups) for the synthesis of DNA, polyamines, amino acids, creatine, and phospholipids. S-adenosylmethionine is a potent aminopropyl and methyl donor within these cycles and serves as the principal substrate for methylation of DNA, associated proteins, and RNA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30412672"}, {"offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "One-carbon (1C) metabolism consists of an integrated series of metabolic pathways that include the folate cycle and methionine remethylation and trans-sulfuration pathways.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25710200"}, {"offsetInBeginSection": 126, "offsetInEndSection": 315, "text": "One-carbon metabolic pathway along with folate and other vitamins plays an important role in DNA synthesis and in the establishment of epigenetic modifications like DNA/histone methylation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23138010"}, {"offsetInBeginSection": 445, "offsetInEndSection": 635, "text": "Folate and normal activity of 1-carbon metabolic pathway enzymes are central to nucleotide synthesis, methylation, and maintenance of genomic integrity as well as protection from DNA damage.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23138010"}, {"offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "One-carbon (1C) metabolism encompasses folate-mediated 1C transfer reactions and related processes, including nucleotide and amino acid biosynthesis, antioxidant regeneration, and epigenetic regulation. 1C pathways are compartmentalized in the cytosol, mitochondria, and nucleus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32879053"}, {"offsetInBeginSection": 0, "offsetInEndSection": 870, "text": "Tetrahydrofolate (THF) polyglutamates are a family of cofactors that carry and chemically activate one-carbon units for biosynthesis. THF-mediated one-carbon metabolism is a metabolic network of interdependent biosynthetic pathways that is compartmentalized in the cytoplasm, mitochondria, and nucleus. One-carbon metabolism in the cytoplasm is required for the synthesis of purines and thymidylate and the remethylation of homocysteine to methionine. One-carbon metabolism in the mitochondria is required for the synthesis of formylated methionyl-tRNA; the catabolism of choline, purines, and histidine; and the interconversion of serine and glycine. Mitochondria are also the primary source of one-carbon units for cytoplasmic metabolism. Increasing evidence indicates that folate-dependent de novo thymidylate biosynthesis occurs in the nucleus of certain cell types.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18804690"}, {"offsetInBeginSection": 0, "offsetInEndSection": 339, "text": "Vitamins B9 (folate) and B12 are essential water-soluble vitamins that play a crucial role in the maintenance of one-carbon metabolism: a set of interconnected biochemical pathways driven by folate and methionine to generate methyl groups for use in DNA synthesis, amino acid homeostasis, antioxidant generation, and epigenetic regulation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32961717"}, {"offsetInBeginSection": 871, "offsetInEndSection": 1159, "text": "Disruption of folate-mediated one-carbon metabolism is associated with many pathologies and developmental anomalies, yet the biochemical mechanisms and causal metabolic pathways responsible for the initiation and/or progression of folate-associated pathologies have yet to be established.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18804690"}, {"offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "The role of folate-dependent one carbon (1C) metabolism in CD4+ T\u00a0cell polarization is incompletely understood.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35021051"}, {"offsetInBeginSection": 169, "offsetInEndSection": 297, "text": "The combination of these folate-dependent reactions constitutes one-carbon metabolism, the name synonymous to folate metabolism.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31737034"}, {"offsetInBeginSection": 218, "offsetInEndSection": 441, "text": "The effects of status in periconception and pregnancy folate, cobalamin, betaine and their interactions on one carbon metabolism (1C), as well as the global effect of 1C on foetal growth and pregnancy outcome, are reviewed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26700149"}, {"offsetInBeginSection": 282, "offsetInEndSection": 447, "text": "Dietary supplementation of 1C components, such as folic acid, vitamin B12, and choline are reported to have beneficial effects on normal and diseased brain function.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37764675"}, {"offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "For many years folic acid has been evaluated for its utility as a chemopreventive agent due to its position at the center of the one-carbon metabolic network.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26207201"}, {"offsetInBeginSection": 335, "offsetInEndSection": 462, "text": "The vitamin B9 (folate) is primarily related to one-carbon and methionine metabolism, participating in methyl donor generation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37864660"}, {"offsetInBeginSection": 189, "offsetInEndSection": 352, "text": "While folate plays a pivotal role in the one-carbon cycle, which is essential for DNA synthesis, repair, and methylation, concerns arise about its excessive intake", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37960352"}, {"offsetInBeginSection": 14, "offsetInEndSection": 143, "text": "Folates, the main actors in one-carbon (C1) metabolism, are involved in synthesising monoamines and maintaining genomic stability", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36816414"}, {"offsetInBeginSection": 101, "offsetInEndSection": 385, "text": "Evidence that folate may play a role in the carcinogenic process via folate-mediated one-carbon metabolism has given rise to the hypothesis that pre-diagnostic folate intake may induce heterogeneous chemosensitivity to FU-containing induction chemotherapy (IC) in head and neck cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37958324"}, {"offsetInBeginSection": 19, "offsetInEndSection": 90, "text": "Folate (vitamin B9) is an essential co-factor for one-carbon metabolism", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37202066"}, {"offsetInBeginSection": 12, "offsetInEndSection": 139, "text": "B vitamins such as folate (B9), B6, and B12 are key in one carbon metabolism, which generates methyl donors for DNA methylation", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37858220"}, {"offsetInBeginSection": 171, "offsetInEndSection": 292, "text": "Folate and choline are water-soluble micronutrients important for fetal development and involved in one-carbon metabolism", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37797585"}, {"offsetInBeginSection": 871, "offsetInEndSection": 1385, "text": "Disruption of folate-mediated one-carbon metabolism is associated with many pathologies and developmental anomalies, yet the biochemical mechanisms and causal metabolic pathways responsible for the initiation and/or progression of folate-associated pathologies have yet to be established. This chapter focuses on our current understanding of mammalian folate-mediated one-carbon metabolism, its cellular compartmentation, and knowledge gaps that limit our understanding of one-carbon metabolism and its regulation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18804690"}, {"offsetInBeginSection": 0, "offsetInEndSection": 350, "text": "One-carbon (1C) metabolism, mediated by the folate cofactor, supports multiple physiological processes. These include biosynthesis (purines and thymidine), amino acid homeostasis (glycine, serine, and methionine), epigenetic maintenance, and redox defense. Both within eukaryotic cells and across organs, 1C metabolic reactions are compartmentalized.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27641100"}, {"offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "One-carbon (1C) metabolism, mediated by the folate cofactor, supports multiple physiological processes. These include biosynthesis (purines and thymidine), amino acid homeostasis (glycine, serine, and methionine), epigenetic maintenance, and redox defense.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27641100"}, {"offsetInBeginSection": 0, "offsetInEndSection": 499, "text": "Folate metabolism supplies one-carbon (1C) units for biosynthesis and methylation and has long been a target for cancer chemotherapy. Mitochondrial serine catabolism is considered the sole contributor of folate-mediated 1C units in proliferating cancer cells. Here, we show that under physiological folate levels in the cell environment, cytosolic serine-hydroxymethyltransferase (SHMT1) is the predominant source of 1C units in a variety of cancers, while mitochondrial 1C flux is overly repressed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33326752"}, {"offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "Folate metabolism supplies one-carbon (1C) units for biosynthesis and methylation and has long been a target for cancer chemotherapy. Mitochondrial serine catabolism is considered the sole contributor of folate-mediated 1C units in proliferating cancer cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33326752"}, {"offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "One-carbon metabolism-genome interactions in folate-associated pathologies.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19812215"}, {"offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Impairments in folate-mediated 1-carbon metabolism are associated with several common diseases and developmental anomalies including intestinal cancers, vascular disease, cognitive decline, and neural tube defects.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19812215"}, {"offsetInBeginSection": 954, "offsetInEndSection": 1193, "text": "This review focuses on the regulation of folate-mediated 1-carbon metabolism and its role in maintaining genome integrity and on strategies for establishing the metabolic pathways and mechanisms that underlie folate-associated pathologies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19812215"}, {"offsetInBeginSection": 741, "offsetInEndSection": 1385, "text": "Increasing evidence indicates that folate-dependent de novo thymidylate biosynthesis occurs in the nucleus of certain cell types. Disruption of folate-mediated one-carbon metabolism is associated with many pathologies and developmental anomalies, yet the biochemical mechanisms and causal metabolic pathways responsible for the initiation and/or progression of folate-associated pathologies have yet to be established. This chapter focuses on our current understanding of mammalian folate-mediated one-carbon metabolism, its cellular compartmentation, and knowledge gaps that limit our understanding of one-carbon metabolism and its regulation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18804690"}, {"offsetInBeginSection": 810, "offsetInEndSection": 960, "text": "te biosynthesis occurs in the nucleus of certain cell types. Disruption of folate-mediated one-carbon metabolism is associated with many pathologies a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18804690"}, {"offsetInBeginSection": 54, "offsetInEndSection": 204, "text": "eries of metabolic pathways that include the folate cycle and methionine remethylation and trans-sulfuration pathways. Most, but not all, 1C metabolic", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25710200"}, {"offsetInBeginSection": 12, "offsetInEndSection": 153, "text": "folate-mediated one carbon (1C) metabolism functions to carry and activate single carbons for the de novo synthesis of purines, thymidylate, ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19033438"}, {"offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Mammalian folate-dependent one-carbon (1C) metabolism provides the building blocks essential during devel", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33829277"}, {"offsetInBeginSection": 51, "offsetInEndSection": 206, "text": "one-carbon (1C) metabolism. B12 deficiency disturbs the 1C cycle and alters DNA methylation which is vital for most metabolic processes. Studies show that ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32632125"}, {"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "One-carbon (1C) metabolism is a universal folate-dependent pathway essential for de novo purine and thymidylate synthes", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29483189"}, {"offsetInBeginSection": 30, "offsetInEndSection": 156, "text": "e levels of one-carbon (1C) metabolism metabolites have been associated with a wide variety of neuropsychiatric diseases. Cere", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22962226"}, {"offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Folates (vitamin B9) are essential for all organisms as cofactors for one-carbon metabolism.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28707064"}, {"offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Folate (vitamin B9) plays a central role in one-carbon metabolism in prokaryotes and eukaryotes. This pathway mediates the transfer of one-carbon units, playing a crucial role in nucleotide synthesis, methylation, and amino acid homeostasis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38000545"}, {"offsetInBeginSection": 455, "offsetInEndSection": 919, "text": "Methyl nutrients include folates (vitamin B9), riboflavin (vitamin B2), cobalamin (vitamin B12), pyridoxine (vitamin B6) and choline (vitamin B4), as well as methionine and betaine. These substances play the role of both substrates and cofactors in transformations related to one-carbon metabolism. The deficiency of methyl nutrients in the body can lead to disturbances in SAM synthesis, which is the primary donor of methyl groups in the DNA methylation process.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34114759"}, {"offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "One-carbon (1C) metabolism comprises a series of interlinking metabolic pathways that include the methionine and folate cycles that are central to cellular function, providing 1C units (methyl groups) for the synthesis of DNA, polyamines, amino acids, creatine, and phospholipids.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30412672"}]}
+{"question_id": "660bb7f9fdcbea915f000029", "question": "What type of drug is administered to the mother for the prevention of lung immaturity when a preterm delivery is anticipated?", "answer": "Corticosteroids administered to the mother accelerate development of immature lung in premature babies intra utero.", "relevant_passage_ids": ["33423644", "35943347", "33368142"], "type": "factoid", "snippets": [{"offsetInBeginSection": 168, "offsetInEndSection": 388, "text": "The administration of antenatal corticosteroids, in cases of imminent preterm delivery, can enhance fetal lung maturation and reduce the incidence of respiratory distress syndrome, leading to improved neonatal outcomes. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33423644"}, {"offsetInBeginSection": 615, "offsetInEndSection": 692, "text": "single course of antenatal corticosteroids from 24 up to 34 gestational weeks", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33423644"}, {"offsetInBeginSection": 35, "offsetInEndSection": 133, "text": "use of antenatal corticosteroids to prevent respiratory distress syndrome (RDS) in preterm infants", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35943347"}, {"offsetInBeginSection": 225, "offsetInEndSection": 386, "text": "beneficial effect of antenatal corticosteroids on fetal lung maturation and widespread recommendations to use this treatment in women at risk of preterm delivery", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33368142"}, {"offsetInBeginSection": 804, "offsetInEndSection": 904, "text": "course of corticosteroids to women prior to anticipated preterm birth (before 37 weeks of pregnancy)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33368142"}, {"offsetInBeginSection": 5025, "offsetInEndSection": 5146, "text": "use of a single course of antenatal corticosteroids to accelerate fetal lung maturation in women at risk of preterm birth", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33368142"}]}
+{"question_id": "65d132101930410b13000035", "question": "Is Depatuxizumab mafodotin effective for glioblastoma?", "answer": "No. Depatuxizumab mafodotin does improve survival of glioblastoma patients.", "relevant_passage_ids": ["37257422", "35849035", "37085569", "34050676", "33601293", "34204877"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1649, "offsetInEndSection": 1805, "text": "RESULTS: The UNITE study was stopped early after interim analysis of separate phase III trial showed no difference in survival from depatuxizumab mafodotin.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37257422"}, {"offsetInBeginSection": 1627, "offsetInEndSection": 1740, "text": "CONCLUSIONS: Interim analysis demonstrated no OS benefit for depatux-m in treating EGFR-amp newly diagnosed GBM. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35849035"}, {"offsetInBeginSection": 735, "offsetInEndSection": 1037, "text": "However, depatuxizumab mafodotin, an ADC targeting wild-type EGFR and EGFR variant III, did not provide a definitive overall survival benefit in patients with newly diagnosed or recurrent EGFR-amplified glioblastoma in phase II and III trials, despite objective radiological responses in some patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37085569"}, {"offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "BACKGROUND: Antibody drug conjugates (ADCs) targeting the epidermal growth factor receptor (EGFR), such as depatuxizumab mafodotin (Depatux-M), is a promising therapeutic strategy for glioblastoma (GBM) but recent clinical trials did not demonstrate a survival benefit. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34050676"}, {"offsetInBeginSection": 1506, "offsetInEndSection": 1698, "text": "CONCLUSIONS: Despite profound intrinsic sensitivity to Depatux-M, limited drug delivery into brain tumor may have been a key contributor to lack of efficacy in recently failed clinical trials.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34050676"}, {"offsetInBeginSection": 1612, "offsetInEndSection": 1799, "text": "CONCLUSIONS: Depatux-M had no impact on HRQoL and NDFS in patients with EGFR-amplified recurrent glioblastoma, except for more visual disorders, an expected side-effect of the study drug.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33601293"}, {"offsetInBeginSection": 1560, "offsetInEndSection": 1926, "text": "CONCLUSIONS: The study reported the first \"real world\" experience of Depatux-M plus temozolomide in recurrent glioblastoma patients. Encouraging clinical benefits were demonstrated, even though most patients were treated beyond second-line therapy. Overall, the results are close to those reported in the previous phase 2 trial. Toxicity was moderate and manageable.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34204877"}]}
+{"question_id": "66099af7fdcbea915f000020", "question": "Is the use of Bevacizumab indicated after progression to a previous regimen with Bevacizumab in advanced colorectal cancer patients?", "answer": "These results from a large, prospective, observational study suggest that continued vascular endothelial growth factor inhibition with bevacizumab beyond initial PD could play an important role improving the overall success of therapy for patients who have metastastic colorectal cancer", "relevant_passage_ids": ["18854571", "23168366", "22782485", "33776758", "22024069", "32164906", "21679003", "25600568", "33909622", "30422156", "30815371", "34715820", "35833561", "23749885", "34335943", "25605741", "27551256", "30253191", "25691669", "26113053", "25083064"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1608, "offsetInEndSection": 1869, "text": "These results from a large, prospective, observational study suggest that continued vascular endothelial growth factor inhibition with bevacizumab beyond initial PD could play an important role improving the overall success of therapy for patients who have mCRC", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18854571"}, {"offsetInBeginSection": 494, "offsetInEndSection": 775, "text": "distant metastasis) stages. In this study, 43 CRC tissues collected from patients who underwent treatment with first-line standard chemotherapeutic regimens in combination with bevacizumab were used to explore the correlation between FOXF1 expression and resistance to bevacizumab.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30253191"}, {"offsetInBeginSection": 1983, "offsetInEndSection": 2172, "text": "In patients who have progressed on a bevacizumab-containing regimen, continuation of bevacizumab is significantly associated with an improved survival based on observational cohort studies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21679003"}, {"offsetInBeginSection": 223, "offsetInEndSection": 598, "text": "Benefit of adding bevacizumab to second-line regimen after failing a bevacizumab-containing regimen, or aflibercept plus FOLFIRI) (irinotecan, 5-FU and leucovorin) after failing first-line oxaliplatin regimen with or without bevacizumab or regorafenib as a salvage therapy, do indicate the addiction to anti-vascular endothelial growth factor (VEGF) agents in these patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23749885"}, {"offsetInBeginSection": 2420, "offsetInEndSection": 2760, "text": "Treatment-related deaths were reported for four patients in the bevacizumab plus chemotherapy group and three in the chemotherapy alone group.INTERPRETATION: Maintenance of VEGF inhibition with bevacizumab plus standard second-line chemotherapy beyond disease progression has clinical benefits in patients with metastatic colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23168366"}, {"offsetInBeginSection": 166, "offsetInEndSection": 960, "text": "We assessed continued use of bevacizumab plus standard second-line chemotherapy in patients with metastatic colorectal cancer progressing after standard first-line bevacizumab-based treatment.METHODS: In an open-label, phase 3 study in 220 centres in Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, the Netherlands, Norway, Portugal, Saudi Arabia, Spain, Sweden, and Switzerland, patients (aged \u226518 years) with unresectable, histologically confirmed metastatic colorectal cancer progressing up to 3 months after discontinuing first-line bevacizumab plus chemotherapy were randomly assigned in a 1:1 ratio to second-line chemotherapy with or without bevacizumab 2\u00b75 mg/kg per week equivalent (either 5 mg/kg every 2 weeks or 7\u00b75 mg/kg every 3 weeks, intravenously).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23168366"}, {"offsetInBeginSection": 211, "offsetInEndSection": 373, "text": "Bevacizumab, an anti-vascular endothelial growth factor agent, has efficacy in both the first-line setting and beyond progression in metastatic colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27551256"}, {"offsetInBeginSection": 6, "offsetInEndSection": 138, "text": "OUND/AIMS: There is little information in the literature on the use of bevacizumab (BV) combination chemotherapy in multiple lines w", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22024069"}, {"offsetInBeginSection": 140, "offsetInEndSection": 307, "text": " cancer. Continuation of bevacizumab beyond progression is an accepted standard of care based on a 1.4-month increase in median overall survival observed in a randomiz", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25691669"}, {"offsetInBeginSection": 1768, "offsetInEndSection": 1990, "text": " consistent with previously reported data.CONCLUSIONS: This study demonstrates that the continuation or the reintroduction of bevacizumab with second-line chemotherapy beyond first progression improves the outcome and supp", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25600568"}, {"offsetInBeginSection": 0, "offsetInEndSection": 392, "text": "Continuous inhibition of angiogenesis beyond progression is an emerging treatment concept in the management of metastatic colorectal cancer patients with prior bevacizumab exposure. Treatment options include the continuation or reintroduction of bevacizumab during the second-line chemotherapy or switching to a different antiangiogenic monoclonal antibody such as aflibercept or ramucirumab.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30815371"}, {"offsetInBeginSection": 0, "offsetInEndSection": 346, "text": "BACKGROUND: Bevacizumab plus fluoropyrimidine-based chemotherapy is standard treatment for first-line and bevacizumab-naive second-line metastatic colorectal cancer. We assessed continued use of bevacizumab plus standard second-line chemotherapy in patients with metastatic colorectal cancer progressing after standard first-line bevacizumab-base", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23168366"}, {"offsetInBeginSection": 520, "offsetInEndSection": 688, "text": "In the second-line treatment for mCRC, maintenance with bevacizumab after progression following first-line treatment is convenient in some groups of patients with mCRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26113053"}, {"offsetInBeginSection": 785, "offsetInEndSection": 1280, "text": "The scenario of second-line treatment has changed dramatically over the years and could currently benefit from several options including chemotherapy with a single agent or in combination and the addition of molecular-targeted agents developed in the last decade, such as epidermal growth factor receptor antibodies (cetuximab, panitumumab) and vascular endothelial growth factor-targeting agents (bevacizumab, aflibercept), with the possibility of bevacizumab use even beyond first progression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25083064"}, {"offsetInBeginSection": 1180, "offsetInEndSection": 1429, "text": "After the first progression, retreatment with the same regimen as that used in the induction phase was the best approach for improving overall survival (median overall survival: 46.5 vs. 27.0 months for the same vs. switched strategy, respectively).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33909622"}]}
+{"question_id": "65f48fa2c4010b4d7800000f", "question": "Please list the psychoactive drugs used to treat mental health disorders.", "answer": "LSD, Psilocybin, MDMA, and Ketamine have been studied preclinically and clinically to treat mental health disorders", "relevant_passage_ids": ["37638529", "37348116", "35747039", "19004414", "36262632", "37231549", "19722729", "36861394", "17630868"], "type": "list", "snippets": [{"offsetInBeginSection": 169, "offsetInEndSection": 318, "text": ". Recently, the use of dissociative psychedelic substances such as ketamine and esketamine for depressive disorders has expanded treatment options. W", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37638529"}, {"offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Therapeutic Protocols Using Ketamine and Esketamine for Depressive Disorders: A Systematic Review.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37638529"}, {"offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Health Benefits and Positive Acute Effects of Psilocybin Consumption: A Quantitative Textual Analysis of User Self-Reported Data.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37348116"}, {"offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "There has been growth in the use of psychedelics by the global population in recent years. In addition to recreational and ritualistic use, recent research into psychedelics has brought advances for treating mental disorders", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37348116"}, {"offsetInBeginSection": 507, "offsetInEndSection": 657, "text": "Psychoactive drugs such as MDMA, ketamine, and psilocybin have been shown to specifically target and decrease fear and anxiety pathways in the brain. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35747039"}, {"offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "MDMA-assisted psychotherapy using low doses in a small sample of women with chronic posttraumatic stress disorder.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004414"}, {"offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "The purpose of this study was to investigate the safety of different doses of MDMA-assisted psychotherapy administered in a psychotherapeutic setting to women with chronic PTSD secondary to a sexual assault, a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004414"}, {"offsetInBeginSection": 1230, "offsetInEndSection": 1580, "text": "In addition, all the substances showed a good tolerability and safety profile, especially in comparison to antipsychotics.CONCLUSION: The results obtained open up the possibility of having a guideline for clinicians/health professionals on the use of cannabidiol, modafinil and ketamine as adjunctive treatment for patients with psychotic conditions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37231549"}, {"offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "The utility of classical drugs used to treat psychiatric disorders (e.g., antidepressants, anxiolytics) is often limited by issues of lack of efficacy, delayed onset of action or side effects.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36262632"}, {"offsetInBeginSection": 1610, "offsetInEndSection": 1869, "text": "In this review we focus on the basis, existing evidence and possible use of synthetic cathinones and psychedelics (specially tryptamines) for the treatment of mental illnesses and the properties that should be found in NPS to obtain new therapeutic compounds.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36262632"}, {"offsetInBeginSection": 988, "offsetInEndSection": 1228, "text": "Such disorders include post-traumatic stress disease and treatment-resistant depression, for which classical drugs such as MDMA, ketamine, psilocybin and LSD, among others, have already been clinically tested, reporting successful outcomes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36262632"}, {"offsetInBeginSection": 0, "offsetInEndSection": 319, "text": "Recent research offers good reason to think that various psychedelic drugs-including psilocybin, ayahuasca, ketamine, MDMA, and LSD-may have significant therapeutic potential in the treatment of various mental health conditions, including post-traumatic stress disorder, depression, existential distress, and addiction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36861394"}, {"offsetInBeginSection": 760, "offsetInEndSection": 1027, "text": "ients requesting one drug from a list of available drugs used for self-medication and containing psychoactive substances (codeine in analgesics, pseudoephedrine, dextromethorphan and histamine H(1) receptor antagonists [antihistamines]) were included in the study. A ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19722729"}, {"offsetInBeginSection": 294, "offsetInEndSection": 513, "text": "The seven most frequently prescribed classes of psychoactive drugs were antidepressants, stimulants, tranquilizers/antipsychotics, anticonvulsants, hypotensive agents, anxiolytic/sedative/hypnotics, and benzodiazepines.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17630868"}]}
+{"question_id": "660d2299fdcbea915f000038", "question": "List of attenuated viral vaccines still in use.", "answer": "Some examples of attenuated viral vaccines still in use include the measles, mumps, and rubella (MMR) vaccine, the oral polio vaccine (OPV), the yellow fever vaccine, the varicella (chickenpox) vaccine, and the rotavirus vaccine.", "relevant_passage_ids": ["25864107", "37286215", "37309028"], "type": "list", "snippets": [{"offsetInBeginSection": 141, "offsetInEndSection": 149, "text": "Smallpox", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25864107"}, {"offsetInBeginSection": 231, "offsetInEndSection": 238, "text": "measles", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25864107"}, {"offsetInBeginSection": 183, "offsetInEndSection": 196, "text": "poliomyelitis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25864107"}, {"offsetInBeginSection": 2249, "offsetInEndSection": 2276, "text": "live attenuated MMR vaccine", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37286215"}, {"offsetInBeginSection": 21, "offsetInEndSection": 88, "text": "live vaccines such as measles, mumps, rubella, and varicella (MMRV)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37309028"}]}
+{"question_id": "65cfd9071930410b13000024", "question": "What was tested in the PATCH-Trauma trial?", "answer": "The Pre-hospital Anti-fibrinolytics for Traumatic Coagulopathy and Haemorrhage (The PATCH-Trauma study) compared TXA, initiated prehospital and continued in hospital over 8\u2009hours, with placebo in patients with severe trauma at risk of acute traumatic coagulopathy.", "relevant_passage_ids": ["37314244", "33722875"], "type": "summary", "snippets": [{"offsetInBeginSection": 2067, "offsetInEndSection": 2542, "text": "ONCLUSIONS: Among adults with major trauma and suspected trauma-induced coagulopathy who were being treated in advanced trauma systems, prehospital administration of tranexamic acid followed by an infusion over 8 hours did not result in a greater number of patients surviving with a favorable functional outcome at 6 months than placebo. (Funded by the Australian National Health and Medical Research Council and others; PATCH-Trauma ClinicalTrials.gov number, NCT02187120.).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37314244"}, {"offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Protocol for a multicentre prehospital randomised controlled trial investigating tranexamic acid in severe trauma: the PATCH-Trauma trial.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33722875"}, {"offsetInBeginSection": 542, "offsetInEndSection": 833, "text": "METHODS AND ANALYSIS: The Pre-hospital Anti-fibrinolytics for Traumatic Coagulopathy and Haemorrhage (The PATCH-Trauma study) is comparing TXA, initiated prehospital and continued in hospital over 8\u2009hours, with placebo in patients with severe trauma at risk of acute traumatic coagulopathy. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33722875"}, {"offsetInBeginSection": 1790, "offsetInEndSection": 1992, "text": "The PATCH-Trauma study aims to provide definitive evidence of the effectiveness of prehospital TXA, when used in conjunction with current advanced trauma care, in improving outcomes after severe injury.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33722875"}, {"offsetInBeginSection": 1790, "offsetInEndSection": 2031, "text": "The PATCH-Trauma study aims to provide definitive evidence of the effectiveness of prehospital TXA, when used in conjunction with current advanced trauma care, in improving outcomes after severe injury.TRIAL REGISTRATION NUMBER: NCT02187120.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33722875"}, {"offsetInBeginSection": 529, "offsetInEndSection": 797, "text": "in uncertain.METHODS AND ANALYSIS: The Pre-hospital Anti-fibrinolytics for Traumatic Coagulopathy and Haemorrhage (The PATCH-Trauma study) is comparing TXA, initiated prehospital and continued in hospital over 8\u2009hours, with placebo in patients with severe trauma at ri", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33722875"}]}
+{"question_id": "66099c01fdcbea915f000023", "question": "What is the most appropriate dose of capecitabine in concurrent treatment with radiotherapy for neoadjuvant therapy of locally advanced rectal cancer patients?", "answer": "capecitabine was administered daily at a dose of 1650 mg/m(2) during the entire course of radiation therapy", "relevant_passage_ids": ["15913913", "17385825", "19508705", "19016023", "19690550", "22621694", "37547762", "36801007", "35633559", "20194850", "17042060", "25102935", "19464823", "20920276", "16979839", "27891147", "37533948", "17987042", "12243814", "18292610", "16282246", "22855196", "27757395"], "type": "factoid", "snippets": [{"offsetInBeginSection": 587, "offsetInEndSection": 694, "text": "capecitabine was administered daily at a dose of 1650 mg/m(2) during the entire course of radiation therapy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15913913"}, {"offsetInBeginSection": 714, "offsetInEndSection": 875, "text": "All patients received neoadjuvant chemoradiotherapy and 45 Gy external beam radiotherapy in 25 fractions over 5 weeks with concurrent oral capecitabine (825 mg/m", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36801007"}, {"offsetInBeginSection": 76, "offsetInEndSection": 374, "text": " T3-4 M0 rectal cancer. In this situation, we compared neoadjuvant radiotherapy plus capecitabine with dose-intensified radiotherapy plus capecitabine and oxaliplatin.PATIENTS AND METHODS: We randomly assigned patients to receive 5 weeks of treatment with radiotherapy 45 Gy/25 fractions with concu", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20194850"}, {"offsetInBeginSection": 0, "offsetInEndSection": 508, "text": "BACKGROUND: This study evaluated the effectiveness and safety of preoperative chemoradiotherapy with capecitabine in patients with locally advanced resectable rectal cancer. This report summarizes the results of the phase II study together with long-term (5-year) follow-up.METHODS: Between June 2004 and January 2005, 57 patients with operable, clinical stage II-III adenocarcinoma of the rectum entered the study. Radiation dose was 45 Gy delivered as 25 fractions of 1.8 Gy. Concurrent chemotherapy with o", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20920276"}, {"offsetInBeginSection": 287, "offsetInEndSection": 522, "text": "(n = 20) or T3N0 (n = 5) rectal cancer received neoadjuvant therapy with radiotherapy (50.4 Gy in 28 fractions over 5.5 weeks), bevacizumab every 2 weeks (3 doses of 5 mg/kg), and capecitabine (900 mg/m(2) orally twice daily only on da", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19464823"}, {"offsetInBeginSection": 801, "offsetInEndSection": 925, "text": "Concurrent chronomodulated capecitabine (Brunch regimen) 1650 mg/m2/daily chemotherapy treatment was applied in both groups.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37547762"}, {"offsetInBeginSection": 0, "offsetInEndSection": 572, "text": "Purpose: To analyse the safety and efficacy of neoadjuvant chemoradiation (NACRT) with dose-escalated image-guided intensity modulated radiation therapy (IG-IMRT) in locally advanced (T3/4; T1-4N1-2) rectal cancers (LARCs).Materials and methods: Twenty patients with the diagnosis of LARC were recruited in this prospective interventional single-arm study treated by IG-IMRT with 45 Gray (Gy) in 25 fractions to elective nodal volumes and 55 Gy in 25 fractions to the gross primary and nodal disease with concurrent capecitabine 825 mg/m2 twice daily on radiotherapy days.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37533948"}, {"offsetInBeginSection": 807, "offsetInEndSection": 944, "text": "atients received radiation therapy (total dose 5000 cGy) and concomitant capecitabine (850 mg/m2) twice daily for 14 days every 3 weeks.R", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17278899"}, {"offsetInBeginSection": 592, "offsetInEndSection": 807, "text": "hemotherapy was administered concurrent with radiotherapy and consisted of 2 cycles of 14-day oral capecitabine (1650 mg/m(2)/day) and leucovorin (20 mg/m(2)/day), each of which was followed by a 7-day rest period. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12243814"}, {"offsetInBeginSection": 756, "offsetInEndSection": 982, "text": " patients received preoperative concurrent chemoradiation (45 Gy/25 fractions over 5 weeks with oral capecitabine 825 mg/m2 twice daily on radiotherapy days), followed after 4-6 weeks by total mesorectal excision technique.RES", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19508705"}, {"offsetInBeginSection": 348, "offsetInEndSection": 571, "text": "r were included. Patients received capecitabine (1,650 mg/m(2) per day; 60% dose at 8:00 AM and 40% dose at 12:00 noon) administered during pelvic radiation (total 50.4 Gy in 28 fractions, 1.8 Gy daily dose between 2:00 p.m", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25102935"}, {"offsetInBeginSection": 806, "offsetInEndSection": 1067, "text": "Phase I and II clinical trials showed that a regimen consisting of capecitabine 825mg/m(2) twice daily for 7 days/week continuous oral administration in combination with RT is an active and well tolerated regimen, thereby being the preferred concurrent regimen.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22621694"}, {"offsetInBeginSection": 653, "offsetInEndSection": 1161, "text": "ith low lying (4-7 cm from anal verge) locally advanced rectal cancer, of which 33 were resectable. All patients received preoperative concurrent chemoradiation (45 Gy/25 fractions over 5 weeks with oral capecitabine 825 mg/m2 twice daily on radiotherapy days), followed after 4-6 weeks by total mesorectal excision technique.RESULTS: Preoperative chemoradiation resulted in a complete pathologic response in 4 patients (9.3%; 95% CI 3-23.1) and an overall downstaging in 32 patients (74.4%; 95% CI 58.5-85).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19508705"}]}
+{"question_id": "6609827afdcbea915f000011", "question": "Is Tako-Tsubo syndrome is an irreversible form of an acute stress-related cardiomyopathy?", "answer": "Tako-Tsubo syndrome is an reversible form of an acute stress-related cardiomyopathy", "relevant_passage_ids": ["38090463", "25788945", "31752657", "21503250", "18407362", "22942784", "20131190", "17403953", "24222823", "24815525", "32693809", "27638018", "21949534", "21769261", "20091403", "23765730", "16387374", "16829194", "31423403", "25380951", "36268377", "31818146", "26904708", "29122235", "22427775", "19185360", "28967342", "20455042", "18597972", "18688681", "35198223"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Takotsubo cardiomyopathy (TC) is a recognized clinical syndrome characterized by reversible cardiomyopathy with a distinctive left ventricular apical ballooning appearance", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38090463"}, {"offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Tako-Tsubo cardiomyopathy (TTC) is a reversible cardiomyopathy characterized by acute left ventricular segmental dysfunction, whose clinical presentation resembles that of acute myocardial infarction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25788945"}, {"offsetInBeginSection": 12, "offsetInEndSection": 178, "text": "Takotsubo Cardiomyopathy (TTC) is an uncommon cause of acute reversible ventricular systolic dysfunction in the absence of obstructive Coronary Artery Disease (CAD). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31752657"}, {"offsetInBeginSection": 4, "offsetInEndSection": 104, "text": "Tako-Tsubo syndrome is a reversible form of an acute stress-related cardiomyopathy that was reported", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22942784"}, {"offsetInBeginSection": 4, "offsetInEndSection": 201, "text": "GROUND: The Tako-Tsubo Syndrome is a clinical entity characterized by acute but rapidly reversible left ventricular systolic dysfunction and triggered by emotional or psychological stress. The aim ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18407362"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "The etiology of a novel cardiac syndrome called \"tako-tsubo\" cardiomyopathy, otherwise known as \"acute onset and reversible", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18597972"}, {"offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "BACKGROUND: The etiology of tako-tsubo cardiomyopathy, defined as a transient left ventricular dysfunction in", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25380951"}, {"offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "The Tako-Tsubo syndrome is a reversible form of an acute stress-related cardiomyopathy that was reported during the last decade.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22942784"}, {"offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Tako-tsubo cardiomyopathy (transient left ventricular apical ballooning) is a reversible form of cardiomyopathy of unknown etiology.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21503250"}, {"offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "Tako-tsubo syndrome (TTS) or stress-related acute reversible ventricular apical dysfunction is an emerging but seemingly under-recognised cardiomyopathy mimicking acute ST elevation myocardial infarction (STEMI) without concomitant epicardial coronary artery disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17403953"}, {"offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "Tako-Tsubo cardiomyopathy (TTC), also known as transient left ventricular apical ballooning syndrome or stress-induced cardiomyopathy, is a novel reversible cardiomyopathy mimicking acute myocardial infarction without epicardial coronary artery disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21949534"}, {"offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Tako-tsubo cardiomyopathy is a form of reversible left ventricular dysfunction, with a clinical and electrocardiographic picture of acute myocardial infarction in the absence of significant coronary disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20091403"}, {"offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Tako-Tsubo's syndrome (apical ballooning or broken heart syndrome) is a reversible left ventricular dysfunction due to apical asynergy that occurs typically after sudden emotional stress in a subject without coronary disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16829194"}, {"offsetInBeginSection": 0, "offsetInEndSection": 327, "text": "Tako-tsubo cardiomyopathy, also known as stress-induced cardiomyopathy, is a temporary left ventricular dysfunction characterised by acute retrosternal rest pain, ST - segment elevation, slight elevation of cardiac necrosis markers, preferential apical akinesia or hypokinesia with basal hypercontractility in echocardiography.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20131190"}, {"offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Takotsubo cardiomyopathy (TTC) is reversible stress-induced cardiomyopathy featuring symptoms of acute myocardial infarction without significant coronary artery abnormalities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31423403"}, {"offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "BACKGROUND AND OBJECTIVE: The Tako-tsubo syndrome (TS) is a reversible acute cardiomyopathy simulating an infarction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24815525"}, {"offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Tako-Tsubo cardiomyopathy (TTC) is an acute reversible cause of segmental myocardial dysfunction that is poorly understood and cannot be explained by the occlusion of a single coronary vessel.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21769261"}, {"offsetInBeginSection": 0, "offsetInEndSection": 422, "text": "Introduction: Takotsubo cardiomyopathy is a transient type of acute heart failure with distinct wall motion abnormalities and unclear pathophysiology. This review focuses on the proposed pathophysiological mechanisms that could be involved in the occurrence takotsubo cardiomyopathy.Main body: Acute stress and subsequent excessive activation of the sympathetic nervous system are major factors in the pathophysiology of t", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36268377"}, {"offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "Takotsubo cardiomyopathy or stress cardiomyopathy is a transient reversible cardiomyopathy characterized by regional wall motion abnormalities that usually extend beyond a single epicardial vascular distribution. It is often precipitated by acute physical or emotional stressors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31818146"}, {"offsetInBeginSection": 14, "offsetInEndSection": 175, "text": "Stress cardiomyopathy, or takotsubo cardiomyopathy, is an acute, reversible left ventricular dysfunction usually initiated by a psychological or physical stress.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26904708"}, {"offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Tako-tsubo syndrome appears to be an apparently reversible form of the cardiomyopathy, but little is known about the long term risk even with normalization of ventricular function.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16387374"}, {"offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Tako-Tsubo cardiomyopathy is characterized by a transient and reversible left ventricular dysfunction possibly due to a catecholamine-mediated myocardial stunning.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19185360"}, {"offsetInBeginSection": 130, "offsetInEndSection": 239, "text": "This reversible cardiomyopathy without epicardial coronary artery disease mimics acute myocardial infarction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23765730"}, {"offsetInBeginSection": 511, "offsetInEndSection": 832, "text": "TURE REVIEW: Tako-tsubo cardiomyopathy is characterized by a reversible left ventricular dysfunction and wall movement abnormalities, without any compromise of the coronary arteries, associated to high plasma levels of catecholamines which in most cases correlates with an acute stress of emotional or physical type.CONCL", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29122235"}, {"offsetInBeginSection": 206, "offsetInEndSection": 389, "text": "colleagues. Takotsubo cardiomyopathy is an increasingly recognized syndrome characterized by transient and reversible systolic dysfunction of the apical and middle segments of the lef", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28967342"}, {"offsetInBeginSection": 0, "offsetInEndSection": 312, "text": "The etiology of a novel cardiac syndrome called \"tako-tsubo\" cardiomyopathy, otherwise known as \"acute onset and reversible left ventricular apical wall motion abnormality (ballooning),\" is very similar to that of acute myocardial infarction; however, it may also be associated with emotional or physical stress.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18597972"}, {"offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Tako-tsubo cardiomyopathy is characterized by a transient and reversible left ventricular dysfunction and shows clinical similarities with the acute coronary syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20455042"}, {"offsetInBeginSection": 4, "offsetInEndSection": 104, "text": "GROUND: The Tako-Tsubo Syndrome is a clinical entity characterized by acute but rapidly reversible l", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18407362"}, {"offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "The etiology of a novel cardiac syndrome called \"tako-tsubo\" cardiomyopathy, otherwise known as \"acute onset and reversible left ventricular apical wall motion abnormality (ballooning),\" is very si", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18597972"}, {"offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Tako-tsubo cardiomyopathy is a form of reversible left ventricular dysfunction, with a clinical and electroca", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20091403"}, {"offsetInBeginSection": 0, "offsetInEndSection": 384, "text": "BACKGROUND: Takotsubo cardiomyopathy is characterized by transient dysfunction of the medial to apical segment of the left ventricle. Recurrence within a few months or years has been reported and serious complications, including arrhythmia, acute cardiac shock and cardiac rupture, can arise; however, recurrence is rare and takotsubo cardiomyopathy is typically a reversible function", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32693809"}, {"offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "BACKGROUND: Takotsubo cardiomyopathy is a novel, yet well-described, reversible cardiomyopathy triggered by profound psychological or physical stress with a female p", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18688681"}, {"offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Takotsubo cardiomyopathy is considered a benign syndrome that presented by transient characteristic left ventricular dysfunction with a variety of wall-motion abnormalities that resolve completely after few weeks.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35198223"}, {"offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Takotsubo syndrome is typically characterized by acute reversible impairment of apical and mid -left ventricular systolic function. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27638018"}]}
+{"question_id": "660d7491fdcbea915f000041", "question": "New treatments in multiple sclerosis.", "answer": "New approaches to treatment for MS include gut microbiome modification, fumarates, interferons, and biologicals.", "relevant_passage_ids": ["33620411", "35674067"], "type": "list", "snippets": [{"offsetInBeginSection": 1687, "offsetInEndSection": 1872, "text": "interferons, glatiramer acetate, teriflunomide, sphingosine 1-phosphate receptor modulators, fumarates, cladribine, and 3 types of monoclonal antibodies. One additional DMT, ocrelizumab", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33620411"}]}
+{"question_id": "65cfcc8f1930410b13000018", "question": "Is UGT1A1 implicated in Crigler\u2013Najjar syndrome?", "answer": "Yes. Crigler-Najjar syndrome is a rare disorder of bilirubin metabolism caused by uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) mutations characterized by hyperbilirubinemia and jaundice.", "relevant_passage_ids": ["36936447", "37137832", "37602038", "37585628", "37759499", "19830808", "22340355", "14550264", "15712364", "25966095", "26250421", "26220753", "11013440", "33102778", "24401909", "25729974", "33604208", "16386929", "23403257", "11868392", "28280378", "23992562", "21319362", "27722180", "9497253", "11855932", "24065680", "22765254", "25315738", "34807779", "23461146", "14616765", "19953640", "10412811", "23875061", "23162302", "31553814", "23290513", "30544479", "29176474", "25319636", "24793765", "32536060", "23430851"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Crigler-Najjar syndrome is a rare disorder of bilirubin metabolism caused by uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) mutations characterized by hyperbilirubinemia and jaundice. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36936447"}, {"offsetInBeginSection": 597, "offsetInEndSection": 829, "text": "Conclusion: The compound heterozygous pathogenic mutations (c.-3279T > G, c.211G > A, and c.1456T > G) at three loci of the UGT1A1 gene may be the feature of the newly discovered CNS-II family genes based on the CNS-II family study.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37137832"}, {"offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Crigler-Najjar syndrome (CNS) type I is a rare genetic disease caused by mutations in the UGT1A1 gene, resulting in a lack of Uridine 5'-diphospho-glucuronosyltransferase (UDPGT) enzyme. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37602038"}, {"offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "BACKGROUND: Patients with the Crigler-Najjar syndrome lack the enzyme uridine diphosphoglucuronate glucuronosyltransferase 1A1 (UGT1A1), the absence of which leads to severe unconjugated hyperbilirubinemia that can cause irreversible neurologic injury and death. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37585628"}, {"offsetInBeginSection": 264, "offsetInEndSection": 430, "text": "A defect in the UGT1A1 enzyme-encoding gene, which is directly responsible for bilirubin conjugation, can cause Crigler-Najjar syndrome (CNS) and Gilbert's syndrome. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37759499"}, {"offsetInBeginSection": 264, "offsetInEndSection": 428, "text": "A defect in the UGT1A1 enzyme-encoding gene, which is directly responsible for bilirubin conjugation, can cause Crigler-Najjar syndrome (CNS) and Gilbert's syndrome", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37759499"}, {"offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Crigler-Najjar syndrome (CNS) type I is a rare genetic disease caused by mutations in the UGT1A1 gene, resulting in a lack of Uridine 5'-diphospho-glucuronosyltransferase (UDPGT) enzyme", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37602038"}, {"offsetInBeginSection": 12, "offsetInEndSection": 261, "text": "Patients with the Crigler-Najjar syndrome lack the enzyme uridine diphosphoglucuronate glucuronosyltransferase 1A1 (UGT1A1), the absence of which leads to severe unconjugated hyperbilirubinemia that can cause irreversible neurologic injury and death", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37585628"}, {"offsetInBeginSection": 107, "offsetInEndSection": 207, "text": "Crigler-Najjar syndrome (CNS) in relation to uridine diphosphate glucuronosyltransferase A1 (UGT1A1)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32536060"}, {"offsetInBeginSection": 181, "offsetInEndSection": 322, "text": "Crigler-Najjar syndrome is another rare disorder of bilirubin metabolism caused by mutation in the gene coding the enzyme UGT1A1. We report a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19953640"}, {"offsetInBeginSection": 12, "offsetInEndSection": 201, "text": "Crigler-Najjar syndromes are familial unconjugated hyperbilirubinemias caused by genetic lesions involving a single complex locus encoding for bilirubin UDP-glucuronosyltransferase (UGT1A1)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16386929"}, {"offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Crigler-Najjar syndrome type I is a severe form of hereditary unconjugated hyperbilirubinemia and is caused by homozygous or compound heterozygous mutations of the bilirubin UDP-glucuronosyltransferase gene (UGT1A1). We analyzed", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14616765"}, {"offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Crigler-Najjar syndrome (CNs) is a rare hereditary unconjugated hyperbilirubinemia caused by mutations in the bilirubin Uridine (UDP) glucuronosyltransferase family 1 member A1 (UGT1A1, ENSG00000241635) gene. Two patients were clinically", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33102778"}, {"offsetInBeginSection": 0, "offsetInEndSection": 412, "text": "Crigler-Najjar syndrome type 1 (CN-1) is a recessively inherited, potentially lethal disorder characterized by severe unconjugated hyperbilirubinemia resulting from deficiency of the hepatic enzyme bilirubin-UDP-glucuronosyltransferase. In all CN-1 patients studied, structural mutations in one of the five exons of the gene (UGT1A1) encoding the uridinediphosphoglucuronate glucuronosyltransferase (UGT) isoform", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9497253"}, {"offsetInBeginSection": 227, "offsetInEndSection": 973, "text": "Crigler-Najjar syndrome type I (CN1), Crigler-Najjar syndrome type II, and Gilbert's syndrome. CN1 is a severe form of unconjugated hyperbilirubinemia caused by homozygous or compound heterozygous mutations in the gene for uridine 5'-diphosphate glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1), resulting in complete loss of enzyme function. Here, we report a novel homozygous mutation of UGT1A1 in a female Thai infant who was diagnosed with CN1, and her parents were found to be heterozygous carriers. The patient was homozygous for the c.558C>A mutation, which resulted in a premature stop codon in exon 1. Her asymptomatic parents were carriers of the nonsense c.558C>A mutation. Our result suggests an important role for homozygous", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25729974"}, {"offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Crigler-Najjar syndrome presents as severe unconjugated hyperbilirubinemia and is characteristically caused by a mutation in the UGT1A1 gene, encoding the enzyme responsible for bilirubin glucuronidation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26220753"}, {"offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Crigler-Najjar syndrome type 1 (CN-1) is characterized by severe unconjugated hyperbilirubinemia due to an inherited deficiency of hepatic bilirubin uridinediphosphoglucuronate glucuronosyltransferase (UGT1A1), inherited as an autosomal recessive characteristic.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11855932"}, {"offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Crigler-Najjar syndrome (CN), caused by deficiency of UGT isoform 1A1 (UGT1A1), is characterized by severe unconjugated hyperbilirubinemia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19830808"}, {"offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Crigler-Najjar syndrome is a rare autosomal recessive disease caused by mutations in the UGT1A1 gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24065680"}, {"offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Mutations in the gene encoding bilirubin UDP-glucuronosyltransferase (UGT1A1) are known to cause Crigler-Najjar syndrome type II (CN-II).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24401909"}, {"offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11013440"}, {"offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Crigler-Najjar syndrome is a severe metabolic disease of the liver due to a reduced activity of the UDP Glucuronosyltransferase 1A1 (UGT1A1) enzyme.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27722180"}, {"offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "UGT1A1 enzyme defects are responsible of both Gilbert syndrome (GS) and Crigler-Najjar syndrome (CNS).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23403257"}, {"offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Gilbert and Crigler-Najjar syndromes are familial unconjugated hyperbilirubinemias caused by genetic lesions involving a single complex locus encoding for bilirubin UDP-glucuronosyltransferase (UGT1A1) gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16386929"}, {"offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Crigler-Najjar syndrome is an autosomal recessive disorder with severe unconjugated hyperbilirubinemia due to deficiency of bilirubin UDP-glucuronosyltransferase isozyme 1A1 (UGT1A1) encoded by the UGT1A1 gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22765254"}, {"offsetInBeginSection": 1142, "offsetInEndSection": 1353, "text": "Crigler-Najjar syndrome is the severe inherited form of unconjugated hyperbilirubinaemia due to mutations in the UGT1A1 gene, which can cause kernicterus early in life and can be even lethal when left untreated.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25315738"}, {"offsetInBeginSection": 490, "offsetInEndSection": 677, "text": "Sequence analysis of the UGT1A1 gene revealed that she was a compound heterozygote with p.[G71R; Y486D] + [Y486D] mutations, which suggests Crigler-Najjar syndrome type II rather than GS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21319362"}, {"offsetInBeginSection": 153, "offsetInEndSection": 301, "text": "Inactivation and very low activity of UGT1A1 in the liver can be fatal or lead to lifelong Gilbert's syndrome (GS) and Crigler-Najjar syndrome (CN).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34807779"}, {"offsetInBeginSection": 0, "offsetInEndSection": 334, "text": "The UDP-glucuronosyltransferase 1A1 gene that encode the enzyme UGT1A1 responsible for glucuronidation undergoes several variations that may affect the enzymatic activity or expression and which are the cause of metabolic disorders related to the glucuronidation of bilirubin, such as Gilbert's syndrome and Crigler Najjar's syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23461146"}, {"offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Mutations in the UGT1A1 gene have been implicated in Gilbert syndrome, which shows mild hyperbilirubinemia, and a more aggressive childhood subtype, Crigler-Najjar syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28280378"}, {"offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Crigler-Najjar syndrome is a rare autosomal recessive disease caused by mutations in the UGT1A1 gene. These mutations result in the deficiency of UGT1A1, a hepatic enzyme essential for bilirubin conjugation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24065680"}, {"offsetInBeginSection": 0, "offsetInEndSection": 580, "text": "Mutations in the UGT1A1 gene cause Crigler-Najjar syndrome (CN), which causes non-hemolytic unconjugated hyperbilirubinemia, and is categorized as CN1 and CN2 according to the severity of bilirubin levels. The UGT1A1 gene is responsible for encoding the liver enzyme uridine diphosphate-glucuronosyltransferase, UGT1A1. This protein adds glucuronic acid to unconjugated bilirubin in bilirubin metabolism to form conjugated bilirubin. CN2 occurs when UGT1A1 activity is low, while CN1 is the absence of UGT1A1 activity; therefore, the CN2 phenotype is not as severe as that of CN1.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25966095"}, {"offsetInBeginSection": 0, "offsetInEndSection": 454, "text": "Crigler-Najjar syndrome types I and II (CN1 and CN2) are usually inherited as autosomal recessive conditions and are characterized by non-hemolytic unconjugated hyperbilirubinaemia. CN1 is the most severe form, associated with the absence of hepatic bilirubin-uridinediphosphoglucuronate glucuronosyltransferase (UGT1A1) activity. CN2 presents intermediate levels of hyperbilirubinaemia as a result of an incomplete deficiency of hepatic UGT1A1 activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15712364"}, {"offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Crigler-Najjar syndrome (CNS) type I and type II are usually inherited as autosomal recessive conditions that result from mutations in the UGT1A1 gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23875061"}, {"offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "Crigler-Najjar syndrome type I is a severe inborn error of bilirubin metabolism caused by a complete deficiency of uridine diphospho-glucuronosyl transferase 1A1 (UGT1A1) and results in life-threatening unconjugated hyperbilirubinemia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20973621"}, {"offsetInBeginSection": 507, "offsetInEndSection": 761, "text": " Homozygous missense mutations of the gene have been generally recognized as responsible for Crigler-Najjar syndrome type II; the results obtained here, however, confirm that Gilbert syndrome may also be caused by a homozygous missense mutation of UGT1A1", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10412811"}, {"offsetInBeginSection": 1366, "offsetInEndSection": 1486, "text": "Therefore, lipid nanoparticle-encapsulated hUGT1A1 mRNA may represent a potential treatment for Crigler-Najjar syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36936447"}, {"offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "UDP-glucuronosyltransferase form 1A1 (UGT1A1) is the only bilirubin-glucuronidating isoform of this protein, and genetic deficiencies of UGT1A1 cause Crigler-Najjar syndrome, a disorder resulting from nonhemolytic unconjugated hyperbilirubinemia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14550264"}, {"offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Crigler-Najjar syndrome is a rare autosomal recessive disease caused by mutations in the UGT1A1 gene", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24065680"}, {"offsetInBeginSection": 21, "offsetInEndSection": 192, "text": "We describe the pathophysiology, treatment, and outcome of Crigler-Najjar type 1 syndrome (CN1) in 28 UGT1A1 c.222C>A homozygotes followed for 520 aggregate patient-years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31553814"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Crigler-Najjar syndrome (CNS) type I and type II are usually inherited as autosomal recessive conditions that result from mutations in the UGT1A1 gene", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23875061"}, {"offsetInBeginSection": 11, "offsetInEndSection": 305, "text": "To assess the clinical utility of UGT1A1 genetic testing and describe the spectrum and prevalence of UGT1A1 variations identified in pediatric unconjugated hyperbilirubinemia (UCH), and to characterize specific genotype-phenotype relationships in suspected Gilbert and Crigler-Najjar syndromes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23290513"}, {"offsetInBeginSection": 328, "offsetInEndSection": 728, "text": "Pfam database, SWISS-model, and Pymol were used for UGT1A1 protein domain analysis and protein modeling for assessing the effect of novel missense variants on protein structure.Seventy four cases, including 21 prolonged unconjugated hyperbilirubinemia (PUCH), 30 Gilbert syndrome (GS), 22 Crigler-Najjar syndrome type II (CNS-II), and 1 Crigler-Najjar syndrome type I (CNS-I) phenotypes were analyzed", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30544479"}, {"offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Mutations in the UGT1A1 gene cause Crigler-Najjar syndrome (CN), which causes non-hemolytic unconjugated hyperbilirubinemia, and is categorized as CN1 and CN2 according to the severity of bilirubin levels", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25966095"}, {"offsetInBeginSection": 12, "offsetInEndSection": 210, "text": "Crigler-Najjar syndrome type I (CNI) arises from biallelic variants of UGT1A1 that abrogate uridine diphosphate glucuronosyltransferase (UGT1A1) activity resulting in unconjugated hyperbilirubinemia", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29176474"}, {"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "A novel stop codon mutation in exon 1 (558C>A) of the UGT1A1 gene in a Thai neonate with Crigler-Najjar syndrome type I.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25729974"}, {"offsetInBeginSection": 125, "offsetInEndSection": 713, "text": "Many mutations have already been identified in patients with inherited disorders with unconjugated hyperbilirubinemia, such as Crigler-Najjar syndromes and Gilbert's syndrome.CASE PRESENTATION: In this report, we presented a boy with intermittent unconjugated hyperbilirubinemia, whose genetic analysis showed a new compound heterozygote determined by three mutations, c.211G > A (p.G71R), c.508_510delTTC (p.F170-) and c.1456\u00a0T > G (p.Y486D) in the hotspot regions of the UGT1A1 gene (exons 1 and 5) in Asian populations, presenting a genotype compatible with clinical picture of CNS-II.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25319636"}, {"offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Crigler-Najjar syndrome is an inborn error of metabolism caused by a point mutation in one of the five exons of UGT1A1 gene, the product of which is responsible for elimination of bilirubin via bile.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33604208"}, {"offsetInBeginSection": 455, "offsetInEndSection": 926, "text": "Here, we present the analysis of UGT1A1 gene in 31 unrelated Crigler-Najjar (CN) syndrome patients. This analysis allowed us to identify 22 mutations, 12 of which were not previously described, expanding the spectrum of known UGT1 mutations to 77. Novel mutations, considered pathogenic, including one nonsense mutation, two altered splice sites, one single base deletion and nine missense mutations were identified in coding exons of the UGT1A1gene and flanking introns.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15712364"}, {"offsetInBeginSection": 0, "offsetInEndSection": 460, "text": "We present a case of severe persisting unconjugated hyperbilirubinemia in a Uigur infant boy, eventually diagnosed as Crigler-Najjar syndrome type I. DNA analysis of his blood of the UGT1A1 gene sequence demonstrated that he was homozygous for an insertion mutation causing a change of the coding exons with a frame-shift, resulting in the substitution of 27 abnormal amino acid residues in his hepatic bilirubin uridine diphosphoglucuronyl transferase enzyme.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22340355"}, {"offsetInBeginSection": 0, "offsetInEndSection": 521, "text": "We present a case of severe persisting unconjugated hyperbilirubinemia in a Uigur infant boy, eventually diagnosed as Crigler-Najjar syndrome type I. DNA analysis of his blood of the UGT1A1 gene sequence demonstrated that he was homozygous for an insertion mutation causing a change of the coding exons with a frame-shift, resulting in the substitution of 27 abnormal amino acid residues in his hepatic bilirubin uridine diphosphoglucuronyl transferase enzyme. Both of his parents were heterozygous for the same mutation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22340355"}, {"offsetInBeginSection": 1006, "offsetInEndSection": 1123, "text": "In addition, the evaluation of Gilbert-type promoter of UGT1A1in Crigler-Najjar (CN) syndrome patients was performed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15712364"}, {"offsetInBeginSection": 0, "offsetInEndSection": 498, "text": "Crigler-Najjar syndrome is an inborn error of metabolism caused by a point mutation in one of the five exons of UGT1A1 gene, the product of which is responsible for elimination of bilirubin via bile.\u00a0A number of hyperbilirubinemia disorders similar to Crigler-Najjar syndrome are reported, but they differ in their level of unconjugated bilirubin and responses to the treatment. Here we report a 14-year-old male patient admitted to hospital with the complaint of vomiting and frequent tonsillitis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33604208"}, {"offsetInBeginSection": 0, "offsetInEndSection": 463, "text": "Crigler-Najjar syndrome (CNs) is a rare hereditary unconjugated hyperbilirubinemia caused by mutations in the bilirubin Uridine (UDP) glucuronosyltransferase family 1 member A1 (UGT1A1, ENSG00000241635) gene. Two patients were clinically diagnosed with Crigler-Najjar Syndrome types II (CNs-II) can be clinically diagnosed which were based on the level of total bilirubin, efficacy of phenobarbital treatment, normal liver architecture and exclusion of hemolysis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33102778"}, {"offsetInBeginSection": 0, "offsetInEndSection": 407, "text": "Crigler-Najjar syndrome type 2 is a rare cause for persistent unconjugated hyperbilirubinemia, inherited in an autosomal recessive manner. Even though it is compatible with normal life span, in the absence of prompt suspicion and intensive management it can prove fatal not only in the neonatal period but also during adult life. Here, we describe a case with a novel homozygous UGT1A1 p.Pro176Leu mutation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23162302"}, {"offsetInBeginSection": 48, "offsetInEndSection": 148, "text": "Crigler-Najjar syndrome and Gilbert syndrome, arise due to deficiency of UGT1A1 enzyme activity. Cri", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23992562"}, {"offsetInBeginSection": 392, "offsetInEndSection": 533, "text": "result of an incomplete deficiency of hepatic UGT1A1 activity. Here, we present the analysis of UGT1A1 gene in 31 unrelated Crigler-Najjar (C", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15712364"}, {"offsetInBeginSection": 45, "offsetInEndSection": 457, "text": "hyperbilirubinemias, Crigler-Najjar syndrome type I, Crigler-Najjar syndrome type II (CN-2), and Gilbert syndrome (GS) all result from mutations of the bilirubin uridine 5'-diphosphate (UDP)-glucuronosyltransferase gene (UGT1A1). Often, to distinguish between CN-2 and GS is difficult because the borderline of the two syndromes is unclear. We analyzed the genotypes and phenotypes of 163 Japanese patients with ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26250421"}, {"offsetInBeginSection": 382, "offsetInEndSection": 1128, "text": "or partial inactivation of the enzyme causing the rare autosomal recessively inherited conditions, Crigler-Najjar syndrome type-1 (CN-1) and type 2 (CN-2), respectively. Inactivation of the enzyme leads to accumulation of unconjugated bilirubin in the serum. Severe hyperbilirubinemia seen in CN-1 can cause bilirubin encephalopathy (kernicterus). Kernicterus can be fatal or may leave behind permanent neurological sequelae. Here, we have compiled more than 50 genetic lesions of UGT1A1 that cause CN-1 (including 9 novel mutations) or CN-2 (including 3 novel mutations) and have presented a correlation of structure to function of UGT1A1. In contrast to Crigler-Najjar syndromes, Gilbert syndrome is a common inherited condition characterized b", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11013440"}, {"offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Crigler-Najjar syndrome (CNs) is a rare hereditary unconjugated hyperbilirubinemia caused by mutations in the bilirubin Uridine (UDP) glucuronosyltransferase family 1 member A1 (UGT1A1, ENSG00000241635) gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33102778"}, {"offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Crigler-Najjar syndrome type I is a severe form of hereditary unconjugated hyperbilirubinemia and is caused by homozygous or compound heterozygous mutations of the bilirubin UDP-glucuronosyltransferase gene (UGT1A1).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14616765"}, {"offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Crigler-Najjar syndrome type I (CN-I, MIM #218800) is a rare and severe autosomal disorder. It is caused by deficiency of the liver enzyme responsible for bilirubin elimination, the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1; EC 2.4.1.17).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23430851"}, {"offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Two inherited unconjugated hyperbilirubinemias, Crigler-Najjar syndrome and Gilbert syndrome, arise due to deficiency of UGT1A1 enzyme activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23992562"}, {"offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Crigler-Najjar syndrome type I (CN-I) is the most severe type of hereditary unconjugated hyperbilirubinemia. It is caused by homozygous or compound heterozygous mutations of the UDP-glycuronosyltransferase gene (UGT1A1) on chromosome 2q37.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24793765"}, {"offsetInBeginSection": 473, "offsetInEndSection": 627, "text": "UGT1A1 conjugates bilirubin, and mutations of the gene cause hereditary unconjugated hyperbilirubinemias (Crigler-Najjar syndrome and Gilbert's syndrome).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11868392"}]}
+{"question_id": "65f77596c4010b4d7800002c", "question": "Should PDYD polymorphism determination be routinely performed in patients with colorectal cancer patients?", "answer": "Prospective DPYD genotyping was feasible in routine clinical practice, and DPYD genotype-based dose reductions improved patient safety of fluoropyrimidine treatment.", "relevant_passage_ids": ["35582139", "30348537", "30551678", "25137161", "11051215", "32546132", "20920994", "18597209", "33280607", "36980706", "35880438", "15213713", "34780066", "25906475", "20637356", "31653159", "36890284", "23335937", "33274825", "36297556", "16537192", "25253112", "29372689", "19239324", "21461655", "24817302", "23942539", "23781135", "12749725", "36524458"], "type": "yesno", "snippets": [{"offsetInBeginSection": 569, "offsetInEndSection": 759, "text": "Host genetic variants in the rate limiting enzyme dihydropyrimidine dehydrogenase (DPYD) gene are related to the occurrence of extremely severe, early onset toxicity in FP treated patients. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35582139"}, {"offsetInBeginSection": 3168, "offsetInEndSection": 3333, "text": "Prospective DPYD genotyping was feasible in routine clinical practice, and DPYD genotype-based dose reductions improved patient safety of fluoropyrimidine treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30348537"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1014, "text": "Colorectal cancer (CCR), which is one of the most common causes of cancer, has benefited from the major advances in the understanding of the intracellular signaling pathways implicated in the initiation, growing and local and metastasis dissemination of tumor, which have occurred during the 20 past years. The pharmacogenomics approach, especially the determination of the genetic polymorphisms, tries to find prognosis and predictive biomarkers permitting to identify patients who could benefit from a particular treatment or those exhibiting higher risks of toxicity. Among the numerous biomarkers, which have been studied, few are currently in use in clinical practice. The phenotyping of DPD and UGT1A1 activities, and to a lesser extent, its genotyping, appears as the most useful tool in terms of prediction of toxicities induced by two major drugs: 5-FU and irinotecan. For oxaliplatin, the determination of the polymorphisms of reparases and detoxification systems such as GSTpi seems interesting, but its", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20637356"}, {"offsetInBeginSection": 22, "offsetInEndSection": 1708, "text": "forms the basis for the chemotherapy of advanced colorectal cancer and of other solid tumours. About 9% of patients suffer from serious, sometimes even life-threatening adverse effects of a 5-FU therapy, such as haemotoxicity, which cannot be reliably predicted by conventional clinical and pharmacokinetic criteria. The systemic exposure to 5-FU is fundamentally determined by the genetically polymorphic enzyme dihydropyrimidine dehydrogenase (DPD). This deficiency is closely related to 5-FU-induced toxicity and a variety of non-synonymous variants has been detected in affected patients. The exon14-skipping mutation is the gene defect most frequently associated with serious 5-FU-related adverse effects and it has been reported ten times more often in affected individuals than in the general population. The 2846A>T polymorphism, which leads to an amino acid substitution, appears to be of comparable importance. While the causative role of premature stop codons - presumably resulting from spontaneous mutations - is very likely, the pathophysiological relevance of various other amino acid changes is still unclear. Patients who harbour a high-risk genotype should not be treated with 5-FU if therapeutic alternatives are available. The present data indicate that complete genotyping of the encoding DPYD gene is desirable, in the interest of drug safety, before treatment is started, although only a small number of patients would actually benefit. A method for the quantification of the DPD activity in vivo would have the advantage of reflecting all genetic and non-genetic influences.' However, no such method is currently available for routine use. Prospective genotyping", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18597209"}, {"offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "AIMS: Cancer patients with reduced dihydropyrimidine dehydrogenase (DPD) activity are at increased risk of severe fluoropyrimidine (FP)-related adverse events (AE).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34780066"}, {"offsetInBeginSection": 768, "offsetInEndSection": 1270, "text": "For each of the tested polymorphisms, variant allele carriers were matched to respective wild type controls (optimal full matching combined with exact matching, in respect to: age, sex, type of cancer, type of FP, DPYD activity score, use of irinotecan/UGT1A1, adjuvant therapy, radiotherapy, biological therapy and genotype on the remaining two tested polymorphisms).RESULTS: Of the 503 included patients (82.3% colorectal cancer), 283 (56.3%) developed grade \u22653 AEs, mostly diarrhoea and neutropenia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34780066"}, {"offsetInBeginSection": 320, "offsetInEndSection": 767, "text": "We evaluated the relationship between three further DPYD polymorphisms: c.496A>G (rs2297595), *6 c.2194G>A (rs1801160) and *9A c.85T>C (rs1801265) and the risk of severe AEs.METHODS: Consecutive FP-treated adult patients were genotyped for \"standard\" and tested DPYD variants, and for UGT1A1*28 if irinotecan was included, and were monitored for the occurrence of grade \u22653 (National Cancer Institute Common Terminology Criteria) vs. grade 0-2 AEs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34780066"}, {"offsetInBeginSection": 1265, "offsetInEndSection": 1481, "text": "The present data indicate that complete genotyping of the encoding DPYD gene is desirable, in the interest of drug safety, before treatment is started, although only a small number of patients would actually benefit.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18597209"}, {"offsetInBeginSection": 1227, "offsetInEndSection": 1487, "text": "The studies we reviewed indicate that pharmacogenetic testing is promising to direct personalised dosing of fluoropyrimidines, although further investigations are needed to establish the role of DPD in severe toxicity in patients treated for colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25906475"}, {"offsetInBeginSection": 165, "offsetInEndSection": 319, "text": "Guidelines recommend FP dosing adjusted to genotype-predicted DPD activity based on four DPYD variants (rs3918290, rs55886062, rs67376798 and rs56038477).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34780066"}, {"offsetInBeginSection": 0, "offsetInEndSection": 847, "text": "OBJECTIVE: To validate the associations previously found in three cohorts of patients from the General University Hospital Gregorio Mara\u00f1\u00f3n, between the polymorphisms rs1128503, rs2032582 and rs1045642 of the ABCB1 gene and the hand-foot syndrome and diarrhea in colorectal cancer patients treated with chemotherapy regimes containing Capecitabine and 5-Fluorouracil, respectively, and between the polymorphisms rs2297595 of the DPYD gene and nausea/vomiting, rs11615 of ERCC1 and neutropenia, and rs28399433 CYP2A6 and neutropenia, in colorectal cancer patients treated with FOLFOX or XELOX as adjuvant therapy.METHOD: Colorectal cancer patients treated with chemotherapy regimes, containing Capecitabine (n = 157), 5-Fluorouracil (n = 99) were included in the study, as well as patients treated with XELOX or FOLFOX (n = 83) as adjuvant therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25137161"}, {"offsetInBeginSection": 1686, "offsetInEndSection": 1842, "text": "Prospective genotyping for the exon 14-skipping and the 2846A>T-polymorphisms may result in a reduction of serious, 5-FU-induced, toxic events of about 25%.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18597209"}, {"offsetInBeginSection": 1343, "offsetInEndSection": 1589, "text": "There was no association between IVS14\u2009+\u20091\u2009G\u2009>\u2009A polymorphism and the occurrence of adverse reactions.CONCLUSION: FOLFOX and FOLFIRI were the most common regimens in CRC patients and their toxicity profile was different in some adverse reactions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32546132"}, {"offsetInBeginSection": 117, "offsetInEndSection": 338, "text": "About 9% of patients suffer from serious, sometimes even life-threatening adverse effects of a 5-FU therapy, such as haemotoxicity, which cannot be reliably predicted by conventional clinical and pharmacokinetic criteria.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18597209"}, {"offsetInBeginSection": 1113, "offsetInEndSection": 1273, "text": "These findings suggest the identification of future predictive biomarkers of effectiveness and toxicity in colorectal cancer patients treated with capecitabine.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36980706"}, {"offsetInBeginSection": 947, "offsetInEndSection": 1112, "text": "This systematic review reveals that several SNPs other than the four DPYD variants that are screened in clinical practice could have an impact on treatment outcomes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36980706"}, {"offsetInBeginSection": 1275, "offsetInEndSection": 1587, "text": "DPYD*2A test results were available in an average of 6\u2009days, causing no significant delays in treatment initiation.CONCLUSION: Upfront genotyping before fluoropyrimidine-based treatment is feasible in clinical practice and can prevent severe toxicities and hospitalizations without delaying treatment initiation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33274825"}, {"offsetInBeginSection": 1156, "offsetInEndSection": 1592, "text": "Our patient may also have benefitted from compound heterozygosis, as shown by no evidence of disease (NED) at 6-month follow-up.CONCLUSION: Pharmacogenetic-guided dosing of DPYD intermediate metabolizer compound heterozygous HapB3 and c.2194G>A variant carries should be managed by a multidisciplinary team with a dose reduction ranging from 25 to 50% to maintain effectiveness and close clinical monitoring for early detection of ADRs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36890284"}, {"offsetInBeginSection": 437, "offsetInEndSection": 933, "text": " The frequency of the polymorphism was examined in 156 patients with colorectal cancer and in 293 healthy controls. The polymorphism analysis was performed by amplifying exon 4 of p53 and digesting the products with restriction enzyme. The frequencies of genotypes: Arg/Arg, Arg/Pro and Pro/Pro were 34.6% (54/156), 43.0% (67/156) and 22.4% (35/156), respectively, in the cases with colorectal cancer, and 28.9% (114/293), 47.8% (140/293) and 13.3% (39/293), respectively, in the healthy controls", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19239324"}, {"offsetInBeginSection": 67, "offsetInEndSection": 184, "text": "+1 G > A genotype of the dihydropyrimidine dehydrogenase (DPD) gene with plasma concentration of 5-fluorouracil (5-FU", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24817302"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1686, "text": "Colorectal cancer (CCR), which is one of the most common causes of cancer, has benefited from the major advances in the understanding of the intracellular signaling pathways implicated in the initiation, growing and local and metastasis dissemination of tumor, which have occurred during the 20 past years. The pharmacogenomics approach, especially the determination of the genetic polymorphisms, tries to find prognosis and predictive biomarkers permitting to identify patients who could benefit from a particular treatment or those exhibiting higher risks of toxicity. Among the numerous biomarkers, which have been studied, few are currently in use in clinical practice. The phenotyping of DPD and UGT1A1 activities, and to a lesser extent, its genotyping, appears as the most useful tool in terms of prediction of toxicities induced by two major drugs: 5-FU and irinotecan. For oxaliplatin, the determination of the polymorphisms of reparases and detoxification systems such as GSTpi seems interesting, but its exact place should be more defined. It is in the field of targeted therapies that the pharmacogenomics approach seems to be the more relevant. KRAS mutation is a dramatic example of single nucleotide polymorphism, which is able to identify a priori patients that could receive or not an anti-EGFR monoclonal antibody such as cetuximab or panitumumab. It is obvious that pre-clinical identification of molecular biomarkers predictive of the sensitivity of the drug targets, which subsequently implicate the selection of patients and the rational evaluation of responses, will be the cornerstone of any clinical trials concerning targeted therapies. Besides the determinati", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20637356"}, {"offsetInBeginSection": 1538, "offsetInEndSection": 2091, "text": "Alterations in gene expression, protein expression and polymorphic variants in genes encoding thymidylate synthase, dihydropyrimidine dehydrogenase, dUTP nucleotidehydrolase and thymidine phosphorylase (for fluoropyrimidine-based chemotherapy), uridine diphosphate glucosyltransferase (UGT) 1A1 and carboxylesterase (for irinotecan therapy), and excision repair cross-complementing genes (ERCC1 and ERCC2) and glutathione-S-transferase P1 (for oxalilplatin-based regimens) may be useful as markers for clinical drug response, survival and host toxicity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12749725"}]}
+{"question_id": "660710b7fdcbea915f000002", "question": "What is the function of the sodium leak channel (NALCN)?", "answer": "The sodium leak channel (NALCN) is widely express in the CNS  has multiple functions including the regulation of neuronal excitability, maintaining resting membrane potential, pacemaking of dopaminergic neuron (DAN) subpopulations and is a key regulator of cancer metastasis and nonmalignant cell dissemination.", "relevant_passage_ids": ["37569281", "37640554", "35911839", "35550517", "36175792", "33203861", "32620897", "33793981", "24904279", "27488637", "25716181", "31601786", "31409833", "32494638", "33766679", "37635635", "33273469", "29610177", "24639627", "24075186", "17448995", "19575010", "22196327", "37046053", "34512260", "37278161", "28968387", "32618095"], "type": "summary", "snippets": [{"offsetInBeginSection": 213, "offsetInEndSection": 326, "text": "Sodium leak channel (NALCN) is widely expressed in the central nervous system and regulates neuronal excitability", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37569281"}, {"offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "We tested the role of the sodium leak channel, NALCN, in pacemaking of dopaminergic neuron (DAN) subpopulations from adult male and female mice. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37640554"}, {"offsetInBeginSection": 11, "offsetInEndSection": 115, "text": " The NALCN encodes a sodium ion leak channel that regulates nerve-resting conductance and excitability. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35911839"}, {"offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "NALCN channel mediates sodium leak currents and is important for maintaining proper resting membrane potential. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35550517"}, {"offsetInBeginSection": 18, "offsetInEndSection": 142, "text": "dium leak channel non-selective protein (NALCN) as a key regulator of cancer metastasis and nonmalignant cell dissemination.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36175792"}, {"offsetInBeginSection": 1, "offsetInEndSection": 74, "text": "he NALCN channel regulates metastasis and nonmalignant cell dissemination", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36175792"}, {"offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Malignant currents: sodium leak channel NALCN propels prostate cancer aggressiveness.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37635635"}, {"offsetInBeginSection": 4, "offsetInEndSection": 252, "text": "sodium-leak channel NALCN forms a subthreshold sodium conductance that controls the resting membrane potentials of neurons. The auxiliary subunits of the channel and their functions in mammals are largely unknown. In this study, we demonstrate that", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32620897"}, {"offsetInBeginSection": 313, "offsetInEndSection": 507, "text": "The sodium leak channel (NALCN), a non-selective cation channel, mediates the background Na+ leak conductance and controls neuronal excitability. It is unknown whether abnormal activity of NALCN", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34512260"}, {"offsetInBeginSection": 929, "offsetInEndSection": 1413, "text": "Thus, Nalcn regulates RTN neuronal excitability and stimulation by CO2, independent of direct pH sensing, potentially contributing to respiratory effects of Nalcn mutations; transmitter modulation of Nalcn may underlie state-dependent changes in breathing and respiratory chemosensitivity.SIGNIFICANCE STATEMENT: Breathing is an essential, enduring rhythmic motor activity orchestrated by dedicated brainstem circuits that require tonic excitatory drive for their persistent function.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27488637"}, {"offsetInBeginSection": 887, "offsetInEndSection": 1010, "text": "Thus, NALCN, a nonselective cation channel, forms the background Na(+) leak conductance and controls neuronal excitability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17448995"}, {"offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "A previously uncharacterized putative ion channel, NALCN (sodium leak channel, non-selective), has been recently shown to be responsible for the tetrodotoxin (TTX)-resistant sodium leak current implicated in the regulation of neuronal excitability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19575010"}, {"offsetInBeginSection": 1654, "offsetInEndSection": 1822, "text": "We show here that Nalcn, a unique channel that generates \"leak\" sodium currents, regulates excitability and neuromodulation of RTN neurons and CO2-stimulated breathing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27488637"}, {"offsetInBeginSection": 539, "offsetInEndSection": 696, "text": "Our data support the notion that NALCN is directly responsible for the increased excitability observed in a variety of neurons in reduced extracellular Ca2+.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32494638"}, {"offsetInBeginSection": 210, "offsetInEndSection": 371, "text": "Here, we show that a leak Na(+) channel, Nalcn, is expressed in the CO2/H(+)-sensitive neurons of the mouse retrotrapezoid nucleus (RTN) that regulate breathing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27488637"}, {"offsetInBeginSection": 219, "offsetInEndSection": 344, "text": "Recent findings suggest that NALCN, in association with UNC79 and UNC80, contributes a basal Na\u207a leak conductance in neurons.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22196327"}, {"offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "The sodium leak channel (NALCN) gene encodes a sodium leak channel that plays an important role in the regulation of the resting membrane potential and the control of neuronal excitability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37046053"}, {"offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "The sodium-leak channel NALCN forms a subthreshold sodium conductance that controls the resting membrane potentials of neurons.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32620897"}, {"offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "The sodium leak channel nonselective protein (NALCN) is a regulator of the pacemaker neurons that are responsible for rhythmic behavior (including respiration), maintaining the resting membrane potential, and are required for action potential production.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29610177"}, {"offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "NALCN-mediated sodium influx confers metastatic prostate cancer cell invasiveness.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37278161"}, {"offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "The sodium leak channel (NALCN) gene encodes a sodium leak channel that plays an important role in the regulation of the resting membrane potential and the control of neuronal excitability", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37046053"}, {"offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "NALCN encodes a sodium ion leak channel expressed in the nervous system that conducts a persistent influx of sodium ions to facilitate action potential formation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32618095"}, {"offsetInBeginSection": 109, "offsetInEndSection": 328, "text": "This review focuses on the sodium leak, G protein-coupled receptors (GPCRs)-activated NALCN channel that is predominantly expressed in neurons where it regulates the resting membrane potential and neuronal excitability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24904279"}, {"offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Sodium leak channel, nonselective (NALCN) is a voltage-independent and cation-nonselective channel that is mainly responsible for the leaky sodium transport across neuronal membranes and controls neuronal excitability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24075186"}, {"offsetInBeginSection": 114, "offsetInEndSection": 482, "text": "The sodium leak channel (NALCN), a non-selective cation channel, mediates the background Na+ leak conductance and controls neuronal excitability and rhythmic behaviors. Here, we show that increases of NALCN expression and function in dorsal root ganglion (DRG) and dorsal spinal cord contribute to chronic constriction injury (CCI)-induced neuropathic pain in rodents.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33766679"}, {"offsetInBeginSection": 114, "offsetInEndSection": 664, "text": "The sodium leak channel (NALCN), a non-selective cation channel, mediates the background Na+ leak conductance and controls neuronal excitability and rhythmic behaviors. Here, we show that increases of NALCN expression and function in dorsal root ganglion (DRG) and dorsal spinal cord contribute to chronic constriction injury (CCI)-induced neuropathic pain in rodents. NALCN current and neuronal excitability in acutely isolated DRG neurons and spinal cord slices of rats were increased after CCI which were decreased to normal levels by NALCN-siRNA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33766679"}, {"offsetInBeginSection": 114, "offsetInEndSection": 282, "text": "The sodium leak channel (NALCN), a non-selective cation channel, mediates the background Na+ leak conductance and controls neuronal excitability and rhythmic behaviors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33766679"}, {"offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "NALCN, a sodium leak channel expressed mainly in the central nervous system, is responsible for the resting Na+ permeability that controls neuronal excitability. Dysfunctions of the NALCN channelosome, NALCN with several auxiliary subunits, are associated with a variety of human diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33203861"}, {"offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "NALCN, a sodium leak channel expressed mainly in the central nervous system, is responsible for the resting Na+ permeability that controls neuronal excitability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33203861"}, {"offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "The sodium leak channel NALCN regulates cell excitability of pituitary endocrine cells.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33793981"}, {"offsetInBeginSection": 68, "offsetInEndSection": 218, "text": "hat plays an important role in the regulation of the resting membrane potential and the control of neuronal excitability. Mutations in the NALCN gene ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37046053"}, {"offsetInBeginSection": 53, "offsetInEndSection": 203, "text": "central nervous system, is responsible for the resting Na+ permeability that controls neuronal excitability. Dysfunctions of the NALCN channelosome, N", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33203861"}, {"offsetInBeginSection": 4, "offsetInEndSection": 102, "text": "sodium leak channel NALCN is a key player in establishing the resting membrane potential (RMP) in ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31601786"}, {"offsetInBeginSection": 563, "offsetInEndSection": 915, "text": "The NALCN family sodium leak channel regulates the resting membrane potential and excitability of invertebrate and vertebrate neurons. Our molecular genetics and electrophysiology analyses show that the C. elegans NALCN, NCA, activates a premotor interneuron network to potentiate persistent motor circuit activity and to sustain C. elegans locomotion.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25716181"}, {"offsetInBeginSection": 0, "offsetInEndSection": 322, "text": "The sodium-leak channel NALCN forms a subthreshold sodium conductance that controls the resting membrane potentials of neurons. The auxiliary subunits of the channel and their functions in mammals are largely unknown. In this study, we demonstrate that two large proteins UNC80 and UNC79 are subunits of the NALCN complex.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32620897"}, {"offsetInBeginSection": 104, "offsetInEndSection": 234, "text": "Sodium leak channels (NALCN) play a key role in rhythmic behaviors by helping set, or subtly changing neuronal resting potential. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24639627"}, {"offsetInBeginSection": 936, "offsetInEndSection": 1072, "text": "Our work points toward formerly unknown contributions of NALCN to neuronal excitability and opens avenues for pharmacological targeting.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32494638"}, {"offsetInBeginSection": 563, "offsetInEndSection": 697, "text": "The NALCN family sodium leak channel regulates the resting membrane potential and excitability of invertebrate and vertebrate neurons.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25716181"}, {"offsetInBeginSection": 82, "offsetInEndSection": 208, "text": "Among these channels, the leak sodium channel NALCN plays a crucial role in the maintenance of the resting membrane potential.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31409833"}, {"offsetInBeginSection": 124, "offsetInEndSection": 247, "text": "The NALCN channel mediates sodium leak currents, which positively adjust resting membrane potential towards depolarization.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33273469"}, {"offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "The NALCN/NCA ion channel is a cation channel related to voltage-gated sodium and calcium channels. NALCN has been reported to be a sodium leak channel with a conserved role in establishing neuronal resting membrane potential, but its precise cellular role and regulation are unclear.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968387"}]}
+{"question_id": "660d70b3fdcbea915f00003f", "question": "Cancer risk in transgender individuals.", "answer": "Transgender people have higher rates of HIV and HPV infection rates, and are thus at higher risk of cancer associated with these viruses. They might also be at higher risk of cancer associated with hormone replacement. Barriers to screening and treatment might translate into worse outcomes.", "relevant_passage_ids": ["36757703", "31027551", "36789830", "30107028", "28486701", "32304336", "37114110", "29974289", "31562693", "36006769", "34157213", "30741605", "32939016", "24010586", "16804313", "37885620", "21831723"], "type": "summary", "snippets": [{"offsetInBeginSection": 12, "offsetInEndSection": 192, "text": "Transgender and gender-diverse individuals face unique challenges, including barriers to health care access and inequities in treatment, that may influence cancer risk and outcomes", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36757703"}, {"offsetInBeginSection": 799, "offsetInEndSection": 959, "text": "Transgender and gender-diverse individuals were less likely to adhere to cancer screening programs and had a higher incidence of HIV- and HPV-associated cancers", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36757703"}, {"offsetInBeginSection": 1290, "offsetInEndSection": 1523, "text": "Discrimination, discomfort caused by gender-labeled oncological services, stigma, and lack of cultural sensitivity of health care practitioners were other barriers met by transgender and gender-diverse persons in the oncology setting", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36757703"}, {"offsetInBeginSection": 1551, "offsetInEndSection": 1679, "text": "The findings suggest that transgender and gender-diverse peoples' needs in the cancer care continuum are not optimally addressed", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36757703"}, {"offsetInBeginSection": 177, "offsetInEndSection": 391, "text": "Because the risk on certain types of cancer differs between men and women, and some of these differences are attributed to exposure to sex hormones, the cancer risk may be altered in transgender people receiving HT", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31027551"}, {"offsetInBeginSection": 789, "offsetInEndSection": 1102, "text": "for transgender patients, it is imperative to understand where a patient is in their gender transition and how hormonal and/or surgical therapies affect their cancer risk and screening. The aim of this article is to describe appropriate cancer screening practices and important care considerations for the primary", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30741605"}, {"offsetInBeginSection": 1651, "offsetInEndSection": 1832, "text": "ng probability of breast cancer in sexual minority can be found. Breast cancer screening program should be offered to all transgender individuals according to national guidelines. V", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29974289"}, {"offsetInBeginSection": 1247, "offsetInEndSection": 1528, "text": "cancer screening based on estrogen therapy, pedigree symbol use, and testing of a minor prior to hormone therapy. This study adds to the growing literature that highlights the educational needs specific to genetic counseling to promote individualized care for transgender patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31562693"}, {"offsetInBeginSection": 0, "offsetInEndSection": 640, "text": "Background: There is a recognized need for evidence to inform breast cancer screening guidelines and services for transgender people, who face barriers to accessing appropriate and inclusive health care.Aims: This review summarized evidence for breast cancer risk and screening guidelines in transgender individuals, including the potential impact of gender-affirming hormone therapy (GAHT); factors that may influence screening decision-making and behaviors; and considerations for providing culturally safe, high-quality screening services.Methods: A protocol was developed based on the Joanna Briggs Institute scoping review methodology.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37114110"}, {"offsetInBeginSection": 2925, "offsetInEndSection": 3243, "text": "Therefore, similar to cis-male patients who have received androgen deprivation therapy for prostate cancer, transgender patients on hormone therapy for gender affirmation may be at risk for both underrecognition and over-grading of prostate cancer, particularly if the pathologist is not aware of the clinical history.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36006769"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Male-to-female (MtF) transgender individuals are at risk for prostate cancer, although guidelines for screening and management in this population are not well established.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36006769"}, {"offsetInBeginSection": 624, "offsetInEndSection": 1033, "text": "The information in these publications were assimilated to produce a review of prostate cancer in transgender women.CONCLUSION: The risk of prostate cancer in transgender women who are not on gender-affirming hormone therapy (GAHT) or who have not had gender-affirming surgery (GAS) and gender non-conforming individuals (who may never commence GAHT or have GAS) is the same as that in the cis male population.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34157213"}, {"offsetInBeginSection": 535, "offsetInEndSection": 847, "text": "Three of the 7 patients diagnosed with prostate cancer had received different types of hormone therapy for gender affirmation before the diagnosis of prostate cancer, and in all 3 of these patients, there was histologic evidence of hormone therapy effect in both benign prostate tissue and/or the adenocarcinoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36006769"}, {"offsetInBeginSection": 2465, "offsetInEndSection": 2668, "text": "In the absence of hormone therapy, the morphology of prostatic adenocarcinoma in transgender patients shows classic morphologic features similar to those seen in cis-male patients not on hormone therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36006769"}, {"offsetInBeginSection": 1490, "offsetInEndSection": 1766, "text": "Three of the 4 patients who underwent radical prostatectomy had received gender-affirming hormone therapy before surgery, and all 3 of these specimens showed hormone therapy effect in non-neoplastic prostate tissue and focal hormone therapy effect in prostatic adenocarcinoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36006769"}, {"offsetInBeginSection": 765, "offsetInEndSection": 974, "text": "As providers are caring for transgender patients, it is imperative to understand where a patient is in their gender transition and how hormonal and/or surgical therapies affect their cancer risk and screening.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30741605"}, {"offsetInBeginSection": 559, "offsetInEndSection": 808, "text": "he main outcomes considered.RESULTS: FtM individuals had a higher risk of developing breast cancer in comparison to cisgender men [standardized incidence ratio (SIR) = 63.4; 95% confidence interval (CI), 32.2-124.9] but a lower risk than cisgender w", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36789830"}, {"offsetInBeginSection": 809, "offsetInEndSection": 1018, "text": "men (SIR = 0.42; 95% CI, 0.07-2.41). Similarly, MtF individuals were at higher risk of developing breast cancer in comparison to cisgender men (SIR = 22.5; 95% CI, 5.54-91.8) and at lower risk than cisgender w", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36789830"}, {"offsetInBeginSection": 505, "offsetInEndSection": 845, "text": "Incidence and breast cancer risk quantification were the main outcomes considered.RESULTS: FtM individuals had a higher risk of developing breast cancer in comparison to cisgender men [standardized incidence ratio (SIR) = 63.4; 95% confidence interval (CI), 32.2-124.9] but a lower risk than cisgender women (SIR = 0.42; 95% CI, 0.07-2.41).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36789830"}, {"offsetInBeginSection": 846, "offsetInEndSection": 1289, "text": "Similarly, MtF individuals were at higher risk of developing breast cancer in comparison to cisgender men (SIR = 22.5; 95% CI, 5.54-91.8) and at lower risk than cisgender women (SIR = 0.30; 95% CI, 0.22-0.42).CONCLUSION: In this systematic study and meta-analysis, we identified that FtM and MtF individuals are at substantially higher risk of developing breast cancer in comparison to cisgender men, though at lower risk than cisgender women.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36789830"}, {"offsetInBeginSection": 106, "offsetInEndSection": 206, "text": "The effects of gender-affirming hormone therapy (GAHT) on sex hormone-dependent tumours are unclear.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30107028"}, {"offsetInBeginSection": 0, "offsetInEndSection": 327, "text": "Transgender and gender diverse (TGD) adolescents and young adults (AYA) face heightened risks of cancer due to cissexism and transphobia in healthcare, low cancer screening rates, limited knowledge and awareness of cancer risk and screenings, poor healthcare experiences, and exposure to sexually transmitted infections (STIs).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37885620"}, {"offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Transgender (TG) individuals have higher rates of mortality associated with cancer diagnoses, in part due to avoidance of gender-assigned cancer screenings resulting in later stages at diagnosis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32304336"}, {"offsetInBeginSection": 1069, "offsetInEndSection": 1211, "text": "Evidence on rates of breast cancer screening among transgender people and the association between GAHT and breast cancer risk was inconclusive", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37114110"}, {"offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Transgender (TG) individuals have higher rates of mortality associated with cancer diagnoses, in part due to avoidance of gender-assigned cancer screenings resulting in later stages at diagnosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32304336"}, {"offsetInBeginSection": 177, "offsetInEndSection": 643, "text": "Because the risk on certain types of cancer differs between men and women, and some of these differences are attributed to exposure to sex hormones, the cancer risk may be altered in transgender people receiving HT. Although reliable epidemiologic data are sparse, the available data will be discussed in this article. Furthermore, recommendations for cancer screening and prevention will be discussed as well as whether to withdraw HT at time of a cancer diagnosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31027551"}, {"offsetInBeginSection": 1627, "offsetInEndSection": 2089, "text": "The incidental findings of high-risk lesions and carcinoma as well as the risk of cancer in residual breast tissue after chest-contouring surgery warrant the consideration of culturally sensitive routine breast cancer screening protocols for transgender men and masculine-centered gender nonconforming individuals. Long-term follow-up studies and molecular investigations are needed to understand the breast cancer risk of transgender individuals who receive TT.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32939016"}, {"offsetInBeginSection": 0, "offsetInEndSection": 495, "text": "Gender-affirming hormonal treatment (HT) in transgender people is considered safe in general, but the question regarding (long-term) risk on sex hormone-related cancer remains. Because the risk on certain types of cancer differs between men and women, and some of these differences are attributed to exposure to sex hormones, the cancer risk may be altered in transgender people receiving HT. Although reliable epidemiologic data are sparse, the available data will be discussed in this article.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31027551"}, {"offsetInBeginSection": 0, "offsetInEndSection": 392, "text": "Gender-affirming hormonal treatment (HT) in transgender people is considered safe in general, but the question regarding (long-term) risk on sex hormone-related cancer remains. Because the risk on certain types of cancer differs between men and women, and some of these differences are attributed to exposure to sex hormones, the cancer risk may be altered in transgender people receiving HT.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31027551"}, {"offsetInBeginSection": 177, "offsetInEndSection": 392, "text": "Because the risk on certain types of cancer differs between men and women, and some of these differences are attributed to exposure to sex hormones, the cancer risk may be altered in transgender people receiving HT.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31027551"}, {"offsetInBeginSection": 177, "offsetInEndSection": 495, "text": "Because the risk on certain types of cancer differs between men and women, and some of these differences are attributed to exposure to sex hormones, the cancer risk may be altered in transgender people receiving HT. Although reliable epidemiologic data are sparse, the available data will be discussed in this article.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31027551"}, {"offsetInBeginSection": 1627, "offsetInEndSection": 1941, "text": "The incidental findings of high-risk lesions and carcinoma as well as the risk of cancer in residual breast tissue after chest-contouring surgery warrant the consideration of culturally sensitive routine breast cancer screening protocols for transgender men and masculine-centered gender nonconforming individuals.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32939016"}, {"offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "INTRODUCTION: Transsexual people receive cross-sex hormones as part of their treatment, potentially inducing hormone-sensitive malignancies.AIM: To examine the occurrence of breast cancer in a large cohort of Dutch male and female transsexual persons, also evaluating whether the epidemiology accords with the natal se", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24010586"}, {"offsetInBeginSection": 254, "offsetInEndSection": 797, "text": "We report only the second case of ovarian cancer in a female-to-male transsexual while on androgen supplementation therapy. Staining of his tumor for androgen receptors showed abundant expression. Androgen supplementation in this population may be associated with an increased risk of both ovarian cancer and of endometrial cancer. Consideration for bilateral salpingo-oophorectomy as part of gender reassignment surgery should be given, especially in this poorly studied group of patients whose overall risk of ovarian cancer remains unknown.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16804313"}, {"offsetInBeginSection": 1019, "offsetInEndSection": 1241, "text": "men (SIR = 0.30; 95% CI, 0.22-0.42).CONCLUSION: In this systematic study and meta-analysis, we identified that FtM and MtF individuals are at substantially higher risk of developing breast cancer in comparison to cisgender", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36789830"}, {"offsetInBeginSection": 559, "offsetInEndSection": 1018, "text": "he main outcomes considered.RESULTS: FtM individuals had a higher risk of developing breast cancer in comparison to cisgender men [standardized incidence ratio (SIR) = 63.4; 95% confidence interval (CI), 32.2-124.9] but a lower risk than cisgender women (SIR = 0.42; 95% CI, 0.07-2.41). Similarly, MtF individuals were at higher risk of developing breast cancer in comparison to cisgender men (SIR = 22.5; 95% CI, 5.54-91.8) and at lower risk than cisgender w", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36789830"}, {"offsetInBeginSection": 355, "offsetInEndSection": 587, "text": "As cross-sex hormones administered for the purposes of gender affirmation may be delivered at high doses and over a period of decades, the carcinogenicity of hormonal therapy in transgender people is an area of considerable concern.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28486701"}, {"offsetInBeginSection": 601, "offsetInEndSection": 825, "text": "An accumulating body of data on breast cancer incidence in TG persons suggests higher than previously believed rates of breast cancer in TG women compared with cisgender men and risk correlating with duration of hormone use.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32304336"}, {"offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Testosterone is important for the development of secondary sexual characteristics in female-to-male (FtM) transsexuals, but it may increase breast cancer risk.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21831723"}, {"offsetInBeginSection": 294, "offsetInEndSection": 430, "text": "We describe 2 cases of breast cancers diagnosed in FtM transsexuals who have been treated with supraphysiological doses of testosterone.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21831723"}]}
+{"question_id": "65d372231930410b13000047", "question": "Does Lenvatinib plus pembrolizumab improve prognosis of advanced hepatocellular carcinoma?", "answer": "No. Lenvatinib plus pembrolizumab did not improve overall survival and progression-free survival versus lenvatinib plus placebo of advanced hepatocellular carcinoma patients.", "relevant_passage_ids": ["38039993"], "type": "yesno", "snippets": [{"offsetInBeginSection": 3603, "offsetInEndSection": 4010, "text": "INTERPRETATION: In earlier studies, the addition of pembrolizumab to lenvatinib as first-line therapy for advanced hepatocellular carcinoma has shown promising clinical activity; however, lenvatinib plus pembrolizumab did not meet prespecified significance for improved overall survival and progression-free survival versus lenvatinib plus placebo. Our findings do not support a change in clinical practice.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38039993"}]}
+{"question_id": "660998d1fdcbea915f000013", "question": "What molecular subtypes of colon cancer are associated to smoking?", "answer": "Cigarette smoking are associated with the MSI-high, CIMP-positive, and BRAF mutation-positive colorectal cancer subtypes.", "relevant_passage_ids": ["20587792", "34377935", "32773458", "34548904", "25280443", "32225169", "22349355", "19755657", "28921583", "37352389", "33442661", "23788674", "29438474", "25587051", "27780077", "23794399", "17148775", "37529669", "26064214", "23539450", "22712570", "7672889", "28275039", "28321693", "28748988"], "type": "list", "snippets": [{"offsetInBeginSection": 2679, "offsetInEndSection": 2800, "text": "cigarette smoking was associated with the MSI-high, CIMP-positive, and BRAF mutation-positive colorectal cancer subtypes,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20587792"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1483, "text": "BACKGROUND: Smoking and alcohol increase risk for colorectal malignancies. However, colorectal cancer (CRC) is a heterogenic disease and associations with the molecular pathological pathways are unclear.METHODS: This population-based case-control study includes 2444 cases with first-diagnosis CRC and 2475 controls. Tumour tissue was analysed for MSI (microsatellite instability), CIMP (CpG island methylator phenotype), BRAF (B-Raf proto-oncogene serine/threonine kinase gene) and KRAS (Kirsten rat sarcoma viral oncogene homologue gene) mutations. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated for associations between alcohol and smoking and CRC molecular subtypes and pathways.RESULTS: Current smoking showed higher ORs for MSI-high (OR\u2009=\u20092.79, 95% CI: 1.86-4.18) compared to MSS (OR\u2009=\u20091.41, 1.14-1.75, p-heterogeneity (p-het)\u2009=\u20090.001), BRAF-mutated (mut) (OR\u2009=\u20092.40, 1.41-4.07) compared to BRAF-wild type (wt) (OR\u2009=\u20091.52, 1.24-1.88, p-het\u2009=\u20090.074), KRAS-wt (OR\u2009=\u20091.70, 1.36-2.13) compared to KRAS-mut (OR\u2009=\u20091.26, 0.95-1.68, p-het\u2009=\u20090.039) and CIMP-high (OR\u2009=\u20092.01, 1.40-2.88) compared to CIMP-low/negative CRC (OR\u2009=\u20091.50, 1.22-1.85, p-het=0.101). Current smoking seemed more strongly associated with sessile serrated pathway (CIMP-high\u2009+\u2009BRAF-mut; OR\u2009=\u20092.39, 1.27-4.52) than with traditional pathway CRC (MSS\u2009+\u2009CIMP-low/negative\u2009+\u2009BRAF-wt; OR\u2009=\u20091.50, 1.16-1.94) and no association was observed with alternate pathway CRC (MSS\u2009+\u2009CIMP-low/negative\u2009+\u2009KRA", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32225169"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1454, "text": "Background: Colorectal cancer (CRC) is a heterogeneous disease that can develop via 3 major pathways: conventional, serrated, and alternate. We aimed to examine whether the risk factor profiles differ according to pathway-related molecular subtypes.Methods: We examined the association of 24 risk factors with 4 CRC molecular subtypes based on a combinatorial status of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and BRAF and KRAS mutations by collecting data from 2 large US cohorts. We used inverse probability weighted duplication-method Cox proportional hazards regression to evaluate differential associations across subtypes.Results: We documented 1175 CRC patients with molecular subtype data: subtype 1 (n\u2009=\u2009498; conventional pathway; non-MSI-high, CIMP-low or negative, BRAF-wild-type, KRAS-wild-type), subtype 2 (n\u2009=\u2009138; serrated pathway; any MSI status, CIMP-high, BRAF-mutated, KRAS-wild-type), subtype 3 (n\u2009=\u2009367; alternate pathway; non-MSI-high, CIMP-low or negative, BRAF-wild-type, KRAS-mutated), and subtype 4 (n\u2009=\u2009172; other marker combinations). Statistically significant heterogeneity in associations with CRC subtypes was found for age, sex, and smoking, with a higher hazard ratio (HR) observed for the subtype 2 (HR per 10\u2009years of age = 2.64, 95% CI = 2.13 to 3.26; HR for female = 2.65, 95% CI = 1.60 to 4.39; HR per 20-pack-year of smoking = 1.29, 95% CI = 1.14 to 1.45) than other CRC subtypes (", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33442661"}, {"offsetInBeginSection": 1524, "offsetInEndSection": 1768, "text": "The association was also stronger in tumors that were CIMP positive, MSI high, or KRAS wild type when combined (P difference < .001).Conclusion: Smoking was associated with differential risk of CRC subtypes defined by molecular characteristics.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34377935"}, {"offsetInBeginSection": 1124, "offsetInEndSection": 1747, "text": "An increase in carcinogenic bacteria (genus Escherichia shigella) and a decrease in probiotics (family Lachnospiraceae and Ruminococcaceae) in type II tumors may drive disease progression by upregulating oncogenic signaling pathways and inflammatory/oxidative stress response pathways, as well as protein phospholipase D1/2, cytochrome C, and prostaglandin-endoperoxide synthase 2 expression.CONCLUSIONS: Smoking was associated with a higher odds of type II colorectal neoplasms but not type I tumors, supporting a potential role for the gut microbiota in mediating the association between smoking and colorectal neoplasms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37529669"}, {"offsetInBeginSection": 1062, "offsetInEndSection": 1211, "text": "The associations differed statistically significantly between all molecular subtypes, which was the most statistically significant for CIMP and BRAF.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34377935"}, {"offsetInBeginSection": 69, "offsetInEndSection": 339, "text": "Previous studies suggested this association may be restricted to certain molecular subtypes of CRC, but large-scale comprehensive analysis is lacking.Methods: A total of 9789 CRC cases and 11 231 controls of European ancestry from 11 observational studies were included.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34377935"}, {"offsetInBeginSection": 861, "offsetInEndSection": 1061, "text": "All statistical tests were 2-sided and adjusted for Bonferroni correction.Results: Heavier smoking was associated with higher risk of CRC overall and stratified by individual markers (P trend < .001).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34377935"}, {"offsetInBeginSection": 1212, "offsetInEndSection": 1523, "text": "Compared with never-smokers, smokers in the fourth quartile of pack-years had a 90% higher risk of CIMP-positive CRC (odds ratio\u2009=\u20091.90, 95% confidence interval = 1.60 to 2.26) but only 35% higher risk for CIMP-negative CRC (odds ratio\u2009=\u20091.35, 95% confidence interval = 1.22 to 1.49; P difference = 2.1 x 10-6).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34377935"}, {"offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Association Between Smoking and Molecular Subtypes of Colorectal Cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34377935"}, {"offsetInBeginSection": 934, "offsetInEndSection": 1337, "text": "ompared with current smokers. Smoking was strongly associated with the risk of CRC, characterized by high CpG island methylator phenotype (RR 1.42; 95% CI 1.20-1.67; number of studies [n] = 4), BRAF mutation (RR 1.63; 95% CI 1.23-2.16; n = 4), or high microsatellite instability (RR 1.56; 95% CI 1.32-1.85; n = 8), but not characterized by KRAS (RR 1.04; 95% CI 0.90-1.20; n = 5) or TP53 (RR 1.13; 95% C", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32773458"}, {"offsetInBeginSection": 825, "offsetInEndSection": 1108, "text": "valuate the association.RESULTS: Smoking showed a significantly positive correlation with P53 mutation (exons 4 to 8), BRAF (codon 600) mutation, MSI positivity, and CIMP positivity, with ORs of 1.25 (95% CI: 1.07-1.45), 1.41 (95% CI: 1.18-1.68), 1.28 (95% CI: 1.12-1.47), and 1.23 (", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26064214"}, {"offsetInBeginSection": 727, "offsetInEndSection": 1096, "text": "Compared with current smoking, 10-19, 20-39, and \u226540 years of smoking cessation were associated with a lower risk of CIMP-high colorectal cancer, with multivariate hazard ratios (95% confidence intervals) of 0.53 (0.29, 0.95), 0.52 (0.32, 0.85), and 0.50 (0.27, 0.94), respectively (Ptrend = 0.001), but not with the risk of CIMP-low/CIMP-negative cancer (Ptrend = 0.25", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23788674"}, {"offsetInBeginSection": 1367, "offsetInEndSection": 1529, "text": "Cigarette smoking was associated with lower overall survival, with suggestive evidence of worse survival for BRAF mutated CRC, but not with CRC-specific survival.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28921583"}, {"offsetInBeginSection": 1283, "offsetInEndSection": 1549, "text": ". Risk factors for CIMP-high-serrated lesions included Caucasian race, current smoking status, and a history of polyps, whereas for serrated lesions with mutant BRAF, the significant risk factors were male sex, current smoking status, obesity, and a history of polyp", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23539450"}, {"offsetInBeginSection": 887, "offsetInEndSection": 1157, "text": "SNP associations observed for colon cancer were: VEGFA rs2010963 with CIMP+ colon tumors; FLT1 rs4771249 and rs7987649 with TP53; FLT1 rs3751397, rs7337610, rs7987649, and rs9513008 and KDR rs10020464, rs11941492, and rs12498529 with MSI+ and CIMP+/KRAS2-mutated tumors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23794399"}, {"offsetInBeginSection": 964, "offsetInEndSection": 1517, "text": "Smoking was strongly associated with the risk of CRC, characterized by high CpG island methylator phenotype (RR 1.42; 95% CI 1.20-1.67; number of studies [n] = 4), BRAF mutation (RR 1.63; 95% CI 1.23-2.16; n = 4), or high microsatellite instability (RR 1.56; 95% CI 1.32-1.85; n = 8), but not characterized by KRAS (RR 1.04; 95% CI 0.90-1.20; n = 5) or TP53 (RR 1.13; 95% CI 0.99-1.29; n = 5) mutations.DISCUSSION: Cigarette smoking increases the risk of CRC in a dose-dependent manner with intensity and duration, and quitting smoking reduces CRC risk.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32773458"}, {"offsetInBeginSection": 1164, "offsetInEndSection": 1554, "text": "Alcohol intake was associated with a modest increase in risk for CRC overall (OR, 1.21; 95% CI, 1.03-1.44 for 12+ drinks per week versus nondrinkers), with more marked increases in risk for MSI-L CRC (OR, 1.85; 95% CI, 1.06-3.24) and rectal cancer (OR, 1.48; 95% CI, 1.08-2.02).CONCLUSIONS: We found associations between cigarette smoking and increased risks of rectal cancer and MSI-H CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19755657"}, {"offsetInBeginSection": 1771, "offsetInEndSection": 2203, "text": "None of the smoking variables were significantly associated with KRAS mutation-positive CRCs (overall or stratified by anatomic subsite).CONCLUSIONS: Data from this prospective study of older women demonstrate differential associations between cigarette smoking and CRC subtypes defined by KRAS mutation status, and are consistent with the hypothesis that smoking adversely affects the serrated pathway of colorectal carcinogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22349355"}, {"offsetInBeginSection": 1532, "offsetInEndSection": 1719, "text": "These molecular pathological epidemiology data suggest a protective effect of smoking cessation on a DNA methylation-related carcinogenesis pathway leading to CIMP-high colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23788674"}, {"offsetInBeginSection": 1029, "offsetInEndSection": 1334, "text": "Our study helps to better define the molecular effects of representative carcinogens from smoking and red/processed meat in normal colon epithelial cells and in the etiology of the MSI-H subtype of CRC, and suggests an overlap between molecular mechanisms involved in inherited and environmental CRC risk.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34548904"}, {"offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Background: Smoking is associated with colorectal cancer (CRC) risk. Previous studies suggested this association may be restricted to certain molecular subtypes of CRC, but large-scale comprehensive analysis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34377935"}, {"offsetInBeginSection": 1181, "offsetInEndSection": 1719, "text": "Differential associations between smoking cessation and cancer risks by microsatellite instability (Pheterogeneity = 0.02), DNMT3B expression (Pheterogeneity = 0.03), and BRAF (Pheterogeneity = 0.10) status appeared to be driven by the associations of CIMP-high cancer with microsatellite instability-high, DNMT3B-positive, and BRAF-mutated cancers. These molecular pathological epidemiology data suggest a protective effect of smoking cessation on a DNA methylation-related carcinogenesis pathway leading to CIMP-high colorectal cancer. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23788674"}, {"offsetInBeginSection": 283, "offsetInEndSection": 1130, "text": "cations to survival.METHODS: Participants in the population-based Seattle Colon Cancer Family Registry were diagnosed with invasive CRC from 1998 through 2007 in western Washington State (N = 2706), and followed for survival through 2012. Tumor samples were collected from 2050 participants and classified into 5 subtypes based on combinations of tumor markers: type 1 (microsatellite instability [MSI]-high, CpG island methylator phenotype [CIMP] -positive, positive for BRAF mutation, negative for KRAS mutation); type 2 (microsatellite stable [MSS] or MSI-low, CIMP-positive, positive for BRAF mutation, negative for KRAS mutation); type 3 (MSS or MSI low, non-CIMP, negative for BRAF mutation, positive for KRAS mutation); type 4 (MSS or MSI-low, non-CIMP, negative for mutations in BRAF and KRAS); and type 5 (MSI-high, non-CIMP, negative for", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25280443"}, {"offsetInBeginSection": 669, "offsetInEndSection": 903, "text": "Importantly, these subtypes are differentially distributed between right- and left-sided CRCs, with greater proportions of the \"microsatellite unstable/immune\" CMS1 and the \"metabolic\" CMS3 subtypes found in right-sided colon cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28275039"}, {"offsetInBeginSection": 1171, "offsetInEndSection": 1578, "text": "LTS: Multiple smoking variables were associated with increased risk for KRAS mutation-negative tumors, including age at initiation (P=0.02), average number of cigarettes per day (P=0.01), cumulative pack-years (P=0.05), and induction period (P=0.04), with the highest point estimate observed for women who smoked \u226540 cigarettes per day on average (RR=2.38; 95% CI=1.25-4.51; compared with never smokers). Fu", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22349355"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Smoking, alcohol consumption and colorectal cancer risk by molecular pathological subtypes and pathways.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32225169"}, {"offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "The effect of duration of cigarette smoking cessation on colorectal cancer risk by molecular subtypes remains unclear", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23788674"}, {"offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Smoking and Colorectal Cancer Risk, Overall and by Molecular Subtypes: A Meta-Analysis.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32773458"}, {"offsetInBeginSection": 143, "offsetInEndSection": 289, "text": "Recent Western studies have proposed that the association between smoking and colorectal cancer is restricted to specific tumor molecular subtypes", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37352389"}, {"offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Risk Factors and Incidence of Colorectal Cancer According to Major Molecular Subtypes.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33442661"}, {"offsetInBeginSection": 1453, "offsetInEndSection": 1669, "text": "Limited evidence for associations between other lifestyle factors and CRC by MSI status exists.Conclusions: Lifestyle factors, such as HRT and smoking are differentially associated with the risk of MSI-H and MSS CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29438474"}, {"offsetInBeginSection": 1527, "offsetInEndSection": 1771, "text": " association was also stronger in tumors that were CIMP positive, MSI high, or KRAS wild type when combined (P difference < .001).Conclusion: Smoking was associated with differential risk of CRC subtypes defined by molecular characteristics. He", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34377935"}, {"offsetInBeginSection": 0, "offsetInEndSection": 338, "text": "Background: Smoking is associated with colorectal cancer (CRC) risk. Previous studies suggested this association may be restricted to certain molecular subtypes of CRC, but large-scale comprehensive analysis is lacking.Methods: A total of 9789 CRC cases and 11 231 controls of European ancestry from 11 observational studies were included", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34377935"}, {"offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Background: Smoking is associated with colorectal cancer (CRC) risk. Previous studies suggested this association may be restricted to certain molecular subtypes of CRC, but large-scale comprehensive analysis is lacking", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34377935"}, {"offsetInBeginSection": 1663, "offsetInEndSection": 1773, "text": "sion: Smoking was associated with differential risk of CRC subtypes defined by molecular characteristics. Heav", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34377935"}, {"offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Age at diagnosis, obesity, smoking, and molecular subtypes in muscle-invasive bladder cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28321693"}, {"offsetInBeginSection": 1132, "offsetInEndSection": 1282, "text": "cular subtypes, which was the most statistically significant for CIMP and BRAF. Compared with never-smokers, smokers in the fourth quartile of pack-ye", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34377935"}, {"offsetInBeginSection": 1903, "offsetInEndSection": 2417, "text": "g (odds ratio [OR] = 12.1), bladder (OR = 2.4), oesophagus (OR = 2.4), stomach (OR = 1.7), and pancreas (OR = 1.6). Population attributable risk percentages due to smoking were 90% for lung, 53% for bladder, 54% for oesophagus, 35% for stomach, and 33% for pancreas.CONCLUSIONS: Of the 21 types of cancer examined, the following were associated with smoking among men in Montreal: lung (including all major histological subtypes), bladder (and its main histological subtypes), oesophagus, stomach and pancreas. Smo", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7672889"}, {"offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "BACKGROUND: The CpG island methylator phenotype (CIMP) represents a subset of colorectal cancers characterized by widespread aberrant DNA hypermethylation a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25587051"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1454, "text": "BACKGROUND: Colorectal cancer (CRC) is an heterogeneous disease. Three carcinogenic pathways determine its molecular profile: microsatellite instability (MSI), chromosomal instability (CIN) and CpG island methylator phenotype (CIMP). Based on the new molecular classification, four consensus CRC molecular subtypes (CMS) are established, which are related to clinical, pathological and biological characteristics of the tumor.AIM: To classify Chilean patients with sporadic CRC according to the new consensus molecular subtypes of carcinogenic pathways.MATERIAL AND METHODS: Prospective analytical study of 53 patients with a mean age of 70 years (55% males) with CRC, operated at a private clinic, without neoadjuvant treatment. From normal and tumor tissue DNA of each patient, CIN, MSI and CIMP were analyzed. Combining these variables, tumors were classified as CMS1/MSI-immune, CMS2/canonical, CMS3/metabolic and CMS4/mesenchymal.RESULTS: CMS1 tumors (19%) were located in the right colon, were in early stages, had MMR complex deficiencies and 67% had an activating mutation of the BRAF oncogene. CMS2 tumors (31%) were located in the left colon, had moderate differentiation, absence of vascular invasion, lymphatic and mucin. CMS3 tumors (29%) were also left-sided, with absence of vascular and lymphatic invasion, and 29% had an activating mutation of the KRAS oncogene. CMS4 tumors (21%) showed advanced stages and presence of metastases.CONCLU", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28748988"}, {"offsetInBeginSection": 0, "offsetInEndSection": 2880, "text": "BACKGROUND: Cigarette smoking is an established risk factor for colorectal cancer. Because colorectal carcinogenesis is a heterogeneous process, we investigated whether cigarette smoking is differentially associated with molecularly defined subtypes of colorectal cancer.METHODS: We evaluated associations between smoking and incident colorectal cancer, overall and by microsatellite instability (MSI) phenotype (MSI-high vs MSI-low or microsatellite stable), CpG island methylator phenotype (CIMP positive or CIMP negative), and BRAF mutation status (BRAF mutation positive or BRAF mutation negative), among 37 399 participants in a population-based cohort study (the Iowa Women's Health Study). Cigarette smoking (and other exposures) was assessed by self-report at baseline in 1986, including smoking status (never and ever [former or current]), age at initiation, total duration, average number of cigarettes smoked per day, cumulative pack-years, and induction period. Vital status and state of residence were determined by mailed follow-up questionnaires in 1987, 1989, 1992, and 1997 and by linkage to Iowa death certificate records. Nonrespondents were checked via the National Death Index to identify descendants. Participants with newly diagnosed (ie, incident) colorectal cancer were identified through annual linkage with the Iowa Cancer Registry. Archived paraffin-embedded tumor tissue specimens were obtained for 555 patients with colorectal cancer who were diagnosed from January 1, 1986, through December 31, 2002, and MSI status, CIMP status, and BRAF status were determined. Multivariable Cox regression models were fit to estimate relative risks (RRs) and 95% confidence intervals (CIs).RESULTS: Ever-smokers were at moderately increased risk for incident colorectal cancer (RR = 1.19, 95% CI = 1.05 to 1.35) compared with never-smokers. Higher risk estimates were observed for current smokers with MSI-high tumors (RR = 1.99, 95% CI = 1.26 to 3.14), CIMP-positive tumors (RR = 1.88, 95% CI = 1.22 to 2.90), and BRAF mutation-positive tumors (RR = 1.92, 95% CI = 1.22 to 3.02). Other smoking-related variables (ie, age at initiation, total duration, average number of cigarettes smoked per day, cumulative pack-years, and induction period) were also associated with MSI-high, CIMP-positive, and BRAF mutation-positive tumor subtypes. Conversely, cigarette smoking status (ever vs never) was not associated with the MSI-low or microsatellite stable (RR = 1.00, 95% CI = 0.79 to 1.25), CIMP-negative (RR = 1.02, 95% CI = 0.81 to 1.30), or BRAF mutation-negative subtypes (RR = 1.00, 95% CI = 0.65 to 1.27).CONCLUSIONS: In this prospective study of older women, cigarette smoking was associated with the MSI-high, CIMP-positive, and BRAF mutation-positive colorectal cancer subtypes, which indicates that epigenetic modification may be functionally involved in sm", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20587792"}, {"offsetInBeginSection": 0, "offsetInEndSection": 964, "text": "Background: Smoking is associated with colorectal cancer (CRC) risk. Previous studies suggested this association may be restricted to certain molecular subtypes of CRC, but large-scale comprehensive analysis is lacking.Methods: A total of 9789 CRC cases and 11 231 controls of European ancestry from 11 observational studies were included. We harmonized smoking variables across studies and derived sex study-specific quartiles of pack-years of smoking for analysis. Four somatic colorectal tumor markers were assessed individually and in combination, including BRAF mutation, KRAS mutation, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI) status. A multinomial logistic regression analysis was used to assess the association between smoking and risk of CRC subtypes by molecular characteristics, adjusting for age, sex, and study. All statistical tests were 2-sided and adjusted for Bonferroni correction.Results: Heavier smoking was ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34377935"}, {"offsetInBeginSection": 784, "offsetInEndSection": 1133, "text": "risk of certain types of CRC. We observed an association between pack-years of smoking and rectal cancer [odds ratio (OR), 1.85; 95% confidence interval (CI), 1.23-2.79 for >40 pack-years versus nonsmokers; P(trend) = 0.03], and there was an increased risk of MSI-H CRC with increasing duration of smoking (OR, 1.94; 95% CI, 1.09-3.46 for >30 years ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19755657"}, {"offsetInBeginSection": 0, "offsetInEndSection": 483, "text": "The effect of duration of cigarette smoking cessation on colorectal cancer risk by molecular subtypes remains unclear. Using duplication-method Cox proportional-hazards regression analyses, we examined associations between duration of smoking cessation and colorectal cancer risk according to status of CpG island methylator phenotype (CIMP), microsatellite instability, v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation, or DNA methyltransferase-3B (DNMT3B) expression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23788674"}, {"offsetInBeginSection": 663, "offsetInEndSection": 1157, "text": "Based on ARTP results, FLT1 was significantly associated with risk of colon cancer (P(ARTP) = 0.045) and VEGFA was significantly associated with rectal cancer (P(ARTP) = 0.036). After stratifying by tumor molecular subtype, SNP associations observed for colon cancer were: VEGFA rs2010963 with CIMP+ colon tumors; FLT1 rs4771249 and rs7987649 with TP53; FLT1 rs3751397, rs7337610, rs7987649, and rs9513008 and KDR rs10020464, rs11941492, and rs12498529 with MSI+ and CIMP+/KRAS2-mutated tumors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23794399"}]}
+{"question_id": "660877c8fdcbea915f000008", "question": "What part of the cell is mitophagy associated with?", "answer": "Mitophagy, or selective autophagy of mitochondria, is an essential pathway to preserve mitochondrial homeostasis by clearing up damaged mitochondria", "relevant_passage_ids": ["37488884", "37549565", "37862201", "33476770", "31550441", "26085571", "36860818", "36974405", "34975548", "25753537", "36092697", "33922020", "34688664", "32587855", "33570005", "32454052", "36625039", "28976890", "35850516", "36740450", "25470007", "30113005", "36283334", "37192628", "37993864", "37678420", "38093134", "31704095", "31776996", "33239048", "36982862", "32131138", "28368777", "25634658", "28324490", "36909283", "21126205", "34099564", "35691026", "34060004", "31956306", "28576471", "34229552", "32820310", "35096821", "29115402", "23985961", "25437922", "34291135"], "type": "factoid", "snippets": [{"offsetInBeginSection": 360, "offsetInEndSection": 510, "text": "Mitophagy, or selective autophagy of mitochondria, is an essential pathway to preserve mitochondrial homeostasis by clearing up damaged mitochondria. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37488884"}, {"offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Mitophagy is an essential physiological process that eliminates damaged mitochondria via lysosomes. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37549565"}, {"offsetInBeginSection": 95, "offsetInEndSection": 250, "text": "Mitophagy selectively clears damaged or dysfunctional mitochondria through autophagic machinery to maintain mitochondrial quality control and homeostasis. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37862201"}, {"offsetInBeginSection": 9, "offsetInEndSection": 133, "text": "increasing evidence that mitophagy, a specialized form of autophagy to degrade and clear long-lived or damaged mitochondria,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34229552"}, {"offsetInBeginSection": 1080, "offsetInEndSection": 1298, "text": "(I) turnover of mitochondria via mitophagy (II) turnover of several vesicular structures via macroautophagy or chaperone-mediated autophagy or (III) general lysosome function. This article is part of a special issue on", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26223426"}, {"offsetInBeginSection": 491, "offsetInEndSection": 671, "text": "Mitochondrial autophagy (mitophagy) is the process through which defective mitochondria are removed from the cell by internalisation into autophagosomes which fuse with a lysosome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36860818"}, {"offsetInBeginSection": 129, "offsetInEndSection": 309, "text": "Through mitophagy (a selective type of autophagy that promotes mitochondrial proteostasis) cells keep a healthy pool of mitochondria, and prevent oxidative stress and inflammation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36092697"}, {"offsetInBeginSection": 340, "offsetInEndSection": 429, "text": "Clearance of bulk mitochondria occurs via a selective form of autophagy termed mitophagy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34688664"}, {"offsetInBeginSection": 378, "offsetInEndSection": 492, "text": "Excessive and dysfunctional/damaged mitochondria are degraded by selective autophagic pathways known as mitophagy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33922020"}, {"offsetInBeginSection": 431, "offsetInEndSection": 604, "text": "Mitophagy, a selective autophagy of mitochondria, can efficiently degrade, remove and recycle the malfunctioning or damaged mitochondria, and is crucial for quality control.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32587855"}, {"offsetInBeginSection": 243, "offsetInEndSection": 424, "text": "Selective autophagic clearance of flawed mitochondria, a process termed mitophagy, is one of the most prominent mechanisms through which cells maintain a healthy mitochondrial pool.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33570005"}, {"offsetInBeginSection": 197, "offsetInEndSection": 323, "text": "Selective autophagy of mitochondria, id est mitophagy, is one of the cellular mechanisms controlling mitochondria homeostasis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32454052"}, {"offsetInBeginSection": 163, "offsetInEndSection": 282, "text": "Mitophagy is a mechanism by which cells selectively wrap and degrade damaged mitochondria to maintain cell homeostasis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36625039"}, {"offsetInBeginSection": 464, "offsetInEndSection": 568, "text": "One critical level of mitochondrial quality control is the removal of damaged mitochondria by mitophagy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28976890"}, {"offsetInBeginSection": 615, "offsetInEndSection": 778, "text": "Mitophagy and mitochondrial-specific autophagy play an important role in maintenance of neuronal health through the removal of dysfunctional and aged mitochondria.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35850516"}, {"offsetInBeginSection": 1664, "offsetInEndSection": 1740, "text": "Colocalization of mitochondria and lysosomes indirectly indicated mitophagy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36740450"}, {"offsetInBeginSection": 348, "offsetInEndSection": 493, "text": "As a part of mitochondrial quality control, the aged and damaged mitochondria are removed through a selective mode of autophagy called mitophagy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33476770"}, {"offsetInBeginSection": 706, "offsetInEndSection": 947, "text": "This unique sensing property was successfully applied to the ratiometric fluorescence imaging of autolysosome formation in selective mitochondrial autophagy (mitophagy), which highlights the utility of this novel probe in autophagy research.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25470007"}, {"offsetInBeginSection": 283, "offsetInEndSection": 445, "text": "ys including autophagy. Mitochondria and mitochondrial autophagy play a vital role in cellular health and failure of these pathways can have a devastating effect ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30113005"}, {"offsetInBeginSection": 144, "offsetInEndSection": 317, "text": "Mitophagy is the process by which autophagy causes disruption inside mitochondria and the total removal of damaged or stressed mitochondria, hence enhancing cellular health.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36974405"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Mitophagy plays an important role in mitochondrial homeostasis by selective degradation of mitochondria.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37192628"}, {"offsetInBeginSection": 225, "offsetInEndSection": 390, "text": "It interacts with the Atg11 protein to initiate mitophagy and with the Atg8 protein to ensure the engulfment of mitochondria into the autophagosomes for elimination.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36283334"}, {"offsetInBeginSection": 1700, "offsetInEndSection": 1981, "text": "Rescue experiments using an AMPK pathway inhibitor (compound C) and an autophagy inhibitor (3-methyladenine) revealed that excessive mitophagy was induced through AMPK/ULK1 pathway activation, worsening mitochondrial damage and subsequent cell death in differentiated SH-SY5Y cells", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37993864"}, {"offsetInBeginSection": 1539, "offsetInEndSection": 1628, "text": "Mitochondria were reduced, and mitophagy was inhibited in aortic cells of the model group", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37678420"}, {"offsetInBeginSection": 579, "offsetInEndSection": 798, "text": "In mitofissin-deficient cells, a part of the mitochondria is recognized by the mitophagy machinery as cargo but cannot be enwrapped by the autophagosome precursor, the phagophore, due to a lack of mitochondrial fission.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37192628"}, {"offsetInBeginSection": 105, "offsetInEndSection": 260, "text": "During mitophagy, mitochondria should be fragmented to allow engulfment within autophagosomes, whose capacity is exceeded by the typical mitochondria mass.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37192628"}, {"offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Mitophagy, a form of selective autophagy, plays an essential role to maintain a population of healthy and functional mitochondria for normal cellular metabolism.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38093134"}, {"offsetInBeginSection": 280, "offsetInEndSection": 400, "text": "Damaged or unwanted mitochondria are selectively removed by mitophagy, which is a crucial determinant of cell viability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34975548"}, {"offsetInBeginSection": 1018, "offsetInEndSection": 1211, "text": "Mitochondria are eliminated by mitophagy. This is a macroautophagy pathway consisting in the engulfment of mitochondria into a double-membrane structure called autophagosome before degradation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29311991"}, {"offsetInBeginSection": 419, "offsetInEndSection": 499, "text": "mitophagy (a specific form of autophagy that removes dysfunctional mitochondria)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34099564"}, {"offsetInBeginSection": 1028, "offsetInEndSection": 1261, "text": " Mitochondria may represent a proximal target of HO-1/CO action. HO-1 may localize to mitochondria in response to stress, while CO can moderate mitochondrial dysfunction and regulate mitochondrial autophagy (mitophagy) and biogenesis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31704095"}, {"offsetInBeginSection": 445, "offsetInEndSection": 536, "text": "Mitophagy is a process for selective degradation of mitochondria, which is well documented.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31776996"}, {"offsetInBeginSection": 375, "offsetInEndSection": 511, "text": "The elimination of dysfunctional mitochondria may function as an effective way employed by mitophagy to keep the immune system in check.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33239048"}, {"offsetInBeginSection": 707, "offsetInEndSection": 918, "text": "In contrast, fission segregates damaged mitochondria from intact and healthy counterparts and is followed by selective clearance of the damaged mitochondria via mitochondrial specific autophagy, i.e., mitophagy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36982862"}, {"offsetInBeginSection": 412, "offsetInEndSection": 573, "text": "To maintain its quantity and quality, mitochondria undergo multiple processes such as fission, fusion, and mitophagy to eliminate or replace damaged mitochondria", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32131138"}, {"offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Mitophagy is a highly specialized process to remove dysfunctional or superfluous mitochondria through the macroautophagy/autophagy pathway, aimed at protecting cells from the damage of disordered mitochondrial metabolism and apoptosis induction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28368777"}, {"offsetInBeginSection": 98, "offsetInEndSection": 195, "text": "Damaged mitochondria can be degraded by a selective type of autophagy, which is termed mitophagy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25634658"}, {"offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "PINK1 and BECN1 relocalize at mitochondria-associated membranes during mitophagy and promote ER-mitochondria tethering and autophagosome formation.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28368777"}, {"offsetInBeginSection": 0, "offsetInEndSection": 335, "text": "Aberrant mitochondrial function is associated with many neurological diseases. Mitophagy is a key mechanism for the elimination of damaged mitochondria and maintenance of mitochondrial homeostasis. Induced pluripotent stem (iPS) cell technologies developed over the last decade have allowed us to analyze functions of the human neuron.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28324490"}, {"offsetInBeginSection": 79, "offsetInEndSection": 335, "text": "Mitophagy is a key mechanism for the elimination of damaged mitochondria and maintenance of mitochondrial homeostasis. Induced pluripotent stem (iPS) cell technologies developed over the last decade have allowed us to analyze functions of the human neuron.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28324490"}, {"offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Mitochondrial dysfunction is associated with ototoxicity, which is caused by external factors. Mitophagy plays a key role in maintaining mitochondrial homeostasis and function and is regulated by a series of key mitophagy regulatory proteins and signaling pathways.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36909283"}, {"offsetInBeginSection": 0, "offsetInEndSection": 371, "text": "Mitochondrial dysfunction is associated with ototoxicity, which is caused by external factors. Mitophagy plays a key role in maintaining mitochondrial homeostasis and function and is regulated by a series of key mitophagy regulatory proteins and signaling pathways. The results of ototoxicity models indicate the importance of this process in the etiology of ototoxicity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36909283"}, {"offsetInBeginSection": 407, "offsetInEndSection": 551, "text": "this paper is on the quality control processes involved in and around mitochondria. Mitochondrial autophagy (mitophagy) is the process through w", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36860818"}, {"offsetInBeginSection": 92, "offsetInEndSection": 216, "text": "the autophagic removal of depolarized mitochondria (mitophagy). Parkin-mediated protein ubiquitinations may be counteracted ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31550441"}, {"offsetInBeginSection": 373, "offsetInEndSection": 499, "text": "both insufficient and excessive mitophagy have been linked to neurodegeneration. Kinases implicated in regulating mammalian mi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21126205"}, {"offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Mitophagy is a critical regulator of mitochondrial quality control and is necessary for elimination of dysfunctional mitochon", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26085571"}, {"offsetInBeginSection": 280, "offsetInEndSection": 621, "text": "Damaged or unwanted mitochondria are selectively removed by mitophagy, which is a crucial determinant of cell viability. Mitochondria-associated Endoplasmic Reticulum Membranes (MAMs) are the cellular structures that connect the ER and mitochondria and are involved in calcium signaling, lipid transfer, mitochondrial dynamic, and mitophagy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34975548"}, {"offsetInBeginSection": 419, "offsetInEndSection": 500, "text": "mitophagy (a specific form of autophagy that removes dysfunctional mitochondria).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34099564"}, {"offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Parkin is an E3 ubiquitin ligase mostly known for its role in regulating the removal of defective mitochondria via mitophagy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35691026"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1049, "text": "Autophagy is a mechanism responsible for the degradation of cellular components to maintain their homeostasis. However, autophagy is commonly altered and compromised in several diseases, including neurodegenerative disorders. Parkinson's disease (PD) can be considered a multifactorial disease because environmental factors, genetic factors, and aging are involved. Several genes are involved in PD pathology, among which the LRRK2 gene and its mutations, inherited in an autosomal dominant manner, are responsible for most genetic PD cases. The R1441G LRRK2 mutation is, after G2019S, the most important in PD pathogenesis. Our results demonstrate a relationship between the R1441G LRRK2 mutation and a mechanistic dysregulation of autophagy that compromises cell viability. This altered autophagy mechanism is associated with organellar stress including mitochondrial (which induces mitophagy) and endoplasmic reticulum (ER) stress, consistent with the fact that patients with this mutation are more vulnerable to toxins related to PD, such as MPP", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34060004"}, {"offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Mitochondria are linked with various radiation responses, including mitophagy, genomic instability, apoptosis, and the bystander effect.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31956306"}, {"offsetInBeginSection": 0, "offsetInEndSection": 737, "text": "Mitochondrial biogenesis and function depend on the intensive exchange of molecules with other cellular compartments. The mitochondrial outer membrane plays a central role in this communication process. It is equipped with a number of specific protein machineries that enable the transport of proteins and metabolites. Furthermore, the outer membrane forms molecular contact sites with other cell organelles like the endoplasmic reticulum (ER), thus integrating mitochondrial function in cellular physiology. The best-studied mitochondrial organelle contact site, the ER-mitochondria encounter structure (ERMES) has been linked to many vital processes including mitochondrial division, inheritance, mitophagy, and phospholipid transport.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28576471"}, {"offsetInBeginSection": 595, "offsetInEndSection": 918, "text": "Fusion connects and unites neighboring depolarized mitochondria to derive a healthy and distinct mitochondrion. In contrast, fission segregates damaged mitochondria from intact and healthy counterparts and is followed by selective clearance of the damaged mitochondria via mitochondrial specific autophagy, i.e., mitophagy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36982862"}, {"offsetInBeginSection": 114, "offsetInEndSection": 433, "text": "Mitochondrial fusion-fission dynamics are critical to maintain normal morphology, distribution and quantity of mitochondria, and ensure the normal activity of cells. In addition, mitochondrial autophagy (mitophagy) plays an important role in maintaining mitochondrial quality by degrading aging or damaged mitochondria.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32820310"}, {"offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Mitochondrial autophagy (or mitophagy) regulates the mitochondrial network and function to contribute to multiple cellular processes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35096821"}, {"offsetInBeginSection": 234, "offsetInEndSection": 414, "text": "Mitochondrial autophagy, also known as mitophagy, which selectively eliminates dysfunctional and unwanted mitochondria, is the most important type of mitochondrial quality control.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29115402"}, {"offsetInBeginSection": 117, "offsetInEndSection": 283, "text": "Mitochondrial autophagy (mitophagy) refers to selective sequestration of mitochondria by autophagosomes, which subsequently deliver them to lysosomes for destruction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23985961"}, {"offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Mitochondrial autophagy (mitophagy) is a core cellular activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25753537"}, {"offsetInBeginSection": 501, "offsetInEndSection": 570, "text": "Mitochondria are eliminated via mitochondrial autophagy or mitophagy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25437922"}, {"offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Mitochondrial autophagy (mitophagy) is the selective clearance of damaged or incomplete mitochondria by autophagy, which is critical for the functional integrity of the entire mitochondrial network and cell survival.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34291135"}]}
+{"question_id": "660d2a50fdcbea915f00003a", "question": "What is the association between statins and stroke?", "answer": "\n The association between statins and stroke is complex and varies by factors such as race and baseline cholesterol levels. While statins have been shown to reduce the incidence of stroke in high-risk populations, including those with a history of cardiovascular disease, the evidence for a benefit in primary prevention is less clear. Some studies have suggested that statins may increase the risk of hemorrhagic stroke, although the evidence is not conclusive. More research is needed to fully understand the relationship.", "relevant_passage_ids": ["34154390", "36706354"], "type": "summary", "snippets": [{"offsetInBeginSection": 23, "offsetInEndSection": 125, "text": " Statins were shown to increase hemorrhagic stroke (HS) in patients with a first cerebrovascular event", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34154390"}, {"offsetInBeginSection": 2046, "offsetInEndSection": 2077, "text": "Statins increase the risk of HS", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34154390"}, {"offsetInBeginSection": 26, "offsetInEndSection": 176, "text": "benefit of statin for stroke is debatable as regular statin users may suffer from myalgia, statin-associated myopathy (SAM), and rarely rhabdomyolysis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36706354"}]}
+{"question_id": "65cfd02e1930410b1300001c", "question": "What channel is targeted by VX-548?", "answer": "VX-548 is an oral, highly selective inhibitor of NaV1.8 that is studied for control of acute pain.", "relevant_passage_ids": ["37530822"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Selective Inhibition of NaV1.8 with VX-548 for Acute Pain.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37530822"}, {"offsetInBeginSection": 148, "offsetInEndSection": 259, "text": "The effect of VX-548, an oral, highly selective inhibitor of NaV1.8, on control of acute pain is being studied.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37530822"}, {"offsetInBeginSection": 148, "offsetInEndSection": 453, "text": "The effect of VX-548, an oral, highly selective inhibitor of NaV1.8, on control of acute pain is being studied.METHODS: After establishing the selectivity of VX-548 for NaV1.8 inhibition in vitro, we conducted two phase 2 trials involving participants with acute pain after abdominoplasty or bunionectomy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37530822"}, {"offsetInBeginSection": 0, "offsetInEndSection": 452, "text": "BACKGROUND: The NaV1.8 voltage-gated sodium channel, expressed in peripheral nociceptive neurons, plays a role in transmitting nociceptive signals. The effect of VX-548, an oral, highly selective inhibitor of NaV1.8, on control of acute pain is being studied.METHODS: After establishing the selectivity of VX-548 for NaV1.8 inhibition in vitro, we conducted two phase 2 trials involving participants with acute pain after abdominoplasty or bunionectomy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37530822"}, {"offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "BACKGROUND: The NaV1.8 voltage-gated sodium channel, expressed in peripheral nociceptive neurons, plays a role in transmitting nociceptive signals. The effect of VX-548, an oral, highly selective inhibitor of NaV1.8, on control of acute pain is being studied", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37530822"}, {"offsetInBeginSection": 147, "offsetInEndSection": 957, "text": " The effect of VX-548, an oral, highly selective inhibitor of NaV1.8, on control of acute pain is being studied.METHODS: After establishing the selectivity of VX-548 for NaV1.8 inhibition in vitro, we conducted two phase 2 trials involving participants with acute pain after abdominoplasty or bunionectomy. In the abdominoplasty trial, participants were randomly assigned in a 1:1:1:1 ratio to receive one of the following over a 48-hour period: a 100-mg oral loading dose of VX-548, followed by a 50-mg maintenance dose every 12 hours (the high-dose group); a 60-mg loading dose of VX-548, followed by a 30-mg maintenance dose every 12 hours (the middle-dose group); hydrocodone bitartrate-acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours); or oral placebo every 6 hours", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37530822"}, {"offsetInBeginSection": 147, "offsetInEndSection": 452, "text": " The effect of VX-548, an oral, highly selective inhibitor of NaV1.8, on control of acute pain is being studied.METHODS: After establishing the selectivity of VX-548 for NaV1.8 inhibition in vitro, we conducted two phase 2 trials involving participants with acute pain after abdominoplasty or bunionectomy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37530822"}, {"offsetInBeginSection": 127, "offsetInEndSection": 251, "text": "nociceptive signals. The effect of VX-548, an oral, highly selective inhibitor of NaV1.8, on control of acute pain is being ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37530822"}]}
+{"question_id": "66099926fdcbea915f000016", "question": "What is the most effective drug for oxaliplatin-induced neuropathy?", "answer": "Duloxetine, a serotonin and norepinephrine reuptake inhibitor, is the best-established treatment for painful chemotherapy-induced peripheral neuropathy (CIPN).  Despite intense investigation at the preclinical and clinical levels, no treatment can be suggested for the prevention of Oxaliplatin-induced peripheral neurotoxicity (OIPN), and only limited evidence for the efficacy of duloxetine in the treatment setting has been provided.", "relevant_passage_ids": ["32471028", "34880120", "25434440", "32347537", "32317735", "31377017", "33573316", "24307899", "11951404", "24355920", "26828020", "31182448", "24412642", "24365057", "37951905", "37946486", "31467537", "35295491", "34686205", "35255440", "25459280", "15590869", "11797144", "28186109", "33010214", "37902612", "35623085", "32965323", "28739131", "22466962", "21907570", "24784702", "26358793", "32416186", "15846125", "20308797", "26536615", "24452412", "26039098", "19816592", "35426033", "20683034", "32440122"], "type": "factoid", "snippets": [{"offsetInBeginSection": 664, "offsetInEndSection": 760, "text": "only limited evidence for the efficacy of duloxetine in the treatment setting has been provided.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32471028"}, {"offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Duloxetine, a serotonin and norepinephrine reuptake inhibitor, is the best-established treatment for painful chemotherapy-induced peripheral neuropathy (CIPN)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34880120"}, {"offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Efficacy and safety of mirogabalin for chemotherapy-induced peripheral neuropathy: a prospective single-arm trial (MiroCIP study).", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37951905"}, {"offsetInBeginSection": 12, "offsetInEndSection": 268, "text": "To analyze the distribution characteristics of Traditional Chinese Medicine (TCM) syndromes in patients with oxaliplatin-induced peripheral neuropathy (OIPN) and observe the clinical efficacy of Bushen Yiqi formula (, BSYQF) in treating patients with OIPN.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37946486"}, {"offsetInBeginSection": 459, "offsetInEndSection": 585, "text": "(Aqu) and two hydroalcoholic (20%HA and 50%HA) extracts were tested in a rat model of oxaliplatin-induced neuropathy. Repeated", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28186109"}, {"offsetInBeginSection": 1385, "offsetInEndSection": 1477, "text": "These results suggest that duloxetine could alleviate the OXA-induced peripheral neuropathy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35623085"}, {"offsetInBeginSection": 1157, "offsetInEndSection": 1377, "text": "These findings provide preliminary evidence of the preventative effects of duloxetine on both oxaliplatin-induced allodynia and hyperalgesia in male and female rats, with a difference noted in response between the sexes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37902612"}, {"offsetInBeginSection": 709, "offsetInEndSection": 841, "text": "In all doses, amifostine prevented the development of mechanical hyperalgesia and thermal allodynia induced by oxaliplatin (P<0.05).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32965323"}, {"offsetInBeginSection": 842, "offsetInEndSection": 915, "text": "Amifostine at the dose of 25 mg/kg provided the best protection (P<0.05).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32965323"}, {"offsetInBeginSection": 1161, "offsetInEndSection": 1357, "text": "In conclusion, amifostine reduced the nociception induced by oxaliplatin in mice, suggesting the possible use of amifostine for the management of oxaliplatin-induced peripheral sensory neuropathy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32965323"}, {"offsetInBeginSection": 764, "offsetInEndSection": 875, "text": "Ibudilast treatment prior to oxaliplatin prevented the development of tactile allodynia and memory impairments.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28739131"}, {"offsetInBeginSection": 1035, "offsetInEndSection": 1171, "text": "These results suggest that Ibudilast could be an effective treatment against oxaliplatin-induced neuropathies and cognitive impairments.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28739131"}, {"offsetInBeginSection": 1476, "offsetInEndSection": 1590, "text": "red with those in nonresponders.CONCLUSION: Our study suggests that mangafodipir can prevent and/or relieve oxalip", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24355920"}, {"offsetInBeginSection": 1392, "offsetInEndSection": 1519, "text": "arbamazepine-induced side effects was low.CONCLUSIONS: These observations demonstrate that oxaliplatin-induced sensory neuropat", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11797144"}, {"offsetInBeginSection": 200, "offsetInEndSection": 389, "text": "In the present study, we attempted to treat L-OHP-induced peripheral neuropathy using the algorithm consisting of pregabalin, duloxetine, and oxycodone at Iwate Medical University Hospital.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25434440"}, {"offsetInBeginSection": 390, "offsetInEndSection": 506, "text": "The first, second, and third stages of the algorithm consist of pregabalin, duloxetine, and oxycodone, respectively.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25434440"}, {"offsetInBeginSection": 961, "offsetInEndSection": 1338, "text": "Among all of the agents, intravenous calcium and magnesium have shown the most promise in prophylaxis and treatment of oxaliplatin-induced neurotoxicity. We report a case of a patient, in which oral calcium supplements not only were successful in treating his neurotoxicity, but we also were able to administer a cumulative dose of 2500 mg/m(2) (990 mg/m(2) with oral calcium).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19816592"}, {"offsetInBeginSection": 11, "offsetInEndSection": 129, "text": "To evaluate the efficacy of Goshajinkigan for oxaliplatin-induced peripheral neuropathy in colorectal cancer patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24307899"}, {"offsetInBeginSection": 481, "offsetInEndSection": 704, "text": "Several scientists have explored the various mechanisms involved in the onset of chemotherapy-related peripheral neurotoxicity identifying molecular targets useful for the development of selected neuroprotective strategies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25459280"}, {"offsetInBeginSection": 653, "offsetInEndSection": 743, "text": "Therefore, donepezil may be useful for managing oxaliplatin-induced peripheral neuropathy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31377017"}, {"offsetInBeginSection": 50, "offsetInEndSection": 350, "text": "The effect of donepezil, a drug used for treatment of Alzheimer's disease, on oxaliplatin-induced peripheral neuropathy was investigated using both in\u00a0vivo and in\u00a0vitro models. Donepezil effectively attenuated oxaliplatin- and cisplatin-induced inhibition of neurite outgrowth in cultured PC12\u00a0cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31377017"}, {"offsetInBeginSection": 50, "offsetInEndSection": 226, "text": "The effect of donepezil, a drug used for treatment of Alzheimer's disease, on oxaliplatin-induced peripheral neuropathy was investigated using both in\u00a0vivo and in\u00a0vitro models.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31377017"}, {"offsetInBeginSection": 50, "offsetInEndSection": 543, "text": "The effect of donepezil, a drug used for treatment of Alzheimer's disease, on oxaliplatin-induced peripheral neuropathy was investigated using both in\u00a0vivo and in\u00a0vitro models. Donepezil effectively attenuated oxaliplatin- and cisplatin-induced inhibition of neurite outgrowth in cultured PC12\u00a0cells. In a rat model, repeated oral administration of donepezil (5 times/week for 4 weeks) ameliorated oxaliplatin-induced mechanical allodynia (von Frey test) and sciatic nerve axonal degeneration.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31377017"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1590, "text": "BACKGROUND: The majority of patients receiving the platinum-based chemotherapy drug oxaliplatin develop peripheral neurotoxicity. Because this neurotoxicity involves ROS production, we investigated the efficacy of mangafodipir, a molecule that has antioxidant properties and is approved for use as an MRI contrast enhancer.METHODS: The effects of mangafodipir were examined in mice following treatment with oxaliplatin. Neurotoxicity, axon myelination, and advanced oxidized protein products (AOPPs) were monitored. In addition, we enrolled 23 cancer patients with grade \u2265 2 oxaliplatin-induced neuropathy in a phase II study, with 22 patients receiving i.v. mangafodipir following oxaliplatin. Neuropathic effects were monitored for up to 8 cycles of oxaliplatin and mangafodipir.RESULTS: Mangafodipir prevented motor and sensory dysfunction and demyelinating lesion formation. In mice, serum AOPPs decreased after 4 weeks of mangafodipir treatment. In 77% of patients treated with oxaliplatin and mangafodipir, neuropathy improved or stabilized after 4 cycles. After 8 cycles, neurotoxicity was downgraded to grade \u2265 2 in 6 of 7 patients. Prior to enrollment, patients received an average of 880 \u00b1 239 mg/m2 oxaliplatin. Patients treated with mangafodipir tolerated an additional dose of 458 \u00b1 207 mg/m2 oxaliplatin despite preexisting neuropathy. Mangafodipir responders managed a cumulative dose of 1,426 \u00b1 204 mg/m2 oxaliplatin. Serum AOPPs were lower in responders compared with those in nonresponders.CONCLUSION: Our study suggests that mangafodipir can prevent and/or relieve oxalip", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24355920"}, {"offsetInBeginSection": 961, "offsetInEndSection": 1819, "text": "Among all of the agents, intravenous calcium and magnesium have shown the most promise in prophylaxis and treatment of oxaliplatin-induced neurotoxicity. We report a case of a patient, in which oral calcium supplements not only were successful in treating his neurotoxicity, but we also were able to administer a cumulative dose of 2500 mg/m(2) (990 mg/m(2) with oral calcium). Although the current recommendations for the management of the acute and cumulative neurotoxicity from oxaliplatin with the use of infusion of Ca/Mg remain valid, our case is the first report demonstrating the role of oral minerals in ameliorating neurotoxicity from oxaliplatin. Future studies to evaluate the role of oral Ca/Mg are warranted, since they could prove to be an effective, less expensive and more convenient way to treat and prevent oxaliplatin-associated toxicity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19816592"}, {"offsetInBeginSection": 128, "offsetInEndSection": 1107, "text": "neuropathy. Exenatide, a glucagon-like peptide-1 (GLP-1) agonist, is an incretin mimetic secreted from ileal L cells, which is clinically used to treat type 2 diabetes mellitus. GLP-1 receptor agonists have been reported to exhibit neuroprotective effects on the central and peripheral nervous systems. In this study, we investigated the effects of exenatide on oxaliplatin-induced neuropathy in rats and cultured cells.METHODS: Oxaliplatin (4 mg/kg) was administered intravenously twice per week for 4 weeks, and mechanical allodynia was evaluated using the von Frey test in rats. Axonal degeneration was assessed by toluidine blue staining of sciatic nerves.RESULTS: Repeated administration of oxaliplatin caused mechanical allodynia from day 14 to 49. Although the co-administration of extended-release exenatide (100 \u03bcg/kg) could not inhibit the incidence of oxaliplatin-induced mechanical allodynia, it facilitated recovery from the oxaliplatin-induced neuropathy with repar", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26536615"}, {"offsetInBeginSection": 224, "offsetInEndSection": 1799, "text": "In the complex pattern of molecular and morphological alterations induced by oxaliplatin in the nervous system, an important activation of glia has been preclinically evidenced. N-Palmitoylethanolamine (PEA) modulates glial cells and exerts antinociceptive effects in several animal models. In order to improve the therapeutic chances for chemotherapy-dependent neuropathy management, the role of PEA was investigated in a rat model of oxaliplatin-induced neuropathy (2.4 mg kg-1 daily, intraperitoneally). On day 21, a single administration of PEA (30 mg kg-1 i.p.) was able to reduce oxaliplatin-dependent pain induced by mechanical and thermal stimuli. The repeated treatment with PEA (30 mg kg-1 daily i.p. for 21 days, from the first oxaliplatin injection) prevented lowering of pain threshold as well as increased pain on suprathreshold stimulation. Ex vivo histological and molecular analysis of dorsal root ganglia, peripheral nerves and spinal cord highlighted neuroprotective effects and glia-activation prevention induced by PEA repeated administration. The protective effect of PEA resulted in the normalization of the electrophysiological activity of the spinal nociceptive neurons. Finally, PEA did not alter the oxaliplatin-induced mortality of the human colon cancer cell line HT-29. The efficacy of PEA in neuropathic pain control and in preventing nervous tissue alteration candidates this endogenous compound as disease modifying agent. These characteristics, joined to the safety profile, suggest the usefulness of PEA in chemotherapy-induced neuropathy. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26039098"}, {"offsetInBeginSection": 246, "offsetInEndSection": 562, "text": "atin therapy. We demonstrated that oxaliplatin alters sodium channel kinetics on sensory neurons. This effect could be antagonized in vitro by the sodium channel blocker carbamazepine. Therefore a pilot study was initiated to investigate if carbamazepine prevents oxaliplatin-induced neuropathy in patients with colo", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11797144"}, {"offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Donepezil ameliorates oxaliplatin-induced peripheral neuropathy via a neuroprotective effect.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31377017"}, {"offsetInBeginSection": 784, "offsetInEndSection": 979, "text": "severity of oxaliplatin-induced sensory neuropathy. Being more potent than gabapentin, pregabalin achieved efficacy at lower doses and should lead to fewer dose-related side effects, although thi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20683034"}, {"offsetInBeginSection": 1202, "offsetInEndSection": 1296, "text": "gnesium solutions, gabapentin, carbamazepine, amifostine, and glutathione. Treatment measures ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15590869"}]}
+{"question_id": "65f37bb1c4010b4d7800000d", "question": "What is Microcoring used for", "answer": "Microcoring (MCT)  is  used skin treatments such as scarless skin removal or treatment of enlarged pores. This minimally invasive technique involves creating controlled damage in cutaneous tissue to induce neocollagenesis and neoelastogenesis. MCT involves hollow microneedles capable of removing excess tissue without inducing scar formation.", "relevant_passage_ids": ["34729291", "37218872", "36683728", "36262685", "35064633", "22180307"], "type": "factoid", "snippets": [{"offsetInBeginSection": 935, "offsetInEndSection": 1188, "text": " MCT treatment of human skin is safe and well tolerated. Although further studies on efficacy are required to evaluate the full potential of MCT in skin rejuvenation, early findings such as skin tightening and increase in skin thickness are encouraging.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34729291"}, {"offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "A novel microcoring technology: A completely new concept of enlarged pore treatment.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37218872"}, {"offsetInBeginSection": 63, "offsetInEndSection": 195, "text": "The micro coring technology, designed to remove small skin columns, was developed to avoid the thermal injury associated with lasers", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36683728"}, {"offsetInBeginSection": 12, "offsetInEndSection": 143, "text": " technology (MCT) removes cores of skin without formation of scars, thereby tightening skin and reducing skin wrinkling. The purpos", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36262685"}, {"offsetInBeginSection": 131, "offsetInEndSection": 242, "text": "Microcoring technology (MCT) uses a modified, hollow hypodermic needle to remove skin safely and without a scar", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34729291"}, {"offsetInBeginSection": 234, "offsetInEndSection": 549, "text": "Despite these efforts, enlarged pores remain problematic for many patients.OBJECTIVES: Microcoring technology has recently been developed to treat pores and serve as a leading primary treatment option to address these concerns.METHODS: Three patients underwent a single treatment of rotational fractional resection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37218872"}, {"offsetInBeginSection": 830, "offsetInEndSection": 991, "text": "Skin area reduction (skin tightening) and increase in skin thickness were observed long term.CONCLUSIONS: MCT treatment of human skin is safe and well tolerated.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34729291"}, {"offsetInBeginSection": 244, "offsetInEndSection": 776, "text": "This method is advantageous compared to other fractional devices, given that it has the same benefits as energy-based devices (removal of skin cores without a scar), with the added value of immediate closure along the relaxed skin tension lines, with significantly less thermal energy.METHODS: Three prospective clinical safety trials analyzing MCT treatment on abdominal and facial skin (short- and long-term) are described.RESULTS: MCT treatment of human skin resulted in scarless skin removal that was well tolerated by patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34729291"}, {"offsetInBeginSection": 131, "offsetInEndSection": 243, "text": "Microcoring technology (MCT) uses a modified, hollow hypodermic needle to remove skin safely and without a scar.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34729291"}, {"offsetInBeginSection": 0, "offsetInEndSection": 650, "text": "BACKGROUND: Microbotox technique, intradermal injection of microdroplets of botulinum toxin, is a favorable rejuvenation approach in subjects who prefer more natural appearance.AIM: To determine the best injection techniques (dosage, concentration, as well as number and location of injection points), efficacy and side effects of this innovative technique for facial rejuvenation.METHODS: We conducted a search in Pubmed, Embase, Web of Science, and Google Scholar databases from conception until October 2021 with keywords \"microbotox\" OR \"mesobotox\" OR \"intradermal injection\" AND \"botulinum toxin\" AND \"rejuvenation\" AND \"wrinkle\" AND \"face-lift.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35064633"}, {"offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Micro-coring technology (MCT) removes cores of skin without formation of scars, thereby tightening skin and reducing skin wrinkling.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36262685"}, {"offsetInBeginSection": 133, "offsetInEndSection": 279, "text": "The purpose of this study was to evaluate the safety and efficacy of MCT with the dermal micro-coring device for the treatment of facial wrinkles.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36262685"}, {"offsetInBeginSection": 650, "offsetInEndSection": 748, "text": "erm) are described.RESULTS: MCT treatment of human skin resulted in scarless skin removal that was", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34729291"}, {"offsetInBeginSection": 298, "offsetInEndSection": 438, "text": "y patients.OBJECTIVES: Microcoring technology has recently been developed to treat pores and serve as a leading primary treatment option to ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37218872"}, {"offsetInBeginSection": 653, "offsetInEndSection": 1020, "text": "Technical issues related to maximizing the diagnostic yield (e.g., rapid on-site cytopathological evaluation, needle diameter, microcore isolation for histopathological examination, and adequate number of needle passes) are discussed and recommendations are made for various settings, including solid and cystic pancreatic lesions, submucosal tumors, and lymph nodes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22180307"}, {"offsetInBeginSection": 311, "offsetInEndSection": 462, "text": "JECTIVES: Microcoring technology has recently been developed to treat pores and serve as a leading primary treatment option to address these concerns.M", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37218872"}, {"offsetInBeginSection": 130, "offsetInEndSection": 528, "text": " Microcoring technology (MCT) uses a modified, hollow hypodermic needle to remove skin safely and without a scar. This method is advantageous compared to other fractional devices, given that it has the same benefits as energy-based devices (removal of skin cores without a scar), with the added value of immediate closure along the relaxed skin tension lines, with significantly less thermal energy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34729291"}, {"offsetInBeginSection": 311, "offsetInEndSection": 550, "text": "JECTIVES: Microcoring technology has recently been developed to treat pores and serve as a leading primary treatment option to address these concerns.METHODS: Three patients underwent a single treatment of rotational fractional resection. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37218872"}, {"offsetInBeginSection": 0, "offsetInEndSection": 528, "text": "BACKGROUND: We introduce an innovative and novel technology that achieves scarless skin removal without the use of thermal energy. Microcoring technology (MCT) uses a modified, hollow hypodermic needle to remove skin safely and without a scar. This method is advantageous compared to other fractional devices, given that it has the same benefits as energy-based devices (removal of skin cores without a scar), with the added value of immediate closure along the relaxed skin tension lines, with significantly less thermal energy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34729291"}, {"offsetInBeginSection": 130, "offsetInEndSection": 668, "text": " Microcoring technology (MCT) uses a modified, hollow hypodermic needle to remove skin safely and without a scar. This method is advantageous compared to other fractional devices, given that it has the same benefits as energy-based devices (removal of skin cores without a scar), with the added value of immediate closure along the relaxed skin tension lines, with significantly less thermal energy.METHODS: Three prospective clinical safety trials analyzing MCT treatment on abdominal and facial skin (short- and long-term) are described", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34729291"}, {"offsetInBeginSection": 311, "offsetInEndSection": 644, "text": "JECTIVES: Microcoring technology has recently been developed to treat pores and serve as a leading primary treatment option to address these concerns.METHODS: Three patients underwent a single treatment of rotational fractional resection. The 0.5\u2009mm diameter rotating scalpels were used to resect the skin pores in the cheek region. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37218872"}, {"offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "BACKGROUND: We introduce an innovative and novel technology that achieves scarless skin removal without the use of thermal energy. Microcoring technology (MCT) uses a modified, hollow hypodermic needle to remove skin safely and without a scar", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34729291"}, {"offsetInBeginSection": 233, "offsetInEndSection": 548, "text": " Despite these efforts, enlarged pores remain problematic for many patients.OBJECTIVES: Microcoring technology has recently been developed to treat pores and serve as a leading primary treatment option to address these concerns.METHODS: Three patients underwent a single treatment of rotational fractional resection", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37218872"}, {"offsetInBeginSection": 233, "offsetInEndSection": 460, "text": " Despite these efforts, enlarged pores remain problematic for many patients.OBJECTIVES: Microcoring technology has recently been developed to treat pores and serve as a leading primary treatment option to address these concerns", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37218872"}, {"offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Micro-coring technology (MCT) removes cores of skin without formation of scars, thereby tightening skin and reducing skin wrinkling. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36262685"}, {"offsetInBeginSection": 0, "offsetInEndSection": 517, "text": "BACKGROUND: We introduce an innovative and novel technology that achieves scarless skin removal without the use of thermal energy. Microcoring technology (MCT) uses a modified, hollow hypodermic needle to remove skin safely and without a scar. This method is advantageous compared to other fractional devices, given that it has the same benefits as energy-based devices (removal of skin cores without a scar), with the added value of immediate closure along the relaxed skin tension lines, with significantly less the", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34729291"}]}
+{"question_id": "660bbc09fdcbea915f00002a", "question": "What symptoms can be expected in women suffering from endometriosis?", "answer": "Women suffering from endometriosis may experience the following symptoms:\n\n1. Pelvic pain, especially during menstruation\n2. Painful periods (dysmenorrhea)\n3. Pain during sex (dyspareunia)\n4. Painful urination or bowel movements during menstruation\n5. Heavy menstrual bleeding\n6. Infertility\n7. Fatigue\n8. Bloating or constipation\n9. Nausea or vomiting during menstruation\n10. Spotting or bleeding between periods (menorrhagia)\n11. Chronic pelvic pain, which may be continuous or worsen during menstruation\n12. Anxiety and depression due to the physical and emotional impact of the condition.\n\nNote that not all women with endometriosis will experience all of these symptoms, and some may not have any symptoms at all. The severity of symptoms can also vary from woman to woman.", "relevant_passage_ids": ["37956828", "37944153", "35713579"], "type": "list", "snippets": [{"offsetInBeginSection": 1547, "offsetInEndSection": 1616, "text": "endometriosis, with and without chronic pain, anxiety, and depression", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37956828"}, {"offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Endometriosis is a chronic condition, with debilitating symptoms affecting all ages. Dysmenorrhea and pelvic pain ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37944153"}, {"offsetInBeginSection": 451, "offsetInEndSection": 497, "text": "recurrent abdominal pain, cramping and anxiety", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35713579"}]}
+{"question_id": "65cf6c301930410b13000008", "question": "What is the mechanism of action of Mirvetuximab Soravtansine?", "answer": "Mirvetuximab soravtansine is an antibody-drug conjugate (ADC), which is comprised of a folate receptor \u03b1 (FR\u03b1) directed antibody conjugated to a microtubule inhibitor via a cleavable linker.", "relevant_passage_ids": ["36736157", "36716407", "37023499", "37229642", "36656533", "37102083", "29098867", "33667670", "29424243", "27889646", "32081463", "30093227", "28440955", "37528890", "37458180", "37594572", "30413525", "32984932", "28029313", "38055253", "30531606", "28534292", "36046840", "28843653", "31369274"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Safety and efficacy of mirvetuximab soravtansine, a folate receptor alpha (FR\u03b1)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36736157"}, {"offsetInBeginSection": 155, "offsetInEndSection": 253, "text": "Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate targeting folate receptor \u03b1 (FR\u03b1). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36716407"}, {"offsetInBeginSection": 917, "offsetInEndSection": 1127, "text": "Consequently, ADCs are gaining traction in gynecologic cancers with the recent US Food and Drug Administration approvals of tisotumab vedotin in cervical cancer and mirvetuximab soravtansine in ovarian cancer. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37023499"}, {"offsetInBeginSection": 500, "offsetInEndSection": 732, "text": "In ovarian cancer, mirvetuximab soravtansine, an ADC targeting alpha-folate receptor (FR\u03b1), received US Food and Drug Administration (FDA) accelerated approval in November 2022 after data from the single-arm phase III SORAYA trial. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37229642"}, {"offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Mirvetuximab soravtansine (mirvetuximab soravtansine-gynx; Elahere\u2122) is an antibody-drug conjugate (ADC), which is comprised of a folate receptor \u03b1 (FR\u03b1) directed antibody conjugated to a microtubule inhibitor via a cleavable linker. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36656533"}, {"offsetInBeginSection": 0, "offsetInEndSection": 336, "text": "Mirvetuximab soravtansine (MIRV) is a first-in-class antibody-drug conjugate (ADC) targeting folate receptor alpha (FR\u03b1) and is indicated for the treatment of adult patients with FR\u03b1-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received 1 to 3 prior systemic treatment regimens.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37102083"}, {"offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Mirvetuximab soravtansine, an antibody-drug conjugate that binds with high affinity to folate receptor-\u03b1 to provide tumor-directed delivery", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29424243"}, {"offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "Mirvetuximab soravtansine (mirvetuximab soravtansine-gynx; Elahere\u2122) is an antibody-drug conjugate (ADC), which is comprised of a folate receptor \u03b1 (FR\u03b1) directed antibody conjugated to a microtubule inhibitor via a cleavable linker. The ADC is being developed by ImmunoGen for the treatment", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36656533"}, {"offsetInBeginSection": 221, "offsetInEndSection": 442, "text": "Mirvetuximab soravtansine (IMGN853) is an antibody-drug conjugate (ADC) that targets FR\u03b1 for tumor-directed delivery of the maytansinoid DM4, a potent agent that induces mitotic arrest by suppressing microtubule dynamics.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27889646"}, {"offsetInBeginSection": 0, "offsetInEndSection": 474, "text": "BACKGROUND: Mirvetuximab soravtansine-gynx (MIRV), a first-in-class antibody-drug conjugate targeting folate receptor \u03b1 (FR\u03b1), is approved for the treatment of platinum-resistant ovarian cancer in the United States.METHODS: We conducted a phase 3, global, confirmatory, open-label, randomized, controlled trial to compare the efficacy and safety of MIRV with the investigator's choice of chemotherapy in the treatment of platinum-resistant, high-grade serous ovarian cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38055253"}, {"offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Mirvetuximab Soravtansine (IMGN853), a Folate Receptor Alpha-Targeting Antibody-Drug Conjugate, Potentiates the Activity of Standard of Care Therapeutics in Ovarian Cancer Models.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27889646"}, {"offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "BACKGROUND: Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate comprising a folate receptor alpha (FR\u03b1)-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33667670"}, {"offsetInBeginSection": 172, "offsetInEndSection": 339, "text": "Mirvetuximab soravtansine is a novel antibody-drug conjugate that targets folate receptor-\u03b1, a validated molecular target for therapeutic intervention in this disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29098867"}, {"offsetInBeginSection": 0, "offsetInEndSection": 598, "text": "PURPOSE: To evaluate the safety and clinical activity of mirvetuximab soravtansine, an antibody-drug conjugate comprising a humanized anti-folate receptor alpha (FR\u03b1) monoclonal antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent, in combination with bevacizumab in patients with FR\u03b1-positive, platinum-resistant ovarian cancer.METHODS: Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer were administered mirvetuximab soravtansine (6\u00a0mg/kg, adjusted ideal body weight) and bevacizumab (15\u00a0mg/kg) once every 3\u00a0weeks.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32081463"}, {"offsetInBeginSection": 0, "offsetInEndSection": 368, "text": "Purpose This phase I expansion cohort study evaluated the safety and clinical activity of mirvetuximab soravtansine (IMGN853), an antibody-drug conjugate consisting of a humanized anti-folate receptor alpha (FR\u03b1) monoclonal antibody linked to the tubulin-disrupting maytansinoid DM4, in a population of patients with FR\u03b1-positive and platinum-resistant ovarian cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28029313"}, {"offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "INTRODUCTION: Mirvetuximab soravtansine (mirvetuximab) is an antibody drug conjugate (ADC) comprised of a humanized folate receptor alpha (FR\u03b1)-binding monoclonal antibody attached via a cleavable linker to the cytotoxic maytansinoid molecule, DM4.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37458180"}, {"offsetInBeginSection": 541, "offsetInEndSection": 808, "text": "Mirvetuximab soravtansine is an ADC comprising an IgG1 monoclonal antibody against the folate receptor alpha (FR\u03b1) conjugated to the cytotoxic maytansinoid effector molecule DM4 that has shown promising clinical activity in patients with FR-\u03b1-positive ovarian cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37528890"}, {"offsetInBeginSection": 172, "offsetInEndSection": 338, "text": "Mirvetuximab soravtansine is a novel antibody-drug conjugate that targets folate receptor-\u03b1, a validated molecular target for therapeutic intervention in this disease", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29098867"}, {"offsetInBeginSection": 14, "offsetInEndSection": 247, "text": "Mirvetuximab soravtansine (mirvetuximab) is an antibody drug conjugate (ADC) comprised of a humanized folate receptor alpha (FR\u03b1)-binding monoclonal antibody attached via a cleavable linker to the cytotoxic maytansinoid molecule, DM4", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37458180"}, {"offsetInBeginSection": 500, "offsetInEndSection": 730, "text": "In ovarian cancer, mirvetuximab soravtansine, an ADC targeting alpha-folate receptor (FR\u03b1), received US Food and Drug Administration (FDA) accelerated approval in November 2022 after data from the single-arm phase III SORAYA trial", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37229642"}, {"offsetInBeginSection": 500, "offsetInEndSection": 731, "text": "In ovarian cancer, mirvetuximab soravtansine, an ADC targeting alpha-folate receptor (FR\u03b1), received US Food and Drug Administration (FDA) accelerated approval in November 2022 after data from the single-arm phase III SORAYA trial.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37229642"}, {"offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "ImmunoGen developed mirvetuximab soravtansine as an antibody-drug conjugate comprising of a humanized anti-folate receptor-\u03b1 (FR\u03b1) monoclonal antibody of IgG1k subtype, a cleavable linker, and a cytotoxic payload, DM4.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37594572"}, {"offsetInBeginSection": 288, "offsetInEndSection": 547, "text": "CENT FINDINGS: Mirvetuximab Soravtansine, IMGN853, is an ADC targeting the folate receptor alpha (FR\u03b1) and has demonstrated promising single agent activity and a favorable toxicity profile in FR\u03b1-positive, platinum-resistant, epithelial ovarian cancer (EOC). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30531606"}, {"offsetInBeginSection": 0, "offsetInEndSection": 332, "text": "Mirvetuximab soravtansine, an antibody-drug conjugate that binds with high affinity to folate receptor-\u03b1 to provide tumor-directed delivery of the potent microtubule-disrupting agent DM4, has emerged as a promising investigational agent for the treatment of ovarian cancer, particularly in the setting of platinum-resistant disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29424243"}, {"offsetInBeginSection": 599, "offsetInEndSection": 770, "text": "Among them, mirvetuximab soravtansine has shown activity in platinum-resistant ovarian cancer with high folate-\u03b1 receptor expression, as a single agent and in combination.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36046840"}, {"offsetInBeginSection": 0, "offsetInEndSection": 362, "text": "PURPOSE: To evaluate the safety and clinical activity of mirvetuximab soravtansine, an antibody-drug conjugate comprising a humanized anti-folate receptor alpha (FR\u03b1) monoclonal antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent, in combination with bevacizumab in patients with FR\u03b1-positive, platinum-resistant ovarian cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32081463"}, {"offsetInBeginSection": 82, "offsetInEndSection": 261, "text": "Mirvetuximab soravtansine is a novel folate receptor alpha (FR\u03b1)-targeting ADC which represents a potential new treatment for patients with ovarian and other FR\u03b1-positive cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28534292"}, {"offsetInBeginSection": 220, "offsetInEndSection": 546, "text": "Herein we summarize the ADC landscape currently in clinical study.RECENT FINDINGS: Mirvetuximab Soravtansine, IMGN853, is an ADC targeting the folate receptor alpha (FR\u03b1) and has demonstrated promising single agent activity and a favorable toxicity profile in FR\u03b1-positive, platinum-resistant, epithelial ovarian cancer (EOC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30531606"}, {"offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Mirvetuximab soravtansine (mirvetuximab soravtansine-gynx; Elahere\u2122) is an antibody-drug conjugate (ADC), which is comprised of a folate receptor \u03b1 (FR\u03b1) directed antibody conjugated to a microtubule inhibitor via a cleavable linker.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36656533"}, {"offsetInBeginSection": 172, "offsetInEndSection": 484, "text": "Mirvetuximab soravtansine is a novel antibody-drug conjugate that targets folate receptor-\u03b1, a validated molecular target for therapeutic intervention in this disease. Here, we examine mirvetuximab soravtansine's mechanism of action and pharmacology, and review its clinical evaluation in ovarian cancer to date.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29098867"}, {"offsetInBeginSection": 172, "offsetInEndSection": 636, "text": "Mirvetuximab soravtansine is a novel antibody-drug conjugate that targets folate receptor-\u03b1, a validated molecular target for therapeutic intervention in this disease. Here, we examine mirvetuximab soravtansine's mechanism of action and pharmacology, and review its clinical evaluation in ovarian cancer to date. We focus on the favorable tolerability and encouraging signals of efficacy that have emerged, most notably in patients with platinum-resistant disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29098867"}, {"offsetInBeginSection": 0, "offsetInEndSection": 484, "text": "Resistance to platinum-based therapy poses a significant clinical challenge for the management of advanced ovarian cancer, a leading cause of cancer mortality among women. Mirvetuximab soravtansine is a novel antibody-drug conjugate that targets folate receptor-\u03b1, a validated molecular target for therapeutic intervention in this disease. Here, we examine mirvetuximab soravtansine's mechanism of action and pharmacology, and review its clinical evaluation in ovarian cancer to date.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29098867"}, {"offsetInBeginSection": 135, "offsetInEndSection": 258, "text": "cancers. Mirvetuximab soravtansine (IMGN853) is the antibody-drug conjugate of FR\u03b1-binding humanized monoclonal antibody M9", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31369274"}, {"offsetInBeginSection": 220, "offsetInEndSection": 440, "text": " Mirvetuximab soravtansine (IMGN853) is an antibody-drug conjugate (ADC) that targets FR\u03b1 for tumor-directed delivery of the maytansinoid DM4, a potent agent that induces mitotic arrest by suppressing microtubule dynamic", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27889646"}, {"offsetInBeginSection": 541, "offsetInEndSection": 806, "text": "Mirvetuximab soravtansine is an ADC comprising an IgG1 monoclonal antibody against the folate receptor alpha (FR\u03b1) conjugated to the cytotoxic maytansinoid effector molecule DM4 that has shown promising clinical activity in patients with FR-\u03b1-positive ovarian cance", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37528890"}, {"offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "INTRODUCTION: Mirvetuximab soravtansine (mirvetuximab) is an antibody drug conjugate (ADC) comprised of a humanized folate receptor alpha (FR\u03b1)-binding monoclonal antibody attached via a cleavable linker to the cytotoxic maytansinoid", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37458180"}, {"offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "ImmunoGen developed mirvetuximab soravtansine as an antibody-drug conjugate comprising of a humanized anti-folate receptor-\u03b1 (FR\u03b1) monoclonal antibody of IgG1k subtype, a cleavable linker, and a cytotoxic payload, DM", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37594572"}, {"offsetInBeginSection": 0, "offsetInEndSection": 331, "text": "Mirvetuximab soravtansine, an antibody-drug conjugate that binds with high affinity to folate receptor-\u03b1 to provide tumor-directed delivery of the potent microtubule-disrupting agent DM4, has emerged as a promising investigational agent for the treatment of ovarian cancer, particularly in the setting of platinum-resistant disease", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29424243"}]}
+{"question_id": "65f778dbc4010b4d78000035", "question": "Is watch-and-wait policy after neoadjuvant therapy a cost-effective policy for locally advanced rectal cancer patients?", "answer": "Using current multi-institutional recurrence estimates, we observed comparable cancer-specific survival, superior quality-adjusted survival, and decreased costs with Watch and Wait compared with upfront Total Mesorectal Excision.", "relevant_passage_ids": ["31930400", "35151941", "34529175", "38051359", "35855528", "32848330", "29746338", "33121903", "28891846", "30964794", "31355776", "35704090", "34454807"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1566, "offsetInEndSection": 1825, "text": "Using current multi-institutional recurrence estimates, we observed comparable cancer-specific survival, superior quality-adjusted survival, and decreased costs with WW compared with upfront TME. Upfront TME was preferred when surgical salvage rates were low.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31930400"}, {"offsetInBeginSection": 1807, "offsetInEndSection": 2092, "text": "This study provides data of cost-effectiveness differences among Standard Surgery, Watch-and-Wait and Robotic Resection approaches in clinical complete response in locally advanced rectal cancer patients after neoadjuvant chemoradiotherapy, showing a benefit for Watch-and-Wait policy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35151941"}, {"offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Cost Effectiveness of Watch and Wait Versus Resection in Rectal Cancer Patients with Complete Clinical Response to Neoadjuvant Chemoradiation.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34529175"}, {"offsetInBeginSection": 22, "offsetInEndSection": 182, "text": "this study was to evaluate the oncological and survival outcomes of a Watch and Wait policy in rectal cancer after a clinical complete response (cCR) following ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29746338"}, {"offsetInBeginSection": 25, "offsetInEndSection": 359, "text": "herapy with neoadjuvant chemoradiation (nCRT), surgery, and adjuvant chemotherapy is the standard treatment for locally advanced rectal cancer. There is evidence that surgery can be deferred in patients with complete response (CR) to nCRT, a strategy termed \"watch-and-wait\" (WW). We compare WW to surgery in patients with CR to nCRT.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33121903"}, {"offsetInBeginSection": 1612, "offsetInEndSection": 2092, "text": "WW is only more effective than SR 55% of the time which implies a significant uncertainty due to the high utility value assigned to cCR after chemoradiotherapy in the RRR alternative.CONCLUSION: This study provides data of cost-effectiveness differences among Standard Surgery, Watch-and-Wait and Robotic Resection approaches in clinical complete response in locally advanced rectal cancer patients after neoadjuvant chemoradiotherapy, showing a benefit for Watch-and-Wait policy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35151941"}, {"offsetInBeginSection": 1124, "offsetInEndSection": 1304, "text": "A willingness-to-pay of per one additional QALY gained was measured to determine which strategies would be most cost-effective.RESULTS: WW is a dominating option over SR ( -75,486.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35151941"}, {"offsetInBeginSection": 1336, "offsetInEndSection": 1746, "text": "The cost-effectiveness analysis was slightly better for the WW group, especially for low rectal cancer compared to medium-high rectal cancer (ICER\u2009=\u2009\u2009-\u2009108,642.1 vs ICER\u2009=\u2009\u2009-\u200942,423).CONCLUSIONS: The WW strategy in locally advanced rectal cancer offers similar oncological outcomes with respect to the surgical group and excellent results in quality of life and cost outcomes, especially for low rectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38051359"}, {"offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "BACKGROUND: The watch-and-wait (WW) strategy is a potential option for patients with rectal cancer who obtain a complete clinic response after neoadjuvant therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38051359"}, {"offsetInBeginSection": 377, "offsetInEndSection": 833, "text": "We use computational techniques to compare these clinical approaches using quality adjusted life years (QALYs).METHODS: A Markov decision analytic model was used in order to perform a cost-utility analysis, comparing standard resection (SR), Robotic Rectal Resection (RRR) and\u202fWatch-and-Wait\u202f(WW) strategies, estimating the incremental cost-effectiveness ratio per QALY to be gained from patients reaching a clinical complete response to chemoradiotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35151941"}, {"offsetInBeginSection": 1262, "offsetInEndSection": 1560, "text": "Probabilistic sensitivity analysis demonstrated that WW was the dominant strategy over both APR and LAR over 100% of iterations across a range of WTP thresholds from $0-250,000.CONCLUSIONS: Our study suggests WW could reduce overall costs and increase effectiveness compared with either LAR or APR.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34529175"}, {"offsetInBeginSection": 1369, "offsetInEndSection": 1611, "text": "The cost-effectiveness plane shows that WW does not always dominate over RRR or SR. WW saves costs in 99.98% of the simulations when compared with either SR or RRR but only 86.9% and 55.38% (respectively) of these fall within the SR quadrant.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35151941"}, {"offsetInBeginSection": 1458, "offsetInEndSection": 1761, "text": "WW remained dominant in sensitivity analysis unless the rate of surgical salvage fell to 73.0%.CONCLUSIONS: Using current multi-institutional recurrence estimates, we observed comparable cancer-specific survival, superior quality-adjusted survival, and decreased costs with WW compared with upfront TME.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31930400"}, {"offsetInBeginSection": 245, "offsetInEndSection": 597, "text": "We hypothesized that a watch-and-wait (WW) strategy offers comparable cancer-specific survival, superior quality-adjusted survival, and reduced cost compared with upfront TME.METHODS: We developed a decision-analytic model to compare WW, low anterior resection, and abdominoperineal resection for patients achieving a clinical complete response to CRT.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31930400"}, {"offsetInBeginSection": 748, "offsetInEndSection": 1110, "text": "Lifetime incremental costs and quality-adjusted life-years (QALY) were calculated between strategies, and sensitivity analyses were performed to study model uncertainty.RESULTS: The base case 5-year cancer-specific survival was 93.5% (95% confidence interval [CI] = 91.5% to 94.9%) on a WW program compared with 95.9% (95% CI = 93.6% to 97.4%) after upfront TME.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31930400"}, {"offsetInBeginSection": 1279, "offsetInEndSection": 1457, "text": "WW was also dominant relative to abdominoperineal resection, with a cost savings of $32\u2009100 (95% CI = $21\u2009800 to $49\u2009200) and incremental QALY of 0.601 (95% CI = 0.213 to 1.208).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31930400"}, {"offsetInBeginSection": 12, "offsetInEndSection": 289, "text": "The \"watch and wait\" approach has recently been proposed as an alternative to surgery in locally-advanced rectal cancer patients that respond to neo-adjuvant chemoradiotherapy, in order to decrease its negative functional consequences upon the quality of life of these patients", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31355776"}, {"offsetInBeginSection": 363, "offsetInEndSection": 811, "text": "-Wait\u202fpolicy. We use computational techniques to compare these clinical approaches using quality adjusted life years (QALYs).METHODS: A Markov decision analytic model was used in order to perform a cost-utility analysis, comparing standard resection (SR), Robotic Rectal Resection (RRR) and\u202fWatch-and-Wait\u202f(WW) strategies, estimating the incremental cost-effectiveness ratio per QALY to be gained from patients reaching a clinical complete response", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35151941"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1661, "text": "BACKGROUND: Watch and wait (WW) protocols have gained increasing popularity for patients diagnosed with locally advanced rectal cancer and presumed complete clinical response after neoadjuvant chemoradiation. While studies have demonstrated comparable survival and recurrence rates between WW and radical surgery, the decision to undergo surgery has significant effects on patient quality of life. We sought to conduct a cost-effectiveness analysis comparing WW with abdominoperineal resection (APR) and low anterior resection (LAR) among patients with stage II/III rectal cancer.METHODS: In this comparative-effectiveness study, we built Markov microsimulation models to simulate disease progression, death, costs, and quality-adjusted life-years (QALYs) for WW or APR/LAR. We assessed cost effectiveness using the incremental cost-effectiveness ratio (ICER), with ICERs under $100,000/QALY considered cost effective. Probabilities of disease progression, death, and health utilities were extracted from published, peer-reviewed literature. We assessed costs from the payer perspective.RESULTS: WW dominated both LAR and APR at a willingness to pay (WTP) threshold of $100,000. Our model was most sensitive to rates of distant recurrence and regrowth after WW. Probabilistic sensitivity analysis demonstrated that WW was the dominant strategy over both APR and LAR over 100% of iterations across a range of WTP thresholds from $0-250,000.CONCLUSIONS: Our study suggests WW could reduce overall costs and increase effectiveness compared with either LAR or APR. Additional clinical research is needed to confirm the clinical efficacy and cost effectiveness of WW", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34529175"}, {"offsetInBeginSection": 0, "offsetInEndSection": 358, "text": "PURPOSE: Watch and wait strategy is a safe and effective alternative to surgery in patients with locally advanced rectal cancer (LARC) who have achieved pathological complete response (pCR) after neoadjuvant therapy (NAT); present restaging methods do not meet clinical needs. This study aimed to construct a machine learning (ML) model to predict pCR preope", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35704090"}]}
+{"question_id": "66088ddbfdcbea915f00000d", "question": "Are senolytics used to treat cardiovascular disease?", "answer": "Yes, senolytics have therapeutic potential in cardiovascular disease.", "relevant_passage_ids": ["35015342", "37747577", "32979174", "34237321", "37880106", "37174697", "32686219", "26864908", "36049114", "32977446", "32916794", "38062873", "36361845", "32823583", "35008500"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Therapeutic opportunities for senolysis in cardiovascular disease.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35015342"}, {"offsetInBeginSection": 737, "offsetInEndSection": 966, "text": "These findings coupled with the emergence of senolytic therapies, to target and eliminate senescent cells, have provided fascinating new avenues for management of several age-related cardiovascular diseases with high prevalence. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35015342"}, {"offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Quercetin and dasatinib, two powerful senolytics in age-related cardiovascular disease.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37747577"}, {"offsetInBeginSection": 303, "offsetInEndSection": 481, "text": "In recent years, the use and study of senolytics increased, representing a promising field for finding accessible and safe therapies for cardiovascular disease (CVD) treatment. T", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37747577"}, {"offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Therapeutic Potential of Senolytics in Cardiovascular Disease", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32979174"}, {"offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Senescence and senolytics in cardiovascular disease: Promise and potential pitfalls.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34237321"}, {"offsetInBeginSection": 132, "offsetInEndSection": 335, "text": "senolytic treatment is unknown. To determine whether long-term senolytic treatment improves vasomotor function, vascular stiffness, and intimal plaque size and composition in aged or hypercholesterolemic", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26864908"}, {"offsetInBeginSection": 185, "offsetInEndSection": 437, "text": "In recent years, therapies targeting senescent cells (senotherapies), particularly senolytics that selectively eliminate senescent cells, have been developed and show promise for treating geriatric syndromes and age-associated diseases, including CVDs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37880106"}, {"offsetInBeginSection": 970, "offsetInEndSection": 1135, "text": "Based on these data we suggest novel indications for senolytics as a treatment of cardiovascular diseases which have yet to be studied in the context of senotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34237321"}, {"offsetInBeginSection": 776, "offsetInEndSection": 1009, "text": "In preclinical CVD models, senolytics appear to improve heart failure, ischemic heart disease, valvular heart disease, atherosclerosis, aortic aneurysm, vascular dysfunction, dialysis arteriovenous fistula patency, and pre-eclampsia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37880106"}, {"offsetInBeginSection": 1443, "offsetInEndSection": 1586, "text": "We comprehensively summarize the preclinical evidence about senotherapies for CVDs and discuss future prospects for their clinical application.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37880106"}, {"offsetInBeginSection": 1036, "offsetInEndSection": 1241, "text": "Therefore, we additionally attempt to clarify the current state of this field with a focus on cardiac senescence and discuss the potential of implementing senolytics as a treatment option in heart disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36049114"}, {"offsetInBeginSection": 303, "offsetInEndSection": 479, "text": "In recent years, the use and study of senolytics increased, representing a promising field for finding accessible and safe therapies for cardiovascular disease (CVD) treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37747577"}, {"offsetInBeginSection": 966, "offsetInEndSection": 1139, "text": "In this review, we discuss the role of senescent cells within the cardiovascular system and highlight the contribution of senescence cells to common cardiovascular diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35015342"}, {"offsetInBeginSection": 784, "offsetInEndSection": 969, "text": "In this review, we discuss the evidence demonstrating that senescence contributes to cardiovascular disease, with a particular focus on studies that indicate the promise of senotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34237321"}, {"offsetInBeginSection": 1140, "offsetInEndSection": 1361, "text": "We discuss the emerging role for senolytics in cardiovascular disease management while highlighting important aspects of senescence biology which must be clarified before the potential of senolytics can be fully realized.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35015342"}, {"offsetInBeginSection": 263, "offsetInEndSection": 450, "text": "In the present study, we assessed the efficacy of fisetin, a natural compound, as a senolytic to reduce vascular cell senescence and SASP factors and improve arterial function in old mice", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38062873"}, {"offsetInBeginSection": 276, "offsetInEndSection": 932, "text": "Therapies targeting senescent cells, especially senolytic drugs that selectively induce senescent cell removal, have been shown to delay, prevent, alleviate, or treat multiple age-associated diseases in preclinical models. Some senolytic clinical trials have already been completed or are underway for a number of diseases and geriatric syndromes. Understanding how cellular senescence affects the various cell types in the cardiovascular system, such as endothelial cells, vascular smooth muscle cells, fibroblasts, immune cells, progenitor cells, and cardiomyocytes, is important to facilitate translation of senotherapeutics into clinical interventions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37174697"}, {"offsetInBeginSection": 848, "offsetInEndSection": 1135, "text": "In preclinical models, senolytics delay, prevent or alleviate frailty, cancers and cardiovascular, neuropsychiatric, liver, kidney, musculoskeletal, lung, eye, haematological, metabolic and skin disorders as well as complications of organ transplantation, radiation and cancer treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32686219"}, {"offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Therapeutic Potential of Senolytics in Cardiovascular Disease.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32979174"}, {"offsetInBeginSection": 895, "offsetInEndSection": 1067, "text": "These senescent cell apoptosis-inducing compounds are termed senolytics and their potential to ameliorate age-associated cardiovascular disease is the focus of this review.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32979174"}, {"offsetInBeginSection": 203, "offsetInEndSection": 714, "text": "Several compounds called senolytics have been designed to eliminate these cells within the tissues. In recent years, the use and study of senolytics increased, representing a promising field for finding accessible and safe therapies for cardiovascular disease (CVD) treatment. This mini-review discusses the changes in the aging heart and the participation of senescent cells in CVD, as well as the use of senolytics to prevent the progression of myocardial damage, mainly the effect of dasatinib and quercetin.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37747577"}, {"offsetInBeginSection": 203, "offsetInEndSection": 479, "text": "Several compounds called senolytics have been designed to eliminate these cells within the tissues. In recent years, the use and study of senolytics increased, representing a promising field for finding accessible and safe therapies for cardiovascular disease (CVD) treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37747577"}, {"offsetInBeginSection": 970, "offsetInEndSection": 1335, "text": "Based on these data we suggest novel indications for senolytics as a treatment of cardiovascular diseases which have yet to be studied in the context of senotherapy. Finally, while the potential benefits are encouraging, several complications may result from senolytic treatment. We, therefore, consider these challenges in the context of the cardiovascular system.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34237321"}, {"offsetInBeginSection": 303, "offsetInEndSection": 827, "text": "In recent years, the use and study of senolytics increased, representing a promising field for finding accessible and safe therapies for cardiovascular disease (CVD) treatment. This mini-review discusses the changes in the aging heart and the participation of senescent cells in CVD, as well as the use of senolytics to prevent the progression of myocardial damage, mainly the effect of dasatinib and quercetin. In particular, the mechanisms and physiological effects of senolytics therapies in the aged heart are discussed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37747577"}, {"offsetInBeginSection": 0, "offsetInEndSection": 479, "text": "Cellular senescence is characteristic of the development and progression of multiple age-associated diseases. Accumulation of senescent cells in the heart contributes to various age-related pathologies. Several compounds called senolytics have been designed to eliminate these cells within the tissues. In recent years, the use and study of senolytics increased, representing a promising field for finding accessible and safe therapies for cardiovascular disease (CVD) treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37747577"}, {"offsetInBeginSection": 634, "offsetInEndSection": 1620, "text": "Senescence-based therapeutic strategies are currently being pursued to treat and prevent CVD in humans in the near-future. In addition, distinct experimental settings allowed researchers to unravel potential approaches to regulate anti-apoptotic pathways, facilitate excessive senescent cell clearance and eventually reverse atherogenesis to improve cardiovascular function. However, a deeper knowledge is required to fully understand cellular senescence, to clarify senescence and atherogenesis intertwining, allowing researchers to establish more effective treatments and to reduce the cardiovascular disorders' burden. Here, we present an objective review of the key senescence-related alterations of the major intracellular organelles and analyze the role of relevant cell types for senescence and atherogenesis. In this context, we provide an updated analysis of therapeutic approaches, including clinically relevant experiments using senolytic drugs to counteract atherosclerosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32977446"}, {"offsetInBeginSection": 1109, "offsetInEndSection": 1358, "text": "Lastly, we identify prospective therapies that may rejuvenate the aged immune system to improve heart function such as anti-inflammatory and senolytic therapies, bone marrow transplant, niche remodeling and regulation of immune cell differentiation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32823583"}, {"offsetInBeginSection": 1229, "offsetInEndSection": 1358, "text": "Hence, targeting SCs appears as an emerging therapeutic option, since senolytic agents favorably disturb atherosclerotic plaques.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35008500"}, {"offsetInBeginSection": 933, "offsetInEndSection": 1266, "text": "This review highlights: (1) the characteristics of senescent cells and their involvement in cardiovascular diseases, focusing on the aforementioned cardiovascular cell types, (2) evidence about senolytic drugs and other senotherapeutics, and (3) the future path and clinical potential of senotherapeutics for cardiovascular diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37174697"}, {"offsetInBeginSection": 1103, "offsetInEndSection": 1365, "text": "The senescence markers are used in therapeutics and currently, senolytics represent one of the emerging treatments where specific targets and clearance of senescent cells are being considered as therapy targets for the prevention or treatment of atherosclerosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36361845"}, {"offsetInBeginSection": 702, "offsetInEndSection": 887, "text": "Understanding the precise mechanisms and consequences of senescent cell accumulation may uncover a new generation of therapies including senolytic and senomorphic compounds against CVD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32916794"}, {"offsetInBeginSection": 10, "offsetInEndSection": 76, "text": "Clinical Implications of Senotherapies for Cardiovascular Disease.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37880106"}]}
+{"question_id": "660c0486fdcbea915f00002d", "question": "What is the cause of Brazilian spotted fever?", "answer": "Brazilian spotted fever is caused by Rickettsia rickettsii.", "relevant_passage_ids": ["32267390", "31504641", "32315604", "27812666", "23168052", "25830998", "24387674", "31490924", "31014644", "31742533", "11980610", "36383899", "28535905", "31969607", "35293560", "17114702", "20624353", "27880877", "24142167", "25483025", "18949349", "31800889", "25501172", "27230435", "28377149", "29050834", "17114770", "21184706", "36169507", "14718082", "28169507", "33825800", "25148391", "30334709", "19538276"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "The bacterium Rickettsia rickettsii is the agent of Brazilian spotted fever (BSF)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31504641"}, {"offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Rickettsia rickettsii is the causative agent of Brazilian spotted fever", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32267390"}, {"offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Brazilian spotted fever (BSF) is caused by the bacterium Rickettsia rickettsii. Because of its high case-fatality rate and apparent increase in areas of transmission,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27812666"}, {"offsetInBeginSection": 10, "offsetInEndSection": 94, "text": "spotted fever (BSF) is a highly lethal disease in southeastern Brazil. BSF is caused", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32315604"}, {"offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Brazilian spotted fever, a zoonotic disease transmitted by ticks, is caused by Rickettsia rickettsii. We report a fulminant case of this zoonosis in a healthy 46-year-old military man in the urban region of Rio de Janeiro city, in October,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36383899"}, {"offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Brazilian spotted fever (BSF), caused by the bacterium Rickettsia rickettsii, is transmitted to humans mainly", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31883907"}, {"offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Brazilian spotted fever (BSF) is an endemic anthropozoonosis caused by Gram-negative bacteria (Rickettsia rickettsii) that is associated with the risk of human infection by ticks. In the city of Americana, S\u00e3o Paulo (SP), Brazil, there were 12 cases (67% lethal)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28377149"}, {"offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Brazilian spotted fever (BSF), caused by Rickettsia rickettsii, is endemic in the municipality of Americana, southeastern Brazil,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24142167"}, {"offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Brazilian spotted fever (BSF), caused by Rickettsia rickettsii, is the most lethal tick-borne disease in the western hemisphere. In Brazil, Amblyomma sculptum ticks are the main vector.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31969607"}, {"offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "BACKGROUND: Brazilian spotted fever (BSF), caused by the bacterium Rickettsia rickettsii, is the deadliest spotted fever of the world.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24387674"}, {"offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Brazilian spotted fever (BSF) is the most important tick-borne disease in Brazil and is caused by Rickettsia rickettsii and transmitted by the Ixodid tick Amblyomma cajennense, its main vector.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17114702"}, {"offsetInBeginSection": 162, "offsetInEndSection": 310, "text": "In Brazil, Rickettsia rickettsii SF is the most serious rickettsiosis and can result in death if not diagnosed and treated at the onset of symptoms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35293560"}, {"offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Brazilian spotted fever, a zoonotic disease transmitted by ticks, is caused by Rickettsia rickettsii.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36383899"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "In S\u00e3o Paulo metropolitan area, Brazil, Amblyomma aureolatum ticks are the main vector of Rickettsia rickettsii, which causes Brazilian spotted fever.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31742533"}, {"offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Brazilian Spotted Fever (BSF) is an often fatal zoonosis caused by the obligate intracellular bacterium Rickettsia rickettsii.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20624353"}, {"offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Brazilian spotted fever (BSF) is caused by the bacterium Rickettsia rickettsii.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27812666"}, {"offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Brazilian spotted fever is an acute febrile infectious disease caused by Rickettsia rickettsii, transmitted by tick bite.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25830998"}, {"offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "Brazilian spotted fever, caused by Rickettsia rickettsii", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11980610"}, {"offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "BACKGROUND: Brazilian spotted fever (BSF), caused by the bacterium Rickettsia rickettsii, has been associated with the transmission by the tick Amblyomma sculptum, and one of its main hosts, the capybara (Hydrochoerus hy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31490924"}, {"offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Amblyomma aureolatum (Pallas) is the main vector of the bacterium Rickettsia rickettsii, the etiological agent of Brazilian spotted fever.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25501172"}, {"offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "The hard tick Amblyomma aureolatum (Pallas) is a vector of the bacterium Rickettsia rickettsii, the etiologic agent of Brazilian spotted fever (BSF) in parts of Brazil.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27230435"}, {"offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Brazilian spotted fever (BSF) is an endemic anthropozoonosis caused by Gram-negative bacteria (Rickettsia rickettsii) that is associated with the risk of human infection by ticks.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28377149"}, {"offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Brazilian spotted fever (BSF) is a potentially lethal human disease caused by Rickettsia rickettsii transmitted by ticks, including Amblyomma sculptum.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29050834"}, {"offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Brazilian spotted fever (BSF) is a highly lethal disease caused by Rickettsia rickettsii.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17114770"}, {"offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Brazilian spotted fever (BSF) caused by Rickettsia rickettsii is the most important rickettsiosis and the only reportable tick-borne disease in Brazil.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23168052"}, {"offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Brazilian spotted fever, caused by Rickettsia rickettsii, has been increasingly reported in Brazil especially in the southeastern states.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11980610"}, {"offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "Brazilian spotted fever (BSF) is a tick-borne disease caused by the bacterium Rickettsia rickettsii, the deadliest spotted fever of the world, transmitted in southeastern Brazil mainly by the tick Amblyomma sculptum, a member of the Amblyomma cajennense species complex.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31014644"}, {"offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Rickettsia rickettsii infection is being increasingly recognized as an important cause of fatal acute illness in Brazil, where this tick-borne disease is designated Brazilian spotted fever (BSF).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25483025"}, {"offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Brazilian spotted fever (BSF) is an emerging disease most likely caused by Rickettsia rickettsii.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21184706"}, {"offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "The bacterium Rickettsia rickettsii is the etiological agent of Brazilian spotted fever (BSF), and its most important vector to humans in Brazil is the tick Amblyomma sculptum. Capybaras are the main hosts of A. sculptum in many BSF-endemic areas and are considered valuable sentinels for BSF surveillance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36169507"}, {"offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "In Brazil, Spotted Fever (SF) is caused by Rickettsia rickettsii and Rickettsia parkeri strain Atlantic Forest.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28535905"}, {"offsetInBeginSection": 178, "offsetInEndSection": 324, "text": "The current reemergence of spotted fever rickettsiosis caused by Rickettsia rickettsii in Brazil has resulted in a high proportion of fatal cases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14718082"}, {"offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "BACKGROUND: Brazilian spotted fever (BSF), caused by the bacterium Rickettsia rickettsii, has been associated with the transmission by the tick Amblyomma sculptum, and one of its main hosts, the capybara (Hydrochoerus hydrochaeris)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31490924"}, {"offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "In Brazil, two pathogenic Rickettsia species have been identified causing tick-borne spotted fever (SF). The aetiological agent Rickettsia rickettsii causes serious illness, particularly in the south-eastern region of the country.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28169507"}, {"offsetInBeginSection": 74, "offsetInEndSection": 169, "text": "These ticks transmit the bacterium Rickettsia rickettsii, which causes Brazilian Spotted Fever.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31800889"}, {"offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Isolation of Rickettsia rickettsii from the tick Amblyomma sculptum from a Brazilian spotted fever-endemic area in the Pampulha Lake region, southeastern Brazil.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31014644"}, {"offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Brazilian spotted fever is an acute febrile infectious disease caused by Rickettsia rickettsii, transmitted by tick bite. As this disease is rare and has high mortality rates in Brazil, the clinical aspects and epidemiological data may help the diagnosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25830998"}, {"offsetInBeginSection": 0, "offsetInEndSection": 552, "text": "Brazilian spotted fever is an acute febrile infectious disease caused by Rickettsia rickettsii, transmitted by tick bite. As this disease is rare and has high mortality rates in Brazil, the clinical aspects and epidemiological data may help the diagnosis. We report a case of Brazilian spotted fever in a 19-year-old patient who presented maculopapular exanthema in the palmar region and upper limbs, lymphadenopathy, fever, chills, headache, conjunctival hyperemia, nausea, vomiting, dyspnea, myalgia, developing neurological signs and abdominal pain.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25830998"}, {"offsetInBeginSection": 0, "offsetInEndSection": 639, "text": "Brazilian spotted fever, caused by Rickettsia rickettsii, has been increasingly reported in Brazil especially in the southeastern states. The severe and fulminant forms of the disease are not unusual but most of the reported fatal cases have shown some typical clinical clue, which leads the attending physician to a correct diagnosis. We report a probable case of atypical fulminant Brazilian spotted fever that presented full-blown septic shock associated with Adult Respiratory Distress Syndrome (ARDS) and delayed uncharacteristic rash with an over four-fold increase in reciprocal IgM, but not IgG titer against Rickettsia rickettsii.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11980610"}, {"offsetInBeginSection": 0, "offsetInEndSection": 335, "text": "Brazilian spotted fever, caused by Rickettsia rickettsii, has been increasingly reported in Brazil especially in the southeastern states. The severe and fulminant forms of the disease are not unusual but most of the reported fatal cases have shown some typical clinical clue, which leads the attending physician to a correct diagnosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11980610"}, {"offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "In S\u00e3o Paulo metropolitan area, Brazil, Amblyomma aureolatum ticks are the main vector of Rickettsia rickettsii, which causes Brazilian spotted fever. In 2013, a boy in S\u00e3o Paulo died of Brazilian spotted fever associated with household dogs and A. aureolatum ticks.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31742533"}, {"offsetInBeginSection": 0, "offsetInEndSection": 337, "text": "In S\u00e3o Paulo metropolitan area, Brazil, Amblyomma aureolatum ticks are the main vector of Rickettsia rickettsii, which causes Brazilian spotted fever. In 2013, a boy in S\u00e3o Paulo died of Brazilian spotted fever associated with household dogs and A. aureolatum ticks. Prompt recognition and treatment of this illness might prevent deaths.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31742533"}, {"offsetInBeginSection": 96, "offsetInEndSection": 180, "text": "Brazilian spotted fever (BSF; caused by Rickettsia rickettsii) in Minas Gerais State", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18949349"}, {"offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Brazilian spotted fever (BSF) is caused by the bacterium Rickettsia rickettsii. Because of its high case-fatality rate and apparent increase in areas of transmission, it is considered to be the rickettsial illness of primary public health ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27812666"}, {"offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Brazilian Spotted Fever (BSF) is a zoonotic disease caused by the bacterium Rickettsia rickettsii. In the S\u00e3o Paulo Metropolitan Region (SPMR) it is transmitted by Amblyomma aureolatum ticks. In this region, annual lethality of the disease can reach 80% and spat", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27880877"}, {"offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Brazilian spotted fever, caused by Rickettsia rickettsii, has been increasingly reported in Brazil especially in the southeastern", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11980610"}, {"offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Brazilian spotted fever (BSF) caused by Rickettsia rickettsii is the most important rickettsiosis and the only reportable tick-borne disease in Brazil. In Brazil, the hard tick Amblyomm", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23168052"}, {"offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Brazilian spotted fever (BSF) is a highly lethal disease in southeastern Brazil. BSF is caused by the bacterium Rickettsia rickettsii and is transmitted by the bites of the tick of the genus Amblyomma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32315604"}, {"offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Brazilian spotted fever (BSF) is a common tick-borne disease caused by Rickettsia rickettsii. Horses are the primary hosts of the main vector, Amblyomma sculptum, and are considered efficient sentinels for circulation of Rickettsia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33825800"}, {"offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "The bacterium Rickettsia rickettsii is the etiological agent of Brazilian spotted fever (BSF), and its most important vector to humans in Brazil is the tick Amblyomma sculptum.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36169507"}, {"offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Brazilian spotted fever (BSF) is caused by the bacterium Rickettsia rickettsii. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27812666"}, {"offsetInBeginSection": 0, "offsetInEndSection": 395, "text": "Brazilian spotted fever (BSF) caused by Rickettsia rickettsii is the most important rickettsiosis and the only reportable tick-borne disease in Brazil. In Brazil, the hard tick Amblyomma cajennense is the most important BSF vector; however, in S\u00e3o Paulo State, A. aureolatum was also recognized as a vector species in remaining Atlantic forest areas near the metropolitan area of S\u00e3o Paulo city.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23168052"}, {"offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Rocky Mountain spotted fever is endemic to the S\u00e3o Paulo metropolitan area, Brazil, where the etiologic agent, Rickettsia rickettsii, is transmitted to humans by adult Amblyomma aureolatum ticks.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25148391"}, {"offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Amblyomma aureolatum ticks are vectors of Rickettsia rickettsii, the etiologic agent of Rocky Mountain spotted fever in Brazil.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30334709"}, {"offsetInBeginSection": 84, "offsetInEndSection": 290, "text": "Rickettsia rickettsii, transmitted by the ticks Amblyomma cajennense, and Amblyomma aureolatum, reported in Colombia, Argentina, and Brazil, where it is the etiological agent of Rocky Mountain spotted fever", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19538276"}]}
+{"question_id": "65cfcf201930410b1300001b", "question": "Can Nitrofurantoin cause Lung Injury?", "answer": "Yes. Nitrofurantoin can cause a spectrum of lung injuries, from acute hypersensitivity reactions that might be fatal to chronic reactions involving fibrosis.", "relevant_passage_ids": ["37809109", "34407964", "33243181", "33088545", "31890712", "33853812", "24772739", "25747822", "27625984", "19534638", "2981942", "29288483", "28306135", "32953319", "35145797", "32238797", "6838054", "10334121", "26912767", "27778245", "464388", "1313237", "18495029", "8234222", "8771575", "7323444", "2644915", "35121574", "22836745", "2703684"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Nitrofurantoin-Induced Lung Injury: A Reminder of an Overlooked Threat.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37809109"}, {"offsetInBeginSection": 112, "offsetInEndSection": 291, "text": "Although relatively rare, nitrofurantoin can cause a spectrum of lung injuries, from acute hypersensitivity reactions that might be fatal to chronic reactions involving fibrosis. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37809109"}, {"offsetInBeginSection": 1882, "offsetInEndSection": 2013, "text": "CONCLUSION: NF can cause marked or irreversible lung complications and there is currently a shortfall in awareness and monitoring. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34407964"}, {"offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Reversible lung fibrosis in a 6-year-old girl after long term nitrofurantoin treatment.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33243181"}, {"offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "BACKGROUND: Pulmonary side effects are well known, including lung fibrosis, in elderly patients treated with long-term nitrofurantoin to prevent urinary tract infections and secondary renal injury.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33243181"}, {"offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "A rare case of nitrofurantoin-induced acute lung injury.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33088545"}, {"offsetInBeginSection": 67, "offsetInEndSection": 189, "text": "Acute lung injury resulting from nitrofurantoin is a rare, life-threatening complication with women being at greater risk.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33088545"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Long-term nitrofurantoin: an analysis of complication awareness, monitoring, and pulmonary injury cases.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34407964"}, {"offsetInBeginSection": 12, "offsetInEndSection": 196, "text": "Pulmonary side effects are well known, including lung fibrosis, in elderly patients treated with long-term nitrofurantoin to prevent urinary tract infections and secondary renal injury", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33243181"}, {"offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "Consider Nitrofurantoin as a Cause of Lung Injury.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31890712"}, {"offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Spontaneous resolution of nitrofurantoin-induced chronic pulmonary toxicity presenting with respiratory failure.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29288483"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "How Common Are Pulmonary and Hepatic Adverse Effects in Older Adults Prescribed Nitrofurantoin?", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28306135"}, {"offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Nitrofurantoin (NF) is a urinary antimicrobial drug which causes pulmonary injury. We measured levels of total lung", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7323444"}, {"offsetInBeginSection": 13, "offsetInEndSection": 112, "text": "lung disease (ILD) is a rare adverse effect of nitrofurantoin and can range from benign infiltrates", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26912767"}, {"offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Nitrofurantoin, a commonly used urinary antiseptic, is associated with significant pulmonary toxicity. This study used a 51Cr rat lung", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6838054"}, {"offsetInBeginSection": 722, "offsetInEndSection": 877, "text": "Pulmonary or hepatic injury caused by nitrofurantoin treatment is rare; their combined occurrence is hardly ever described. Combined drug-induced pulmonary", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10334121"}, {"offsetInBeginSection": 138, "offsetInEndSection": 303, "text": "nitrofurantoin is one of the commonest causes of drug-induced pulmonary disease, which can be potentially serious and even fatal. Knowledge of such potential adverse", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22836745"}, {"offsetInBeginSection": 89, "offsetInEndSection": 369, "text": "Our study indicates that nitrofurantoin may produce lung injury by directly stimulating lung parenchymal cells to generate toxic oxygen species such as superoxide and hydrogen peroxide, which can overwhelm cellular antioxidant defenses and result in permanent injury to the cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2981942"}, {"offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Nitrofurantoin, a urinary antiseptic, is associated with significant pulmonary toxicity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2981942"}, {"offsetInBeginSection": 814, "offsetInEndSection": 1391, "text": "It is important that clinicians are aware of the spectrum of side effects associated with nitrofurantoin so as to monitor patients.LEARNING POINTS: It is crucial to ensure that a thorough medical history with a systems review and a complete drug history are carried out.Chronic pulmonary toxicity due to nitrofurantoin is rare and it occurs primarily in older women who have been prescribed relatively small doses of nitrofurantoin for UTI prevention.The cessation of nitrofurantoin is the basis of the treatment and may be sufficient for clinical and radiological improvement.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31890712"}, {"offsetInBeginSection": 0, "offsetInEndSection": 26, "text": "Fatal nitrofurantoin lung.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24772739"}, {"offsetInBeginSection": 814, "offsetInEndSection": 1041, "text": "These data suggest that nitrofurantoin can directly injure lung parenchymal cells, probably through oxidant mechanisms, and this might suggest alternative approaches in the evaluation and therapy of patients with this disorder.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6838054"}, {"offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Nitrofurantoin-induced diffuse lung toxicity is well documented in the literature but is often misdiagnosed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31890712"}, {"offsetInBeginSection": 1068, "offsetInEndSection": 1249, "text": "are carried out.Chronic pulmonary toxicity due to nitrofurantoin is rare and it occurs primarily in older women who have been prescribed relatively small doses of nitrofurantoin for", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31890712"}, {"offsetInBeginSection": 288, "offsetInEndSection": 449, "text": "We describe the case of a 73-year-old female who developed interstitial lung disease following chronic use of nitrofurantoin for a urinary tract infection (UTI).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27778245"}, {"offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Nitrofurantoin-induced pulmonary fibrosis: a case report.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18495029"}, {"offsetInBeginSection": 0, "offsetInEndSection": 38, "text": "Acute lung toxicity by nitrofurantoin.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33853812"}, {"offsetInBeginSection": 384, "offsetInEndSection": 466, "text": "One of the medications that can cause interstitial lung disease is nitrofurantoin.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32238797"}, {"offsetInBeginSection": 479, "offsetInEndSection": 818, "text": "A 88-year-old man with recurrent urinary tract infections was treated with long-term nitrofurantoin prophylactic therapy. He took 100 mg of nitrofurantoin on a daily basis for over 10 years as prophylactic therapy for recurrent urinary tract infections, and subsequently developed chronic respiratory failure requiring supplemental oxygen.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32238797"}, {"offsetInBeginSection": 333, "offsetInEndSection": 486, "text": "Nitrofurantoin-associated pulmonary injuries occur in 1% of patients, presenting with dyspnoea and dry cough, and it can mimic interstitial lung disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33853812"}, {"offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "Nitrofurantoin is a commonly prescribed antibiotic for urinary tract infection (UTI) treatment and prophylaxis. Although relatively rare, nitrofurantoin can cause a spectrum of lung injuries, from acute hypersensitivity reactions that might be fatal to chronic reactions involving fibrosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37809109"}, {"offsetInBeginSection": 0, "offsetInEndSection": 400, "text": "Nitrofurantoin is frequently used by the physiatrist for treatment of urinary tract infections or for urinary antimicrobial prophylaxis. There is a substantial risk of acute and chronic pulmonary side effects with this medication. The acute pulmonary toxicity presents with fever, leukocytosis, dyspnea, and nonproductive cough. Chronic nitrofurantoin use can lead to interstitial pulmonary fibrosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2644915"}, {"offsetInBeginSection": 0, "offsetInEndSection": 404, "text": "Nitrofurantoin is one of the most common drugs implicated in drug-induced pulmonary toxicities, the manifestations of which range from dose-independent acute self-limiting reactions to chronic dose-dependent pathologies. The severity of these pulmonary adverse effects may range from trivial hypersensitivity reactions to extensive and irreversible lung fibrosis leading to respiratory failure and death.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29288483"}, {"offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Nitrofurantoin lung toxicity was diagnosed among ten patients receiving 50 mg/day to prevent recurrent urinary tract infection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19534638"}, {"offsetInBeginSection": 406, "offsetInEndSection": 649, "text": "Data from this study showed that nitrofurantoin (200 mg/kg, s.c.) resulted in transient but measurable lung damage as evidenced by the increases in wet lung weight/body weight ratio and decreases in lung angiotensin converting enzyme activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1313237"}, {"offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Nitrofurantoin has been documented as a cause of acute, sub-acute, and chronic pulmonary injury.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27625984"}, {"offsetInBeginSection": 1307, "offsetInEndSection": 1400, "text": "LUSION: This case shows that the use of nitrofurantoin may cause severe pulmonary disease. Pa", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18495029"}, {"offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "The subcutaneous administration of nitrofurantoin to rats caused severe pulmonary damage, characterized by edema, congestion, and hemorrhage.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/464388"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "This paper describes a case of lung injury attributed to the use of Nitrofurantoin and a review of the relevant literature.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25747822"}, {"offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Acute pulmonary reactions to nitrofurantoin are an uncommon side effect of therapy and can cause minor or life-threatening pulmonary dysfunction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8771575"}, {"offsetInBeginSection": 86, "offsetInEndSection": 272, "text": "Since this chemotherapeutic agent was introduced in the fifties, quite a number of cases of acute and chronic pulmonary damage have been reported that were conditioned by nitrofurantoin.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8234222"}, {"offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Pulmonary toxicity is the most well-known severe complication related to both methotrexate and nitrofurantoin, which can present as acute, subacute, and chronic", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35145797"}, {"offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Nitrofurantoin-Induced Pulmonary Toxicity: Always Review the Medication List.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32953319"}, {"offsetInBeginSection": 54, "offsetInEndSection": 158, "text": " Long-term nitrofurantoin: an analysis of complication awareness, monitoring, and pulmonary injury cases", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35121574"}, {"offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Nitrofurantoin (NF) is a urinary antimicrobial drug which causes pulmonary injury.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7323444"}, {"offsetInBeginSection": 112, "offsetInEndSection": 478, "text": "Although relatively rare, nitrofurantoin can cause a spectrum of lung injuries, from acute hypersensitivity reactions that might be fatal to chronic reactions involving fibrosis. Therefore, treating physicians' awareness and regular monitoring is essential for early recognition, drug withdrawal, avoiding unnecessary treatment, and preventing irreversible fibrosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37809109"}, {"offsetInBeginSection": 67, "offsetInEndSection": 295, "text": "Acute lung injury resulting from nitrofurantoin is a rare, life-threatening complication with women being at greater risk. Symptoms include respiratory distress with fevers, rash, eosinophilia, and new-onset atrial fibrillation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33088545"}, {"offsetInBeginSection": 67, "offsetInEndSection": 396, "text": "Acute lung injury resulting from nitrofurantoin is a rare, life-threatening complication with women being at greater risk. Symptoms include respiratory distress with fevers, rash, eosinophilia, and new-onset atrial fibrillation. Treatment includes discontinuing the drug and possibly glucocorticoids for persistent oxygen demand.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33088545"}, {"offsetInBeginSection": 69, "offsetInEndSection": 478, "text": "It acts by damaging bacterial DNA. It is given in dose of 50-100 mg orally and is generally considered a safe drug but has occasionally been known to cause pulmonary toxicity which is usually reversible and only rarely fatal. We present a case of an elderly lady receiving nitrofurantoin for her urinary tract infection who developed sudden acute lung injury to which she finally succumbed within a few weeks.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24772739"}, {"offsetInBeginSection": 333, "offsetInEndSection": 467, "text": "Nitrofurantoin-associated pulmonary injuries occur in 1% of patients, presenting with dyspnoea and dry cough, and it can mimic interst", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33853812"}, {"offsetInBeginSection": 13, "offsetInEndSection": 168, "text": "lung disease (ILD) is a rare adverse effect of nitrofurantoin and can range from benign infiltrates to a fatal condition. Nitrofurantoin acts via inhibitin", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26912767"}, {"offsetInBeginSection": 722, "offsetInEndSection": 887, "text": "Pulmonary or hepatic injury caused by nitrofurantoin treatment is rare; their combined occurrence is hardly ever described. Combined drug-induced pulmonary and hepat", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10334121"}, {"offsetInBeginSection": 0, "offsetInEndSection": 881, "text": "Acute pulmonary reactions to nitrofurantoin are an uncommon side effect of therapy and can cause minor or life-threatening pulmonary dysfunction. Symptoms include fever, chills, cough, pleuritic chest pain, dyspnea. Rarely, pleural effusion and/or pulmonary hemorrhage may occur. Diagnosis is made by clinical suspicion and exclusion of other causes of respiratory compromise. Bronchoalveolar lavage (BAL) may be used to rule out infectious etiologies, and an increase in BAL fluid eosinophils is suggestive of drug-induced toxicity. The acute reaction to nitrofurantoin is believed to be mediated by an immune mechanism. Treatment is mainly discontinuation of the drug, however, corticosteroid therapy is recommended for severe reactions. A chronic reaction associated with long-term treatment with nitrofurantoin has also been reported and causes irreversible pulmonary fibrosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8771575"}, {"offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "Nitrofurantoin is a widely prescribed antibiotic used for the treatment of urinary tract infections. In some patients it can produce an acute pulmonary reaction ranging from mild dyspnea to noncardiogenic pulmonary edema. Symptoms include fever, dyspnea, chills, cough, and chest pain.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2703684"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1461, "text": "INTRODUCTION: Nitrofurantoin is a commonly used drug in the treatment and prevention of urinary tract infections. Many adverse effects of nitrofurantoin have been documented, including aplastic anemia, polyneuritis, and liver and pulmonary toxicity.CASE PRESENTATION: We describe the clinical history and the autopsy findings in a 51-year-old woman with lung fibrosis of unknown etiology. She had a history of recurrent urinary tract infections, treated with nitrofurantoin for many years. She was referred to our hospital for screening for lung transplantation because of severe pulmonary restriction and dyspnea. Unfortunately, she died as a result of progressive respiratory insufficiency. At autopsy bilateral patchy, sharply circumscribed fibrotic areas in the upper and lower lobes of the lungs were seen with honeycombing. Microscopically, end-stage interstitial fibrosis with diffuse alveolar damage was observed. Due to the atypical distribution of the fibrosis involving both the lower and upper lobes of the lung, the microscopic pattern of the fibrosis and the history of long-term nitrofurantoin use, we concluded that this drug induced the lung fibrosis. The recurrent urinary tract infections were probably caused by a diverticulum of the urinary bladder, which was discovered at autopsy.CONCLUSION: This case shows that the use of nitrofurantoin may cause severe pulmonary disease. Patients with long-term use of nitrofurantoin should be monitor", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18495029"}, {"offsetInBeginSection": 0, "offsetInEndSection": 593, "text": "Nitrofurantoin is frequently used by the physiatrist for treatment of urinary tract infections or for urinary antimicrobial prophylaxis. There is a substantial risk of acute and chronic pulmonary side effects with this medication. The acute pulmonary toxicity presents with fever, leukocytosis, dyspnea, and nonproductive cough. Chronic nitrofurantoin use can lead to interstitial pulmonary fibrosis. A case is reported of a 47-year-old spinal cord injured woman with an acute pulmonary reaction to nitrofurantoin. The literature pertaining to pulmonary toxicity of nitrofurantoin is reviewed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2644915"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1375, "text": "Nitrofurantoin-induced diffuse lung toxicity is well documented in the literature but is often misdiagnosed. We describe an 82-year-old female medicated with nitrofurantoin for the previous 2 years who was admitted for dyspnoea, dry cough and fatigue for 4 months. She was febrile and tachypnoeic and she presented with bilateral basal crackles, hypoxaemic respiratory failure and slightly elevated C-reactive protein levels. A chest radiograph showed bilateral air-space consolidation and interstitial infiltrates and the high-resolution computed tomography scan was evocative of a perilobular pattern of organising pneumonia (OP). Due to the clinical-radiological context, she was diagnosed with a presumable nitrofurantoin-induced OP. She was started on prednisolone 60 mg daily with a progressive improvement. It is important that clinicians are aware of the spectrum of side effects associated with nitrofurantoin so as to monitor patients.LEARNING POINTS: It is crucial to ensure that a thorough medical history with a systems review and a complete drug history are carried out.Chronic pulmonary toxicity due to nitrofurantoin is rare and it occurs primarily in older women who have been prescribed relatively small doses of nitrofurantoin for UTI prevention.The cessation of nitrofurantoin is the basis of the treatment and may be sufficient for clinical and radiologi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31890712"}, {"offsetInBeginSection": 135, "offsetInEndSection": 323, "text": "Nitrofurantoin acts via inhibiting the protein synthesis in bacteria by helping reactive intermediates and is known to produce primary lung parenchymal injury through an oxidant mechanism.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26912767"}]}
+{"question_id": "66099a25fdcbea915f00001e", "question": "What is the first-line treatment for BRAF mutated advanced colorectal cancer patients?", "answer": "The current standard therapies for first-line treatment of BRAF-mutated mCRC are chemotherapy with bevacizumab as well as 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab in patients with a good performance status. FOLFOXIRI plus bevacizumab is a feasible treatment option for those patients who meet the inclusion criteria of the present study, irrespective of baseline clinical characteristics and RAS or BRAF mutational status", "relevant_passage_ids": ["26338525", "33836264", "24138831", "36849918", "28214977", "23666916", "24390240", "33734401", "35649231", "37639010", "37971411", "30120161", "37455182", "35130499", "31661924", "27943689", "32867715", "36475784", "37815847", "33108877", "30592501", "37760573", "32326305", "33914242", "33987088", "37352476", "37369457", "34761599", "32318348", "31455117"], "type": "factoid", "snippets": [{"offsetInBeginSection": 883, "offsetInEndSection": 1132, "text": "The current standard therapies for first-line treatment of BRAF-mutated mCRC are chemotherapy with bevacizumab as well as 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab in patients with a good performance status", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33836264"}, {"offsetInBeginSection": 2733, "offsetInEndSection": 2947, "text": "FOLFOXIRI plus bevacizumab is a feasible treatment option for those patients who meet the inclusion criteria of the present study, irrespective of baseline clinical characteristics and RAS or BRAF mutational status", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26338525"}, {"offsetInBeginSection": 2292, "offsetInEndSection": 2621, "text": "Median overall survival was 37\u00b71 months (95% CI 29\u00b77-42\u00b77) in the RAS and BRAF wild-type subgroup compared with 25\u00b76 months (22\u00b74-28\u00b76) in the RAS-mutation-positive subgroup (HR 1\u00b749, 95% CI 1\u00b711-1\u00b799) and 13\u00b74 months (8\u00b72-24\u00b71) in the BRAF-mutation-positive subgroup (HR 2\u00b779, 95% CI 1\u00b775-4\u00b746; likelihood-ratio test p<0\u00b70001). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26338525"}, {"offsetInBeginSection": 49, "offsetInEndSection": 329, "text": "the most frequently used first-line treatments for patients with BRAF-mutant colorectal cancer (CRC), while second-line treatment requires extensive further research. In this pooled analysis, we evaluate the impact of anti-angiogenics in patients with pre-treated BRAF-mutant CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32326305"}, {"offsetInBeginSection": 579, "offsetInEndSection": 822, "text": "for patients with BRAFV600E-mutated metastatic colorectal cancer include first-line cytotoxic chemotherapy plus bevacizumab and subsequent therapy with the BRAF inhibitor encorafenib and antiepidermal growth factor receptor antibody cetuximab.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35649231"}, {"offsetInBeginSection": 131, "offsetInEndSection": 300, "text": "However, there are no clear recommendations regarding first-line therapy for patients with early recurrent BRAF V600E-mutated CRC, during or after adjuvant chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36475784"}, {"offsetInBeginSection": 1313, "offsetInEndSection": 1730, "text": "The Binimetinib, Encorafenib, And Cetuximab cOmbiNed to treat BRAF-mutant ColoRectal Cancer (BEACON CRC) study represents the largest study in this population to date and has given strong clinical evidence to support BRAF and epidermal growth factor receptor inhibition with the combination of encorafenib plus cetuximab.CONCLUSIONS: The treatment of BRAF-mutated mCRC has evolved rapidly over the last several years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33836264"}, {"offsetInBeginSection": 1635, "offsetInEndSection": 1959, "text": "Surgical treatment of the primary tumor (P\u2009=\u20090.041; HR, 0.523; 95% CI, 0.280-0.974) was significantly associated with PFS too.CONCLUSION: For patients with BRAF V600E-mutated advanced CRC, chemotherapy alone did not differ significantly in OS and PFS compared with chemotherapy\u2009+\u2009bevacizumab for advanced first-line therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36849918"}, {"offsetInBeginSection": 504, "offsetInEndSection": 822, "text": "On the basis of recent clinical trials, current standard-of-care therapies for patients with BRAFV600E-mutated metastatic colorectal cancer include first-line cytotoxic chemotherapy plus bevacizumab and subsequent therapy with the BRAF inhibitor encorafenib and antiepidermal growth factor receptor antibody cetuximab.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35649231"}, {"offsetInBeginSection": 855, "offsetInEndSection": 1105, "text": "es in this setting.RESULTS: The current standard therapies for first-line treatment of BRAF-mutated mCRC are chemotherapy with bevacizumab as well as 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab in patients wit", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33836264"}, {"offsetInBeginSection": 1571, "offsetInEndSection": 1685, "text": "domised trials in this specific molecular subgroup, FOLFOXIRI plus bevacizumab might be a reasonable option for th", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24138831"}, {"offsetInBeginSection": 2659, "offsetInEndSection": 2874, "text": " different across molecular subgroups (pinteraction=0\u00b752).INTERPRETATION: FOLFOXIRI plus bevacizumab is a feasible treatment option for those patients who meet the inclusion criteria of the present study, irrespecti", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26338525"}, {"offsetInBeginSection": 1037, "offsetInEndSection": 1276, "text": "Despite the lack of a randomized phase 3 study dedicated to BRAF-mutated CRC, chemotherapy intensification combining a quadruple association of 5-fluorouracil, oxaliplatin, irinotecan (FOLFOXIRI), and bevacizumab seems like a valid option.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28214977"}, {"offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "BACKGROUND: FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab has shown to be one of the therapeutic regimens in first line with the highest activity in patients (pts.)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32867715"}, {"offsetInBeginSection": 770, "offsetInEndSection": 1282, "text": "This article reviews the progress of clinical research on molecularly targeted drugs, immune checkpoint inhibitors, first-line chemotherapeutic agents, and different combination therapy regimens (including different targeted drug combinations, immune combination targeting, and chemotherapy combination targeting) for colorectal cancer patients with BRAF V600E mutation, which provides a reference for further in-depth clinical exploration of the treatment of colorectal cancer patients with BRAF V600E mutation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37639010"}, {"offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "TRESBIEN (OGSG 2101): encorafenib, binimetinib and cetuximab for early recurrent stage II/III ", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36475784"}, {"offsetInBeginSection": 1458, "offsetInEndSection": 1763, "text": "Median OS analyzed at an event rate of 64.5% showed a trend toward shorter survival in cetuximab-treated patients (12.9 months v 17.1 months; HR, 1.4; P = .20).CONCLUSION: To our knowledge, FIRE-4.5 is the first prospective and randomized study investigating first-line treatment of BRAFV600E-mutant mCRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37352476"}, {"offsetInBeginSection": 1914, "offsetInEndSection": 2028, "text": "Bevacizumab-based chemotherapy remains the preferable first-line treatment of patients with BRAFV600E-mutant mCRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37352476"}, {"offsetInBeginSection": 429, "offsetInEndSection": 657, "text": "Chemotherapy plus bevacizumab is the current standard therapy in first-line treatment of BRAF-mutated metastatic CRC (mCRC), with triplet (FOLFOXIRI) plus bevacizumab as a valid option in patients with a good performance status.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31661924"}, {"offsetInBeginSection": 1147, "offsetInEndSection": 1353, "text": "95% CI, 0.41-0.56; P<.001). Only 3% of patients with BRAF mutations received first-line FOLFOXIRI \u00b1 bevacizumab, with a median OS of 13.8 months compared with 15.5 months in those treated with doublet chemo", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35130499"}, {"offsetInBeginSection": 1354, "offsetInEndSection": 1629, "text": "herapy \u00b1 bevacizumab (P=.38). In patients with BRAF mutations, propensity-weighted analysis did not detect a significant improvement in OS with FOLFIRI + bevacizumab (HR, 0.90; 95% CI, 0.58-1.39; P=.63) or FOLFOX/CAPEOX + bevacizumab (HR, 0.81; 95% CI, 0.52-1.26; P=.35) vers", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35130499"}, {"offsetInBeginSection": 1009, "offsetInEndSection": 1318, "text": "Currently, three biologic agents-bevacizumab, cetuximab, and panitumumab-are approved for first-line treatment of metastatic colorectal cancer. For patients with mutant RAS and likely mutant BRAF V600E tumors, bevacizumab is the only biologic agent that can be used in conjunction with cytotoxic chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27943689"}, {"offsetInBeginSection": 1153, "offsetInEndSection": 1318, "text": "For patients with mutant RAS and likely mutant BRAF V600E tumors, bevacizumab is the only biologic agent that can be used in conjunction with cytotoxic chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27943689"}, {"offsetInBeginSection": 1049, "offsetInEndSection": 1377, "text": "Multivariate analysis indicated that age (HR:0.41,p=0.045), primary tumor resection (HR:0.41,p=0.037) and primary tumor localization (HR:0.38,p=0.021) for PFS and age (HR:0.39, p=0.09), the presence of BRAF mutation (HR:0.59,p=0.019) and the type of targeted therapy (HR:3.16,p=0.025) for OS were independent prognostic factors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34761599"}, {"offsetInBeginSection": 499, "offsetInEndSection": 1208, "text": "ing. On the basis of recent clinical trials, current standard-of-care therapies for patients with BRAFV600E-mutated metastatic colorectal cancer include first-line cytotoxic chemotherapy plus bevacizumab and subsequent therapy with the BRAF inhibitor encorafenib and antiepidermal growth factor receptor antibody cetuximab. Treatment regimens currently under exploration in BRAFV600E-mutant metastatic colorectal cancer include combinatorial options of various pathway-targeted therapies, cytotoxic chemotherapy, and/or immune checkpoint blockade, among others. Circumvention of adaptive and acquired resistance to BRAF-targeted therapies is a significant challenge to be overcome in BRAF-mutated advanced col", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35649231"}, {"offsetInBeginSection": 499, "offsetInEndSection": 1045, "text": "ing. On the basis of recent clinical trials, current standard-of-care therapies for patients with BRAFV600E-mutated metastatic colorectal cancer include first-line cytotoxic chemotherapy plus bevacizumab and subsequent therapy with the BRAF inhibitor encorafenib and antiepidermal growth factor receptor antibody cetuximab. Treatment regimens currently under exploration in BRAFV600E-mutant metastatic colorectal cancer include combinatorial options of various pathway-targeted therapies, cytotoxic chemotherapy, and/or immune checkpoint blockade", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35649231"}, {"offsetInBeginSection": 499, "offsetInEndSection": 812, "text": "ing. On the basis of recent clinical trials, current standard-of-care therapies for patients with BRAFV600E-mutated metastatic colorectal cancer include first-line cytotoxic chemotherapy plus bevacizumab and subsequent therapy with the BRAF inhibitor encorafenib and antiepidermal growth factor receptor antibody ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35649231"}, {"offsetInBeginSection": 216, "offsetInEndSection": 562, "text": " BRAF mutated colorectal cancer define specific challenging subgroup associated with dismal prognosis, lower rate of response rate, shorter progression free survival and overall survival. Current treatment choices are associated with poor outcomes. For the first line treatment doublet or triplet chemotherapy plus antiangiogenic antibody is used", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33108877"}, {"offsetInBeginSection": 2023, "offsetInEndSection": 2173, "text": "utated mCRC with progression following first-line with FOLFOXIRI plus bevacizumab, although tolerability was acceptable. Our trial suggests that explo", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30120161"}, {"offsetInBeginSection": 802, "offsetInEndSection": 1852, "text": "mCRC, with a focus on recent clinical research advances in this setting.RESULTS: The current standard therapies for first-line treatment of BRAF-mutated mCRC are chemotherapy with bevacizumab as well as 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab in patients with a good performance status. Combination strategies involving mitogen-activated protein kinase (MAPK) pathway blockade have shown promising results for the treatment of patients with BRAF V600E-mutated mCRC. The Binimetinib, Encorafenib, And Cetuximab cOmbiNed to treat BRAF-mutant ColoRectal Cancer (BEACON CRC) study represents the largest study in this population to date and has given strong clinical evidence to support BRAF and epidermal growth factor receptor inhibition with the combination of encorafenib plus cetuximab.CONCLUSIONS: The treatment of BRAF-mutated mCRC has evolved rapidly over the last several years. Recently, combination strategies involving MAPK pathway blockade have shown promising results in BRAF V600E-mutated mCRC,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33836264"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1528, "text": "Colorectal cancer (CRC) is a highly lethal disease worldwide. The majority of patients receiving targeted therapy or chemotherapy develop drug resistance, while its molecular mechanism remains to be elucidated. The plasma circulating tumor DNA (ctDNA) exhibited the potential in identifying gene variations and monitoring drug resistance in CRC treatment. In this study, we monitored the ctDNA mutational changes in advanced CRC patients underwent first-line therapy with bevacizumab and cetuximab combined with chemotherapy. The mutation spectrum of 43 patients was established by a 605-gene next-generation sequencing (NGS) panel. The baseline measurement shows that genes with the highest mutation frequency were TP53 (74%), APC (58%), KRAS (40%), SYNE1 (33%), LRP1B (23%), TOP1 (23%), and PIK3CA (21%). Mutations in TP53, APC, and KRAS were detected in 29 paired plasma and tissue samples with the consistency of 81, 67, and 42%, respectively. Clinically targetable gene mutations, such as APC, RNF43, SMAD4, BRAD1, KRAS, RAF1, and TP53, were also identified in ctDNA. The overall consistency between ctDNA and tissue samples was 54.6%. Alleviation of mutational burden in BRAF, KRAS, AMER1, and other major driving genes was observed following the first-line therapy. Patients with KRAS and TP53 mutations in tissues appeared to benefit more than the wild-type counterpart. The dynamic change of plasma mutation status was consistent with the tissue tumor burden and was closely correlated with disease progression. In conc", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32318348"}, {"offsetInBeginSection": 453, "offsetInEndSection": 845, "text": "r outcomes. For the first line treatment doublet or triplet chemotherapy plus antiangiogenic antibody is used. To date, there were no reasonable treatment options in the second line settings. Recently published BEACON trial sets new standard of treatment with combination of encorafenib plus cetuximab, which led to significantly longer overall survival and overall response compared to stand", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33108877"}, {"offsetInBeginSection": 292, "offsetInEndSection": 473, "text": " trial that FOLFOXIRI (5-FU/LV+Oxaliplatin+Irinotecan) plus bevacizumab might allow to achieve remarkable results in terms of PFS and Overall Survival (OS) also in this poor-prognos", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24138831"}, {"offsetInBeginSection": 1508, "offsetInEndSection": 1685, "text": "rol rate were 72% and 88%, respectively.CONCLUSION: Lacking randomised trials in this specific molecular subgroup, FOLFOXIRI plus bevacizumab might be a reasonable option for th", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24138831"}]}
+{"question_id": "65f1d9f8c4010b4d78000006", "question": "List the causes of Restrictive cardiomyopathy (RCM)", "answer": "Three of the leading causes of Restrictive Cardiomyopathy RCM include cardiac amyloidosis, cardiac sarcoidosis, and cardiac hemochromatosis.", "relevant_passage_ids": ["28912185", "23079066", "18006163", "30260051", "20617149", "35345275", "22683325", "23906401", "34062949", "37719596", "34057638"], "type": "list", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 552, "text": "Restrictive cardiomyopathy (RCM) is characterized by nondilated left or right ventricle with diastolic dysfunction. The restrictive cardiomyopathies are a heterogenous group of myocardial diseases that vary according to pathogenesis, clinical presentation, diagnostic evaluation and criteria, treatment, and prognosis. In this review, an overview of RCMs will be presented followed by a detailed discussion on 3 major causes of RCM, for which tailored interventions are available: cardiac amyloidosis, cardiac sarcoidosis, and cardiac hemochromatosis. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28912185"}, {"offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Restrictive cardiomyopathy (RCM) has been linked to mutations in the thin filament regulatory protein cardiac troponin I (cTnI).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22683325"}, {"offsetInBeginSection": 2034, "offsetInEndSection": 2199, "text": "rapidly after diagnosed as primary RCM. Three heterozygous mutations including two in TNNI3 and one in TNNT2 gene are identified in the three RCMs respectively, whic", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23906401"}, {"offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Cardiac troponin mutations and restrictive cardiomyopathy.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20617149"}, {"offsetInBeginSection": 114, "offsetInEndSection": 247, "text": "In contrast, mutations in only desmin and cardiac troponin T and I (TNNI3) have been shown to cause restrictive cardiomyopathy (RCM).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18006163"}, {"offsetInBeginSection": 270, "offsetInEndSection": 479, "text": "To date, dominant variants causing RCM have been reported in a small number of sarcomeric or cytoskeletal genes, but the genetic causes in a majority of cases remain unexplained, especially in early childhood.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30260051"}, {"offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Cardiac amyloidosis is restrictive cardiomyopathy, commonly classified as either light-chain amyloidosis (AL) or transthyretin amyloidosis (ATTR), which can be further subdivided into wild-type (systemic senile amyloidosis) and hereditary ATTR amyloidosis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37719596"}, {"offsetInBeginSection": 588, "offsetInEndSection": 723, "text": "RCM can be idiopathic, familial, or secondary to a systemic disorder, such as amyloidosis, sarcoidosis, and hereditary hemochromatosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35345275"}, {"offsetInBeginSection": 724, "offsetInEndSection": 899, "text": "Approximately 30% of cases are familial RCM, and the genes that have been linked to RCM are cTnT, cTnI, MyBP-C, MYH7, MYL2, MYL3, DES, MYPN, TTN, BAG3, DCBLD2, LNMA, and FLNC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35345275"}, {"offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "Mutations in sarcomeric proteins have recently been established as heritable causes of Restrictive Cardiomyopathy (RCM). RCM is clinically characterized as a defect in cardiac diastolic function, such as, impaired ventricular relaxation, reduced diastolic volume and increased end-diastolic pressure.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20617149"}, {"offsetInBeginSection": 0, "offsetInEndSection": 425, "text": "Restrictive cardiomyopathy (RCM) is a rare primary myocardial disease, and its pathological features are yet to be determined. Restrictive cardiomyopathy with MHY7 mutation was diagnosed in a 65-year-old Japanese woman. Electron microscopy of a myocardial biopsy revealed electron-dense materials resulting from focal myocyte degeneration and necrosis as well as tubular structures and pseudo-inclusion bodies in some nuclei.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34057638"}, {"offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Hypertrophic cardiomyopathy (HCM) and primary restrictive cardiomyopathy (RCM) have a similar genetic background as they are both caused mainly by variants in sarcomeric genes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34062949"}, {"offsetInBeginSection": 0, "offsetInEndSection": 666, "text": "Hypertrophic cardiomyopathy (HCM) and primary restrictive cardiomyopathy (RCM) have a similar genetic background as they are both caused mainly by variants in sarcomeric genes. These \"sarcomeric cardiomyopathies\" also share diastolic dysfunction as the prevalent pathophysiological mechanism. Starting from the observation that patients with HCM and primary RCM may coexist in the same family, a characteristic pathophysiological profile of HCM with restrictive physiology has been recently described and supports the hypothesis that familiar forms of primary RCM may represent a part of the phenotypic spectrum of HCM rather than a different genetic cardiomyopathy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34062949"}, {"offsetInBeginSection": 664, "offsetInEndSection": 827, "text": "M patients (98.6%). RCM diagnoses included idiopathic (n = 227, 42%), amyloid (n = 142, 26%), sarcoid (n = 81, 15%), radiation/chemotherapy (XRT) (n = 35, 6%) and ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23079066"}]}
+{"question_id": "660d17dffdcbea915f000037", "question": "Trends of acute epiglottitis in children.", "answer": "Mortality due to epiglottitis in children has decreased since the adoption of the Haemophilus influenza Type b vaccination (Hib) in pediatric populations.", "relevant_passage_ids": ["33429180", "8143009", "17892608", "7602678", "7834888", "7651772", "7619418", "10542929", "24163979", "20018387", "11667996", "29926438", "21106138", "18502071", "16288684"], "type": "summary", "snippets": [{"offsetInBeginSection": 1323, "offsetInEndSection": 1421, "text": "Mortality from acute epiglottitis decreased after widespread adoption of Hib vaccination in the US", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33429180"}, {"offsetInBeginSection": 1423, "offsetInEndSection": 1492, "text": "Adults are now more likely than children to die of acute epiglottitis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33429180"}, {"offsetInBeginSection": 17, "offsetInEndSection": 106, "text": "acute epiglottitis in children is declining in the province of Quebec, Canada. In 1988, a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7602678"}, {"offsetInBeginSection": 0, "offsetInEndSection": 608, "text": "OBJECTIVE: To examine secular trends in the epidemiology, bacteriology, and clinical presentation of acute epiglottitis in children in the years surrounding the introduction of vaccine against Haemophilus influenzae type b.DESIGN: Retrospective chart review of patient series.SETTING: Large, urban, tertiary care pediatric hospital.SUBJECTS: One hundred forty-two children with epiglottitis admitted during a 14-year period (1979 through 1992).MAIN RESULTS: The average annual incidence of epiglottitis declined from 10.9 per 10,000 admissions before 1990 to 1.8 per 10,000 admissions from 1990 through 1992.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8143009"}, {"offsetInBeginSection": 1182, "offsetInEndSection": 1384, "text": "No important differences were found in any of a number of clinical characteristics based on causative organism or year of diagnosis.CONCLUSION: Acute epiglottitis has diminished in frequency since 1990.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8143009"}, {"offsetInBeginSection": 943, "offsetInEndSection": 1084, "text": "All patients recovered completely.CONCLUSIONS: In the H influenzae type b vaccine era, acute epiglottitis in children has almost disappeared.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17892608"}, {"offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Acute epiglottitis in children has almost vanished since the start of Hib vaccinations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163979"}, {"offsetInBeginSection": 1275, "offsetInEndSection": 1561, "text": "No marked change in the adult patient profile was found during this increase, however.CONCLUSION: Acute epiglottitis practically vanished among young children in this population after conjugate H influenzae vaccination, but adult cases increased, the patient profile remaining the same.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7619418"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "The incidence of acute epiglottitis in children is declining in the province of Quebec, Canada.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7602678"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "The incidence of acute epiglottitis in children has declined with the introduction of the Haemophilus influenzae b vaccine in 1992.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11667996"}, {"offsetInBeginSection": 208, "offsetInEndSection": 378, "text": "The incidence of Hib-induced epiglottitis in children has declined since the introduction of vaccinations in countries where such vaccinations are routinely administered.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29926438"}, {"offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Cases of acute epiglottitis in children have become very uncommon in recent years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10542929"}, {"offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Once a prevalent disease, acute epiglottitis in children has become a rare entity. The introduction of the Haemophilus influenzae type b vaccine has had a dramatic impact on the number of invasive infections caused by this organism.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20018387"}, {"offsetInBeginSection": 575, "offsetInEndSection": 958, "text": "erformed using gel precipitation.RESULTS: The overall incidence of acute epiglottitis was 0.98 cases/100,000/year, compared with 4.5 cases/100,000/year before the vaccination programme. The incidence was reduced both in children and adults, compared with pre-vaccination values. However, the incidence of Streptococcus pneumoniae epiglottitis in adults increased from 0.1 to 0.28 cas", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21106138"}, {"offsetInBeginSection": 557, "offsetInEndSection": 720, "text": "Childhood epiglottitis disappeared after introduction of Haemophilus influenzae type b (Hib) vaccination in 1989 but adult disease showed non-significant increase.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18502071"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1605, "text": "OBJECTIVE: To examine secular trends in the epidemiology, bacteriology, and clinical presentation of acute epiglottitis in children in the years surrounding the introduction of vaccine against Haemophilus influenzae type b.DESIGN: Retrospective chart review of patient series.SETTING: Large, urban, tertiary care pediatric hospital.SUBJECTS: One hundred forty-two children with epiglottitis admitted during a 14-year period (1979 through 1992).MAIN RESULTS: The average annual incidence of epiglottitis declined from 10.9 per 10,000 admissions before 1990 to 1.8 per 10,000 admissions from 1990 through 1992. The median age increased from 35.5 months in the earlier period to 80.5 months (P = .007). Overall, H influenzae type b was identified as the causative organism in 76% of patients, but in only 25% of the cases since 1990 (P = .004). Of the eight cases from 1990 through 1992, three had group A beta-hemolytic streptococcus isolated from a surface culture of the epiglottis; three other cases of group A beta-hemolytic streptococcus were identified earlier. These patients were significantly older than those with H influenzae type b disease (117.5 vs 35 months, P = .004). No important differences were found in any of a number of clinical characteristics based on causative organism or year of diagnosis.CONCLUSION: Acute epiglottitis has diminished in frequency since 1990. Patients whose conditions have been diagnosed since then tend to be older and to have disease caused by organisms other than H influenzae type b (particularly group A beta-hemolytic streptococcus). However, the clinical ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8143009"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1051, "text": "Over a period of 18 years 219 consecutive cases of acute epiglottitis were diagnosed and subsequently investigated in order to elucidate the aetiology, epidemiology and outcome of this disease in a well-defined population in Sweden before general vaccination against Haemophilus influenzae type b infection was introduced. Compared with the results from other parts of the industrialized world, high incidence rates were found in both children (14/100,000/year) and adults (2.3/100,000/year). The annual trend showed a significant decline in incidence among children, whereas in adults it remained unchanged. In cases where the aetiological agent could be determined, infection with H. influenzae type b was the main cause of disease in all age groups. However, in adults 27% (6/22) had a disease caused by micro-organisms other than H. influenzae type b that were verified with a blood culture. Sixty-eight per cent had a negative blood culture. The mortality rate was 0.5% (1/219) and 6% (13/219) developed a significant complication of the disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7834888"}, {"offsetInBeginSection": 0, "offsetInEndSection": 495, "text": "Paediatric cases of epiglottitis declined markedly in England following the introduction of safe effective immunization against Haemophilus influenzae type b (Hib). With the recently described resurgence in Hib infections, a corresponding rise in the number of presentations of clinical epiglottitis in children was observed, although numbers were still well below those reported prior to vaccine availability. This was seen both in microbiology reports and hospital admissions data for England.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16288684"}]}
+{"question_id": "65d12c451930410b13000032", "question": "Is Omaveloxolone effective for Friedreich Ataxia?", "answer": "Yes. Omaveloxolone is effective and approved for Friedreich Ataxia.", "relevant_passage_ids": ["33068037", "33430645", "38020600", "37691319", "37155124", "37219716", "36708320", "30065630", "38043492", "34845147"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1587, "offsetInEndSection": 1796, "text": "INTERPRETATION: In the MOXIe trial, omaveloxolone significantly improved neurological function compared to placebo and was generally safe and well tolerated. It represents a potential therapeutic agent in FA. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33068037"}, {"offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Omaveloxolone: potential new agent for Friedreich ataxia.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33430645"}, {"offsetInBeginSection": 517, "offsetInEndSection": 786, "text": "In this work, we review the evidence for use of omaveloxolone in FRDA from recent clinical trials. Though not at present approved for any indication, the present data suggest that this agent acting though increases in Nrf2 activity may provide a novel therapy for FRDA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33430645"}, {"offsetInBeginSection": 366, "offsetInEndSection": 506, "text": "Omaveloxolone has been recently approved as the first pharmacological treatment for FRDA in adults and adolescents aged 16\u2009years and older. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38020600"}, {"offsetInBeginSection": 1450, "offsetInEndSection": 1684, "text": "INTERPRETATION: These results suggest a meaningful slowing of Friedreich ataxia progression with omaveloxolone, and consequently detail how propensity-matched analysis may contribute to understanding of effects of therapeutic agents. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37691319"}, {"offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Omaveloxolone (SKYCLARYS\u2122) is an orally active, small molecule semi-synthetic triterpenoid drug that increases antioxidant activity, which is being developed by Reata Pharmaceuticals, Inc. for the treatment of Friedreich's ataxia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37155124"}, {"offsetInBeginSection": 588, "offsetInEndSection": 685, "text": "Omaveloxolone was approved in February 2023 in the USA for the treatment of Friedreich's ataxia. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37155124"}, {"offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "A Milestone in the Treatment of Ataxias: Approval of Omaveloxolone for Friedreich Ataxia.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37219716"}, {"offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "The exciting news about the US FDA approval of omaveloxolone as the first-ever drug to be approved for an inherited ataxia is welcome news for patients and families that deal with this devastating disease as well as for health care providers and investigators with an interest in this and other rare diseases. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37219716"}, {"offsetInBeginSection": 475, "offsetInEndSection": 703, "text": "Currently, the FDA has approved the Nrf2 activators dimethyl fumarate (DMF) and Omaveloxolone (Omav) as novel first-line oral drugs for the treatment of patients with relapsing forms of multiple sclerosis and Friedreich's ataxia", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38043492"}, {"offsetInBeginSection": 1466, "offsetInEndSection": 1682, "text": "These results suggest a meaningful slowing of Friedreich ataxia progression with omaveloxolone, and consequently detail how propensity-matched analysis may contribute to understanding of effects of therapeutic agents", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37691319"}, {"offsetInBeginSection": 685, "offsetInEndSection": 882, "text": "This article summarizes the milestones in the development of omaveloxolone leading to this first approval for the treatment of Friedreich's ataxia in adults and adolescents aged 16 years and older.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37155124"}, {"offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Omaveloxolone: an activator of Nrf2 for the treatment of Friedreich ataxia.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36708320"}, {"offsetInBeginSection": 278, "offsetInEndSection": 401, "text": "ars.RECENT FINDINGS: Recently, the use of omaveloxolone for 2\u200ayears significantly improved upright stability in Friedreich'", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34845147"}, {"offsetInBeginSection": 555, "offsetInEndSection": 716, "text": "Omaveloxolone (Omav) as novel first-line oral drugs for the treatment of patients with relapsing forms of multiple sclerosis and Friedreich's ataxia. A promising", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38043492"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1770, "text": "Friedreich's Ataxia (FRDA) is an autosomal recessive neurodegenerative disorder, affecting dorsal root ganglia (DRG), cerebellar dentate nuclei and heart. It is caused by a GAA repeat expansion mutation within the frataxin gene (FXN). This impedes FXN transcription resulting in a progressive decrease of the mitochondrial protein, frataxin. Increased oxidative stress leading to a chronic depletion of endogenous antioxidants affects the survival of the cells and causes neurodegeneration. In particular, cerebellar granule neurons (CGNs) show a significant increase of reactive oxygen species (ROS), lipid peroxidation and lower level of reduced glutathione (GSH). In FRDA, one of the major pathways of oxidant scavengers, the Nrf2 antioxidant pathway, is defective. Previous studies on FRDA-like CGNs showed that the reduced level of frataxin and the oxidative stress induce mitochondrial impairments. By triggering the Nrf2 endogenous pathway pharmacologically we determined whether this could promote mitochondrial fitness and counteract oxidative stress. In this work, we sought to investigate the beneficial effect of a promising Nrf2-inducer, omaveloxolone (omav), in CGNs from two FRDA mouse models, KIKO and YG8R, and human fibroblasts from patients. We found that CGNs from both KIKO and YG8R presented Complex I deficiency and that omav was able to restore substrate availability and Complex I activity. This was also confirmed in human primary fibroblasts from FRDA patients. Although fibroblasts are not the major tissue affected, we found that they show significant differences recapitulating the disease; this is therefore an important tool to investigate patients' pathophysiology. Interestingly, we found that patient fibroblasts had an increased level", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30065630"}, {"offsetInBeginSection": 710, "offsetInEndSection": 1020, "text": "In the present report, we have reviewed the basic and clinical literature on Nrf2 deficiency in FRDA, and evidence for the benefit of omaveloxolone.EXPERT OPINION: The present perspective suggests that omaveloxolone is a rational and efficacious therapy that is possibly disease modifying in treatment of FRDA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36708320"}, {"offsetInBeginSection": 475, "offsetInEndSection": 704, "text": "Currently, the FDA has approved the Nrf2 activators dimethyl fumarate (DMF) and Omaveloxolone (Omav) as novel first-line oral drugs for the treatment of patients with relapsing forms of multiple sclerosis and Friedreich's ataxia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38043492"}]}
+{"question_id": "6609997ffdcbea915f000019", "question": "What non-colonic tumors are associated with Lynch syndrome?", "answer": "Following colorectal cancer, carriers of MMR gene mutations had the following 10-year risk of cancers in other organs: kidney, renal pelvis, ureter, and bladder (2%, 95% confidence interval [CI] = 1% to 3%); small intestine, stomach, and hepatobiliary tract (1%, 95% CI = 0.2% to 2%); prostate (3%, 95% CI = 1% to 5%); endometrium (12%, 95% CI = 8% to 17%); breast (2%, 95% CI = 1% to 4%); and ovary (1%, 95% CI = 0% to 2%). They were at elevated risk compared with the general population: cancers of the kidney, renal pelvis, and ureter (SIR = 12.54, 95% CI = 7.97 to 17.94), urinary bladder (SIR = 7.22, 95% CI = 4.08 to 10.99), small intestine (SIR = 72.68, 95% CI = 39.95 to 111.29), stomach (SIR = 5.65, 95% CI = 2.32 to 9.69), and hepatobiliary tract (SIR = 5.94, 95% CI = 1.81 to 10.94) for both sexes; cancer of the prostate (SIR = 2.05, 95% CI = 1.23 to 3.01), endometrium (SIR = 40.23, 95% CI = 27.91 to 56.06), breast (SIR = 1.76, 95% CI = 1.07 to 2.59), and ovary (SIR = 4.19, 95% CI = 1.28 to 7.97).", "relevant_passage_ids": ["22933731", "34247540", "23787146", "17539897", "29528821", "34909397", "35530545", "27014339", "10208097", "18550572", "20533284", "25173403", "36177269", "37301271", "37030500", "18558577", "7675541", "37018159", "7979195", "12385019", "20697958", "15131405", "18715695", "32942876", "10432927", "15222003", "23938213", "16136386", "23176623", "26319271", "23392234", "26143115", "19341971", "23588873", "15770724", "21795835", "8364086", "22694112", "4016685", "29383008", "30560308", "8387880", "18049911", "19821155", "17939062", "8622885", "27979364", "23700068", "15745097", "16884359", "8221644", "7481452"], "type": "list", "snippets": [{"offsetInBeginSection": 789, "offsetInEndSection": 1801, "text": "Following colorectal cancer, carriers of MMR gene mutations had the following 10-year risk of cancers in other organs: kidney, renal pelvis, ureter, and bladder (2%, 95% confidence interval [CI] = 1% to 3%); small intestine, stomach, and hepatobiliary tract (1%, 95% CI = 0.2% to 2%); prostate (3%, 95% CI = 1% to 5%); endometrium (12%, 95% CI = 8% to 17%); breast (2%, 95% CI = 1% to 4%); and ovary (1%, 95% CI = 0% to 2%). They were at elevated risk compared with the general population: cancers of the kidney, renal pelvis, and ureter (SIR = 12.54, 95% CI = 7.97 to 17.94), urinary bladder (SIR = 7.22, 95% CI = 4.08 to 10.99), small intestine (SIR = 72.68, 95% CI = 39.95 to 111.29), stomach (SIR = 5.65, 95% CI = 2.32 to 9.69), and hepatobiliary tract (SIR = 5.94, 95% CI = 1.81 to 10.94) for both sexes; cancer of the prostate (SIR = 2.05, 95% CI = 1.23 to 3.01), endometrium (SIR = 40.23, 95% CI = 27.91 to 56.06), breast (SIR = 1.76, 95% CI = 1.07 to 2.59), and ovary (SIR = 4.19, 95% CI = 1.28 to 7.97).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22933731"}, {"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Background: Lynch syndrome (LS) is associated with the early onset of carcinoma and the development of numerous types o", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36761424"}, {"offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Lynch syndrome (LS) is a genetic predisposition leading to colorectal and non-colorectal tumors such as endometrial, upper urinary tract, small intestine, ovarian, gastric, biliary duct cancers and glioblastoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37301271"}, {"offsetInBeginSection": 439, "offsetInEndSection": 598, "text": "It seems that most sarcomas developed in patients with a germline mutation of MSH2 (57 %) exhibit a dMMR (81 %) or MSI (77 %) phenotype, as in other LS-tumors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37301271"}, {"offsetInBeginSection": 1040, "offsetInEndSection": 1416, "text": "Breast carcinoma with medullary features were shown to be associated with Lynch syndrome (standardized incidence ratio = 38.8, 95% confidence interval = 16.7 to 76.5).CONCLUSIONS: In individuals with Lynch syndrome, MSI-H/dMMR occurs in more than one-half of the malignancies other than colorectal and endometrial carcinomas, including tumor types without increased incidence.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37018159"}, {"offsetInBeginSection": 332, "offsetInEndSection": 438, "text": "This systematic review of literature identified 44 studies (N\u00a0=\u00a095) of LS patients who developed sarcomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37301271"}, {"offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Special features of sarcomas developed in patients with Lynch syndrome: A systematic review.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37301271"}, {"offsetInBeginSection": 711, "offsetInEndSection": 899, "text": "A variety of extracolonic tumors may be encountered in HNPCC, including cancers of the endometrium, stomach, small bowel, urinary tract (renal pelvis and ureter), biliary system and ovary.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7979195"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Endometrial carcinoma (EC) is the most common extracolonic tumor associated with hereditary nonpolyposis colorectal cancer (HNPCC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12385019"}, {"offsetInBeginSection": 934, "offsetInEndSection": 1200, "text": "By far, breast cancer (32 cases) was the most frequent extracolonic manifestation in women followed by endometrial (20 cases) and uterine cervix cancer (20 cases). For man, prostate (16 cases) and stomach (12 cases) cancer were the most frequent extracolonic tumors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20697958"}, {"offsetInBeginSection": 1409, "offsetInEndSection": 1671, "text": " extra-colonic tumors (47 in men and 36 in women). The most frequent extra-colonic primary sites among the HNPCC families were: endometrium (26.5%) and breast (26.5%) (women), and stomach (35.1%) (men). Among the FCC families, the most common primary sites were:", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15131405"}, {"offsetInBeginSection": 843, "offsetInEndSection": 973, "text": "to occur at a rate x22 higher than the general population. Upper urinary tract tumors rank third (5%) after colon (63%) and endome", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18715695"}, {"offsetInBeginSection": 347, "offsetInEndSection": 677, "text": "Lynch syndrome (hereditary nonpolypous colorectal cancer - HNPCC) is an autosomal dominant genetic condition that is associated with a high risk of colorectal cancer or other extracolonic tumors (adenocarcinoma of endometrium, stomach, ovarian carcinoma, carcinoma of urinary tract, small intestine, brain tumors and skin cancer).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32942876"}, {"offsetInBeginSection": 193, "offsetInEndSection": 272, "text": "Endometrial and ovarian cancers are common extracolonic tumors in this syndrome", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10432927"}, {"offsetInBeginSection": 272, "offsetInEndSection": 385, "text": "Patients inheriting this predisposition are susceptible to colorectal, endometrial and other extracolonic tumors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23938213"}, {"offsetInBeginSection": 216, "offsetInEndSection": 384, "text": "Individuals presenting with colorectal cancer are diagnosed with Lynch I, whereas individuals who present with extra-colonic tumors (such as endometrial, stomach, etc.)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17539897"}, {"offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "A patient is described, with Lynch syndrome, typified by hereditary appearance in young age of synchronous and metachronous proximal colorectal cancer, without polyposis, and often associated with extracolonic cancer, particularly ovarian and endometrial carcinomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10208097"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1028, "text": "BACKGROUND: In Lynch syndrome, inherited mismatch repair (MMR) defects predispose to colorectal cancer and to a wide spectrum of extra-colorectal tumours. Utilising a cohort study design, we aimed to determine the risk of extra-colorectal cancer and to identify yet unrecognised tumour types.METHODS: Data from 1624 Lynch syndrome mutation carriers in the Danish hereditary non-polyposis colorectal cancer register were used to estimate the sex- and age-specific incidence rate ratios (IRRs) for 30 extra-colorectal malignancies with comparison to the general population.RESULTS: Significantly increased IRRs were identified for 13 cancer types with differences related to gender, age and disease-predisposing gene. The different cancer types showed variable peak age incidence rates (IRs) with the highest IRs for ovarian cancer at age 30-49 years, for endometrial cancer, breast cancer, renal cell cancer and brain tumours at age 50-69 years, and for urothelial cancer, small bowel cancer, gastric cancer, pancreatic cancer an", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29065108"}, {"offsetInBeginSection": 0, "offsetInEndSection": 630, "text": "Hereditary non-polyposis colorectal cancer (HNPCC) is an inherited multiorgan cancer syndrome, which when caused by a germline mutation in the mismatch repair (MMR) genes is known as Lynch syndrome (LS). Mutation carriers are at risk for developing cancers primarily in the colon, rectum and endometrium, but also other extra-colonic cancers. Urinary tract cancers (UTC) have in many studies been reported increased in LS and it has been discussed among researchers and clinicians whether or not screening for urological tumours should be included in the surveillance programme and if so what screening procedures are justifiable.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23700068"}, {"offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Lynch syndrome (LS) is an inherited cancer predisposition syndrome associated with high lifetime risk of developing tumours, most notably colorectal and endometrial.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37197422"}, {"offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disease, characterized by the occurrence of predominantly colon and endometrial cancer and, less frequently, cancer of the small bowel, stomach, hepatobiliary tract, ureter, renal pelvis, ovaries and brain.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18049911"}, {"offsetInBeginSection": 0, "offsetInEndSection": 469, "text": "Lynch syndrome is an autosomal dominant cancer predisposition syndrome caused by germline mutations in one of the mismatch repair (MMR) genes: MLH1, MSH2, MSH6 and PMS2. Clinically, Lynch syndrome is characterized by early onset (45 years) of colorectal cancer (CRC), as well as extra-colonic cancer. Male and female carriers of Lynch syndrome-associated mutations have different lifetime risks for CRC and in women endometrial cancer (EC) may be the most common tumor.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19821155"}, {"offsetInBeginSection": 356, "offsetInEndSection": 523, "text": "The aim of this review is to discuss the risks, surveillance tests and guidelines for the management of colonic and extracolonic tumors associated with Lynch syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23176623"}, {"offsetInBeginSection": 177, "offsetInEndSection": 547, "text": "An increased predisposition to the development of multiple familial tumors is described as characteristic of this syndrome where visceral and cutaneous malignancies may appear at an early age namely endometrial, gastric, small bowel, ureteral and renal pelvis, ovarian, hepatobiliary tract, pancreatic, brain (Turcot Syndrome) and sebaceous glands (Muir-Torre Syndrome).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26143115"}, {"offsetInBeginSection": 174, "offsetInEndSection": 374, "text": "Other cancers associated with Lynch syndrome include cancers of the ovary, stomach, urothelial tract, and small bowel, and less frequently, cancers of the brain, biliary tract, pancreas, and prostate.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29528821"}, {"offsetInBeginSection": 113, "offsetInEndSection": 304, "text": "Lynch syndrome is also associated with a high risk of extracolonic cancers, including endometrial, stomach, small bowel, pancreas, biliary tract, ovary, urinary tract, brain, and skin cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19341971"}, {"offsetInBeginSection": 217, "offsetInEndSection": 289, "text": "1 and MSH2. HNPCC patients are at increased risk of developing extracolo", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23588873"}, {"offsetInBeginSection": 2109, "offsetInEndSection": 2183, "text": "previous generation. Many extracolonic cancers were found to be associated", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15770724"}, {"offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder characterized by an excess of extracolonic malignancies including those of the urinary tract.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21795835"}, {"offsetInBeginSection": 410, "offsetInEndSection": 610, "text": "Lynch syndrome II manifests all of the features of Lynch syndrome I but, in addition, shows an integral association with extracolonic cancers, particularly carcinomas of the endometrium and the ovary.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8364086"}, {"offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "Lynch syndrome is an autosomal dominant syndrome that can be subdivided into Lynch syndrome I, or site-specific colonic cancer, and Lynch syndrome II, or extracolonic cancers, particularly carcinomas of the stomach, endometrium, biliary and pancreatic systems, and urinary tract", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29383008"}, {"offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Lynch syndrome (LS) is an autosomal-dominant inherited disorder characterized by a predisposition to colorectal cancer and extracolonic cancers (particularly endometrium, ovary, stomach, small bowel, hepatobiliary tract, pancreas, urothelial tract, brain, and skin)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30560308"}, {"offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "BACKGROUND: Hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome) is an autosomal dominant disease characterized by early-onset intestinal neoplasms, localization of tumors in the proximal colon, and frequent association with cancers at other sites, especially the endometrium, skin, and stomach.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8387880"}, {"offsetInBeginSection": 85, "offsetInEndSection": 394, "text": " In the setting of a pre-existing colorectal carcinoma this would constitute a hereditary non-polyposis colorectal cancer, Lynch 2 syndrome, accounting for 5 to 10% of colon cancer cases. We unveil a case of 'giant' ovarian tumors mimicking primary ovarian cancer; ostensibly the first reported in East Africa", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23787146"}, {"offsetInBeginSection": 82, "offsetInEndSection": 244, "text": "Lynch syndrome is characterized by a significantly increased risk for colon cancer and endometrial cancer and a smaller risk for several other associated cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23176623"}, {"offsetInBeginSection": 158, "offsetInEndSection": 308, "text": "acolonic cancers, particularly carcinomas of the stomach, endometrium, biliary and pancreatic systems, and urinary tract. Lynch syndrome is associated", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29383008"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1889, "text": "The family histories of 130 individuals with documented hereditary non-polyposis colorectal cancer (HNPCC) (caused by mutations in mismatch-repair (MMR) genes MSH2 (n = 64), MLH1 (n = 62) or MSH6 (n = 4)) were obtained, and incidence of cancers in those families was compared to that in the general population. There were a total of 982 cancers in 723 individuals. Colorectal cancer (CRC) was the commonest type (64% and 55% in individuals from families with germline MLH1 and MSH2 mutations respectively). Median age at diagnosis of first CRC in MSH6 mutation families was 59 years compared to 45 years in both MLH1 and MSH2 mutation families. The relative risk (RR) of endometrial cancer was 55 in MSH2 mutation families, compared with 27 in MLH1 mutation families, and 37 in MSH6 mutation families; median age at diagnosis 49 years. Even within MSH2 families, endometrial cancer tended to cluster, with 28 of the 58 cases coming from families with three or more cases (P < 0.001). Absolute risk of endometrial cancer in MLH1 families was still greater than any other cancer (other than CRC). 5% of cancers in both MLH1 and MSH2 mutation families were gastric (RR = 12); 53% of these were diagnosed before 50 years. Seven cases of small intestinal cancer occurred in MSH2 and MLH1 mutation families (RR = 26). There were 13 cases of cancer of the ureter; all were in MSH2 families. These cancers tended to cluster within families (P < 0.001); three of seven families with urothelial cancer had such cases in two or more individuals; two others had kidney cancer. Nineteen of 27 ovarian cancers (70%) were in MSH2 mutation families and 70% of these were diagnosed before age 50 years. There were 9 cases of sebaceous skin cancer, 3 in two MLH1 and 6 in four MSH2 mutation families. Of 22 pancreatic cancers, 14 were known to be diagnosed before 60 years. Breast cancer RR was 1.7 overall.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17939062"}, {"offsetInBeginSection": 0, "offsetInEndSection": 331, "text": "Lynch syndrome (LS) is a genetic predisposition leading to colorectal and non-colorectal tumors such as endometrial, upper urinary tract, small intestine, ovarian, gastric, biliary duct cancers and glioblastoma. Though not classically associated with LS, growing literature suggests that sarcomas might develop in patients with LS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37301271"}, {"offsetInBeginSection": 0, "offsetInEndSection": 392, "text": "BACKGROUND: Lynch syndrome (LS) is a hereditary cancer predisposition syndrome associated with increased risk of multiple cancers. While colorectal cancer surveillance decreases mortality in LS and is recommended by guidelines, there is lack of evidence for the efficacy of surveillance for extra-colonic cancers associated with LS, including small intestinal cancer (SIC) and urinary tract c", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34909397"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1566, "text": "Heredity non-polyposis colorectal cancer (HNPCC) is associated with an increased predisposition to colorectal cancer and extra-colonic cancers of the gastro-intestinal, urological and female reproductive tracts. These tumours are characterised by an underlying defect in DNA mismatch repair and exhibit numerous replication errors throughout the genome (RER+ phenotype). HNPCC-associated gastric tumours, and a subset of sporadic, distally-located gastric tumours exhibit this RER+ phenotype. It is recognised that proximal and distal gastric tumours exhibit distinct epidemiological features. In this study we investigated the occurrence of microsatellite instability in a series of 38 primary gastric adenocarcinomas, arising in the proximal stomach. A total of 138 microsatellite markers, comprising mainly dinucleotide and tetranucleotide repeat units and covering all autosomal arms, excluding acrocentric arms, were analysed. One tumour demonstrated somatic microsatellite alterations at 62% (26 of 42) of loci tested. A further 32 tumours demonstrated levels of microsatellite instability ranging from 0.8% (1 of 28)-11.4% (15 of 132) of loci tested. Five tumours demonstrated no microsatellite alterations at any of the loci tested. These findings suggest that a high percentage of proximal gastric carcinomas exhibit a low level of microsatellite alterations at dinucleotide and tetranucleotide repeat loci. However, ubiquitous somatic alterations at these loci, characteristic of HNPCC-associated tumours, occur in a relatively small proportion of tumours.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8622885"}, {"offsetInBeginSection": 156, "offsetInEndSection": 275, "text": "A broad spectrum of neoplasms exhibits MSI phenotype, mainly colorectal cancer, endometrial cancer, and gastric cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27979364"}, {"offsetInBeginSection": 474, "offsetInEndSection": 652, "text": "there is increased risk for cancer development in certain extracolonic sites, such as the endometrium, ovary, stomach, small bowel, hepatobiliary tract, ureter, and renal pelvis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15745097"}, {"offsetInBeginSection": 424, "offsetInEndSection": 658, "text": "Lynch syndrome II shows the same colonic features but includes an excess of extra-colonic CRCs, namely carcinoma of the endometrium, ovary, small bowel, stomach, pancreas and transitional cell carcinoma of the ureter and renal pelvis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7675541"}, {"offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "Hereditary nonpolyposis colorectal cancer (HNPCC) is characterized by a familial predisposition to colorectal carcinoma and extracolonic cancers of the gastrointestinal, urological, and female reproductive tracts, notably the endometrium.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8221644"}, {"offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "Hereditary nonpolyposis colorectal cancer (HNPCC) is comprised of the following: the cancer family syndrome (CFS), or Lynch syndrome II, which shows early-onset proximal colonic cancer predominance and other associated extracolonic adenocarcinomas, particularly endometrial carcinoma;", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4016685"}, {"offsetInBeginSection": 379, "offsetInEndSection": 530, "text": "al cancers. Lynch syndrome II shares the same features, but shows association with extracolonic cancers, particularly carcinomas of endometrium, ovary ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7481452"}]}
+{"question_id": "65d3715b1930410b13000046", "question": "Is Durvalumab effective for locally advanced cervical cancer?", "answer": "Durvalumab concurrent with chemoradiotherapy was well tolerated in participants with locally advanced cervical cancer, however it did not significantly improve progression-free survival in a biomarker unselected, all-comers population.", "relevant_passage_ids": ["38039991"], "type": "yesno", "snippets": [{"offsetInBeginSection": 3283, "offsetInEndSection": 3534, "text": "INTERPRETATION: Durvalumab concurrent with chemoradiotherapy was well tolerated in participants with locally advanced cervical cancer, however it did not significantly improve progression-free survival in a biomarker unselected, all-comers population.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38039991"}, {"offsetInBeginSection": 3289, "offsetInEndSection": 3539, "text": "RETATION: Durvalumab concurrent with chemoradiotherapy was well tolerated in participants with locally advanced cervical cancer, however it did not significantly improve progression-free survival in a biomarker unselected, all-comers population. Conc", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38039991"}]}
+{"question_id": "66099c57fdcbea915f000025", "question": "What clinical conditions influence the prognostic after the liver metastasis resection from colorectal cancer patients?", "answer": "Seven factors were found to be significant and independent predictors of poor long-term outcome by multivariate analysis: positive margin (p = 0.004), extrahepatic disease (p = 0.003), node-positive primary (p = 0.02), disease-free interval from primary to metastases <12 months (p = 0.03), number of hepatic tumors >1 (p = 0.0004), largest hepatic tumor >5 cm (p = 0.01), and carcinoembryonic antigen level >200 ng/ml (p = 0.01).", "relevant_passage_ids": ["10493478", "30692347", "16798225", "10749608", "16687081", "22692571", "16619547", "26404693", "19366082", "29340767", "26421789", "36108955", "18027020", "32011815", "23782400", "34133525", "16734266", "21584664", "30116264", "10770561", "36008803", "34224023", "24477647", "26158168", "24615606", "33832313", "18953839", "25436344", "23933928", "25889950", "35372009", "36338597", "37943377", "35126849", "36018430", "9276706", "11521792", "16965660", "16734265", "20945037", "33829254", "30350532", "15720359", "21723689", "28234125", "24760056", "20875094", "22079259", "30345050", "19333049", "10201774", "26421031", "24157119", "35863820", "36773544", "37305574", "37194000", "37466736", "32153041", "30783050", "29108374", "35859226", "29394750", "30777694", "23979110", "27621747", "17109105", "35786533", "33133385", "35050522", "12035044", "31201596", "11383067", "27916360", "26003673", "22086199", "11379296", "36858891", "14530655"], "type": "list", "snippets": [{"offsetInBeginSection": 714, "offsetInEndSection": 1147, "text": ". Seven factors were found to be significant and independent predictors of poor long-term outcome by multivariate analysis: positive margin (p = 0.004), extrahepatic disease (p = 0.003), node-positive primary (p = 0.02), disease-free interval from primary to metastases <12 months (p = 0.03), number of hepatic tumors >1 (p = 0.0004), largest hepatic tumor >5 cm (p = 0.01), and carcinoembryonic antigen level >200 ng/ml (p = 0.01). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10493478"}, {"offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "AST\u00b7MLR index and operation injury condition are novel prognostic predictor for the prediction of survival in patients with colorectal cancer liver metastases undergoing surgical resection.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36008803"}, {"offsetInBeginSection": 356, "offsetInEndSection": 469, "text": "Factors affecting the curative resection and prognosis were analyzed in patients with stage IV colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22692571"}, {"offsetInBeginSection": 358, "offsetInEndSection": 1121, "text": " Therefore, determination of the factors that influence outcome after resection of synchronous liver metastases is more important than with metachronous liver metastasis.METHOD: We studied patients who had been followed for more than 5 years after undergoing resection of synchronous liver metastases from colorectal cancer.RESULTS: Among the 12 prognostic factors studied (age, gender, adjuvant chemotherapy, tumor site, CEA level, tumor differentiation, tumor size, regional lymph node metastatic status, distribution of liver metastases, number of liver metastases, tumor size and pathological margin), regional lymph node metastatic status and pathological margin were significant prognostic factors by univariate analysis (p = 0.0002 and 0.005, respectively)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10770561"}, {"offsetInBeginSection": 530, "offsetInEndSection": 1123, "text": "THOD: We studied patients who had been followed for more than 5 years after undergoing resection of synchronous liver metastases from colorectal cancer.RESULTS: Among the 12 prognostic factors studied (age, gender, adjuvant chemotherapy, tumor site, CEA level, tumor differentiation, tumor size, regional lymph node metastatic status, distribution of liver metastases, number of liver metastases, tumor size and pathological margin), regional lymph node metastatic status and pathological margin were significant prognostic factors by univariate analysis (p = 0.0002 and 0.005, respectively). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10770561"}, {"offsetInBeginSection": 530, "offsetInEndSection": 1235, "text": "THOD: We studied patients who had been followed for more than 5 years after undergoing resection of synchronous liver metastases from colorectal cancer.RESULTS: Among the 12 prognostic factors studied (age, gender, adjuvant chemotherapy, tumor site, CEA level, tumor differentiation, tumor size, regional lymph node metastatic status, distribution of liver metastases, number of liver metastases, tumor size and pathological margin), regional lymph node metastatic status and pathological margin were significant prognostic factors by univariate analysis (p = 0.0002 and 0.005, respectively). Regional lymph node metastatic status was a significant prognostic factor by multivariate analysis (p = 0.031). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10770561"}, {"offsetInBeginSection": 160, "offsetInEndSection": 452, "text": " Although many studies have been performed to determine prognostic factors for tumor recurrence and survival after resection of colorectal liver metastases, there are few prognostic scoring systems stratifying patients undergoing surgery for colorectal liver metastases into risk group models", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26421789"}, {"offsetInBeginSection": 203, "offsetInEndSection": 681, "text": " Some reports have shown that the prognosis for patients with synchronous liver metastases is worse than that for those with metachronous liver metastases. Therefore, determination of the factors that influence outcome after resection of synchronous liver metastases is more important than with metachronous liver metastasis.METHOD: We studied patients who had been followed for more than 5 years after undergoing resection of synchronous liver metastases from colorectal cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10770561"}, {"offsetInBeginSection": 160, "offsetInEndSection": 825, "text": " Although many studies have been performed to determine prognostic factors for tumor recurrence and survival after resection of colorectal liver metastases, there are few prognostic scoring systems stratifying patients undergoing surgery for colorectal liver metastases into risk group models.OBJECTIVES: To identify, evaluate and compare the existing prognostic scores for survival after surgery for resection of colorectal liver metastases.MATERIAL AND METHODS: Electronic search in PubMed, Cochrane and Embase from 1990 to 2013 using the terms '\u0080\u0098hepatic resection', '\u0080\u0098colorectal cancer'\u0080\u0099, 'liver metastasis', '\u0080\u0098hepatectomy', '\u0080\u0098prognostic'\u0080\u0099, and '\u0080\u0098score'\u0080\u0098", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26421789"}, {"offsetInBeginSection": 160, "offsetInEndSection": 601, "text": " Although many studies have been performed to determine prognostic factors for tumor recurrence and survival after resection of colorectal liver metastases, there are few prognostic scoring systems stratifying patients undergoing surgery for colorectal liver metastases into risk group models.OBJECTIVES: To identify, evaluate and compare the existing prognostic scores for survival after surgery for resection of colorectal liver metastases", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26421789"}, {"offsetInBeginSection": 0, "offsetInEndSection": 357, "text": "BACKGROUND: The prognosis for patients with liver metastases from colorectal cancer is still poor. Thus, patient selection for hepatic resection is essential to improve the poor results of the procedure. Some reports have shown that the prognosis for patients with synchronous liver metastases is worse than that for those with metachronous liver metastases", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10770561"}, {"offsetInBeginSection": 358, "offsetInEndSection": 681, "text": " Therefore, determination of the factors that influence outcome after resection of synchronous liver metastases is more important than with metachronous liver metastasis.METHOD: We studied patients who had been followed for more than 5 years after undergoing resection of synchronous liver metastases from colorectal cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10770561"}, {"offsetInBeginSection": 986, "offsetInEndSection": 1339, "text": "Remained as independent negative predictive factors: lymphovascular invasion (HR=2.7; CI 95% 1.106-6.768; p=0.029), synchronous metastasis (HR=2.8; CI 95% 1.069-7.365; p=0.036) and four or more liver metastasis (HR=1.7; CI 95% 1.046-2.967; p=0.033).CONCLUSION: The resection of liver metastasis of colorectal adenocarcinoma leads to good survival rates.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34133525"}, {"offsetInBeginSection": 1831, "offsetInEndSection": 2155, "text": "Cox regression analysis showed that inadequate resection margin and centrally located liver metastasis were significant predictors of shorter overall survival.CONCLUSIONS: In colorectal cancer, centrally located liver metastasis represents a poor prognostic factor after hepatectomy, and is associated with early recurrence.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25889950"}, {"offsetInBeginSection": 128, "offsetInEndSection": 637, "text": "Liver resection is associated with improvement in survival in comparison to chemotherapy alone.AIM: To analyze the overall survival in patients submitted to liver resection of colorectal cancer metastasis and prognostic factors related to the primary and secondary tumors.METHODS: A retrospective analysis of a prospectively maintained database regarding demographic, primary tumor and liver metastasis characteristics.RESULTS: There were 84 liver resections due to colorectal cancer metastasis in the period.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34133525"}, {"offsetInBeginSection": 1259, "offsetInEndSection": 1611, "text": "In patients with multiple bilobar tumor nodules, adjuvant chemotherapy had a positive impact on disease-free survival and overall survival.CONCLUSIONS: Patients who survived for\u2009>\u200910\u00a0years after liver resection for CRLM tended to have normal preoperative hemoglobin level, unilobar disease, fewer tumor nodules, and have received adjuvant chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36018430"}, {"offsetInBeginSection": 1401, "offsetInEndSection": 2130, "text": "In the adjusted multivariate analysis, age < 65 years (OS: p=0.002, CSS: p=0.002) was associated with better long-term outcomes, and primary tumors located on the left side of the colon (OS: p=0.004, CSS: p=0.006) or rectum (OS: p=0.004, CSS: p=0.006), T3 stage (OS: p<0.001, CSS: p<0.001), number of regional lymph nodes examined \u2265 12 (OS: p<0.001, CSS: p=0.001), and CRC LM (OS: p<0.001, CSS: p<0.001) were positive prognostic factors for survival after resection of metastatic tumors.Conclusion: Age < 65 years is associated with better long-term outcomes in colorectal cancer patients with LM and/or PM, analogously to the left sided primary tumor, T3 stage, number of regional lymph nodes examined \u2265 12 and liver metastases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35372009"}, {"offsetInBeginSection": 0, "offsetInEndSection": 401, "text": "BACKGROUND: Hepatic resection has become the preferred treatment of choice for colorectal liver metastasis (CLM) patients.AIM: To identify the prognostic factors and to formulate a new scoring system for management of CLM.METHODS: Clinicopathologic and long-term survival data were analyzed to identify the significant predictors of survival by univariate and multivariate analyses with the Cox model.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35126849"}, {"offsetInBeginSection": 1021, "offsetInEndSection": 1710, "text": "In the multivariable analyses, after adjusting for clinical risk scores calculated using six factors (timing of liver metastasis, primary tumor lymph node status, number of liver tumors, size of the largest tumor, extrahepatic metastatic disease, and carbohydrate antigen 19-9 level) to predict recurrence following hepatectomy for CRLM, preoperative frailty was found to be an independent risk factor for DFS (hazard ratio [HR]:2.37, 95% confidence interval [CI] 1.06-4.72, P\u2009=\u20090.036), OS (HR:4.17, 95% CI 1.43-10.89, P\u2009=\u20090.011), and CSS (HR:3.49, 95% CI 1.09-9.60, P\u2009=\u20090.036).CONCLUSION: Preoperative frailty was associated with worse DFS, OS, and CSS after upfront hepatectomy for CRLM.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37943377"}, {"offsetInBeginSection": 1427, "offsetInEndSection": 1540, "text": "Synchronous disease and four or more metastasis were the most significant factors related to the secondary tumor.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34133525"}, {"offsetInBeginSection": 81, "offsetInEndSection": 638, "text": "The present review revealed that hepatic resection is the best treatment modality, although the overall survival rate after hepatectomy for metastatic colorectal cancer is still low (20-40%). Various prognostic factors analyzed by many authors are controversial. The number of hepatic metastases and the surgical margin were the most important prognostic factors, as seen in 10 papers previously reported including our data. A clear surgical margin is achievable, but the prognosis of patients with four or more metastatic nodules in the liver remains poor.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9276706"}, {"offsetInBeginSection": 582, "offsetInEndSection": 970, "text": "The five-year survival rate after surgical resection varies from 20% to 45% according to several prognostic factors. The longer survival is observed in patients with fewer than four lesions, with lesions smaller than 4 cm, without extra-hepatic disease, with lesions that appeared more than two years after the resection of a stage I or II colorectal cancer and whose CEA level is normal.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11521792"}, {"offsetInBeginSection": 666, "offsetInEndSection": 1088, "text": " rates were 59.04%, 17.73%, and 11.48%. Univariate analysis revealed that extrahepatic invasion, primary tumor resection, liver metastasis resection, type of primary tumor, serum CEA concentration, number and size of liver metastases, and distribution of liver metastases were associated with prognosis. Multivariate analysis identified that the resection of liver metastases, serum CEA concentration, number and size of l", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16965660"}, {"offsetInBeginSection": 838, "offsetInEndSection": 1271, "text": "Favorable patient selection criteria for liver resection are: 1) medical fitness for hepatectomy; 2) radical resection of the primary colorectal lesion; 3) metastatic tumors anatomically confined within the liver allowing adequate preservation of the liver parenchyma; 4) no signs of disseminated disease; 5) no signs of hepatic lymph node metastases; 6) four or fewer metastatic tumors; and 7) resection margins of 10 mm or greater.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16734265"}, {"offsetInBeginSection": 765, "offsetInEndSection": 1170, "text": "Univariate analysis indicated that degree of primary tumor differentiation, resection margin, preoperative carcinoembryonic antigen (CEA) level, number of liver metastases, and resection of liver metastases were associated with prognosis (P < 0.05). In multivariate analysis, the last three factors were found to be independent prognostic factors. The resection of liver metastases was a favorable factor.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20945037"}, {"offsetInBeginSection": 155, "offsetInEndSection": 993, "text": "The retrospective analysis included 297 liver resections for colorectal metastases.METHODS: The variables considered included disease stage, differentiation grade, site and nodal metastasis of the primary tumor, number and diameter of the lesions, time from primary cancer to metastasis, preoperative carcinoembryonic antigen (CEA) level, adjuvant chemotherapy, type of resection, intraoperative ultrasonography and portal clamping use, blood loss, transfusions, complications, hospitalization, surgical margins status, and a clinical risk score (MSKCC-CRS).RESULTS: The univariate analysis revealed a significant difference (p < 0.05) in overall 5-year survival rates depending on the differentiation grade, preoperative CEA >5 and >200 ng/ml, diameter of the lesion >5 cm, time from primary tumor to metastases >12 months, MSKCC-CRS >2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18027020"}, {"offsetInBeginSection": 1515, "offsetInEndSection": 1619, "text": "Extrahepatic tumour had a negative influence on the extrahepatic recurrence and on the overall survival.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29340767"}, {"offsetInBeginSection": 29, "offsetInEndSection": 141, "text": "his study was to identify the influencing factors related to outcome of patients of colorectal cancer with liver", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25436344"}, {"offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "BACKGROUND: The prognosis for patients with liver metastases from colorectal cancer is still poor. Thus, patient selection for hepatic resection is essential to improve the poor results of the procedure. Some reports have shown that the prognosis for p", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10770561"}, {"offsetInBeginSection": 274, "offsetInEndSection": 900, "text": "and prognosis, including recurrence. A total of 107 patients who underwent initial hepatic resection for resectable synchronous liver metastasis from colorectal cancer were retrospectively analyzed. The 5-year disease-free survival rates were 16.4 per cent in the simultaneous group, and 24.0 per cent in the staged group (P = 0.5486). The 5-year overall survival rates were 70.7 per cent in the simultaneous group and 67.9 per cent in the staged group (P = 0.8254). Perioperative chemotherapy did not have a significant effect. Tumor depth of CRC (\u2265pT4) was the only key factor influencing prognosis. Postoperative intestinal", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28234125"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1170, "text": "AIMS: To analyse patient survival after the resection of lung metastases from colorectal carcinoma and specifically to verify whether presence of liver metastasis prior to lung metastasectomy affects survival.METHODS: All patients who, between 1998 and 2008, underwent lung metastasectomy due to colorectal cancer were included in the study. Kaplan-Meier survival analysis was performed with the log-rank test and Cox regression multivariate analysis.RESULTS: During this period, 101 metastasectomies were performed on 84 patients. The median age of patients was 65.4 years, and 60% of patients were male. The 30-day mortality rate was 2%, and incidence of complications was 7%. The overall survival was 72 months, with 3-and 5-year survival rates of 70% and 54%, respectively. A total of 17 patients (20%) had previously undergone resection of liver metastasis. No significant differences were found in the distribution of what were supposed to be the main variables between patients with and without previous hepatic metastases. Multivariate analysis identified the following statistically significant factors affecting survival: previous liver metastasectomy (p\u00a0=\u00a00.0", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21723689"}, {"offsetInBeginSection": 119, "offsetInEndSection": 1885, "text": "indications and prognostic factors are inconsistent. We sought to identify poor prognostic factors preoperatively and to retrospectively evaluate preoperative clinical indications for surgery.METHODS: A total of 75 patients with colorectal cancer had pulmonary metastases excised from 1986 to 2003. Tumor size, number, laterality, hilar or mediastinal lymphadenopathy, and carcinoembryonic antigen level were possible risk factors for metastatic tumors, with primary site of colorectal tumor, disease-free interval, and hepatectomy for liver metastasis possible risk factors for primary tumors. Prognostic factors in univariate and multivariate analyses also included age and sex.RESULTS: Five-year survival rates were 41.3% after pulmonary excision and 73.1% after primary colorectal resection. Three factors identified as significant by univariate log-rank test for overall survival after pulmonary resection were carcinoembryonic antigen (p < 0.0001), tumor laterality (p = 0.0205), and number of pulmonary metastases (p = 0.0028). Multivariate analysis found that carcinoembryonic antigen, tumor number, tumor size, and patient's age were also independent prognostic factors. In contrast, carcinoembryonic antigen, number of metastases, and disease-free interval predicted prognosis after primary colorectal resection. Prior hepatectomy for metastases did not influence prognosis after pulmonary metastasectomy.CONCLUSIONS: Elevated carcinoembryonic antigen level and multiple metastases are preoperative predictors of poor prognosis after resection of pulmonary metastases from colorectal cancer. Survival rate is sufficient to justify pulmonary metastasectomy if there is no local or distant metastatic lesion other than in the liver; if needed, sequential pul", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16798225"}, {"offsetInBeginSection": 193, "offsetInEndSection": 833, "text": "tal cancer. We analyzed the treatment outcome and prognostic factors affecting survival in this subset of patients.MATERIALS AND METHODS: Between October 1994 and December 2004, 59 patients underwent curative resection for pulmonary metastases of colorectal cancer. Uncontrollable synchronous liver and lung metastasis or synchronous colorectal cancer with isolated lung metastasis were excluded from this study. A retrospective review of patient characteristics and factors influencing survival was performed. Survival was analyzed by the Kaplan-Meier method. Comparison between groups were performed by a log-rank analysis and the Cox pro", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17109105"}, {"offsetInBeginSection": 19, "offsetInEndSection": 877, "text": "aimed to investigate the clinical characteristics, prognostic factors, survival times, and therapy outcomes of brain metastases (BM) from colorectal cancer (CRC).METHODS: The clinical characteristics of 25 patients with BM from CRC were retrospectively analyzed. The time of the occurrence of BM after diagnosis of CRC was recorded. Meanwhile, the time from the occurrence of lung, bone, liver, and other extracranial metastases to the occurrence of BM was also recorded. We evaluate the time factors affecting the length of the occurrence of BM and the potential prognostic factors after BM diagnosis. The influences of patients undergoing surgery-based comprehensive treatment, radiotherapy-based comprehensive treatment, and co-medication were also assessed.RESULTS: In patients with BM from CRC, lung metastases (13/25) occurred at a higher frequency tha", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37466736"}, {"offsetInBeginSection": 107, "offsetInEndSection": 629, "text": "r pulmonary metastases of colorectal carcinoma, and to clarify prognostic factors for survival that could be used to identify patients likely to benefit most from pulmonary resection.METHODS: Data on 113 patients who underwent R0 resection of pulmonary metastases from colorectal cancer were reviewed. Overall median follow-up was 49 (range 1-140) months. Clinical and pathological factors were reviewed, and prognostic factors influencing survival were identified.RESULTS: The overall 5-year survival rate was 67.8 per ce", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19672932"}, {"offsetInBeginSection": 0, "offsetInEndSection": 505, "text": "Hepatic metastasis of colorectal cancer is a life-threatening prognostic factor. The present review revealed that hepatic resection is the best treatment modality, although the overall survival rate after hepatectomy for metastatic colorectal cancer is still low (20-40%). Various prognostic factors analyzed by many authors are controversial. The number of hepatic metastases and the surgical margin were the most important prognostic factors, as seen in 10 papers previously reported including our data.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9276706"}, {"offsetInBeginSection": 823, "offsetInEndSection": 994, "text": "all survival, at 38.45%. Carcinoembryonic antigen levels \u2265 50 ng/mL and presence of three or more liver metastasis were limiting factors for disease-free survival, but did", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24760056"}, {"offsetInBeginSection": 1322, "offsetInEndSection": 1554, "text": "urvived beyond 40 months.CONCLUSIONS: Although Carcinoembryonic antigen levels and number of metastases are prognostic factors that limit disease-free survival, they had no impact on 5-year survival and, therefore, should not determ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24760056"}, {"offsetInBeginSection": 1069, "offsetInEndSection": 1219, "text": "ariate analysis (p = 0.0002 and 0.005, respectively). Regional lymph node metastatic status was a significant prognostic factor by multivariate analys", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10770561"}, {"offsetInBeginSection": 629, "offsetInEndSection": 779, "text": "% and 25.0%, respectively. The lymph node metastasis and vascular invasion by cancer cells from the primary tumour were found to affect prognosis sign", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18953839"}, {"offsetInBeginSection": 609, "offsetInEndSection": 759, "text": "tes were 86.3%, 40.9% and 25.0%, respectively. The lymph node metastasis and vascular invasion by cancer cells from the primary tumour were found to a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18953839"}, {"offsetInBeginSection": 1456, "offsetInEndSection": 1606, "text": " patients with liver metastasis (all P<0.05), while primary tumor differentiation, CEA level, and radical resection were independent prognostic factor", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26404693"}, {"offsetInBeginSection": 678, "offsetInEndSection": 828, "text": "59.04%, 17.73%, and 11.48%. Univariate analysis revealed that extrahepatic invasion, primary tumor resection, liver metastasis resection, type of prim", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16965660"}, {"offsetInBeginSection": 607, "offsetInEndSection": 757, "text": " colorectal liver metastases at MD Anderson Cancer Center and had RAS mutational data. A Cox proportional hazards model analysis was used to develop a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33829254"}, {"offsetInBeginSection": 516, "offsetInEndSection": 798, "text": "urvival time was 25 months. Univariate analysis clarified that the significant prognostic factors for poor survival were depth of primary colorectal cancer (\u2265 serosal invasion), hepatic resection margin (< 5 mm), presence of portal vein invasion of CRCLM, and the presence of intra-", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20875094"}, {"offsetInBeginSection": 799, "offsetInEndSection": 935, "text": "and extrahepatic recurrence. Multivariate analysis indicated the presence of intra- and extrahepatic recurrence as independent predictiv", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20875094"}, {"offsetInBeginSection": 936, "offsetInEndSection": 1079, "text": " factors for poor prognosis. Risk factors for intrahepatic recurrence were resection margin (< 5 mm) of CRCLM, while no risk factors for extrah", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20875094"}, {"offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "The aim of the present study was to retrospectively identify prognostic factors for long-term cumulative survival following liver resection in patients with primarily unresectable colorectal cancer who had previously received conversion therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30345050"}, {"offsetInBeginSection": 810, "offsetInEndSection": 1197, "text": "tectomy was 40 percent. Univariate analysis identified three risk factors confirmed by log-rank test and multivariate Cox regression analysis: serum carcinoembryonic antigen concentrations >5 ng/ml at first hepatectomy (HR = 2.265; CI = 1.140-4.497; P = 0.020), anatomic resection (HR = 2.124; CI = 1.069-4.218; P = 0.031), and tumors > or =3 cm at the second resection (HR = 2.039; CI =", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19333049"}, {"offsetInBeginSection": 1399, "offsetInEndSection": 2000, "text": "In the present paper we present the clinico-pathologic characteristics,the pre- and postoperative management and the outcome of a patient with unresectable colorectal liver metastases who underwent liver transplantation in a very advanced state of the disease (when he developed subacute liver failure due to insufficient functional liver parenchyma and toxicity of chemotherapy).We consider useful to present such observations,because collecting the data presented by different centers maybe contributive to identification of a selected group of patients who could benefit from liver transplantation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24157119"}, {"offsetInBeginSection": 12, "offsetInEndSection": 195, "text": "More than 50% of all patients with colorectal cancer (CRC) develop liver metastases (CLM), a clinical condition characterized by poor prognosis and lack of reliable prognostic markers", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35863820"}, {"offsetInBeginSection": 952, "offsetInEndSection": 1233, "text": "Patients with a low CALLY index had significantly more postoperative complications than those with a high CALLY index (29% vs. 11%, p\u00a0<\u00a00.01).CONCLUSION: The CALLY index may be an independent and significant indicator of outcomes in patients who underwent liver resection for CRLM.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36773544"}, {"offsetInBeginSection": 108, "offsetInEndSection": 322, "text": "We aimed to investigate whether the CALLY can predict the prognosis in patients with colorectal liver metastases (CRLM) after hepatic resection.METHODS: We included 183 patients with CRLM who underwent hepatectomy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36773544"}, {"offsetInBeginSection": 2011, "offsetInEndSection": 2724, "text": "Finally, synchronous liver metastasis (HR = 2.059, 95%CI: 1.087-3.901 p=0.027), more than one liver metastases ((HR =2.025, 95%CI: 1.120-3.662 p=0.020),higher serum CA199 (HR =2.914, 95%CI: 1.497-5.674 p=0.002), present LVI (HR = 2.055, 95%CI: 1.183-4.299 p=0.001), higher Ki67 (HR = 3.190, 95%CI: 1.648-6.175 p=0.001) and pMMR(HR = 1.676, 95%CI: 1.772-3.637 p=0.047) predicted worse DFS, and the nomogram achieved an effective level of predictive ability.Conclusion: This study showed that MMR, Ki67, and Lymphovascular invasion were independent risk factors for the postoperative survival of CRLM patients, and a nomogram model was constructed to predict the OS of these patients after liver metastasis surgery.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37305574"}, {"offsetInBeginSection": 391, "offsetInEndSection": 569, "text": "We investigated the association of the CALLY index with overall survival by univariate and multivariate analyses.RESULTS: In total, 101 (55%) patients had a low CALLY index (<4).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36773544"}, {"offsetInBeginSection": 137, "offsetInEndSection": 655, "text": "We conducted a retrospective comparative study of the relationship of liver sinusoidal disorders and liver function with the prognosis in patients who underwent hepatectomy for colorectal liver metastasis (CRLM).Methods: In total, 158 patients who underwent hepatectomy for CRLM were included in the study, and the effect of chemotherapy-associated liver damage on the prognosis was examined.Results: Preoperative oxaliplatin was used in 75 of 158 patients; of these 75 patients, 26 had intraoperative blue liver (BL).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36338597"}, {"offsetInBeginSection": 0, "offsetInEndSection": 342, "text": "BACKGROUND: To explore the clinical prognostic utility of the preoperative cholesterol-to-lymphocyte ratio (CLR) in outcomes for colorectal cancer liver metastasis (CRLM) patients receiving simultaneous resection of the primary lesion and liver metastases.METHODS: A total of 444 CRLM patients receiving simultaneous resections were enrolled.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37194000"}, {"offsetInBeginSection": 1321, "offsetInEndSection": 1499, "text": "SIONS: Liver metastasis resection, serum CEA concentration, number and size of liver metastases are important prognostic factors for liver metastases from colorectal cancer. In o", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16965660"}, {"offsetInBeginSection": 1282, "offsetInEndSection": 1780, "text": "tivariate analysis showed that primary tumor differentiation, CEA level, adjuvant chemotherapy, and radical resection were independent prognostic factors of colorectal cancer patients with liver metastasis (all P<0.05), while primary tumor differentiation, CEA level, and radical resection were independent prognostic factors of synchronous liver metastasis (all P<0.05), and primary tumor location and CEA level were independent prognostic factors of metachronous liver metastasis (all P<0.05).CON", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26404693"}, {"offsetInBeginSection": 1160, "offsetInEndSection": 1334, "text": " factors most often included were: number of liver metastases, regional lymph node metastization of primary tumor, preoperative CEA level and maximum size of metastases. The ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26421789"}, {"offsetInBeginSection": 240, "offsetInEndSection": 714, "text": "THODS: The variables considered included disease stage, differentiation grade, site and nodal metastasis of the primary tumor, number and diameter of the lesions, time from primary cancer to metastasis, preoperative carcinoembryonic antigen (CEA) level, adjuvant chemotherapy, type of resection, intraoperative ultrasonography and portal clamping use, blood loss, transfusions, complications, hospitalization, surgical margins status, and a clinical risk score (MSKCC-CRS).R", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18027020"}, {"offsetInBeginSection": 254, "offsetInEndSection": 968, "text": " Surgical resection, radiofrequency ablation, and chemotherapy had been used in clinical treatment for liver metastasis from colorectal cancer with various outcomes. This study was to explore the treatment efficacy of surgical management for liver metastasis from colorectal cancer.METHODS: Clinical data of 198 patients with liver metastasis from colorectal cancer, treated from Jan. 1995 to Jan. 2000, were studied retrospectively. Of the 198 patients, 46 (23.2%) received radical resection, 43 (21.7%) received palliative resection, 29 (14.6%) received exploratory operation or supportive treatment, 41 (20.7%) received adjuvant hepatic arterial infusion, and 39 (19.7%) received adjuvant systemic chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16687081"}, {"offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Numerous factors affect the prognosis of colorectal liver metastasis (CRLM) patients after hepatic resection. We investigated several factors related to overall survival in patients with", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29108374"}, {"offsetInBeginSection": 38, "offsetInEndSection": 633, "text": "cornerstone in the management of colorectal cancer (CRC) liver metastases. The aim of this study is to identify clinicopathological factors affecting disease-free (DFS) and overall survival (OS) in patients undergoing potentially curative liver resection for CRC metastasis.METHODS: All consecutive patients undergoing liver resection for first recurrence of CRC from February 2006 to February 2018 were included. Prognostic impact of factors related to the patient, primary and metastatic tumors, was retrospectively tested through univariate and multivariate analyses.RESULTS: Seventy patients", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30116264"}, {"offsetInBeginSection": 19, "offsetInEndSection": 814, "text": "on of liver metastasis from colorectal cancer is known to improve prognosis; therefore, surgical treatment is recommended for resectable metastases in the Japanese Society for Cancer of the Colon and Rectum Guidelines for the Treatment of Colorectal Cancer. In this study, we investigated factors that affect the prognosis of resection of such metastatic liver tumors.RESULTS: Thirty-three cases of liver resection performed during the period from 1998 to 2017 were investigated. The 5-year overall survival rate after liver resection was 47.3%, and the 5-year recurrence-free survival rate after liver resection was 29.9%. Univariate analysis identified CA19-9(p=0.02)and operative procedure(p=0.0046)as prognostic factors, while multivariate analysis revealed operative procedure(p=0.03)to be ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29394750"}, {"offsetInBeginSection": 129, "offsetInEndSection": 700, "text": "ic and pulmonary metastases of colorectal cancer (CRC) are under discussion. Our analysis focused on a surgical series of such patients and our final aim consisted in identifying potential prognostic factors.METHODS: Eighty-five patients undergoing resection of both hepatic and pulmonary metastases at 2 Healthcare Institutions from January 1993 to June 2015 were retrospectively reviewed as concerned clinical information, surgical notes and pathological features. Patient, treatment, and outcome variables were analyzed by use of log-rank tests, Cox regression, and Ka", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30783050"}, {"offsetInBeginSection": 0, "offsetInEndSection": 647, "text": "Importance: Currently, surgical resection of distant metastatic lesions has become the preferred treatment for select colorectal cancer (CRC) patients with liver metastasis (LM) and/or pulmonary metastasis (PM). Metastasectomy is the most common curative method. However, evidence of the factors affecting the prognosis of CRC patients after resection of LM and/or PM is still insufficient.Objective: To explore the prognostic factors of CRC patients with LM and/or PM who have undergone resection of metastatic tumors and to provide reliable selection factors for surgical treatment in patients affected by LM and/or PM from CRC.Methods: The SEER", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35372009"}, {"offsetInBeginSection": 4, "offsetInEndSection": 1378, "text": "OSE: The investigation of the predictors of outcome after hepatic resection for solitary colorectal liver metastasis.METHODS: We recruited 350 patients with solitary colorectal liver metastasis at the University Hospitals of Jena and Magdeburg, who underwent curative liver resection between 1993 and 2014. All patients had follow-up until death or till summer 2016.RESULTS: The follow-up data concern 96.6% of observed patients. The 5- and 10-year overall survival rates were 47 and 28%, respectively. The 5- and 10-year disease-free survival rates were 30 and 20%, respectively. The analysis of the prognostic factors revealed that the pT category of primary tumour, size and grade of the metastasis and extension of the liver resection had no statistically significant impact on survival and recurrence rates. In multivariate analysis, age, status of lymph node metastasis at the primary tumour, location of primary tumour, time of appearance of the metastasis, the use of preoperative chemotherapy and the presence of extrahepatic tumour proved to be independent statistically significant predictors for the prognosis. Moreover, patients with rectal cancer had a lower intrahepatic recurrence rate, but a higher extrahepatic recurrence rate.CONCLUSION: The long-term follow-up of patients with R0-resected liver metastasis is multifactorially influenced. Age and comorbi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29340767"}, {"offsetInBeginSection": 87, "offsetInEndSection": 361, "text": "predicting oncological outcomes after hepatectomy for colorectal liver metastases (CRLMs) and to investigate the variable prognostic implications of POCs according to the modified clinical score (M-CS). We identified 751 patients who underwent curative hepatic resection for", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35859226"}, {"offsetInBeginSection": 35, "offsetInEndSection": 1208, "text": "ions affect both the short-term and long-term outcomes. The aim of this study was to identify specific prognostic factors among complications after hepatectomy for colorectal liver metastasis (CRLM).METHODS: Between 2002 and 2014, 427 patients underwent initial hepatectomy for CRLM. The\u00a0clinicopathological\u00a0parameters including postoperative complications were evaluated to identify the prognostic factors for the overall (OS) and relapse-free survival (RFS).RESULTS: One hundred and forty-nine patients (34%) developed postoperative complications, including surgical site infection (n\u00a0=\u00a049, 11.4%), bile leakage (n\u00a0=\u00a041, 9.6%), posthepatectomy liver failure (PHLF) (n\u00a0=\u00a026, 6.0%), and pulmonary complication (n\u00a0=\u00a020, 4.6%). The independent predictors of RFS included primary nodal metastasis, abnormal CA19-9 levels, extrahepatic metastasis, bilateral CRLMs, \u22655 CRLMs, preoperative chemotherapy, lack of adjuvant chemotherapy and PHLF. The 5-year RFS rates in patients with and without PHLF were 8% and 32%, respectively (P\u00a0<\u00a00.001). The independent prognostic factors for OS included primary nodal metastasis, abnormal CA19-9 levels, extrahepatic metastasis, positive su", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30777694"}, {"offsetInBeginSection": 0, "offsetInEndSection": 362, "text": "PURPOSE: We investigated the predictive indicator for a good prognosis of surgical resection for liver metastasis of colorectal cancer.METHOD: Between 1990 and 2009 at our institute, 117 patients underwent 132 hepatic resections for liver metastasis of colorectal cancer. The clinical, pathological, and outcome parameters affecting their prognoses were analyzed", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23979110"}, {"offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Prognostic Factors after Liver Resection for Colorectal Liver Metastasis.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26421789"}, {"offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Prognostic indicator for the resection of liver metastasis of colorectal cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23979110"}, {"offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "[Prognostic factors of colorectal cancer patients with synchronous liver metastasis treated with simultaneous liver and colorectal resection].", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18953839"}, {"offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "PURPOSE: We investigated the predictive indicator for a good prognosis of surgical resection for liver metastasis of colorectal cancer.METHOD: Between 1990 and 2009 at our institute, 117 patients underwent 132 hepatic resections for liver metastasis of colorectal cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23979110"}, {"offsetInBeginSection": 0, "offsetInEndSection": 326, "text": "OBJECTIVE: To investigate the prognostic factors of colorectal cancer patients with liver metastasis in order to provide reference for clinical practice.METHODS: Clinicopathological and follow-up data of 264 cases of colorectal liver metastasis in our department from January 1997 to January 2012 were analyzed retrospectively", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26404693"}, {"offsetInBeginSection": 1238, "offsetInEndSection": 1495, "text": "The results indicated that for cases of colorectal cancer with synchronous liver metastasis, primary lesion wall depth and liver metastasis Grade were prognostic factors, and that the treatment strategy did not necessarily have to consider resection timing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30692347"}, {"offsetInBeginSection": 0, "offsetInEndSection": 387, "text": "OBJECTIVE: To analyze the prognostic factors of colorectal cancer patients with synchronous liver metastasis treated by simultaneous colorectal and liver resection.METHODS: The clinical and follow-up data of 44 colorectal cancer patients with synchronous liver metastases who underwent simultaneous colorectal and liver resection from Jan. 1993 to Jan. 2003 were analyzed retrospectively", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18953839"}, {"offsetInBeginSection": 660, "offsetInEndSection": 1778, "text": "linicopathological features and treatment scheme affecting prognosis were analyzed and prognostic stratification analysis was performed according to emergence time of liver metastasis (synchronous or metachronous).RESULTS: Of 264 patients, 1-, 3-, and 5-year overall survival rates were 77.0%, 31.7%, and 14.0%; median survival time was 25 months; 1-, 3-, and 5-year survival rates of synchronous colorectal liver metastasis were 68.8%, 22.3%, and 7.7%; 1-, 3-, and 5-year survival rates of metochronous colorectal liver metastasis were 95.8%, 49.0%, and 21.3%, whose difference was statistically significant (P<0.05). Multivariate analysis showed that primary tumor differentiation, CEA level, adjuvant chemotherapy, and radical resection were independent prognostic factors of colorectal cancer patients with liver metastasis (all P<0.05), while primary tumor differentiation, CEA level, and radical resection were independent prognostic factors of synchronous liver metastasis (all P<0.05), and primary tumor location and CEA level were independent prognostic factors of metachronous liver metastasis (all P<0.05).C", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26404693"}, {"offsetInBeginSection": 0, "offsetInEndSection": 438, "text": "The aim of this study was to clarify prognosis for curative resection performed for cases of colorectal cancer with synchronous liver metastasis and to use the findings as future treatment indices. Subjects comprised 61 patients who underwent curative resection at our hospital for colorectal cancer accompanied by synchronous liver metastasis between 1996 and 2014. The degree of liver metastasis was H1 for 47 cases and H2 for 14 cases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30692347"}, {"offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "INTRODUCTION: Liver resection is the only curative treatment for colorectal liver metastasis. The identification of predictive factors leads to personalize patient management to enhance their long-term outcomes. This population-based study aimed to characterize factors associated with, and survival impact o", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36108955"}, {"offsetInBeginSection": 42, "offsetInEndSection": 762, "text": "l cancer to the liver impacts prognosis. Advances in chemotherapy have resulted in increased resectability rates and thereby improved survival in patients with colorectal liver metastases (CRLM). However, criteria are needed to ensure that patients selected for hepatic resection benefit from the invasive therapy. The study aimed to construct a predictive model for overall survival (OS) in patients with CRLM, based on preoperatively available information.METHODS: The retrospective cohort study reviewed all patients with CRLM discussed at multidisciplinary team conference at Karolinska University Hospital, Stockholm, Sweden, 2013-2018. Independent prognostic factors for OS were identified, based on which a score ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35786533"}, {"offsetInBeginSection": 32, "offsetInEndSection": 1640, "text": "mary tumour is a prerequisite for cure in patients with colorectal cancer, but hepatic metastasectomy has been used increasingly with curative intent. This national registry study examined prognostic factors for radically treated primary tumours, including the subgroup of patients undergoing liver metastasectomy.METHODS: Patients who had radical resection of primary colorectal cancer in 2009-2013 were identified in a population-based Swedish colorectal registry and cross-checked in a registry of liver tumours. Data on primary tumour and patient characteristics were extracted and prognostic impact was analysed.RESULTS: Radical resection was registered in 20\u2009853 patients; in 38\u00b77 per cent of those registered with liver metastases, surgery or ablation was performed. The age-standardized relative 5-year survival rate after radical resection of colorectal cancer was 80\u00b79 (95 per cent c.i. 80\u00b72 to 81\u00b76) per cent,\u00a0and the rate after surgery for colorectal liver metastases was 49\u00b76 (46\u00b70 to 53\u00b72) per cent. Multivariable analysis identified lymph node status, multiple sites of metastasis, high ASA grade and postoperative complications after resection of the primary tumour as strong risk factors after primary resection and following subsequent liver resection or ablation. Age, sex and primary tumour location had no prognostic impact on mortality after liver resection.CONCLUSION: Lymph node status and complications have a negative impact on outcome after both primary resection and liver surgery. Older age and female sex were underrepresented in the liver surgical cohort, but these factors did", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32011815"}, {"offsetInBeginSection": 24, "offsetInEndSection": 2294, "text": "ancer (CRC) is one of the most common malignant tumors in China, and the liver is the most common metastatic site in patients with advanced CRC. Hepatectomy is the gold standard treatment for colorectal liver metastases. For patients who cannot undergo radical resection of liver metastases for various reasons, ablation therapy, interventional therapy, and systemic chemotherapy can be used to improve their quality of life and prolong their survival time.AIM: To explore the prognostic factors and treatments of liver metastases of CRC.METHODS: A retrospective analysis was conducted on 87 patients with liver metastases from CRC treated at the Liaoning Cancer Hospital and Institute between January 2005 and March 2011. According to different treatments, the patients were divided into the following four groups: Surgical resection group (36 patients); ablation group (23 patients); intervention group (15 patients); and drug group (13 patients). The clinicopathological data and postoperative survival of the four groups were analyzed. The Kaplan-Meier method was used for survival analysis, and the Cox proportional hazards regression model was used for multivariate analysis.RESULTS: The median survival time of the 87 patients was 38.747 \u00b1 3.062 mo, and the 1- and 3-year survival rates were 87.5% and 53.1%, respectively. The Cox proportional hazards model showed that the following factors were independent factors affecting prognosis: The degree of tumor differentiation, the number of metastases, the size of metastases, and whether the metastases are close to great vessels. The results of treatment factor analysis showed that the effect of surgical treatment was better than that of drugs, intervention, or ablation alone, and the median survival time was 48.83 \u00b1 4.36 mo. The drug group had the worst prognosis, with a median survival time of only 13.5 \u00b1 0.7 mo (P < 0.05). For patients with liver metastases of CRC near the great vessels, the median survival time (27.3 mo) of patients undergoing surgical resection was better than that of patients using other treatments (20.6 mo) (P < 0.05).CONCLUSION: Patients with a low degree of primary tumor differentiation, multiple liver metastases (number of tumors > 4), and maximum diameter of liver metastas", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33133385"}, {"offsetInBeginSection": 0, "offsetInEndSection": 649, "text": "BACKGROUND: The clinical course of patients experiencing recurrence following hepatectomy for colorectal cancer metastases (CRM) is poorly defined. Previous studies associated shorter time to recurrence (TTR) in months, node-positive primary tumor, and more than one site of recurrence with worse outcomes.METHODS: We conducted a retrospective cohort study across four Canadian institutions to externally validate previously established prognostic factors of overall survival (OS). We included consecutive adult patients who had a recurrence following curative-intent liver resection for CRM. Prognostic factors were explored using a multivariable C", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35050522"}, {"offsetInBeginSection": 792, "offsetInEndSection": 1101, "text": "al and recurrence rates. In multivariate analysis, age, status of lymph node metastasis at the primary tumour, location of primary tumour, time of appearance of the metastasis, the use of preoperative chemotherapy and the presence of extrahepatic tumour proved to be independent statistically significant pred", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29340767"}, {"offsetInBeginSection": 1020, "offsetInEndSection": 1197, "text": "4%. There were 19 actual 5-year survivors to date. By multivariate regression analysis (proportional hazard model), more than one lesion and tumor size larger than 5 cm were ind", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12035044"}, {"offsetInBeginSection": 1288, "offsetInEndSection": 1705, "text": ", p\u2009<\u20090.001, respectively). On multivariate analysis, poorer survival after C-PH was associated with age\u2009>\u200970\u00a0years (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.0-2.5, p\u2009<\u20090.001), perineural invasion (HR 1.5, 95% CI 1.2-1.9, p\u2009<\u20090.001), kras mutation (HR 1.5, 95% CI 1.1-2.1, p\u2009=\u20090.006), positive circumferential margin (HR 1.3, 95% CI 1.0-1.7, p\u2009=\u20090.03), and omission of postoperative chemotherapy (HR 1.4,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31201596"}, {"offsetInBeginSection": 857, "offsetInEndSection": 1332, "text": ". Tumor-free survival is 35 +/- 5% at 5 years. In the multivariate analysis the following factors are associated with decreased crude survival: extrahepatic tumor (P < 0.0001), intraoperative hypotension (P = 0.0001), non-anatomical procedures (P = 0.0002), a metastasis diameter > or = 5 cm (P = 0.0002), unfavourable grading of the primary tumor (P = 0.0003), satellite metastases (P = 0.0069), mesenteric lymph node involvement (P = 0.0260), use of FFP (P = 0.0307) and sy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11383067"}, {"offsetInBeginSection": 1040, "offsetInEndSection": 1541, "text": " the resection-only group. Multivariate analysis identified four independent predictors of decreased OS in the resection-RFA group. Three were related to tumor biology: primary tumor nodal metastases (hazard ratio [HR], 2.32; 95% confidence interval (95% CI), 1.16-4.64], Kirsten rat sarcoma viral oncogene homolog mutation (HR, 2.64; 95% CI, 1.36-5.14), and preoperative high carcinoembryonic antigen (HR, 2.33; 95% CI, 1.13-4.81), and one related to tumor morphology-ablated lesions \u22653 (HR, 2.05; 95", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27916360"}, {"offsetInBeginSection": 1314, "offsetInEndSection": 1588, "text": "Significant association with poorer PFS and OS was found for low grades of pathological response (p = 0.009 and p < 0.001, respectively), R2 resection or presence of extrahepatic disease (both p < 0.001) and presence of KRAS mutation (p = 0.007 and p < 0.001, respectively).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26003673"}, {"offsetInBeginSection": 1292, "offsetInEndSection": 1492, "text": " had disease recurrence. N stage of the primary (p\u2009=\u20090.035), high-risk Petersen Index of the primary (p\u2009=\u20090.010) and Clinical Risk Score\u2009\u2265\u20093 (p\u2009=\u20090.005) were associated with poorer recurrence-free and", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086199"}, {"offsetInBeginSection": 685, "offsetInEndSection": 1013, "text": "h a stage IVB (P < 0.0001). Of the 11 independent prognostic factors identified, eight with a hazard ratio greater than 1.3 (depth of tumor invasion, regional lymph node metastasis, histologic grade, liver metastasis, lung metastasis, distant lymph node metastasis, peritoneal metastasis, and curative resection) were used in th", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22692571"}, {"offsetInBeginSection": 1238, "offsetInEndSection": 1698, "text": "In the multivariate analysis, the disease-specific survival and recurrence rates were statistically significantly influenced by more than three lymph node metastases of the primary tumor, more than two lesions within the liver, and the presence of extrahepatic tumor.CONCLUSIONS: From these data, we have developed a simple score for the risk stratification which may be useful for future studies on interdisciplinary management of colorectal liver metastases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21584664"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "PURPOSE: Prognosis after resection of liver metastases of colorectal cancer is influenced by a variety of clinical factors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21584664"}, {"offsetInBeginSection": 529, "offsetInEndSection": 765, "text": "Post-resection outcome of the patients with colorectal liver metastases was significantly influenced by 1) depth of invasion, 2) grade of lymph node metastasis , 3) number of metastatic lymph nodes and 4) Dukes stage of primary disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16734266"}, {"offsetInBeginSection": 1081, "offsetInEndSection": 1237, "text": "The prognosis after treatment of any recurrence was best after the accomplishment of a repeated R0 situation, independent of the location of the recurrence.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21584664"}, {"offsetInBeginSection": 243, "offsetInEndSection": 590, "text": "We evaluated the influence of various clinical and pathological factors on survival and recurrence and developed a simple model for risk stratification.METHODS: We have analyzed a total of 13 prognostic factors in 382 consecutive and prospectively enrolled R0-resected patients and applied our data set to ten published prognostic scoring systems.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21584664"}, {"offsetInBeginSection": 463, "offsetInEndSection": 573, "text": "The number of hepatic metastases and the surgical margin are probably the most significant prognostic factors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11379296"}, {"offsetInBeginSection": 1022, "offsetInEndSection": 1385, "text": "ents with resectable metastases. The commonly reported prognostic factors after repeat hepatectomy were R0 resection, carcinoembryonic antigen level, the presence of extrahepatic disease, a short disease-free interval between initial and repeat hepatectomy, the number (> 1) and size (\u2265 5\u00a0cm) of hepatic lesions, requiring blood transfusion, and no adjuvant chemo", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36858891"}, {"offsetInBeginSection": 1037, "offsetInEndSection": 1289, "text": "rds for multi-variable analysis. No prognostic factor was common in all models, though there was a tendency towards the number of metastases, CRC spread to lymph nodes, maximum size of metastases, preoperative CEA level and extrahepatic spread as repre", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22079259"}, {"offsetInBeginSection": 927, "offsetInEndSection": 1291, "text": "and other (7.2 percent). Factors of the primary tumor adversely affecting prognosis after hepatectomy for hepatic metastasis included poorly differentiated adenocarcinoma or mucinous carcinoma, depth of invasion of si/ai, lymph-node metastasis of Stage n3 and n4 by the Japanese classification of colorectal carcinoma, number of metastatic lymph nodes of more than", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14530655"}, {"offsetInBeginSection": 1292, "offsetInEndSection": 1777, "text": "four, and Dukes Stage D. Factors at the time of hepatectomy adversely affecting prognosis after surgery for hepatic metastasis included residual tumor, extrahepatic metastasis, hepatic metastasis of degree H3 stipulated by the Japanese classification of colorectal carcinoma, number of metastases of four or more, pathology of hepatic metastasis of poorly differentiated adenocarcinoma, resection margin of <10 mm, and carcinoembryonic antigen value higher than normal preoperative and", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14530655"}, {"offsetInBeginSection": 1434, "offsetInEndSection": 1802, "text": "4% and 34.2%, respectively. Univariate analysis revealed that centrally located metastasis, primary tumor in the transverse colon, metastasis in regional lymph nodes, initial extrahepatic metastasis, synchronous liver metastasis, multiple lesions, poorly differentiated tumor, and resection margin <10 mm were significant poor prognostic factors for recurrence-free su", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25889950"}, {"offsetInBeginSection": 664, "offsetInEndSection": 1095, "text": "colorectal cancer.RESULTS: Among the 12 prognostic factors studied (age, gender, adjuvant chemotherapy, tumor site, CEA level, tumor differentiation, tumor size, regional lymph node metastatic status, distribution of liver metastases, number of liver metastases, tumor size and pathological margin), regional lymph node metastatic status and pathological margin were significant prognostic factors by univariate analysis (p = 0.000", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10770561"}, {"offsetInBeginSection": 519, "offsetInEndSection": 775, "text": "d 51 per cent respectively. All of the independent factors associated with poor prognosis after hepatic resection were tumour-related factors, such as the number of tumours (four or more), presence of portal vein invasion, hepatic vein invasion and absence", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10201774"}]}
+{"question_id": "661be07748a2c27714000002", "question": "What is Lennox-Gastaut syndrome?", "answer": "Lennox-Gastaut syndrome is a severe early onset, rug-resistant developmental and epileptic encephalopathy with slow spike and wave on EEG (DEE-SSW) composing about 1-2% of epilepsy patients", "relevant_passage_ids": ["37054522", "37353676", "36700706", "23827423", "21353345", "9796756", "11918467", "30410820", "21351810", "22883278", "19081517", "28689466", "20542434", "29126048", "29124439", "33764203", "34315269", "33243685", "31770718", "31286465", "33721709", "34183143", "22592511", "20518600", "11952036", "32467926", "21790560", "7813093", "34513391", "21341220", "14734932", "25400619", "28461749", "15362174", "11993741", "32207730", "28479797", "18541034", "19898669", "20970386", "9390695", "25284032", "37176165", "37823366", "20158289", "36332460"], "type": "summary", "snippets": [{"offsetInBeginSection": 14, "offsetInEndSection": 252, "text": "Lennox Gastaut syndrome (LGS) can be conceptualised as a \"secondary network epilepsy\", in which the shared electroclinical manifestations reflect epileptic recruitment of a common brain network, despite a range of underlying aetiologies. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37054522"}, {"offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Lennox-Gastaut syndrome is a severe drug-resistant developmental and epileptic encephalopathy with slow spike and wave on EEG (DEE-SSW) composing about 1-2% of epilepsy patients. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37353676"}, {"offsetInBeginSection": 12, "offsetInEndSection": 96, "text": "Lennox-Gastaut syndrome (LGS) is a severe childhood-onset pharmacoresistant epilepsy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36700706"}, {"offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy with childhood onset that usually continues through adolescence and into adulthood. In the long term, patients with this condition still have intractable seizures, intellectual disability, behavioral problems, and physical comorbidities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29126048"}, {"offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Lennox-Gastaut syndrome is one of the rare childhood-onset epileptic encephalopathies, characterized by multiple type seizure disorder, the typical pattern on electroencephalogram and intellectual disability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30410820"}, {"offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "Lennox-Gastaut syndrome is one of the rare childhood-onset epileptic encephalopathies, characterized by multiple type seizure disorder, the typical pattern on electroencephalogram and intellectual disability. Tonic-type seizures are most commonly seen in these patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30410820"}, {"offsetInBeginSection": 0, "offsetInEndSection": 398, "text": "Lennox-Gastaut syndrome is one of the rare childhood-onset epileptic encephalopathies, characterized by multiple type seizure disorder, the typical pattern on electroencephalogram and intellectual disability. Tonic-type seizures are most commonly seen in these patients. Behavioral disturbances and cognitive decline are gradual-onset and last long after the first episode of epileptiform activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30410820"}, {"offsetInBeginSection": 0, "offsetInEndSection": 367, "text": "Lennox-Gastaut syndrome is a type of childhood epilepsy that has enormous detrimental effects on the patient's physical and developmental health and can also take a dramatic toll on the well-being of the patient's family. Lennox-Gastaut syndrome is characterized by variable etiology, multiple types of intractable seizures, and cognitive impairment in most patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11918467"}, {"offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Lennox-Gastaut syndrome is a relatively rare epilepsy syndrome that usually begins in early-mid childhood and is characterized by multiple seizure types, particularly generalized seizures, which are often resistant to antiepileptic drug medication.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20518600"}, {"offsetInBeginSection": 0, "offsetInEndSection": 430, "text": "Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy with childhood onset that usually continues through adolescence and into adulthood. In the long term, patients with this condition still have intractable seizures, intellectual disability, behavioral problems, and physical comorbidities. The aim of this study was to describe the clinical and EEG characteristics of a group of adults with Lennox-Gastaut syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29126048"}, {"offsetInBeginSection": 0, "offsetInEndSection": 502, "text": "Lennox-Gastaut syndrome is a type of childhood epilepsy that has enormous detrimental effects on the patient's physical and developmental health and can also take a dramatic toll on the well-being of the patient's family. Lennox-Gastaut syndrome is characterized by variable etiology, multiple types of intractable seizures, and cognitive impairment in most patients. It is one of the most difficult epilepsy syndromes to treat and is frequently resistant to treatment with standard antiepilepsy drugs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11918467"}, {"offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "Lennox-Gastaut syndrome is an epilepsy syndrome that begins in childhood (between 1 and 8 years of age), worsens during latency and persists frequently into adulthood, is refractory to antiepileptic medications, and results in cognitive decline and behavioral problems in affected individuals.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21351810"}, {"offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "Lennox-Gastaut syndrome (LGS) is considered an epileptic encephalopathy and is defined by a triad of multiple drug-resistant seizure types, a specific EEG pattern showing bursts of slow spike-wave complexes or generalized paroxysmal fast activity, and intellectual disability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29124439"}, {"offsetInBeginSection": 0, "offsetInEndSection": 334, "text": "INTRODUCTION: Lennox-Gastaut syndrome is a severe form of pediatric epilepsy that is classically defined by a triad of drug-resistant seizures, including atonic, tonic, and atypical absence seizures; slow spike-and-wave discharges and paroxysmal fast activity on electroencephalography (EEG); and cognitive and behavioral dysfunction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34315269"}, {"offsetInBeginSection": 523, "offsetInEndSection": 595, "text": "Lennox-Gastaut syndrome may be considered as secondary network epilepsy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29124439"}, {"offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Lennox-Gastaut syndrome (LGS) is a rare epileptic encephalopathy with a peak age of onset of 3-5 years of age.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21790560"}, {"offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Lennox-Gastaut Syndrome is a severe childhood epilepsy syndrome characterised by the diagnostic triad of a slow spike and wave pattern on electroencephalogram, multiple seizure types and developmental delay.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20542434"}, {"offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Lennox-Gastaut syndrome is one of the most severe epileptic encephalopathies of childhood onset.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19081517"}, {"offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Lennox-Gastaut syndrome is a severe childhood epilepsy disorder characterized by encephalopathy and multiple, often intractable, seizure types.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22883278"}, {"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Lennox-Gastaut syndrome (LGS) is a severe form of childhood-onset epilepsy associated with high morbidity and mortality.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28689466"}, {"offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "INTRODUCTION: The Lennox-Gastaut syndrome (LGS) is one of the most severe epileptic encephalopathies of childhood, characterized by electro-clinical triad of generalized spike-wave activity, slow (POL) in the electroencephalogram (EEG), multiple types of seizures and deve", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21353345"}, {"offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "The Lennox-Gastaut syndrome (LGS) is an electro-clinical syndrome of early childhood that consists of mental retardation, intractable generalized epilepsy with multiple seizure types, and typical EEG findings.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7813093"}, {"offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Lennox-Gastaut syndrome (LGS) is a childhood-onset epileptic encephalopathy characterized by multiple types of medically intractable seizures, cognitive impairment, and generalized slow spike-wave discharges in electroencephalography (EEG).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33243685"}, {"offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "Lennox-Gastaut syndrome (LGS)\u00a0is a childhood epilepsy disorder seen between\u00a0the ages of one to eight years\u00a0with the electroencephalogram (EEG) changes showing\u00a0slow spiked-wave complex bursts or paroxysms of generalized fast activity and intellectual disability\u00a0and often needing multiple lines of treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34513391"}, {"offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "INTRODUCTION: Lennox-Gastaut syndrome (LGS) is an epileptic encephalopathy that starts in childhood and has an unknown pathophysiologi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21341220"}, {"offsetInBeginSection": 232, "offsetInEndSection": 547, "text": "Although Lennox-Gastaut syndrome is commonly characterised by a triad of signs, which include multiple seizure types, slow spike-wave complexes on electroencephalographic (EEG) recordings, and impairment of cognitive function, there is debate with regard to the precise limits, cause, and diagnosis of the syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19081517"}, {"offsetInBeginSection": 548, "offsetInEndSection": 722, "text": "Tonic seizures, which are thought to be a characteristic sign of Lennox-Gastaut syndrome, are not present at onset and the EEG features are not pathognomonic of the disorder.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19081517"}, {"offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "Lennox-Gastaut syndrome is a severe, childhood-onset electroclinical syndrome comprised of multiple seizure types, intellectual and behavioral disturbances and characteristic findings on electroencephalogram of slow spike and wave complexes and paroxysmal fast frequency activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28461749"}, {"offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Lennox-Gastaut (L-G) syndrome is an intractable generalized epilepsy of childhood onset, associated with spike waves at a slow rate and paroxysmal fast activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15362174"}, {"offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Lennox-Gastaut syndrome (childhood epileptic encephalopathy).", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14734932"}, {"offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Lennox-Gastaut Syndrome (LGS) is a category of severe, disabling epilepsy, characterized by frequent, treatment-resistant seizures, and cognitive impairment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25400619"}, {"offsetInBeginSection": 0, "offsetInEndSection": 398, "text": "Lennox-Gastaut syndrome (LGS) is a severe form of childhood-onset epilepsy associated with high morbidity and mortality. The peak period for manifestations of Lennox-Gastaut syndrome is between ages 3 and 5 years, a time of critical brain development and corresponding vulnerability to the electroclinical dysfunction arising from Lennox-Gastaut syndrome. Diagnosis is based on a triad of symptoms:", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28689466"}, {"offsetInBeginSection": 0, "offsetInEndSection": 287, "text": "BACKGROUND: Lennox-Gastaut syndrome (LGS) is a severe form of childhood epilepsy that is defined by generalized multiple type seizures, slowness of intellectual growth, and a specific EEG disturbance. Children affected might previously have infantile spasms or underlying brain disorder ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18541034"}, {"offsetInBeginSection": 0, "offsetInEndSection": 420, "text": "Lennox-Gastaut Syndrome (LGS) is a category of severe, disabling epilepsy, characterized by frequent, treatment-resistant seizures, and cognitive impairment. Electroencephalography (EEG) shows characteristic generalized epileptic activity that is similar in those with lesional, genetic, or unknown causes, suggesting a common underlying mechanism. The condition typically begins in young children, leaving many severely", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25400619"}, {"offsetInBeginSection": 21, "offsetInEndSection": 220, "text": "Lennox-Gastaut syndrome are rare but are important to child neurologists because of the intractable nature of the seizures and the serious neurologic comorbidities. New antiepileptic drugs offer more", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11952036"}, {"offsetInBeginSection": 0, "offsetInEndSection": 374, "text": "OBJECTIVE: Children with infantile spasms may develop Lennox-Gastaut syndrome. The diagnostic criteria for Lennox-Gastaut syndrome are vague, and many experts use varying combinations of the following criteria for diagnosis: paroxysmal fast activity on electroencephalography (EEG), slow spike and wave on EEG, developmental delay, multiple seizure types, and nocturnal toni", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33764203"}, {"offsetInBeginSection": 222, "offsetInEndSection": 367, "text": "Lennox-Gastaut syndrome is characterized by variable etiology, multiple types of intractable seizures, and cognitive impairment in most patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11918467"}, {"offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Lennox-Gastaut syndrome (LGS) is one of the intractable epilepsies of childhood that is associated with an epileptic encephalopathy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9390695"}, {"offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy that shares many features and characteristics of other treatment-resistant childhood epilepsies. Accurate and early diagnosis is essential to both prognosis and overall patient management.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25284032"}, {"offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "The Lennox-Gastaut syndrome (LGS) is widely known as one of the most severe and prognostically unfavourable epileptic conditions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11993741"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Children with childhood epileptic encephalopathy (Lennox-Gastaut syndrome) frequently have both multiple seizure types and nonepileptic stereotyped ev", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9796756"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Lennox-Gastaut syndrome is a type of childhood epilepsy that has enormous detrimental effects on the patient's physical and developmental health and c", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11918467"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Lennox-Gastaut syndrome is an intractable epileptic encephalopathy, with most patients experiencing daily seizures despite therapy with multiple antie", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20970386"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "OBJECTIVES: Lennox-Gastaut syndrome is a catastrophic epileptic encephalopathy. In Lennox-Gastaut syndrome, seizures are resistant to pharmacological ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28479797"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "INTRODUCTION: Lennox-Gastaut syndrome is a severe form of pediatric epilepsy that is classically defined by a triad of drug-resistant seizures, includ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34315269"}, {"offsetInBeginSection": 19, "offsetInEndSection": 169, "text": "s the problem of the diagnosis of Lennox-Gastaut syndrome, a severe epileptic encephalopathy. Despite the presence of a vivid clinical and encephalogr", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32207730"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Lennox-Gastaut syndrome (LGS) is a severe form of childhood-onset epilepsy associated with high morbidity and mortality. The peak period for manifesta", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28689466"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "The Lennox-Gastaut syndrome is a devastating early-onset epileptic encephalopathy, associated with severe behavioural abnormalities. Its pathophysiolo", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32467926"}, {"offsetInBeginSection": 29, "offsetInEndSection": 179, "text": "izes the treatment of Lennox-Gastaut syndrome, an intractable epileptic encephalopathy of early childhood. In particular, the review focuses on rufina", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19898669"}, {"offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Lennox-Gastaut syndrome (LGS) is a rare epileptic encephalopathy with a peak age of onset of 3-5 years of age. Reported prevalence rates for LGS vary widely from 1-10% of all childhood epilepsies. Incidence rates are much lower.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21790560"}, {"offsetInBeginSection": 229, "offsetInEndSection": 573, "text": "LGS is characterized by intractable, multiple, generalized seizure types and an interictal electroencephalogram showing bursts of slow spike-and-wave, paroxysmal bursts of generalized polyspikes, and a slow background. All patients have tonic seizures during sleep that may be subtle, and nearly all have treatment-resistant, lifelong epilepsy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21790560"}, {"offsetInBeginSection": 760, "offsetInEndSection": 965, "text": "018 were included. Lennox-Gastaut syndrome was defined as having 3 of 5 of the following characteristics: paroxysmal fast activity, slow spike and wave, current developmental delay, multiple seizure types,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33764203"}, {"offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Lennox-Gastaut Syndrome (LGS) is a developmental and epileptic encephalopathy (DEE) characterized by multiple seizure types, electroencephalogram (EEG) patterns, and cognitive decline", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37176165"}, {"offsetInBeginSection": 11, "offsetInEndSection": 164, "text": "Lennox-Gastaut syndrome (LGS) is a severe form of epileptic encephalopathy, presenting during the first years of life, and is very resistant to treatment", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37823366"}, {"offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "The Lennox-Gastaut syndrome is a devastating early-onset epileptic encephalopathy, associated with severe behavioural abnormalities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32467926"}, {"offsetInBeginSection": 0, "offsetInEndSection": 333, "text": "INTRODUCTION: Lennox-Gastaut syndrome is a severe form of pediatric epilepsy that is classically defined by a triad of drug-resistant seizures, including atonic, tonic, and atypical absence seizures; slow spike-and-wave discharges and paroxysmal fast activity on electroencephalography (EEG); and cognitive and behavioral dysfunction", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34315269"}, {"offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "OBJECTIVES: Lennox-Gastaut syndrome is a catastrophic epileptic encephalopathy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28479797"}, {"offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Lennox-Gastaut syndrome is an intractable epileptic encephalopathy, with most patients experiencing daily seizures despite therapy with multiple antiepileptic drugs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20970386"}, {"offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Children with childhood epileptic encephalopathy (Lennox-Gastaut syndrome) frequently have both multiple seizure types and nonepileptic stereotyped events that are difficult to differentiate.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9796756"}, {"offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "BACKGROUND: Lennox-Gastaut syndrome is a catastrophic childhood cryptogenic or symptomatic epilepsy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23827423"}, {"offsetInBeginSection": 0, "offsetInEndSection": 366, "text": "INTRODUCTION: Lennox-Gastaut syndrome is a severe form of pediatric epilepsy that is classically defined by a triad of drug-resistant seizures, including atonic, tonic, and atypical absence seizures; slow spike-and-wave discharges and paroxysmal fast activity on electroencephalography (EEG); and cognitive and behavioral dysfunction. In the vast majority, Lennox-Ga", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34315269"}, {"offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Lennox-Gastaut syndrome is one of the rare childhood-onset epileptic encephalopathies, characterized by multiple type seizure disorder, the typical", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30410820"}, {"offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "Lennox-Gastaut syndrome (LGS) is a rare, age-related\u00a0syndrome, characterized by multiple seizure types, mental regression, and specific EEG abnormalities. It is one of the most challenging epilepsy: treatment\u00a0is rarely effective and the final prognosis remains poor, despite the availability of several antiepileptic", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31286465"}, {"offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy with childhood onset that usually continues through adolescence and into adulthood. In the long term, patients with this condition still have intractable seizures, intellectual disability, behavioral problems, and physical", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29126048"}, {"offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Lennox-Gastaut syndrome is a severe drug-resistant developmental and epileptic encephalopathy with slow spike and wave on EEG (DEE-SSW) composing about 1-2% of epilepsy patients. Seizures in", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37353676"}, {"offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "PURPOSE: Lennox-Gastaut syndrome (LGS) is a severe childhood-onset epileptic encephalopathy characterized by the presence of multiple types of intractable seizures, cognitive impairment, and specific electroencephalogram (EEG) patterns. The ai", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33721709"}, {"offsetInBeginSection": 53, "offsetInEndSection": 290, "text": "Lennox-Gastaut syndrome, a severe epileptic encephalopathy. Despite the presence of a vivid clinical and encephalographic picture, classical Lennox-Gastaut syndrome, which meets all of its diagnostic criteria, is quite rare. Many authors", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32207730"}, {"offsetInBeginSection": 0, "offsetInEndSection": 379, "text": "Lennox-Gastaut syndrome (LGS) is considered an epileptic encephalopathy and is defined by a triad of multiple drug-resistant seizure types, a specific EEG pattern showing bursts of slow spike-wave complexes or generalized paroxysmal fast activity, and intellectual disability. The prevalence of LGS is estimated between 1 and 2% of all patients with epilepsy. The etiology of LGS", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29124439"}, {"offsetInBeginSection": 222, "offsetInEndSection": 502, "text": "Lennox-Gastaut syndrome is characterized by variable etiology, multiple types of intractable seizures, and cognitive impairment in most patients. It is one of the most difficult epilepsy syndromes to treat and is frequently resistant to treatment with standard antiepilepsy drugs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11918467"}, {"offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Lennox-Gastaut syndrome occurs in 3% of children with epilepsy and is characterized by multiple seizure types, slow spike-and-wave discharges and a poor prognosis for seizure control and cognitive development.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20158289"}, {"offsetInBeginSection": 0, "offsetInEndSection": 503, "text": "Lennox-Gastaut syndrome (LGS) is a severe form of childhood-onset epilepsy associated with high morbidity and mortality. The peak period for manifestations of Lennox-Gastaut syndrome is between ages 3 and 5 years, a time of critical brain development and corresponding vulnerability to the electroclinical dysfunction arising from Lennox-Gastaut syndrome. Diagnosis is based on a triad of symptoms: multiple seizure types, cognitive impairment, and slow spike-and-wave pattern on electroencephalography.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28689466"}, {"offsetInBeginSection": 0, "offsetInEndSection": 355, "text": "Lennox-Gastaut syndrome (LGS) is a severe form of childhood-onset epilepsy associated with high morbidity and mortality. The peak period for manifestations of Lennox-Gastaut syndrome is between ages 3 and 5 years, a time of critical brain development and corresponding vulnerability to the electroclinical dysfunction arising from Lennox-Gastaut syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28689466"}, {"offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "OBJECTIVES: Lennox-Gastaut syndrome is a catastrophic epileptic encephalopathy. In Lennox-Gastaut syndrome, seizures are resistant to pharmacological treatment. In this prospective study, we evaluated the clinical features, neuroimaging, and response to treatment", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28479797"}, {"offsetInBeginSection": 222, "offsetInEndSection": 770, "text": "Lennox-Gastaut syndrome is characterized by variable etiology, multiple types of intractable seizures, and cognitive impairment in most patients. It is one of the most difficult epilepsy syndromes to treat and is frequently resistant to treatment with standard antiepilepsy drugs. This article reviews the etiology of Lennox-Gastaut syndrome, characteristics of predominant seizure types, methods of evaluating patients for Lennox-Gastaut syndrome, and available treatments including antiepilepsy drug therapy, ketogenic diet, and surgical options.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11918467"}, {"offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "INTRODUCTION: Lennox Gastaut syndrome (LGS) is an epileptic encephalopathy characterized by tonic, atonic, and atypical absence seizures usually refractory to pharmacological treatment. Patients generally continue with seizures despite treatment with the commercially available antiepileptic drugs (AEDs)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22592511"}, {"offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "BACKGROUND: Lennox Gastaut Syndrome (LGS) is an epilepsy syndrome presenting in childhood, classically charac", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36332460"}, {"offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Lennox Gastaut Syndrome (LGS) is a severe developmental epileptic encephalopathy with onset in childhood characterized by multiple seizure types and characteristic electroencephalogram findings. The majority of patients develop", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34183143"}, {"offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "Lennox-Gastaut syndrome (LGS)\u00a0is a childhood epilepsy disorder seen between\u00a0the ages of one to eight years\u00a0with the electroencephalogram (EEG) changes showing\u00a0slow spiked-wave complex bursts or paroxysms of generalized fast activity and intellectual disability", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34513391"}, {"offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Lennox-Gastaut syndrome (LGS) denotes a refractory epileptic encephalopathy of childhood onset with the triad of generalized slow spike-wave (GSSW) on interictal scalp electroencephalogram (EEG), multiple seizure types, and intellectual impairment. The neurobiology of", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31770718"}, {"offsetInBeginSection": 229, "offsetInEndSection": 447, "text": "LGS is characterized by intractable, multiple, generalized seizure types and an interictal electroencephalogram showing bursts of slow spike-and-wave, paroxysmal bursts of generalized polyspikes, and a slow background.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21790560"}, {"offsetInBeginSection": 68, "offsetInEndSection": 374, "text": " syndrome. The diagnostic criteria for Lennox-Gastaut syndrome are vague, and many experts use varying combinations of the following criteria for diagnosis: paroxysmal fast activity on electroencephalography (EEG), slow spike and wave on EEG, developmental delay, multiple seizure types, and nocturnal toni", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33764203"}]}
+{"question_id": "6616547dfdcbea915f00004f", "question": "What is the prevalence of neurofibromatosis?", "answer": "Neurofibromatosis is a common genetic disorder that affects the growth and development of nerve tissue. It is typically inherited in an autosomal dominant pattern and there are 2 main subtypes: neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). The prevalence of NF1 is approximately 1 in 3,000 births, while NF2 is less common with a prevalence of approximately 1 in 25,000 births.", "relevant_passage_ids": ["37710322", "29215653", "15655144", "10469430", "16583938", "32657748", "20412983", "19117870", "9864698", "22041820", "36317063", "19587630", "1600579", "26854064", "20082463", "8880865", "15105854", "34408961", "19568505", "31763299", "8953130", "22357435", "21232201", "17509168", "24621365", "32499294", "3088347", "23162593", "31625703", "33395412", "25838692", "21707352"], "type": "factoid", "snippets": [{"offsetInBeginSection": 926, "offsetInEndSection": 979, "text": "Pooled NF2 birth incidence was 1.08 per 50,000 births", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37710322"}, {"offsetInBeginSection": 782, "offsetInEndSection": 823, "text": "NF1 pooled birth incidence was 1 in 2,662", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37710322"}, {"offsetInBeginSection": 562, "offsetInEndSection": 598, "text": "Pooled NF1 prevalence was 1 in 3,164", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37710322"}, {"offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Neurofibromatosis type 1 (NF1) is an autosomal dominant condition with a worldwide incidence of approximately 1 per 2500 to 3000 individuals.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19117870"}, {"offsetInBeginSection": 0, "offsetInEndSection": 485, "text": "OBJECTIVE: To determine the prevalence of neurofibromatosis 1 (NF1) among 6-year-old children in Germany.SETTING AND PATIENTS: A total of 152819 children aged 6 years in 6 German states were screened for NF1 during routine medical examinations at elementary school enrollment in cooperation with local health departments in 2000 and 2001.MAIN OUTCOME MEASURE: The prevalence of NF1 among 6-year-old German children was estimated to be 1:2996 (95% confidence interval, 1:2260 to 1:3984)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15655144"}, {"offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder with an estimated prevalence of about 1/3000.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20412983"}, {"offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "Neurofibromatosis type 1 (NF1) is an autosomal dominant condition with a worldwide incidence of approximately 1 per 2500 to 3000 individuals. Caused by a germ-line-inactivating mutation in the NF1 gene on chromosome 17, the disease is associated with increased morbidity and mortality.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19117870"}, {"offsetInBeginSection": 0, "offsetInEndSection": 435, "text": "Neurofibromatosis type 1 (NF1) is an autosomal dominant condition with a worldwide incidence of approximately 1 per 2500 to 3000 individuals. Caused by a germ-line-inactivating mutation in the NF1 gene on chromosome 17, the disease is associated with increased morbidity and mortality. In the past several years, significant progress has been made in standardizing management of the major clinical features of neurofibromatosis type 1.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19117870"}, {"offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder with an estimated prevalence of about 1/3000. Several authors mention the occurrence of various types of speech abnormalities associated with NF1.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20412983"}, {"offsetInBeginSection": 926, "offsetInEndSection": 1152, "text": "Pooled NF2 birth incidence was 1.08 per 50,000 births (95%CI: 1 in 32,829-1 in 65,019).CONCLUSION: We present updated estimates of the incidence and prevalence of NF1 and NF2, to help plan for healthcare access and allocation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37710322"}, {"offsetInBeginSection": 782, "offsetInEndSection": 855, "text": "NF1 pooled birth incidence was 1 in 2,662 (95%CI: 1 in 1,968-1 in 3,601).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37710322"}, {"offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "INTRODUCTION: The prevalence and the type of seizures associated with neurofibromatosis\u00a01 (NF1) and 2 (NF2) are not adequately characterized.STATE OF THE ART: NF1 has a birth incidence of one in 2500, and NF2 one in 25000.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22041820"}, {"offsetInBeginSection": 631, "offsetInEndSection": 781, "text": "This was higher in studies that screened for NF1, compared to identification of NF1 through medical records (1 in 2,020 and 1 in 4,329, respectively).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37710322"}, {"offsetInBeginSection": 235, "offsetInEndSection": 317, "text": "NF1 is the most common neurogenetic disorder, with a birth incidence of 1 in 3000.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19587630"}, {"offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Neurofibromatosis (NF) is a serious, common, genetically determined neurological disorder; with a prevalence of about 1:4000 births it affects both sexes and all races and ethnic groups.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1600579"}, {"offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "The neurofibromatoses (NF) are a group of rare genetic disorders that can affect all races equally at an incidence from 1:3000 (NF1) to a log unit lower for NF2 and schwannomatosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26854064"}, {"offsetInBeginSection": 618, "offsetInEndSection": 710, "text": "Disease prevalence in order of frequency were for neurofibromatosis type 1 (NF1): 1 in 4,560", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20082463"}, {"offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "Neurofibromatosis 1 and 2 (NF1 and NF2) are autosomal dominantly inherited disorders with close to 100% penetrance. NF1 is one of the most frequent human genetic diseases with an incidence of 1:3000. The incidence of NF2 is about 10 fold lower.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8880865"}, {"offsetInBeginSection": 886, "offsetInEndSection": 1176, "text": "When the survival rates of NF1 patients and the Finnish population were combined with an estimate of NF1 incidence, a prevalence of 1/2,052 (95% CI 1/2,176-1/1,941) was estimated for NF1 in a population aged 0-74 years.CONCLUSION: NF1 is a much more common disorder than previously thought.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29215653"}, {"offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "PURPOSE: The incidence of neurofibromatosis 1 (NF1) is ~1/2,000 live births, but the current estimates of prevalence vary greatly.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29215653"}, {"offsetInBeginSection": 611, "offsetInEndSection": 720, "text": "rates. Disease prevalence in order of frequency were for neurofibromatosis type 1 (NF1): 1 in 4,560; familial", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20082463"}, {"offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Neurofibromatosis type 1 (NF1) is an autosomal dominant disease with a prevalence of about 1/3000. The clinical", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16583938"}, {"offsetInBeginSection": 228, "offsetInEndSection": 341, "text": "NF1 represents 95% of neurofibromatoses cases. Its incidence is 1 for 3,500 newborns, its prevalence 1 for 4,500.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9864698"}, {"offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "The prevalence of neurofibromatosis type 1 (NF1) is about 1/3,000.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10469430"}, {"offsetInBeginSection": 130, "offsetInEndSection": 378, "text": "Neurofibromatosis type 1 (NF1), also known as von Recklinghausen's disease, is the most common type of NF and accounts for about 90% of all cases. It is one of the most frequent human genetic diseases, with a prevalence of one case in 3,000 births.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15105854"}, {"offsetInBeginSection": 530, "offsetInEndSection": 597, "text": "e included in the final review. Pooled NF1 prevalence was 1 in 3,16", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37710322"}, {"offsetInBeginSection": 446, "offsetInEndSection": 492, "text": "NF2 incidence is 1 for 33,000-40,000 newborns.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9864698"}, {"offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "BACKGROUND: Neurofibromatosis of types 1 and 2 (NF1, NF2) and schwannomatosis are the diseases that make up the neurofibromatosis spectrum. With respective incidences of 1 in 3000, 1 in 33 000, and 1 in 60 000 births, they form part of the group of rare tumor-suppresso", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32657748"}, {"offsetInBeginSection": 530, "offsetInEndSection": 981, "text": "e included in the final review. Pooled NF1 prevalence was 1 in 3,164 (95%CI: 1 in 2,132-1 in 4,712). This was higher in studies that screened for NF1, compared to identification of NF1 through medical records (1 in 2,020 and 1 in 4,329, respectively). NF1 pooled birth incidence was 1 in 2,662 (95%CI: 1 in 1,968-1 in 3,601). There were only 2 studies on NF2 prevalence, so data were not pooled. Pooled NF2 birth incidence was 1.08 per 50,000 births (", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37710322"}, {"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Neurofibromatosis type 1 is one of the most common genetic autosomal dominant disorders described, with a prevalence of 1 in 2000 to 1 in 3000 individuals.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36317063"}, {"offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "PURPOSE: The incidence of neurofibromatosis 1 (NF1) is ~1/2,000 live births, but the current estimates of prevalence vary greatly. This retrospective total-population study was aimed at determining the p", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29215653"}, {"offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Neurofibromatosis type-1 (NF1), also known as von Recklinghausen disease, is a common autosomal dominant condition with an approximate incidence of one per 3000 births.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19568505"}, {"offsetInBeginSection": 335, "offsetInEndSection": 511, "text": "NF1, also known as von Recklinghausen's disease or peripheral neurofibromatosis, is an autosomal dominant multisystem disorder that approximately affects 1 in 2500-3000 births.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31763299"}, {"offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Neurofibromatosis type 1 (NF1) is an autosomal dominant disease with a prevalence of about 1/3000.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16583938"}, {"offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Neurofibromatosis type 1 (NF1), or von Recklinghausen disease, is a genetically transmitted autosomal dominant disease, with a prevalence of one per 4000 live births.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34408961"}, {"offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "With an incidence of 1 in 3,000, neurofibromatosis type 1 (NF1), or von Recklinghausen disease, is one of the most common genetic disorders encountered by primary care physicians.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8953130"}, {"offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Type I Neurofibromatosis (NF1) is an autosomal-dominant inheritable disorder, with an incidence of 1:3,000, and a prevalence of 1:4,000 to 5,000.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22357435"}, {"offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Neurofibromatosis 1 is an autosomal dominant disease with an estimated incidence 1:2500 to 1:3000 live newborns.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21232201"}, {"offsetInBeginSection": 293, "offsetInEndSection": 441, "text": "Von Recklinghausen's disease is an autosomal dominant disorder that is localized at the long arm of chromosome 17 and affects 1 in 4000 individuals.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17509168"}, {"offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Neurofibromatosis type-1 (NF1), also known as Von Recklinghausen disease, is an autosomal dominant disorder with incidence of one per 4000.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24621365"}, {"offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Neurofibromatosis type 1 (NF1, Von Recklinghausen disease) is an autosomal dominant disease with a birth incidence of 1/2500-3000.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32499294"}, {"offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Neurofibromatosis is a neurocutaneous systemic disease that occurs in 1:2500 to 3300 live births.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3088347"}, {"offsetInBeginSection": 130, "offsetInEndSection": 379, "text": "Neurofibromatosis type 1 (NF1), also known as von Recklinghausen's disease, is the most common type of NF, and accounts for about 90% of all cases. It is one of the most frequent human genetic diseases, with a prevalence of one case in 3,000 births.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23162593"}, {"offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Neurofibromatosis type 1 (NF-1; also known as Von Recklinghausen's disease) is a common autosomal dominant disease that occurs in the general population at the rate of 1 in 3000.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31625703"}, {"offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "BACKGROUND: Neurofibromatosis type 1 (NF-1) is an autosomal dominant disease that affects one in every 3000 ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33395412"}, {"offsetInBeginSection": 226, "offsetInEndSection": 415, "text": "NFI, also known as von Recklinghausen's neurofibromatosis, is an autosomal dominantly inherited neurogenetic disorder affecting 1:3000 newborn (Bongiorno et al., Oral Dis 12:125-129, 2006).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25838692"}, {"offsetInBeginSection": 394, "offsetInEndSection": 465, "text": "NF-1 occurs in about 1 in 2,500 to 3,300 individuals in the population.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21707352"}]}
+{"question_id": "661d96c9eac11fad33000028", "question": "What is the key transcription factor for melanocyte development and differentiation?", "answer": "Certain transcription factors have vital roles in lineage development, including the specification of cell types and control of differentiation. Microphthalmia-associated transcription factor (MITF) is a key transcription factor for melanocyte development and differentiation. MITF regulates the expression of numerous pigmentation genes to promote melanocyte differentiation, as well as fundamental genes for maintaining cell homeostasis, including genes encoding proteins involved in apoptosis (eg, BCL2) and the cell cycle (eg, CDK2).", "relevant_passage_ids": ["28263292", "30150413", "16140982", "21326905", "28649789", "16899407", "15277526", "12789278", "37847239", "37823232", "37770430", "37240204", "32854423", "9500554", "19995375", "10938265", "17000761", "11764295", "18028952", "14717844", "12859621", "10080955", "20144786", "12235125", "33940580", "16757562", "18628967", "34003523", "33438577", "27827304", "18829533", "17237008", "25670789", "11478782", "25803486", "30705290", "11211309", "15716956", "11886515", "18316599", "35580127", "35682684", "37752231", "1631016", "15250933", "21965087", "18971960", "33439865", "11041373"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 529, "text": "Certain transcription factors have vital roles in lineage development, including specification of cell types and control of differentiation. Microphthalmia-associated transcription factor (MITF) is a key transcription factor for melanocyte development and differentiation. MITF regulates expression of numerous pigmentation genes to promote melanocyte differentiation, as well as fundamental genes for maintaining cell homeostasis, including genes encoding proteins involved in apoptosis (eg, BCL2) and the cell cycle (eg, CDK2).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28263292"}, {"offsetInBeginSection": 171, "offsetInEndSection": 394, "text": "In mammals, the core gene regulatory network for melanocytes (their only pigment cell type) contains three transcription factors, Sox10, Pax3 and Mitf, with the latter considered a master regulator of melanocyte development", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37823232"}, {"offsetInBeginSection": 253, "offsetInEndSection": 404, "text": "The microphthalmia-associated transcription factor MITF is a lineage-survival oncogene that plays a crucial role in melanocyte development and melanoma", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37770430"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Microphthalmia-associated transcription factor (MITF) is an important regulator of melanogenesis and melanocyte development", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37240204"}, {"offsetInBeginSection": 141, "offsetInEndSection": 529, "text": "Microphthalmia-associated transcription factor (MITF) is a key transcription factor for melanocyte development and differentiation. MITF regulates expression of numerous pigmentation genes to promote melanocyte differentiation, as well as fundamental genes for maintaining cell homeostasis, including genes encoding proteins involved in apoptosis (eg, BCL2) and the cell cycle (eg, CDK2).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28263292"}, {"offsetInBeginSection": 141, "offsetInEndSection": 272, "text": "Microphthalmia-associated transcription factor (MITF) is a key transcription factor for melanocyte development and differentiation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28263292"}, {"offsetInBeginSection": 0, "offsetInEndSection": 332, "text": "Microphthalmia transcription factor (Mitf) is implicated as the master gene for survival of melanocytes, as well as a key transcription factor regulating the expression of major melanogenic proteins. We have shown that Mitf is a novel prognostic marker in patients with melanoma and that it plays a role in melanoma differentiation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18028952"}, {"offsetInBeginSection": 0, "offsetInEndSection": 393, "text": "Microphthalmia transcription factor (Mitf) is implicated as the master gene for survival of melanocytes, as well as a key transcription factor regulating the expression of major melanogenic proteins. We have shown that Mitf is a novel prognostic marker in patients with melanoma and that it plays a role in melanoma differentiation. Melanocyte-stimulating hormone up-regulates Mitf expression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18028952"}, {"offsetInBeginSection": 0, "offsetInEndSection": 362, "text": "Microphthalmia-associated transcription factor (MITF) acts as a master regulator of melanocyte development, function and survival by modulating various differentiation and cell-cycle progression genes. It has been demonstrated that MITF is an amplified oncogene in a fraction of human melanomas and that it also has an oncogenic role in human clear cell sarcoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16899407"}, {"offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Certain transcription factors have vital roles in lineage development, including specification of cell types and control of differentiation. Microphthalmia-associated transcription factor (MITF) is a key transcription factor for melanocyte development and differentiation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28263292"}, {"offsetInBeginSection": 0, "offsetInEndSection": 432, "text": "Microphthalmia-associated transcription factor (MITF) acts as a master regulator of melanocyte development, function and survival by modulating various differentiation and cell-cycle progression genes. It has been demonstrated that MITF is an amplified oncogene in a fraction of human melanomas and that it also has an oncogenic role in human clear cell sarcoma. However, MITF also modulates the state of melanocyte differentiation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16899407"}, {"offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Microphthalmia-associated transcription factor (MITF) M-form is a melanocyte-specific transcription factor that plays a key role in melanocyte development, survival, and differentiation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16140982"}, {"offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Microphthalmia-associated transcription factor (MITF) acts as a master regulator of melanocyte development, function and survival by modulating various differentiation and cell-cycle progression genes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16899407"}, {"offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Microphthalmia-associated Transcription Factor, MITF, is a master regulator of melanocyte development, differentiation, migration, and survival.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21326905"}, {"offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "Microphthalmia-associated transcription factor (MITF) was initially shown to play a key role in melanocyte differentiation through the direct transcriptional control of TYROSINASE, TYRP1 and DCT genes, encoding the three enzymes involved in melanin synthesis or melanogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19995375"}, {"offsetInBeginSection": 355, "offsetInEndSection": 519, "text": "We have previously shown that MITF transactivates the gene for tyrosinase, a key enzyme for melanogenesis, and is critically involved in melanocyte differentiation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9500554"}, {"offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "The transcription factor Microphthalmia-associated transcription factor (MITF) is a lineage-determination factor, which modulates melanocyte differentiation and pigmentation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12235125"}, {"offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "Commitment to the melanocyte lineage is characterized by the onset of expression of the microphthalmia-associated transcription factor (Mitf). This transcription factor plays a fundamental role in melanocyte development and maintenance and seems to be crucial for the survival of malignant melanocytes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17000761"}, {"offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Although microphthalmia-associated transcription factor (MITF) has been known for decades as a key regulator for melanocytic differentiation", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33940580"}, {"offsetInBeginSection": 274, "offsetInEndSection": 520, "text": "In both zebrafish and mice, one transcription factor, SOX10, controls the expression of another, MITF (microphthalmia-associated transcription factor), which in turn regulates a set of genes critical for pigment cell development and pigmentation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16757562"}, {"offsetInBeginSection": 0, "offsetInEndSection": 340, "text": "The Microphthalmia-associated transcription factor (MITF) is an important regulator of cell-type specific functions in melanocytic cells. MITF is essential for the survival of pigmented cells, but whereas high levels of MITF drive melanocyte differentiation, lower levels are required to permit proliferation and survival of melanoma cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18628967"}, {"offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "The microphthalamia-associated transcription factor (MITF) is an integral transcriptional regulator in melanocyte, the lineage from which melanoma cells originate.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12789278"}, {"offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Microphthalmia-associated transcription factor (MITF) is essential for melanocyte differentiation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11478782"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Microphthalmia-associated transcription factor (MITF) is the master regulator of the melanocyte lineage.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25803486"}, {"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "The MITF transcription factor is a master regulator of melanocyte development and a critical factor in melanomagenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30705290"}, {"offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Microphthalmia transcription factor, a melanocytic nuclear protein critical for the embryonic development and postnatal viability of melanocytes, is a master regulator in modulating extracellular signals.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11211309"}, {"offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Microphthalmia-associated transcription factor (MITF) plays a pivotal role in melanocyte survival and differentiation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12859621"}, {"offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Microphthalmia-associated transcription factor (MITF) is an important regulator of melanogenesis and melanocyte development.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37240204"}, {"offsetInBeginSection": 112, "offsetInEndSection": 289, "text": "In melanoma and in melanocyte development, the microphthalmia-associated transcription factor (Mitf) controls survival, differentiation, proliferation, and migration/metastasis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18829533"}, {"offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Micropthalmia-associated transcription factor (MITF) is the master regulator of melanocyte development, survival, and function.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18316599"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Microphthalmia-associated transcription factor (MITF) is an important regulator of melanogenesis and melanocyte development", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35682684"}, {"offsetInBeginSection": 188, "offsetInEndSection": 311, "text": "MITF is a key regulator of melanocyte-associated genes, and essential to proper development of the melanocyte cell lineage.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37752231"}, {"offsetInBeginSection": 141, "offsetInEndSection": 802, "text": "Microphthalmia-associated transcription factor (MITF) is a key transcription factor for melanocyte development and differentiation. MITF regulates expression of numerous pigmentation genes to promote melanocyte differentiation, as well as fundamental genes for maintaining cell homeostasis, including genes encoding proteins involved in apoptosis (eg, BCL2) and the cell cycle (eg, CDK2). Loss-of-function mutations of MITF cause Waardenburg syndrome type IIA, whose phenotypes include depigmentation due to melanocyte loss, whereas amplification or specific mutation of MITF can be an oncogenic event that is seen in a subset of familial or sporadic melanomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28263292"}, {"offsetInBeginSection": 175, "offsetInEndSection": 278, "text": "Microphthalmia-associated transcription factor (MITF) controls melanocyte survival and differentiation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10938265"}, {"offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Microphthalmia transcription factor (Mitf) is implicated as the master gene for survival of melanocytes, as well as a key transcription factor regulating the expression of major melanogenic proteins.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18028952"}, {"offsetInBeginSection": 434, "offsetInEndSection": 658, "text": "The microphthalmia-associated transcription factor MITF plays a crucial role in the development of melanocytes, the retinal pigment epithelium, osteoclasts, and mast cells and acts as a lineage survival oncogene in melanoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30150413"}, {"offsetInBeginSection": 288, "offsetInEndSection": 483, "text": "PAX3 and SOX10 are two transcription factors that can activate the expression of microphthalmia-associated transcription factor (MITF), a critical transcription factor for melanocyte development.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21965087"}, {"offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Microphthalmia-associated transcription factor (MiTF) is a key transcription factor for melanocyte lineage survival.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18971960"}, {"offsetInBeginSection": 704, "offsetInEndSection": 773, "text": "Mitfa has been identified as the master regulator of melanocyte fate.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33439865"}]}
+{"question_id": "661d48a2eac11fad33000018", "question": "What is the cause of Phenylketonuria (PKU)?", "answer": "Phenylketonuria (PKU) is caused by mutations in the phenylalanine hydroxylase (PAH) gene that result in deficiencies in phenylalanine (Phe) metabolism.", "relevant_passage_ids": ["35356682", "23771645", "25894915", "37924808", "26835324", "24130151", "35854334", "37922902", "37865339", "37863349", "37456395", "34017006", "12714182", "30389586", "2884570", "8629090", "19629656", "37553307", "31883647", "37446577", "18566668", "37105048", "10527663", "32039316", "14726806", "33970801", "18985011", "10495930", "30258912", "1968617", "23148178", "36500989", "12052659", "30067850", "15640093", "22572109", "26413448", "9427141", "14654665", "32668217", "29025426", "32605583", "30159852", "29114196", "29909188", "30504004", "1677790", "1959225", "36791482", "26503515", "30055544", "23220018", "26425393", "9323556", "25614310", "8100164", "20187763"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Phenylketonuria (PKU) is an inborn error caused by deficiencies in phenylalanine (Phe) metabolism", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35356682"}, {"offsetInBeginSection": 99, "offsetInEndSection": 348, "text": "Mutations in the phenylalanine hydroxylase (PAH) gene are the main cause of the disease whose signature hallmarks of toxically elevated levels of Phe accumulation in plasma and organs such as the brain, result in irreversible intellectual disability", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35356682"}, {"offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "The c.1222C>T (p.Arg408Trp) phenylalanine hydroxylase (PAH) variant is the most frequent cause of phenylketonuria (PKU), an autosomal recessive disorder characterized by accumulation of blood phenylalanine (Phe) to neurotoxic levels", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37922902"}, {"offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "The c.1222C>T (p.Arg408Trp) variant in the phenylalanine hydroxylase gene (PAH) is the most frequent cause of phenylketonuria (PKU), the most common inborn error of metabolism", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37924808"}, {"offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene, resulting in phenylalanine accumulation and impaired tyrosine production", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37865339"}, {"offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Phenylketonuria (PKU) is the most common inherited metabolic disorders caused by severe deficiency or absence of phenylalanine hydroxylase activity that converts phenylalanine (Phe) to tyrosine", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37863349"}, {"offsetInBeginSection": 0, "offsetInEndSection": 317, "text": "Phenylketonuria (PKU), the most frequent disorder of amino acid metabolism, is caused by mutations in human phenylalanine hydroxylase gene (PAH), leading to deficient enzyme activity. Previously reported but uncharacterized PAH gene mutation, p.S231F (c.692C > T), was detected in Serbian patients with classical PKU.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19629656"}, {"offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Phenylketonuria (PKU), the most frequent disorder of amino acid metabolism, is caused by mutations in human phenylalanine hydroxylase gene (PAH), leading to deficient enzyme activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19629656"}, {"offsetInBeginSection": 0, "offsetInEndSection": 434, "text": "Phenylketonuria (PKU), the most frequent disorder of amino acid metabolism, is caused by mutations in human phenylalanine hydroxylase gene (PAH), leading to deficient enzyme activity. Previously reported but uncharacterized PAH gene mutation, p.S231F (c.692C > T), was detected in Serbian patients with classical PKU. We analyzed p.S231F PAH protein in prokaryotic (Escherichia coli) and eukaryotic expression system (hepatoma cells).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19629656"}, {"offsetInBeginSection": 0, "offsetInEndSection": 444, "text": "BACKGROUND: Phenylalanine hydroxylase deficiency (PAHD) is an autosomal recessive disorder affecting phenylalanine (Phe) metabolism caused by mutations in the phenylalanine hydroxylase (PAH) gene. It has a complex phenotype with many variants and genotypes in various populations. This study sets out to analyze the screening results of children with phenylketonuria (PKU) in Yinchuan City and characterize the mutation variants of the PAH gene", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37553307"}, {"offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine (Phe) metabolism resulting from deficiency of phenylalanine hydroxylase (PAH).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18566668"}, {"offsetInBeginSection": 446, "offsetInEndSection": 591, "text": "The autosomal recessive disease phenylketonuria (PKU) is the result of a deficiency of PheOH enzymatic activity due to mutations in the PAH gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10527663"}, {"offsetInBeginSection": 157, "offsetInEndSection": 270, "text": "Most forms of PKU and hyperphenylalaninaemia (HPA) are caused by mutations in the PAH gene on chromosome 12q23.2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18566668"}, {"offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Phenylketonuria (PKU) is an autosomal recessive human genetic disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH, phenylalanine 4-monooxygenase, EC 1.14.16.1).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2884570"}, {"offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Classic phenylketonuria (PKU) is caused by defective activity of phenylalanine hydroxylase (PAH), the enzyme that coverts phenylalanine (Phe) to tyrosine.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37105048"}, {"offsetInBeginSection": 192, "offsetInEndSection": 342, "text": "Mutations in the phenylalanine hydroxylase (PAH) gene are the major cause of PKU, due to the loss of the catalytic activity of the enzyme product PAH.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26835324"}, {"offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH), and is performed with newborn mass screening.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8629090"}, {"offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by mutational inactivation of the phenylalanine hydroxylase (PAH) gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24130151"}, {"offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "The c.1222C>T (p.Arg408Trp) phenylalanine hydroxylase (PAH) variant is the most frequent cause of phenylketonuria (PKU), an autosomal recessive disorder characterized by accumulation of blood phenylalanine (Phe) to neurotoxic levels.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37922902"}, {"offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine (Phe) metabolism resulting from deficiency of phenylalanine hydroxylase (PAH). Most forms of PKU and hyperphenylalaninaemia (HPA) are caused by mutations in the PAH gene on chromosome 12q23.2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18566668"}, {"offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Phenylketonuria (PKU) is caused by phenylalanine hydroxylase (PAH) gene variants.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32039316"}, {"offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "PURPOSE: Phenylketonuria (PKU) is an autosomal recessive disorder caused by mutations in the phenylalanine hydroxylase (P", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14726806"}, {"offsetInBeginSection": 116, "offsetInEndSection": 280, "text": "PKU, an autosomal recessive disease, is an inborn error of phenylalanine (Phe) metabolism caused by pathogenic variants in the phenylalanine hydroxylase (PAH) gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35854334"}, {"offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Phenylketonuria is an autosomal recessive disorder caused by mutations in the phenylalanine hydroxylase gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33970801"}, {"offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Phenylketonuria (PKU; MIM 261600) is an autosomal recessive metabolic disorder caused by a deficiency of phenylalanine hydroxylase (PAH; EC 1.14.16.1).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18985011"}, {"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Phenylketonuria (PKU), an autosomal recessive disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH), is clinically very heterogeneous.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10495930"}, {"offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Phenylketonuria (PKU) is a metabolic disease caused by recessive mutations of the gene encoding the hepatic enzyme phenylalanine hydroxylase (PAH).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1968617"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "UNLABELLED: Phenylketonuria (PKU) is caused by variants in the phenylalanine hydroxylase (PAH) gene. We systematically inve", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25894915"}, {"offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Phenylketonuria (PKU) is an inherited disorder of amino acid metabolism caused by deficiency of the enzyme phenylalanine hydroxylase (PAH).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23148178"}, {"offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Phenylketonuria is an inherited disorder of metabolism of the amino acid phenylalanine caused by a deficit of the enzyme phenylalanine hydroxylase.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23771645"}, {"offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "This article highlights the significance of inborn errors of metabolism and focuses specifically on phenylketonuria (PKU), a well-known inheritance disorder caused by the deficiency or absence of phenylalanine hydroxylase (PAH).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37456395"}, {"offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Phenylketonuria (PKU) is an inherited disorder in which phenylalanine (Phe) is not correctly metabolized leading to an abnormally high plasma Phe concentration that causes profound neurologic damage if left untreated.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36500989"}, {"offsetInBeginSection": 592, "offsetInEndSection": 829, "text": "Phenylketonuria (PKU) is a genetic defect in phenylalanine (Phe) metabolism. Offspring of phenylketonuric mothers not under strict dietary control are born with maternal PKU (mPKU), a syndrome with similar characteristics as FAS and FSS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12052659"}, {"offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Phenylketonuria is an inherited disease caused by mutations in the phenylalanine hydroxylase gene PAH.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30067850"}, {"offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Phenylketonuria (PKU) is one kinds of autosomal recessive disease caused by phenylalanine hydroxylase (PAH) gene mutation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15640093"}, {"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by a deficiency of phenylalanine hydroxylase.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22572109"}, {"offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Phenylketonuria (PKU) is an autosomal recessive disease which results from mutations in the phenylalanine hydroxylase (PAH) gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26413448"}, {"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Classical phenylketonuria (PKU) is a metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9427141"}, {"offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Mutations in the gene encoding for phenylalanine hydroxylase (PAH) result in phenylketonuria (PKU) or hyperphenylalaninemia (HPA).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14654665"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Phenylketonuria (PKU), caused by variants in the phenylalanine hydroxylase (PAH) gene, is the most common autosomal-recessive Mendelian phenotype of amino acid metabolism.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32668217"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by deficiency of phenylalanine hydroxylase (PAH).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30258912"}, {"offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine (phe) metabolism caused by a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30504004"}, {"offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine metabolism caused by deficiency in the", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29025426"}, {"offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine metabolism caused by defic", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32605583"}, {"offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Phenylketonuria (PKU) is a prevalent inherited metabolic disorder caused by a phenylalanine hydroxylase (PAH) or tetrahydrobiopterin (BH4) deficiency, which leads to the accumulation of phenylalanine (PHE). High", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29909188"}, {"offsetInBeginSection": 16, "offsetInEndSection": 203, "text": "(PKU; also known as phenylalanine hydroxylase (PAH) deficiency) is an autosomal recessive disorder of phenylalanine metabolism, in which especially high phenylalanine concentrations cause", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34017006"}, {"offsetInBeginSection": 98, "offsetInEndSection": 431, "text": "disorders. Phenylketonuria (PKU), a relatively common disorder that is responsive to treatment, is an inherited autosomal recessive disorder caused by a deficiency in phenylalanine hydroxylase (PAH) or one of several enzymes mediating biosynthesis or regeneration of the PAH cofactor tetrahydrobiopterin. The objective of this review", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29114196"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "In phenylketonuria (PKU) usually there is a defect in the phenylalanine hydroxylase (PAH) gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1677790"}, {"offsetInBeginSection": 0, "offsetInEndSection": 327, "text": "In phenylketonuria (PKU) usually there is a defect in the phenylalanine hydroxylase (PAH) gene. Eight restriction fragment length polymorfisms (RFLP's) in the PAH gene together constitute the haplotype. A considerable number of mutations, responsible for the gene defect, some of which are rather frequent, have been described.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1677790"}, {"offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "In phenylketonuria (PKU) usually there is a defect in the phenylalanine hydroxylase (PAH) gene. Eight restriction fragment length polymorfisms (RFLP's) in the PAH gene together constitute the haplotype.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1677790"}, {"offsetInBeginSection": 0, "offsetInEndSection": 399, "text": "Phenylketonuria (PKU) has become a paradigm of a disease that can be identified by screening in the newborn period and treated to prevent serious complications. After many years of experience treating PKU, new challenges have emerged. It has become apparent that defective activity of phenylalanine hydroxylase leads to a spectrum of clinical presentations that has led to subclassifications of PKU.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1959225"}, {"offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "Phenylketonuria (PKU) is a rare metabolic disorder caused by mutations in the phenylalanine hydroxylase gene. Depending on the severity of the genetic mutation, medical treatment, and patient dietary management, elevated phenylalanine (Phe) may occur", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37446577"}, {"offsetInBeginSection": 152, "offsetInEndSection": 422, "text": "PKU is caused by autosomal recessive mutations in phenylalanine hydroxylase (PAH) and manifests with elevation of phenylalanine (Phe) in plasma and urine. Untreated PKU manifests with intellectual disability including seizures, microcephaly and behavioral abnormalities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36791482"}, {"offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Classic phenylketonuria (PKU) is caused by defective activity of phenylalanine hydroxylase (PAH), the enzyme that coverts phenylalanine (Phe) to tyrosine. Toxic accumulation of phenylalanine and its metabolites,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37105048"}, {"offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive disease caused by mutations in the PAH gene, resulting in deficiency of p", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31883647"}, {"offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Phenylketonuria (PKU) is an inherited autosomal recessive disorder of phenylalanine metabolism, mainly caused by a deficiency of phenylalanine hydroxylase (PAH).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26503515"}, {"offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Phenylketonuria (PKU) is an autosomal recessive disorder caused by the deficiency of phenylalanine hydroxylase enzyme that catalyzes the conversion of L-phenylalanine to L-tyrosine using tetrahydrobiopterin (BH4) as a cofactor.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30055544"}, {"offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Phenylketonuria is an autosomal recessive inborn error of metabolism resulting from phenylalanine hydroxylase deficiency.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23220018"}, {"offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism caused by the deficiency of phenylalanine hydroxylase.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26425393"}, {"offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Phenylketonuria (PKU) is an autosomal recessive disease caused by the deficiency of a liver-specific enzyme, phenylalanine hydroxylase (PAH).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9323556"}, {"offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Phenylketonuria (PKU) is caused by a deficiency or inactivity of the enzyme phenylalanine hydroxylase that converts phenylalanine (Phe) to tyrosine (Tyr).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25614310"}, {"offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Phenylketonuria (PKU) is a metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30389586"}, {"offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Phenylketonuria (PKU) is an autosomal recessive genetic disorder caused by phenylalanine hydroxylase (PAH) deficiency.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8100164"}, {"offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "AIM: Phenylalanine hydroxylase (PAH) deficiency is caused by mutations in the PAH gene resulting in a primary deficiency of the PAH enzyme activity, intolerance to the dietary intake of phenylalanine (Phe), and production of the phenylketonuria dis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20187763"}, {"offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Phenylalanine hydroxylase (PAH) deficiency is caused by mutations in the PAH gene (12q22-q24) resulting in a primary deficiency of the PAH enzyme activity, intolerance to the dietary intake of phenylalanine (Phe) and production of the phenylketonuria (PKU) disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12714182"}]}
+{"question_id": "65cebc0c1930410b13000003", "question": "Which disease is treated with nirsevimab?", "answer": "Nirsevimab can be used for treatment of respiratory syncytial virus disease.", "relevant_passage_ids": ["36599520", "36634694", "36577878", "32726528", "34937485", "37743207", "37616235", "35235726", "38070539", "36922390", "37095249", "37901217", "38095041", "38085019", "38062942", "38061043", "38058503", "38057209", "37097594", "34456918", "38032456", "37829940", "34813073", "36328884", "37468530", "36940703", "38026446", "37276355", "37082704", "37641189", "37824423", "37498791", "35968866", "35968865", "34543489", "37466917", "34933044", "37914061", "35572550", "36280532"], "type": "factoid", "snippets": [{"offsetInBeginSection": 1438, "offsetInEndSection": 1695, "text": "Novelties include the recommendation of routine administration of nirsevimab to neonates and infants aged less than 6 months for passive immunization against RSV, and the recommendations regarding the hexavalent vaccine are consolidated in a single section.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36599520"}, {"offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "Efficacy of nirsevimab against respiratory syncytial virus lower respiratory tract infections in preterm and term infants, and pharmacokinetic extrapolation to infants with congenital heart disease and chronic lung disease: a pooled analysis of randomised controlled trials.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36634694"}, {"offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "BACKGROUND: In a phase 2b trial and the phase 3 MELODY trial, nirsevimab, an extended half-life, monoclonal antibody against respiratory syncytial virus (RSV), protected healthy infants born preterm or at full term against medically attended RSV lower respiratory tract infection (LRTI). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36634694"}, {"offsetInBeginSection": 3947, "offsetInEndSection": 4121, "text": "INTERPRETATION: A single dose of nirsevimab protected healthy infants born at term or preterm from medically attended RSV LRTI, associated hospital admission, and severe RSV.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36634694"}, {"offsetInBeginSection": 4262, "offsetInEndSection": 4496, "text": "Together, these data suggest that nirsevimab has the potential to change the landscape of infant RSV disease by reducing a major cause of infant morbidity and the consequent burden on caregivers, clinicians, and health-care providers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36634694"}, {"offsetInBeginSection": 0, "offsetInEndSection": 388, "text": "Nirsevimab (Beyfortus\u00ae), a long-acting intramuscular recombinant neutralising human IgG1\u0138 monoclonal antibody to the prefusion conformation of the respiratory syncytial virus (RSV) F protein that has been modified with a triple amino acid substitution in the Fc region to extend the serum half-life, is being jointly developed by AstraZeneca and Sanofi for the prevention of RSV disease. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36577878"}, {"offsetInBeginSection": 495, "offsetInEndSection": 846, "text": "Nirsevimab was approved in the EU on 3 November 2022 and in the UK on 7 November 2022 for the prevention of RSV lower respiratory tract disease in neonates and infants during their first RSV season. This article summarizes the milestones in the development of nirsevimab leading to this first approval for the prevention of RSV disease in all infants.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36577878"}, {"offsetInBeginSection": 840, "offsetInEndSection": 1048, "text": "This maternal vaccine showed 70.9% efficacy against severe RSV infection within 150\u200adays after birth; the mAb nirsevimab reduces medically attended RSV infections by 79.5% within 150\u200adays after administration", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38085019"}, {"offsetInBeginSection": 968, "offsetInEndSection": 1369, "text": "The monoclonal antibody nirsevimab was approved by the FDA and recommended by the CDC for prevention of RSV-associated lower respiratory tract infection in infants younger than age 8 months who are born during or entering their first RSV season and for infants and children aged 8-19 months who are at high risk for RSV-associated lower respiratory tract infection and entering their second RSV season", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38061043"}, {"offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "The introduction of nirsevimab (a respiratory syncytial virus [RSV] monoclonal antibody that can protect for minimum 5 months with a single dose) and RSV maternal vaccines to protect young infants has the potential to dramatically decrease RSV hospitalizations in Canada", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38058503"}, {"offsetInBeginSection": 12, "offsetInEndSection": 132, "text": "The approval of nirsevimab brings light to reducing the heavy disease burden caused by respiratory syncytial virus (RSV)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38057209"}, {"offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Breakthrough therapy designation of nirsevimab for the prevention of lower respiratory tract illness caused by respiratory syncytial virus infections (RSV).", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34937485"}, {"offsetInBeginSection": 0, "offsetInEndSection": 376, "text": "INTRODUCTION: Respiratory syncytial virus (RSV) is associated with significant morbidity worldwide, especially among infants. We evaluated the potential impact of prophylactic nirsevimab, a monoclonal antibody, in infants experiencing their first RSV season, and the number of medically-attended lower respiratory tract infection episodes caused by RSV (RSV-MALRTI) in the USA", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34813073"}, {"offsetInBeginSection": 125, "offsetInEndSection": 376, "text": " We evaluated the potential impact of prophylactic nirsevimab, a monoclonal antibody, in infants experiencing their first RSV season, and the number of medically-attended lower respiratory tract infection episodes caused by RSV (RSV-MALRTI) in the USA", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34813073"}, {"offsetInBeginSection": 0, "offsetInEndSection": 353, "text": "INTRODUCTION: Respiratory Syncytial Virus (RSV) is a major cause of acute lower respiratory tract infections (ALRI) in infants. There are no licensed vaccines and only one monoclonal antibody available to protect infants from disease. A new and potentially longer-lasting monoclonal antibody, Nirsevimab, showed promising results in phase IIb/III trials", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36328884"}, {"offsetInBeginSection": 0, "offsetInEndSection": 562, "text": "INTRODUCTION: Respiratory syncytial virus (RSV) is associated with significant morbidity worldwide, especially among infants. We evaluated the potential impact of prophylactic nirsevimab, a monoclonal antibody, in infants experiencing their first RSV season, and the number of medically-attended lower respiratory tract infection episodes caused by RSV (RSV-MALRTI) in the USA.METHODS: We developed an age-structured, dynamic, deterministic compartmental model reflecting RSV natural history, incorporating USA demographic data and an age-specific contact matrix", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34813073"}, {"offsetInBeginSection": 125, "offsetInEndSection": 562, "text": " We evaluated the potential impact of prophylactic nirsevimab, a monoclonal antibody, in infants experiencing their first RSV season, and the number of medically-attended lower respiratory tract infection episodes caused by RSV (RSV-MALRTI) in the USA.METHODS: We developed an age-structured, dynamic, deterministic compartmental model reflecting RSV natural history, incorporating USA demographic data and an age-specific contact matrix", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34813073"}, {"offsetInBeginSection": 125, "offsetInEndSection": 684, "text": " We evaluated the potential impact of prophylactic nirsevimab, a monoclonal antibody, in infants experiencing their first RSV season, and the number of medically-attended lower respiratory tract infection episodes caused by RSV (RSV-MALRTI) in the USA.METHODS: We developed an age-structured, dynamic, deterministic compartmental model reflecting RSV natural history, incorporating USA demographic data and an age-specific contact matrix. We assumed either no effect of nirsevimab on transmission (scenario 1) or a 50% reduction of viral shedding (scenario 2)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34813073"}, {"offsetInBeginSection": 0, "offsetInEndSection": 435, "text": "INTRODUCTION: Nirsevimab, a monoclonal antibody for the prevention of disease caused by respiratory syncytial virus (RSV), has recently been approved for use in Europe and Spain.OBJECTIVES: To provide recommendations for the administration of nirsevimab for prevention of RSV disease.METHODS: The approach chosen to develop these recommendations involved a critical review of the literature and the use of the Delphi and GRADE methods.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37743207"}, {"offsetInBeginSection": 495, "offsetInEndSection": 693, "text": "Nirsevimab was approved in the EU on 3 November 2022 and in the UK on 7 November 2022 for the prevention of RSV lower respiratory tract disease in neonates and infants during their first RSV season.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36577878"}, {"offsetInBeginSection": 0, "offsetInEndSection": 387, "text": "Nirsevimab (Beyfortus\u00ae), a long-acting intramuscular recombinant neutralising human IgG1\u0138 monoclonal antibody to the prefusion conformation of the respiratory syncytial virus (RSV) F protein that has been modified with a triple amino acid substitution in the Fc region to extend the serum half-life, is being jointly developed by AstraZeneca and Sanofi for the prevention of RSV disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36577878"}, {"offsetInBeginSection": 694, "offsetInEndSection": 846, "text": "This article summarizes the milestones in the development of nirsevimab leading to this first approval for the prevention of RSV disease in all infants.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36577878"}, {"offsetInBeginSection": 0, "offsetInEndSection": 287, "text": "BACKGROUND: In a phase 2b trial and the phase 3 MELODY trial, nirsevimab, an extended half-life, monoclonal antibody against respiratory syncytial virus (RSV), protected healthy infants born preterm or at full term against medically attended RSV lower respiratory tract infection (LRTI).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36634694"}, {"offsetInBeginSection": 1298, "offsetInEndSection": 1720, "text": "In patients in whom palivizumab is currently indicated, its substitution by nirsevimab is recommended to reduce the burden of bronchiolitis.CONCLUSIONS: Routine administration of nirsevimab to all infants aged less than 6 months born during the RSV season or aged less than 6 months at the start of the winter season is recommended to reduce the burden of disease and the frequency of hospitalization due to bronchiolitis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37743207"}, {"offsetInBeginSection": 94, "offsetInEndSection": 315, "text": "In July 2023, the Food and Drug Administration approved nirsevimab, a long-acting monoclonal antibody, for passive immunization to prevent RSV-associated lower respiratory tract infection among infants and young children.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37616235"}, {"offsetInBeginSection": 388, "offsetInEndSection": 494, "text": "The extended serum half-life allows administration of nirsevimab as a single dose to cover the RSV season.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36577878"}, {"offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Passive immunization with nirsevimab protects infants from severe RSV disease without impairing the immune response to natural infection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37276355"}, {"offsetInBeginSection": 357, "offsetInEndSection": 504, "text": " development. Nirsevimab (MEDI8897) is a monoclonal antibody with an extended half-life developed to protect infants for an entire RSV season with ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34937485"}, {"offsetInBeginSection": 0, "offsetInEndSection": 315, "text": "Respiratory syncytial virus (RSV) is the leading cause of hospitalization among U.S. infants. In July 2023, the Food and Drug Administration approved nirsevimab, a long-acting monoclonal antibody, for passive immunization to prevent RSV-associated lower respiratory tract infection among infants and young children.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37616235"}, {"offsetInBeginSection": 376, "offsetInEndSection": 536, "text": "In July 2023, the U.S. Food and Drug Administration approved nirsevimab for the prevention of RSV-associated lower respiratory tract infections for all infants.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38070539"}, {"offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "INTRODUCTION: Nirsevimab, a monoclonal antibody for the prevention of disease caused by respiratory syncytial virus (RSV), has recently been appro", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37743207"}, {"offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "BACKGROUND: In a phase 2b trial and the phase 3 MELODY trial, nirsevimab, an extended half-life, monoclonal antibody against respiratory syncytial virus (RSV), protected healthy infants born preterm or at full term against ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36634694"}, {"offsetInBeginSection": 379, "offsetInEndSection": 641, "text": "disease. The extended serum half-life allows administration of nirsevimab as a single dose to cover the RSV season. Nirsevimab was approved in the EU on 3 November 2022 and in the UK on 7 November 2022 for the prevention of RSV lower respiratory tract disease in", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36577878"}, {"offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Nirsevimab is an extended half-life monoclonal antibody specific for the prefusion conformation of the respiratory syncytial virus (RSV)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37095249"}, {"offsetInBeginSection": 856, "offsetInEndSection": 1244, "text": "rom AstraZeneca and Sanofi.EXPERT OPINION: Nirsevimab (MEDI8897) is an RSV F protein monoclonal antibody and the next-generation RSV medicine having an extended half-life developed for the prevention of LRTI caused by RSV. Nirsevimab will supplant the current standard of care for RSV prevention. Importantly, nirsevimab requires a single dose to last the entire RSV season and may be giv", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34937485"}, {"offsetInBeginSection": 958, "offsetInEndSection": 1074, "text": "Nirsevimab can prevent severe RSV disease among infants and young children at increased risk for severe RSV disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37616235"}, {"offsetInBeginSection": 358, "offsetInEndSection": 712, "text": "Nirsevimab (formerly MEDI8897) is a highly potent, long-acting, human, recombinant mAb that received approval for the prevention of RSV infection in newborns and infants during their first RSV season from the EMA and the UK's Medicines and Healthcare products Regulatory Agency in November 2022 based on positive results in Phase 2b and 3 clinical trials", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36922390"}, {"offsetInBeginSection": 180, "offsetInEndSection": 344, "text": "Nirsevimab is a monoclonal antibody with an extended half-life that is being developed to protect infants for an entire RSV season with a single intramuscular dose.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32726528"}, {"offsetInBeginSection": 625, "offsetInEndSection": 959, "text": "Major updates for pediatric clinicians include a new recommendation for the monoclonal antibody nirsevimab for prevention of RSV disease in all infants, recommendations regarding use of 20-valent pneumococcal conjugate vaccine, and discussion of potential forthcoming changes to meningococcal and COVID-19 vaccination recommendations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37641189"}, {"offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "INTRODUCTION: Nirsevimab, a monoclonal antibody for the prevention of disease caused by respiratory syncytial virus (RSV), has recently been approved for use in Europe and Spain.OBJECTIVES: To provide recommendations for the administration of nirsevimab for prevention of RSV disease", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37743207"}, {"offsetInBeginSection": 0, "offsetInEndSection": 434, "text": "INTRODUCTION: Nirsevimab, a monoclonal antibody for the prevention of disease caused by respiratory syncytial virus (RSV), has recently been approved for use in Europe and Spain.OBJECTIVES: To provide recommendations for the administration of nirsevimab for prevention of RSV disease.METHODS: The approach chosen to develop these recommendations involved a critical review of the literature and the use of the Delphi and GRADE methods", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37743207"}, {"offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "INTRODUCTION: Nirsevimab, a monoclonal antibody for the prevention of disease caused by respiratory syncytial virus (RSV), has recently been approved for use in Europe and Spain", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37743207"}, {"offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Use of Nirsevimab for the Prevention of Respiratory Syncytial Virus Disease Among Infants and Young Children: Recommendations of the Advisory Committee on Immunization Practices - United States, 2023.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37616235"}, {"offsetInBeginSection": 647, "offsetInEndSection": 858, "text": "S: In the general neonatal population, routine administration of nirsevimab is recommended to reduce the frequency of illness and hospitalisation for bronchiolitis and RSV lower respiratory tract infection. Nirs", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37743207"}, {"offsetInBeginSection": 180, "offsetInEndSection": 436, "text": "JECTIVES: To provide recommendations for the administration of nirsevimab for prevention of RSV disease.METHODS: The approach chosen to develop these recommendations involved a critical review of the literature and the use of the Delphi and GRADE methods. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37743207"}, {"offsetInBeginSection": 180, "offsetInEndSection": 464, "text": "JECTIVES: To provide recommendations for the administration of nirsevimab for prevention of RSV disease.METHODS: The approach chosen to develop these recommendations involved a critical review of the literature and the use of the Delphi and GRADE methods. An expert group was formed. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37743207"}, {"offsetInBeginSection": 0, "offsetInEndSection": 361, "text": "In children with congenital heart disease and/or chronic lung disease entering their second respiratory syncytial virus (RSV) season, 200 mg nirsevimab had a similar safety profile to that of palivizumab and resulted in nirsevimab serum exposures associated with efficacy in healthy infants, supporting efficacy in this population at risk of severe RSV disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37466917"}, {"offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection and hospitalization in infants. Nirsevimab is a monoclonal antibody to the RSV fusion protein that has an extended half-life. The efficacy and safety of nirsevimab in healthy late-preterm and term infants are uncertain", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35235726"}, {"offsetInBeginSection": 0, "offsetInEndSection": 609, "text": "BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants, and a need exists for prevention of RSV in healthy infants. Nirsevimab is a monoclonal antibody with an extended half-life that is being developed to protect infants for an entire RSV season with a single intramuscular dose.METHODS: In this trial conducted in both northern and southern hemispheres, we evaluated nirsevimab for the prevention of RSV-associated lower respiratory tract infection in healthy infants who had been born preterm (29 weeks 0 days to 34 weeks 6 days of gestation)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32726528"}, {"offsetInBeginSection": 0, "offsetInEndSection": 343, "text": "BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants, and a need exists for prevention of RSV in healthy infants. Nirsevimab is a monoclonal antibody with an extended half-life that is being developed to protect infants for an entire RSV season with a single intramuscular dose", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32726528"}, {"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Nirsevimab for the prevention of respiratory syncytial virus disease in children. Statement of the Spanish Society of Paediatric Infectious Disease (SEIP).", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37743207"}, {"offsetInBeginSection": 623, "offsetInEndSection": 843, "text": "virus in the body. Nirsevimab is expected to significantly reduce the health and economic burdens of RSV. This article provides an overview of nirsevimab, potential adverse effects, and implications for nursing practice.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38070539"}, {"offsetInBeginSection": 848, "offsetInEndSection": 1351, "text": "leases from AstraZeneca and Sanofi.EXPERT OPINION: Nirsevimab (MEDI8897) is an RSV F protein monoclonal antibody and the next-generation RSV medicine having an extended half-life developed for the prevention of LRTI caused by RSV. Nirsevimab will supplant the current standard of care for RSV prevention. Importantly, nirsevimab requires a single dose to last the entire RSV season and may be given to term, preterm, and high-risk infants. However, even with nirsevimab approval there remains a need for", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34937485"}, {"offsetInBeginSection": 312, "offsetInEndSection": 546, "text": "e measures. Recent evidence suggests the potential of nirsevimab in preventing RSV infection.Objective: This study aims to determine the efficacy and safety of nirsevimab in preventing RSV infection among infants using a review of rel", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37082704"}, {"offsetInBeginSection": 0, "offsetInEndSection": 320, "text": "Introduction: Nirsevimab is an extended half-life (M252Y/S254T/T256E [YTE]-modified) monoclonal antibody to the pre-fusion conformation of the respiratory syncytial virus (RSV) Fusion protein, with established efficacy in preventing RSV-associated lower respiratory tract infection in infants for the duration of a typic", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37901217"}, {"offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection and hospitalization in infants. Nirsevimab is a monoclonal antibody to the RSV fusion protein that has an extende", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35235726"}, {"offsetInBeginSection": 1758, "offsetInEndSection": 1947, "text": "7.3%) who received placebo.CONCLUSIONS: A single injection of nirsevimab administered before the RSV season protected healthy late-preterm and term infants from medically attended RSV-assoc", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35235726"}, {"offsetInBeginSection": 1944, "offsetInEndSection": 2151, "text": "hypersensitivity reactions.CONCLUSIONS: A single injection of nirsevimab resulted in fewer medically attended RSV-associated lower respiratory tract infections and hospitalizations than placebo throughout th", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32726528"}, {"offsetInBeginSection": 478, "offsetInEndSection": 611, "text": "Nirsevimab is a human-derived, highly potent monoclonal antibody (mAb) with an extended half-life for RSV prophylaxis in all infants.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34456918"}, {"offsetInBeginSection": 968, "offsetInEndSection": 1370, "text": "The monoclonal antibody nirsevimab was approved by the FDA and recommended by the CDC for prevention of RSV-associated lower respiratory tract infection in infants younger than age 8 months who are born during or entering their first RSV season and for infants and children aged 8-19 months who are at high risk for RSV-associated lower respiratory tract infection and entering their second RSV season.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38061043"}, {"offsetInBeginSection": 94, "offsetInEndSection": 234, "text": "Nirsevimab (Bevfortus, Sanofi and AstraZeneca) is recommended to prevent RSV-associated lower respiratory tract infection (LRTI) in infants.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37824423"}, {"offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "INTRODUCTION: Nirsevimab, a monoclonal antibody for the prevention of disease caused by respiratory syncytial virus (RSV), has recently been approved for use in Eur", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37743207"}]}
+{"question_id": "660998ecfdcbea915f000014", "question": "Why does rectal cancer have worse prognosis than other colon tumors?", "answer": "Rectal cancer differs respect to colon cancer in etiology, carcinogenesis, pathology, genetics, anatomy and treatment response, surgical topography, procedures and multimodal treatment", "relevant_passage_ids": ["27497831", "30200215", "28365687", "32651860", "32789859", "18334831", "34732442", "30577807", "35714342", "29156800", "2305211", "24265711", "34276258", "31974054", "20577916", "17560986", "36538637", "37481501", "37726508", "28365393", "23115484", "37670964", "32051712", "35411179", "33611650", "33211264", "20947885", "29790124"], "type": "summary", "snippets": [{"offsetInBeginSection": 9, "offsetInEndSection": 146, "text": "Many apparent differences exist in aetiology, genetics, anatomy and treatment response between colon cancer (CC) and rectal cancer (RC). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27497831"}, {"offsetInBeginSection": 528, "offsetInEndSection": 655, "text": "Obvious differences exist in molecular carcinogenesis, pathology, surgical topography and procedures, and multimodal treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30200215"}, {"offsetInBeginSection": 214, "offsetInEndSection": 593, "text": "Although rectal cancer is thought to be biologically similar to colon cancer, the anatomic complexity of the pelvis makes therapy for this disease considerably more complicated. Local recurrence is also a greater concern in rectal cancer than in colon cancer. The choice of surgical therapy depends on the location of the tumor, depth of rectal wall invasion, and clinical stage.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17560986"}, {"offsetInBeginSection": 77, "offsetInEndSection": 473, "text": "Despite recent advances in radiation and chemotherapy, surgical resection remains an integral part of curative therapy for this disease. Although rectal cancer is thought to be biologically similar to colon cancer, the anatomic complexity of the pelvis makes therapy for this disease considerably more complicated. Local recurrence is also a greater concern in rectal cancer than in colon cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17560986"}, {"offsetInBeginSection": 214, "offsetInEndSection": 473, "text": "Although rectal cancer is thought to be biologically similar to colon cancer, the anatomic complexity of the pelvis makes therapy for this disease considerably more complicated. Local recurrence is also a greater concern in rectal cancer than in colon cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17560986"}, {"offsetInBeginSection": 214, "offsetInEndSection": 391, "text": "Although rectal cancer is thought to be biologically similar to colon cancer, the anatomic complexity of the pelvis makes therapy for this disease considerably more complicated.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17560986"}, {"offsetInBeginSection": 392, "offsetInEndSection": 473, "text": "Local recurrence is also a greater concern in rectal cancer than in colon cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17560986"}, {"offsetInBeginSection": 0, "offsetInEndSection": 660, "text": "OBJECTIVE: To explore the difference in tumor biological behaviors and prognosis between recurrent colon cancer and recurrent rectal cancer after radical operation.METHODS: Complete clinical and follow-up data of 132 patients with colorectal cancer developed recurrence,including 36 colon cancers and 96 rectal cancers, after curative resection were retrospectively analyzed and compared with respect of clinical pathological features and prognosis between colon and rectal cancer.RESULTS: Significant differences were found in primary tumor gross type, histological type, tumor differentiation and lymph node metastasis between colon and rectal cancer(P<0.05)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20577916"}, {"offsetInBeginSection": 166, "offsetInEndSection": 826, "text": "THODS: Complete clinical and follow-up data of 132 patients with colorectal cancer developed recurrence,including 36 colon cancers and 96 rectal cancers, after curative resection were retrospectively analyzed and compared with respect of clinical pathological features and prognosis between colon and rectal cancer.RESULTS: Significant differences were found in primary tumor gross type, histological type, tumor differentiation and lymph node metastasis between colon and rectal cancer(P<0.05). Colon cancer recurred earlier than rectal cancer after radical surgery with the median time to recurrence being 14.0 months and 21.5 months, respectively(P=0.028). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20577916"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1104, "text": "BACKGROUND: Although right-sided colon cancer is increasingly recognized as having a worse prognosis than left-sided colorectal cancer for colorectal liver metastases, little is known about the differences between the left-sided colon and rectum.OBJECTIVE: This study evaluated the prognostic value of primary tumor location in patients with colorectal liver metastases by examining the left-sided colon and rectum separately.DESIGN: This was a retrospective study from 2003 to 2017.SETTINGS: The study was conducted in a National Cancer Center Hospital.PATIENTS: The study cohort included 489 patients with colorectal liver metastases from right-sided colon cancer ( n = 119, 24%), left-sided colon cancer ( n = 251, 51%), or rectal cancer ( n = 119, 24%) who underwent hepatic resection.MAIN OUTCOME MEASURES: Primary outcomes were relapse-free survival and overall survival.RESULTS: Five-year relapse-free survival rates for patients with right-sided colon cancer, left-sided colon cancer, and rectal cancer were 28.6%, 34.1%, and 26.4%, and 5-year overall survival rates were 53.9%, 70.3%, and 60.8%.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35714342"}, {"offsetInBeginSection": 1551, "offsetInEndSection": 2072, "text": "In patients with recurrence ( n = 325), left-sided colon cancer had the lowest multiple-site recurrence rate and the highest surgical resection rate for recurrence (left-sided colon cancer, 20%/46%; right-sided colon cancer, 32%/30%; rectal cancer, 26%/39%).LIMITATIONS: This study was retrospective in design.CONCLUSIONS: Rectal cancer was associated with worse relapse-free survival and overall survival compared with left-sided colon cancer in patients with colorectal liver metastases who underwent hepatic resection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35714342"}, {"offsetInBeginSection": 335, "offsetInEndSection": 502, "text": "Utilizing a novel in silico clonal evolution algorithm, we identified common tumor-initiating events involving APC, KRAS and TP53 genes in RCC, LCC and rectal cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30577807"}, {"offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "BACKGROUND AND OBJECTIVES: It has been suggested that tumor deposits (TDs) may have a worse prognosis in rectal cancer compared with colonic cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32789859"}, {"offsetInBeginSection": 125, "offsetInEndSection": 346, "text": "tems. It is unclear whether colon cancer and rectal cancer are associated with different prognostic factors based on the anatomic difference.METHODS: We assessed the prognostic factors and survival outcomes of patients wi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31974054"}, {"offsetInBeginSection": 1249, "offsetInEndSection": 1837, "text": "hough, colon patients MAC showed an entirely worse survival rate than AC, rectum patients MAC showed a similar prognosis to AC. We found that in patients with rectal tumors, SRC had a worse 3 and 5-year prognosis than AC. However, for colon cancers, the prognosis of SRC was similar to that of AC. Histology was not found to be an independent prognostic factor in multivariate survival analysis.CONCLUSIONS: MAC and SRC are two distinct subtypes of colorectal cancer that require special attention despite their relatively rare prevalence. pT1 patients with SRC of the rectum and patients", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28365687"}, {"offsetInBeginSection": 1667, "offsetInEndSection": 1881, "text": "TD-positive pN1a-b patients had significantly worse outcomes whereas TDs did not affect outcomes in pN2a-b patients.CONCLUSION: This study suggests that TDs have a negative impact on the prognosis in rectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36538637"}, {"offsetInBeginSection": 681, "offsetInEndSection": 942, "text": "g metastases were multiple in rectal cancer. Compared to LCC, the adjusted hazard ratio (HR) for overall survival was 1.19 [95% confidence interval (CI)=1.01-1.39, p=0.032] in RCC and 1.03 (95% CI=0.86-1.23, p=0.77) in rectal cancer.CONCLUSION: RCC was independ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34732442"}, {"offsetInBeginSection": 1479, "offsetInEndSection": 1629, "text": "ve worse prognosis if they have a history of liver metastasis, multiple pulmonary metastases, or abnormal preoperative CEA. These results may help ass", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31974054"}, {"offsetInBeginSection": 224, "offsetInEndSection": 775, "text": "Patients with DNA diploid tumours had a significant survival advantage compared with patients with non-diploid tumours, but DNA ploidy did not confer any significant additional prognostic information when tumour site, Dukes's stage, the invasiveness of the tumour, and the number of lymph node metastases were adjusted for in a proportional hazards regression analysis (Cox). It is concluded that DNA ploidy does not contribute significantly to the explanation of why patients with rectal cancer have a poorer prognosis than those with colonic cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2305211"}, {"offsetInBeginSection": 660, "offsetInEndSection": 885, "text": "ng Cancer Center (MSKCC) models.RESULTS: High NLR was significantly associated with worse DFS (HR, 1.36; 95% confidence interval [CI], 1.08-1.70; P\u00a0= .009) and OS (HR, 1.65; 95% CI, 1.29-2.10; P\u00a0< .0005) in all stages for pat", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28365393"}, {"offsetInBeginSection": 587, "offsetInEndSection": 718, "text": "worse histological tumor grade. Patients with rectal cancer had significantly higher TP expression in mucosa and tumors compared wi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23115484"}, {"offsetInBeginSection": 267, "offsetInEndSection": 489, "text": "Studies have demonstrated significant difference in survival of patients with primary colon and rectal tumors both in local and in metastatic setting; but only few assessed outcomes of CRS/HIPEC for rectal and colon tumors", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37726508"}, {"offsetInBeginSection": 12, "offsetInEndSection": 266, "text": "Although previous studies have demonstrated that tumor deposits (TDs) are associated with worse prognosis in colon cancer, their clinical significance in rectal cancer has not been fully elucidated, especially in the lateral pelvic lymph node (LPLN) area", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37481501"}, {"offsetInBeginSection": 945, "offsetInEndSection": 1352, "text": "months; rectum group: 67.88 \u00b11.95 months). There was no significant difference (p = 0.493) between patients who had colon or rectum cancer. The forward stepwise Cox regression analysis results indicated that perineural invasion, distant metastasis, age, pathological differentiation grade, and obstruction were statistically significant for patients who had CRC, colon cancer or rectum cancer.CONCLUSIONS: T", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32051712"}, {"offsetInBeginSection": 169, "offsetInEndSection": 1586, "text": "nocarcinoma (AC). We aimed to compare two anatomic locations in terms of LNM and prognosis using a comprehensive statistical analysis of a large population.Methods: The Surveillance, Epidemiology, and End Results (SEER) database and our center (First Affiliated Hospital of Nanchang University) were used to extract patient information. Univariate and multivariate logistic or Cox regression and propensity score matching were used to explore the association between LNM/survival and tumor site.Results: Information for 12,404 patients, including 9655 colonic AC and 2749 rectal AC patients, was extracted from the SEER database. The 516 AC patients included 184 colonic and 332 rectal AC patients from our center. Multivariate logistic regression analysis revealed a correlation between LNM and tumor site (colon vs rectum, odds ratio [OR] =1.52, 95% CI, 1.349-1.714, P<0.001). Additionally, we found that younger age, T1b stage, poor differentiation, and lymphatic invasion were risk factors for LNM. After adjusting for confounding factors by PSM, we found that the location of the rectum remained a higher risk factor for LNM. However, we found that patients diagnosed with rectal AC had a prognosis similar to that of patients diagnosed with colonic AC, which was demonstrated by the analysis of SEER data and data from our center.Conclusion: T1-stage rectal AC may have a higher risk of LNM than colonic AC, whi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35411179"}, {"offsetInBeginSection": 731, "offsetInEndSection": 1086, "text": "m, colon cancer patients had better survival than those with rectal cancer, by a margin of 4 months in stage IIB. In stage IIIC and stage IV, rectal cancer patients had better survival than colon cancer patients, by about 3 months. Stage IIB colorectal cancer patients had a poorer prognosis than those with stage IIIA and IIIB colorectal cancer. After ad", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24265711"}, {"offsetInBeginSection": 645, "offsetInEndSection": 1355, "text": " 2012. Relapse-free survival (RFS) after primary surgery and overall survival (OS) after recurrence were examined.RESULTS: Rectal cancer (n\u2009=\u20092922) was associated with worse RFS compared to right-sided colon cancer (n\u2009=\u20092362) (hazard ratio (HR) 0.65; 95% CI 0.59-0.72; p\u2009<\u20090.001) and left-sided colon cancer (n\u2009=\u20093910) (HR 0.72; 95% CI 0.66-0.78; p\u2009<\u20090.001) after adjusting for key clinical factors (i.e., sex, age, histological type, CEA, adjuvant therapy, T category, and N category). Among patients with recurrence (n\u2009=\u20092823), rectal cancer was associated with better OS compared to right-sided colon cancer (HR 1.23; 95% CI 1.08-1.40; p\u2009=\u20090.002) and worse OS compared to left-sided colon cancer (HR 0.88; 9", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32651860"}, {"offsetInBeginSection": 14, "offsetInEndSection": 820, "text": "ctal cancer accounts for one-third of all colorectal cancer (CRC) cases. Due to physiological and anatomical differences, some researchers consider rectal cancer as a separate organ malignancy during the recent decades. However, limited studies have been conducted in this regard in Iran. Therefore, the aim of this study is to determine survival of rectal cancer and its, affecting factors in Fars province, southern Iran.METHODS: In this cohort study, we used the data of 387 patients with rectal cancer gathered by the Colorectal Research Center of Shiraz University of Medical Sciences between 2007 and 2015. The impact of 35 explanatory factors including demographic information, medical history, pathologic data, and imaging findings was evaluated using Cox regression analysis.RESULTS: Out of all pa", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33211264"}, {"offsetInBeginSection": 568, "offsetInEndSection": 1960, "text": "January 2005 and December 2019 in the same hospital center were included. Overall survival (OS), cancer-related survival (CRS), time to recurrence (TTR), relapse-free survival (RFS) and postrecurrence survival (PRS) were analyzed, and the results were classified by tumor stage. The results were compared among patients with right colon (RS), left colon (LS) and rectal tumors. Results: In the entire cohort, patients with RS tumors had lower OS and lower CRS at 60 months after diagnosis than did patients with LS or rectal tumors. In the regression analysis, the localization of the primary tumor was an independent prognostic indicator for OS and CRS. Analysis by tumor stage showed that patients with RS stage III tumors had lower OS and lower CRS at 60 months than did patients with LS and rectal tumors (42%, 59% and 53%, respectively, p = 0.006; and 48%, 63% and 57%, respectively, p = 0.025). Additionally, patients with RS Stage IV tumors had lower OS and lower CRS at 36 months than did patients with LS and rectal tumors (9%, 24%, 24%, respectively, p < 0.001; and 10%, 24% and 24%, respectively, p < 0.001). No differences were found in TTR and RFS among patients with stage I and II RS, LS, and rectal tumors. In contrast, patients with stage RS III tumors had significantly poorer PRS (9% for RS tumors, 13% for LS tumors, and 22% for rectal tumors) (p < 0.001). Conclusion: The", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37670964"}, {"offsetInBeginSection": 1117, "offsetInEndSection": 1307, "text": "c rectal biopsies.RESULTS: HSP27 overexpression was strongly associated with poor cancer-specific survival in rectal cancer (n=205, p=0.0063) but not colon cancer (n=199, p=0.7385) in the co", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20947885"}]}
+{"question_id": "661a6733fdcbea915f00005c", "question": "Is Loeys-Dietz syndrome (LDS) associated with Aortic Aneurysm?", "answer": "Loeys-Dietz syndrome (LDS) is an autosomal connective tissue disorder commonly presenting with hypertelorism, bifid uvula, aortic aneurysms, and arterial tortuosity.", "relevant_passage_ids": ["37916856", "37755470", "37823753", "29687491", "26617788", "32559129", "21801912", "28252349", "27125181", "32462795", "29022822", "24355917", "30625890", "17257922", "36237225", "21949523", "36308480", "37948688", "37876949", "37126428", "34807419", "33204949", "33289867", "23401778", "18630721", "20662229", "33487195", "31724649", "30534260", "32339686", "26290839", "32062130", "30833837", "31085000", "26652537", "26131745", "22563345", "37719708", "37677958", "27521346", "24443024", "36219981", "36356561", "35662564", "36483799", "26655350", "28737872", "29320330", "28230898"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Loeys-Dietz syndrome (LDS) is an autosomal connective tissue disorder commonly presenting with hypertelorism, bifid uvula, aortic aneurysms, and arterial tortuosity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37916856"}, {"offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Hereditary thoracic aortic diseases (HTAD) such as Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), and vascular Ehlers-Danlos syndrome (VEDS) frequently result in complex cardiovascular pathology that can lead to premature death", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37755470"}, {"offsetInBeginSection": 12, "offsetInEndSection": 166, "text": "Loeys-Dietz syndrome (LDS) is an inherited connective tissue disorder associated with aortic root enlargement and risk of thoracic aortic dissection (AD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37823753"}, {"offsetInBeginSection": 11, "offsetInEndSection": 227, "text": "Loeys-Dietz syndrome (LDS) is a heritable aortopathy associated with craniofacial abnormalities and dilatation and dissection of the aorta and its branches, as well as increased risk for intracranial aneurysms (ICAs)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37948688"}, {"offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Loeys-Dietz syndrome (LDS) is an autosomal connective tissue disorder commonly presenting with hypertelorism, bifid uvula, aortic aneurysms, and arterial tortuosity", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37916856"}, {"offsetInBeginSection": 171, "offsetInEndSection": 272, "text": "Loeys-Dietz syndrome (LDS) is less commonly seen as a cause of ascending aortic aneurysms in children", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37876949"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Loeys-Dietz syndrome (LDS) is a recently reported autosomal dominant aortic aneurysm syndrome with widespread systemic involvement.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31724649"}, {"offsetInBeginSection": 0, "offsetInEndSection": 329, "text": "Loeys-Dietz syndrome (LDS) is a recently reported autosomal dominant aortic aneurysm syndrome with widespread systemic involvement. Although connective tissue diseases carry a theoretical risk of aneurysmal degeneration in vein grafts, there are no reports of vein graft aneurysm (VGA) in patients with connective tissue disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31724649"}, {"offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "BACKGROUND: Loeys-Dietz syndrome (LDS) is a recently recognized aggressive aortic disorder characterized by root aneurysm, arterial tortuosity, hypertelorism, and bifid uvula or cleft palate", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21801912"}, {"offsetInBeginSection": 171, "offsetInEndSection": 273, "text": "Loeys-Dietz syndrome (LDS) is less commonly seen as a cause of ascending aortic aneurysms in children.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37876949"}, {"offsetInBeginSection": 171, "offsetInEndSection": 474, "text": "Loeys-Dietz syndrome (LDS) is less commonly seen as a cause of ascending aortic aneurysms in children. In this case report, we describe pediatric Bentall procedure, which we successfully performed to a child with LDS (Type I) with giant ascending aortic enlargement and significant aortic regurgitation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37876949"}, {"offsetInBeginSection": 299, "offsetInEndSection": 553, "text": "After the 1st operation, she was diagnosed with Loeys-Dietz syndrome (LDS), which is recently described as an autosomal dominant aortic aneurysm syndrome caused by heterozygous mutations in the transforming growth factor-beta receptor type 1 and 2 genes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20662229"}, {"offsetInBeginSection": 0, "offsetInEndSection": 481, "text": "Loeys-Dietz syndrome (LDS) is a recently reported autosomal dominant aortic aneurysm syndrome with widespread systemic involvement. Although connective tissue diseases carry a theoretical risk of aneurysmal degeneration in vein grafts, there are no reports of vein graft aneurysm (VGA) in patients with connective tissue disease. We herein report the first case of a giant VGA that was manifested 5\u00a0years after the reconstruction of a popliteal artery aneurysm associated with LDS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31724649"}, {"offsetInBeginSection": 299, "offsetInEndSection": 663, "text": "After the 1st operation, she was diagnosed with Loeys-Dietz syndrome (LDS), which is recently described as an autosomal dominant aortic aneurysm syndrome caused by heterozygous mutations in the transforming growth factor-beta receptor type 1 and 2 genes. Only 2 months after the 1st operation, she developed heart failure due to recurrence of aortic regurgitation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20662229"}, {"offsetInBeginSection": 0, "offsetInEndSection": 327, "text": "Loeys-Dietz syndrome is a connective tissue disorder known to cause aggressive aortopathy in paediatric patients, but it is extremely rare for cardiovascular events to present during infancy. We report the first successful aortic repair in a neonate with LDS presenting in extremis with an early onset, massive aortic aneurysm.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33487195"}, {"offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "BACKGROUND: Loeys-Dietz syndrome (LDS) is a recently recognized aggressive aortic disorder characterized by root aneurysm, arterial tortuosity, hypertelorism, and bifid uvula or cleft palate. The results of prophylactic root replacement using valve-sparing procedures (valve-sparing root replacement [VSRR]) in patients with LDS is not known", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21801912"}, {"offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Loeys-Dietz syndrome (LDS) is characterised by a mutation in the transforming growth factor beta receptor, and is strongly associated with aortic aneurysms and rupture.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28252349"}, {"offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Loeys-Dietz syndrome (LDS) is a connective tissue disorder that is characterized by skeletal abnormalities, craniofacial malformations, and a high predisposition for aortic aneurysm.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24355917"}, {"offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Background: Loeys-Dietz syndrome (LDS) is a heritable disorder that presents with thoracic aortic aneurysm and/or dissection caused by a mutation in one of the transforming growth factor-B receptor or ligand genes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36237225"}, {"offsetInBeginSection": 538, "offsetInEndSection": 731, "text": "On further investigation of her family history, it was revealed that she had a strong positive family history of aortic rupture and aneurysms associated with genetically confirmed atypical LDS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28252349"}, {"offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Loeys-Dietz syndrome due to mutations in TGFBR1 and 2 is associated with early and aggressive aortic aneurysm and branch vessel disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27125181"}, {"offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Aortic aneurysms in childhood are rare disease entities and are usually seen in patients with genetic connective tissue disorders such as Marfans, Ehler-Danlos, and Loeys-Dietz syndrome (LDS).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29687491"}, {"offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Loeys-Dietz syndrome is a genetic disorder that predisposes patients to aortic aneurysms. If left untreated, the natural history of the associated aortopathy often culminates in fatal aortic dissection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30833837"}, {"offsetInBeginSection": 154, "offsetInEndSection": 376, "text": "Loeys-Dietz syndrome is a connective tissue disorder characterized by aortic aneurysms, arterial tortuosity, and aortic dissections. It is caused by mutations in the genes affecting the transforming growth factor \u03b2 pathway", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31085000"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Loeys-Dietz syndrome presents early in life with rapidly progressive aortic aneurysmal disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26652537"}, {"offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder that is characterized by aggressive arterial and aortic disease, often involving the formation of aortic aneurysms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26290839"}, {"offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "BACKGROUND: Loeys-Dietz syndrome is a connective tissue disorder accompanied by life-threatening vascular abnormalities such as aneurysms and ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26131745"}, {"offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Loeys-Dietz syndrome (LDS) is an autosomal dominant genetic connective tissue disorder, and most of LDS patients will develop into aortic aneurysm.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26617788"}, {"offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "Loeys-Dietz syndrome is a recently described autosomal dominant disorder caused by mutations in the genes for transforming growth factor-beta receptor type 1 or 2 (TGF-\u00dfR 1/2). The syndrome predisposes patients to aortic aneurysm and dissections, along with craniofacial and musculoskeletal abnormalities", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22563345"}, {"offsetInBeginSection": 614, "offsetInEndSection": 769, "text": "The discovery of a new aortic aneurysm syndrome, the Loeys-Dietz syndrome (LDS), confirmed the importance of the cytokine TGFbeta in aneurysm pathogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18630721"}, {"offsetInBeginSection": 12, "offsetInEndSection": 165, "text": "Loeys-Dietz syndrome (LDS) is an inherited connective tissue disorder associated with aortic root enlargement and risk of thoracic aortic dissection (AD)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37823753"}, {"offsetInBeginSection": 17, "offsetInEndSection": 121, "text": " variants cause Loeys-Dietz syndrome type 5, a syndromic form of thoracic aortic aneurysm and dissection", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37719708"}, {"offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Loeys-Dietz syndrome (LDS) is a connective tissue disease related to \u03b2-transforming growth factor mutations, which causes aneurysms formation, vascular tortuosity and skeletal manifestations", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37677958"}, {"offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Background: Loeys-Dietz syndrome (LDS) is a heritable disorder that presents with thoracic aortic aneurysm and/o", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36237225"}, {"offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "BACKGROUND: Loeys-Dietz syndrome (LDS) is a genetic connective tissue disorder, which is characterized by rapid development of aortic and peripheral arterial aneurysms. Loeys-Dietz syndrome has some", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33204949"}, {"offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Loeys-Dietz syndrome (LDS) is characterised by a mutation in the transforming growth factor beta receptor, and is strongly associated with aortic aneurysms and rupture. Most cases of LDS present in the second decade", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28252349"}, {"offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Loeys-Dietz syndrome (LDS) is characterised by a mutation in the transforming growth factor beta receptor, and is strongly associated with aortic aneurysms and rupture. Most cases of LDS present in the second decade", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29022822"}, {"offsetInBeginSection": 90, "offsetInEndSection": 184, "text": "rare. An association of these aneurysms with Loeys-Dietz syndrome (LDS) in older age-groups is", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26655350"}, {"offsetInBeginSection": 0, "offsetInEndSection": 322, "text": "Loeys-Dietz Syndrome (LDS) is an autosomal dominant connective tissue disorder with multisystem involvement of wide spectrum, found to be associated with transforming growth factor-\u03b2 pathway. LDS is characterized by craniofacial, skeletal, cutaneous, vascular abnormalities along with aortic aneurysm and aortic dissection", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37126428"}, {"offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Loeys-Dietz syndrome (LDS) is characterised by a mutation in the transforming growth factor beta receptor, and is strongly associated with aortic aneurysms and rupture.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29022822"}, {"offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "OBJECTIVE: Loeys-Dietz syndrome (LDS) is a rare autosomal dominant condition characterized by aneurysms of the aorta, aortic branches, and intracranial arteries; skeletal and cutaneous abnormalities; and craniofacial mal", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36308480"}, {"offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Marfan Syndrome (MFS) and Loeys-Dietz Syndrome (LDS) represent heritable connective tissue disorders that segregate with a similar pattern of cardiovascular defects (thoracic aortic aneurysm, mitral valve prolapse/regurgitation, and aortic dilatation with regurgitation).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34807419"}, {"offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "Marfan Syndrome (MFS) and Loeys-Dietz Syndrome (LDS) represent heritable connective tissue disorders that cosegregate with a similar pattern of cardiovascular defects (thoracic aortic aneurysm, mitral valve prolapse/regurgitation, and aortic root dilatation with regurgitation).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24443024"}, {"offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "Loeys-Dietz syndrome is a heritable disorder of the connective tissue leading to multisystem involvement including craniofacial features, skeletal abnormalities, cutaneous findings and early-onset and aggressive disease of the aorta and its branches.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32462795"}, {"offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Loeys-Dietz Syndrome (LDS) is an autosomal dominant connective tissue disorder. The major hallmark of LDS is thoracic aortic aneurysm and dissection (TAAD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36219981"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Loeys-Dietz syndrome (LDS) is a rare connective tissue disorder characterized by a genetic predisposition for thoracic aortic aneurysm and dissection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32062130"}, {"offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Loeys-Dietz syndrome is an autosomal dominant connective tissue disorder that is characterized by skeletal abnormalities, craniofacial malformations, and predisposition for aortic aneurysm with tortuosity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30534260"}, {"offsetInBeginSection": 50, "offsetInEndSection": 215, "text": "Loeys-Dietz syndrome (LDS) is a genetic aortic aneurysm syndrome caused by mutations in the transforming growth factor-receptor type I or II gene (TGFBR1 or TGFBR2).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21949523"}, {"offsetInBeginSection": 427, "offsetInEndSection": 503, "text": "LDS is characterized by aggressive and rapid progression of aortic aneurysm.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21949523"}, {"offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder presenting with a variety of cardiovascular, skeletal, craniofacial and cutaneous manifestations. Aortic rupture or dissection of a thoracic aortic aneurysm (TAA) is the most life-threatening complication.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36356561"}, {"offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "Ascending aortic aneurysm is very rare in children, and is usually seen in patients with underlying connective tissue disorders such as Marfans and Ehler-Danlos syndrome. Loeys-Dietz syndrome (LDS) is less commonly seen as a cause of ascending aortic aneurysms in children.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37876949"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Loeys-Dietz syndrome (LDS) is a rare autosomal-dominant connective tissue disorder that can lead to aortic aneurysm and dissection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32339686"}, {"offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "BACKGROUND: Loeys-Dietz syndrome (LDS) is a rare autosomal-dominant connective tissue disorder characterized by arterial aneurysms and vascular", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33289867"}, {"offsetInBeginSection": 12, "offsetInEndSection": 213, "text": "Loeys-Dietz syndrome (LDS) is a heritable disorder that presents with thoracic aortic aneurysm and/or dissection caused by a mutation in one of the transforming growth factor-B receptor or ligand genes", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36237225"}, {"offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "BACKGROUND: Loeys-Dietz syndrome (LDS) is a recently described genetic aortic aneurysm syndrome resulting from mutations in receptors for the cytokine transforming growth factor-beta.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17257922"}, {"offsetInBeginSection": 0, "offsetInEndSection": 327, "text": "There are many genetic syndromes associated with the aortic aneurysmal disease which include Marfan syndrome (MFS), Ehlers-Danlos syndrome (EDS), Loeys-Dietz syndrome (LDS), familial thoracic aortic aneurysms and dissections (TAAD), bicuspid aortic valve disease (BAV), and autosomal dominant polycystic kidney disease (ADPKD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23401778"}, {"offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Loeys-Dietz Syndrome (LDS) is a recently described autosomal dominant aortic aneurysm syndrome with widespread systemic involvement.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30625890"}, {"offsetInBeginSection": 44, "offsetInEndSection": 194, "text": "ominant genetic connective tissue disorder, and most of LDS patients will develop into aortic aneurysm. Unfortunately, there is no known cure, and a h", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26617788"}, {"offsetInBeginSection": 1460, "offsetInEndSection": 1621, "text": "SIONS: Loeys-Dietz syndrome is an aggressive aortic aneurysm syndrome that can be addressed by prophylactic aortic root replacement with low operative risk. Valv", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21801912"}, {"offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Loeys-Dietz Syndrome (LDS) is a recently described autosomal dominant aortic aneurysm syndrome with widespread systemic involvement. It is characterized", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30625890"}, {"offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Loeys-Dietz syndrome (LDS) is a recently described genetic connective tissue disorder with a wide spectrum of multisystem involvement. LDS is characterized by rapidly progressive aortic and peripheral arterial aneurysmal", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29320330"}, {"offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Loeys-Dietz Syndrome is an autosomal dominant disease with aortic aneurysms, arterial tortuosity with hypertelorism and bifid", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28737872"}, {"offsetInBeginSection": 168, "offsetInEndSection": 553, "text": "She underwent a valve sparing operation with graft replacement of the ascending aorta and the proximal portion of the aortic arch. After the 1st operation, she was diagnosed with Loeys-Dietz syndrome (LDS), which is recently described as an autosomal dominant aortic aneurysm syndrome caused by heterozygous mutations in the transforming growth factor-beta receptor type 1 and 2 genes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20662229"}, {"offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Loeys-Dietz syndrome (LDS) is a rare autosomal-dominant connective tissue disorder that can lead to aortic aneurysm", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32339686"}, {"offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "BACKGROUND: Loeys-Dietz syndrome (LDS) is an inherited connective tissue disorder associated with aortic root enlargement and risk of thoracic aorti", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37823753"}, {"offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "BACKGROUND: Loeys-Dietz syndrome (LDS) is a rare autosomal dominant syndrome characterized by heterozygous mutations causing multisystemic alterations. It was recently described in 2005, and today at least six different subtypes have been identified. Classically presenting with aortic root enlargement ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36483799"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1080, "text": "INTRODUCTION: Loeys-Dietz syndrome (LDS) is a connective tissue disorder that arises from mutations altering the transforming growth factor \u03b2 signalling pathway. Due to the recent discovery of the underlying genetic mutations leading to LDS, the spectrum of characteristics and complications is not fully understood.METHODS: Our search included five databases (Pubmed, SCOPUS, Web of Science, EMBASE and google scholar) and included variations of \"Loeys-Dietz Syndrome\" as search terms, using all available data until February 2021. All study types were included. Three reviewers screened 1394 abstracts, of which 418 underwent full-text review and 392 were included in the final analysis.RESULTS: We identified 3896 reported cases of LDS with the most commonly reported features and complications being: aortic aneurysms and dissections, arterial tortuosity, high arched palate, abnormal uvula and hypertelorism. LDS Types 1 and 2 share many clinical features, LDS Type 2 appears to have a more aggressive aortic disease. LDS Type 3 demonstrated an increased prevalence of mitral", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35662564"}, {"offsetInBeginSection": 527, "offsetInEndSection": 833, "text": "Loeys-Dietz syndrome is an autosomal dominant genetic disorder which has combined and multi-systemic manifestations. The increased breakdown of extracellular matrix predisposes an individual to developing aneurysms in the aortic tree which is undoubtedly the most significant complication of this disorder.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32559129"}, {"offsetInBeginSection": 1052, "offsetInEndSection": 1195, "text": "Loeys-Dietz syndrome is an aggressive genetic condition that predisposes an individual to the development of life-threatening aortic aneurysms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32559129"}, {"offsetInBeginSection": 154, "offsetInEndSection": 286, "text": "Loeys-Dietz syndrome is a connective tissue disorder characterized by aortic aneurysms, arterial tortuosity, and aortic dissections.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31085000"}, {"offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Loeys-Dietz syndrome is a genetic disorder that predisposes patients to aortic aneurysms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30833837"}, {"offsetInBeginSection": 80, "offsetInEndSection": 156, "text": "The major hallmark of LDS is thoracic aortic aneurysm and dissection (TAAD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36219981"}, {"offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Loeys-Dietz syndrome (LDS) is an autosomal dominant genetic connective tissue disorder associated with aortic aneurysmal disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27521346"}, {"offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Loeys-Dietz syndrome is a recently described autosomal dominant disorder with underlying vasculopathy characterized by aortic and other vascular aneurysmal dissection/rupture.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28230898"}]}
+{"question_id": "66150366fdcbea915f000046", "question": "What is borderline personality disorder?", "answer": "Borderline personality disorder (BPD) is a mental disorder characterized by instability in interpersonal, affective, cognitive, self-identity, and behavioral domains. It is marked by sudden shifts in identity, interpersonal relationships, and affect, as well as impulsive behavior, periodic intense anger, feelings of emptiness, suicidal behavior, self-mutilation, transient, stress-related paranoid ideation, and severe dissociative symptoms. Patients with BPD often have high health care utilization, health-sabotaging behaviors, chronic or vague somatic concerns, aggressive outbursts, high-risk sexual behaviors, and substance use. The disorder imposes a considerable burden on patients, their family members, and the healthcare system.", "relevant_passage_ids": ["29795363"], "type": "summary", "snippets": [{"offsetInBeginSection": 261, "offsetInEndSection": 480, "text": "BPD is found in \u223c1.7% of the general population but in 15-28% of patients in psychiatric clinics or hospitals and in a large proportion of individuals seeking help for psychological problems in general health facilities", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29795363"}, {"offsetInBeginSection": 482, "offsetInEndSection": 679, "text": "BPD is characterized by extreme sensitivity to perceived interpersonal slights, an unstable sense of self, intense and volatile emotionality and impulsive behaviours that are often self-destructive", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29795363"}, {"offsetInBeginSection": 980, "offsetInEndSection": 1089, "text": "many patients with persistent and severe social disabilities related to depression or self-harming behaviours", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29795363"}]}
+{"question_id": "661d9cc3eac11fad33000029", "question": "What is the role of the FOXA1 transcription factor in estrogen-receptor-positive (ER+) breast cancer?", "answer": "Aberrant activation of the forkhead protein FOXA1 is observed in advanced hormone-related cancers, such as ER+ breast cancer. However, the key mediators of high FOXA1 signaling remain elusive. FOXA1 can act as a pioneer factor for estrogen receptor (ER), dictating its binding location and therefore its transcriptional activity. In ER+ breast cancer, FOXA1 plays a pivotal role from early-stage cancer to drug-resistant and metastatic disease. Due to this key role in mediating ER function, FOXA1 is not only an attractive therapeutic target but could potentially function as a novel biomarker.", "relevant_passage_ids": ["22649425", "37467106", "22476979", "17163418", "17671124", "22391567", "21503684", "27791031", "30572598", "34027035", "32888433", "31826955", "34680352", "25707489", "31871111", "31562808", "36930833", "23810008", "30840881", "33417085", "27062924", "22313737", "35812039", "25155268", "18538561", "37568077", "27473079", "29137314", "18037662", "19261198", "17373880", "36204307"], "type": "summary", "snippets": [{"offsetInBeginSection": 120, "offsetInEndSection": 727, "text": "FoxA1 acts as a pioneer factor for both androgen receptor (AR) and estrogen receptor-\u03b1 (ER), dictating the binding location, and therefore function of these transcription factors. It is an essential protein for the transcriptional activity of both ER and AR, yet it has distinct roles with the two different nuclear receptors. In both malignancies, FoxA1 plays a pivotal role from early stage cancer through to drug resistant and metastatic disease. Due to this key role in mediating ER and AR function, FoxA1 is not only an attractive therapeutic target but could potentially function as a novel biomarker.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22649425"}, {"offsetInBeginSection": 0, "offsetInEndSection": 326, "text": "Aberrant activation of the forkhead protein FOXA1 is observed in advanced hormone-related cancers. However, the key mediators of high FOXA1 signaling remain elusive. We demonstrate that ectopic high FOXA1 (H-FOXA1) expression promotes estrogen receptor-positive (ER+) breast cancer (BC) metastasis in a xenograft mouse model. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37467106"}, {"offsetInBeginSection": 140, "offsetInEndSection": 556, "text": "Forkhead box A1 (FOXA1) is a member of the forkhead box transcription factor family and functions as a pioneer factor of the estrogen receptor (ER) in breast cancer. In the present study, we demonstrate that FOXA1 mRNA was upregulated by estrogen and that estrogen receptor-\u03b1 (ER\u03b1) recruitment to ER-binding sites in the vicinity of the FOXA1 gene was increased by estrogen in ER\u03b1-positive MCF-7 breast cancer cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22476979"}, {"offsetInBeginSection": 140, "offsetInEndSection": 643, "text": "Forkhead box A1 (FOXA1) is a member of the forkhead box transcription factor family and functions as a pioneer factor of the estrogen receptor (ER) in breast cancer. In the present study, we demonstrate that FOXA1 mRNA was upregulated by estrogen and that estrogen receptor-\u03b1 (ER\u03b1) recruitment to ER-binding sites in the vicinity of the FOXA1 gene was increased by estrogen in ER\u03b1-positive MCF-7 breast cancer cells. The estrogen-induced FOXA1 upregulation was repressed by 4-hydroxytamoxifen treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22476979"}, {"offsetInBeginSection": 0, "offsetInEndSection": 556, "text": "Breast cancer is primarily a hormone-dependent tumor that can be regulated by the status of the steroid hormones estrogen and progesterone. Forkhead box A1 (FOXA1) is a member of the forkhead box transcription factor family and functions as a pioneer factor of the estrogen receptor (ER) in breast cancer. In the present study, we demonstrate that FOXA1 mRNA was upregulated by estrogen and that estrogen receptor-\u03b1 (ER\u03b1) recruitment to ER-binding sites in the vicinity of the FOXA1 gene was increased by estrogen in ER\u03b1-positive MCF-7 breast cancer cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22476979"}, {"offsetInBeginSection": 0, "offsetInEndSection": 370, "text": "Forkhead box protein A1 (FOXA1) is a \"pioneer factor\" that plays a role in controlling nearly 50% of estrogen receptor target genes. FOXA1 expression correlates with estrogen receptor (ER)-positivity especially in luminal subtype A breast cancers. The aim of this study was to investigate the precise role of FOXA1 in breast cancer using a large population-based cohort.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21503684"}, {"offsetInBeginSection": 306, "offsetInEndSection": 556, "text": "In the present study, we demonstrate that FOXA1 mRNA was upregulated by estrogen and that estrogen receptor-\u03b1 (ER\u03b1) recruitment to ER-binding sites in the vicinity of the FOXA1 gene was increased by estrogen in ER\u03b1-positive MCF-7 breast cancer cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22476979"}, {"offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Forkhead box protein A1 (FOXA1) is a pioneer factor of estrogen receptor \u03b1 (ER)-chromatin binding and function, yet its aberration in endocrine-resistant (Endo-R) breast cancer is unknown.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27791031"}, {"offsetInBeginSection": 1386, "offsetInEndSection": 1792, "text": "In luminal subtype A patient subgroup, FOXA1 expression was associated with better cancer-specific survival (P = 0.024) and in ER-positive subgroup, it was better predictor of cancer-specific survival (P = 0.009) than PR (P = 0.213).CONCLUSION: FOXA1 expression correlates with luminal subtype A breast cancer and it is significant predictor of cancer-specific survival in patients with ER-positive tumors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17671124"}, {"offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Forkhead box protein A1 (FOXA1) is a pioneer transcription factor that contributes to chromatin opening to allow binding of estrogen receptor (ER) in ER+ breast cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34027035"}, {"offsetInBeginSection": 1807, "offsetInEndSection": 2099, "text": "These results suggest that FOXA1 plays an important role in the proliferation and migration of breast cancer cells by modulating estrogen signaling and that the double-positive immunoreactivities of FOXA1 and FOXP1 are associated with a favorable prognosis of tamoxifen-treated breast cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22476979"}, {"offsetInBeginSection": 133, "offsetInEndSection": 247, "text": "FOXA1 expression correlates with estrogen receptor (ER)-positivity especially in luminal subtype A breast cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21503684"}, {"offsetInBeginSection": 1551, "offsetInEndSection": 1713, "text": "FOXA1 is a significant marker of good prognosis in breast cancer; it also identifies a subset of ER-positive tamoxifen treated patients at low risk of recurrence.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21503684"}, {"offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "FOXA1 is an independent prognostic marker for ER-positive breast cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21503684"}, {"offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "The forkhead-box A1 (FOXA1) controls downstream transcription of oestrogen receptor (ER)-regulated genes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18538561"}, {"offsetInBeginSection": 120, "offsetInEndSection": 307, "text": "Forkhead box A1 (FOXA1) is a key pioneer factor mediating ER-chromatin interactions and endocrine response in ER+ breast cancer, but its role in ESR1-mutant breast cancer remains unclear.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36930833"}, {"offsetInBeginSection": 235, "offsetInEndSection": 402, "text": "Forkhead box A1 (FOXA1) is a member of the forkhead box transcription factor family and functions as a pioneer factor in estrogen receptor (ER)-positive breast cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22313737"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "The transcription factor FOXA1, which is a member of the forkhead class of DNA-binding proteins, interacts with Estrogen Receptor (ER) to mediate breast cancer progression", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35812039"}, {"offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Mutations in the pioneer transcription factor FOXA1 are a hallmark of estrogen receptor-positive (ER+) breast cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32888433"}, {"offsetInBeginSection": 140, "offsetInEndSection": 305, "text": "Forkhead box A1 (FOXA1) is a member of the forkhead box transcription factor family and functions as a pioneer factor of the estrogen receptor (ER) in breast cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22476979"}, {"offsetInBeginSection": 166, "offsetInEndSection": 325, "text": "We demonstrate that ectopic high FOXA1 (H-FOXA1) expression promotes estrogen receptor-positive (ER+) breast cancer (BC) metastasis in a xenograft mouse model.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37467106"}, {"offsetInBeginSection": 149, "offsetInEndSection": 320, "text": "Hyperactive FOXA1 signaling due to gene amplification or overexpression has been reported in estrogen receptor-positive (ER+) endocrine-resistant metastatic breast cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31826955"}, {"offsetInBeginSection": 242, "offsetInEndSection": 424, "text": "Expression of the forkhead box transcription factor, FOXA1, similarly correlates with the luminal subtype and patient survival, but is also present in a subset of ER-negative tumors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22391567"}, {"offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Forkhead box protein A1 (FOXA1) is a \"pioneer factor\" that plays a role in controlling nearly 50% of estrogen receptor target genes. FOXA1 expression correlates with estrogen receptor (ER)-positivity especially in luminal subtype A breast cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21503684"}, {"offsetInBeginSection": 553, "offsetInEndSection": 779, "text": "FOXA1 is a 'pioneer' factor that binds to chromatinized DNA, opens the chromatin and enhances binding of ERalpha to its target genes. It is essential for the expression of approximately 50% of ERalpha:estrogen-regulated genes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17373880"}]}
+{"question_id": "661d62dceac11fad33000026", "question": "How is Huntington's Disease inherited?", "answer": "Huntington's disease is inherited in an autosomal dominant pattern.", "relevant_passage_ids": ["35829908"], "type": "summary", "snippets": [{"offsetInBeginSection": 12, "offsetInEndSection": 151, "text": "Huntington's disease is a rare neurodegenerative illness of the central nervous system that is inherited in an autosomal dominant pattern. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35829908"}]}
+{"question_id": "65cfcd541930410b13000019", "question": "Burrow Ink Test can be used to diagnose which disease?", "answer": "Burrow Ink Test is used to diagnose scabies.", "relevant_passage_ids": ["23904181", "23205026", "21268539", "8308357", "37518420", "26792847"], "type": "factoid", "snippets": [{"offsetInBeginSection": 598, "offsetInEndSection": 897, "text": "Alternative diagnostic methods include the burrow ink test, video-dermatoscopy, newly serologic tests like PCR/ELISA, and specific IgE directed toward major mite components. Treatment of scabies consists of either topical permethrin or oral ivermectin, although the optimal regimen is still unclear.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23904181"}, {"offsetInBeginSection": 1211, "offsetInEndSection": 1722, "text": " Two tests are used - the burrow ink test and handheld dermatoscopy. The burrow ink test is a simple, rapid, noninvasive test that can be used to screen a large number of patients. Handheld dermatoscopy is an accurate test, but requires special equipment and trained practitioners. Given the morbidity and costs of scabies infection, and that studies to date lack adequate internal and external validity, research to identify or develop accurate diagnostic tests for scabies infection is needed and justifiable.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23205026"}, {"offsetInBeginSection": 134, "offsetInEndSection": 408, "text": "tudy was carried out on 200 patients referred to dermatology outpatient clinics in Sirte-Libya. Each was subjected to detailed questionnaire, dermatological skin examination, parasitological skin scraping test (SST), burrow ink test (BIT), drug administration and follow up.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21268539"}, {"offsetInBeginSection": 0, "offsetInEndSection": 367, "text": "This study is a parasitological and clinical study on human scabies. This study was carried out on 100 patients attending the Dermatology Outpatient Clinic at Ain Shams University Hospitals, including 54 males and 46 females. All patients were subjected to detailed history taking, complete dermatological examination including Skin Scraping Test and Burrow Ink Test.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8308357"}, {"offsetInBeginSection": 116, "offsetInEndSection": 267, "text": "Nocturnal pruritus in 13 relatives, presence of burrows on clinical exam, and the positive scabies preparation led to the diagnosis of crusted scabies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37518420"}, {"offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "The pruritic skin disease scabies is caused by the burrowing of the itch mite Sarcoptes scabiei (De Geer).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26792847"}, {"offsetInBeginSection": 803, "offsetInEndSection": 1397, "text": "ies infection. Dermatoscopy by a trained practitioner has a positive likelihood ratio of 6.5 (95% CI 4.1 to 10.3) and a negative likelihood ratio of 0.1 (95% CI 0.06 to 0.2) for diagnosing scabies. The accuracy of other diagnostic tests could not be calculated from the data in the literature.CONCLUSIONS: In the face of such diagnostic inaccuracy, clinical judgment is still practical in diagnosing scabies. Two tests are used - the burrow ink test and handheld dermatoscopy. The burrow ink test is a simple, rapid, noninvasive test that can be used to screen a large number of patients. Handh", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23205026"}]}
+{"question_id": "6609994bfdcbea915f000017", "question": "What drugs are effective for the treatment of EGFR inhibitors skin rash?", "answer": "The Skin Toxicity Evaluation Protocol With Panitumumab trial found reduced incidence of skin toxicity and quality of life impairment with preemptive use of doxycycline hyclate, topical corticosteroids, moisturizers, and sunscreen, demonstrating the benefit of prophylactic treatment for skin toxicity", "relevant_passage_ids": ["32609305", "20142600", "33026750", "29423677", "18543329", "30232957", "20208331", "33028137", "19229368", "22472354", "20101558", "18192159", "36165327", "27833902", "33910927", "19452131", "37269194", "34137354", "24422792", "34558677", "37221285", "33568043", "22988651", "33993601", "20871265", "17239286", "33378750", "16800173", "16012181", "25908911", "24723942", "23314653", "30607677", "35352492", "31264159", "34811916", "24748906", "27449521"], "type": "list", "snippets": [{"offsetInBeginSection": 733, "offsetInEndSection": 743, "text": "doxycyclin", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20142600"}, {"offsetInBeginSection": 712, "offsetInEndSection": 727, "text": "topical steroid", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20142600"}, {"offsetInBeginSection": 701, "offsetInEndSection": 710, "text": "sunscreen", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20142600"}, {"offsetInBeginSection": 682, "offsetInEndSection": 699, "text": "skin moisturizers", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20142600"}, {"offsetInBeginSection": 1980, "offsetInEndSection": 2006, "text": "topical corticosteroid use", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32609305"}, {"offsetInBeginSection": 2064, "offsetInEndSection": 2086, "text": "topical antibiotic use", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32609305"}, {"offsetInBeginSection": 1904, "offsetInEndSection": 1927, "text": "preemptive tetracycline", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32609305"}, {"offsetInBeginSection": 225, "offsetInEndSection": 525, "text": "The Skin Toxicity Evaluation Protocol With Panitumumab trial found reduced incidence of skin toxicity and quality of life impairment with preemptive use of doxycycline hyclate, topical corticosteroids, moisturizers, and sunscreen, demonstrating the benefit of prophylactic treatment for skin toxicity", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32609305"}, {"offsetInBeginSection": 433, "offsetInEndSection": 563, "text": "We performed a single-arm, prospective, open-label, multi-institutional phase II trial for comprehensive skin toxicity prophylaxis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37269194"}, {"offsetInBeginSection": 0, "offsetInEndSection": 366, "text": "Skin rash is a side effect of drugs that inhibit epithelial growth factor receptor (EGFR) as a part of targeted therapy of cancer. Its appearance and severity correlates with survival. Minocycline, an oral tetracycline antibiotic, is recommended as treatment (and increasingly, for prevention) of the rash, though infection is seen in only one-third of the patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27833902"}, {"offsetInBeginSection": 185, "offsetInEndSection": 705, "text": "Minocycline, an oral tetracycline antibiotic, is recommended as treatment (and increasingly, for prevention) of the rash, though infection is seen in only one-third of the patients. Minocycline has additional anticancer properties such as poly(ADP-ribose) polymerase inhibition. It is proposed that such properties contribute to the efficacy of EGFR inhibitors and can also explain the positive correlation between grade of rash and survival as patients with higher grades of rash are more likely to receive minocycline.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27833902"}, {"offsetInBeginSection": 136, "offsetInEndSection": 463, "text": " Treatment recommendations from studies and expert panels include, amongst others, oral tetracyclines. The efficacy of retarded low-dose doxycycline (rld-doxycycline), however, has not been investigated. The objective was to review the response and development of EGFRi- and MEKi-induced rash under therapy with rld-doxycycline", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24422792"}, {"offsetInBeginSection": 0, "offsetInEndSection": 338, "text": "BACKGROUND: Epidermal growth factor receptor inhibitors (EGFRi) and MEK inhibitors (MEKi) are notorious for causing papulopustular rash. Treatment recommendations from studies and expert panels include, amongst others, oral tetracyclines. The efficacy of retarded low-dose doxycycline (rld-doxycycline), however, has not been investigated", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24422792"}, {"offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "BACKGROUND: Epidermal growth factor receptor inhibitors (EGFRi) and MEK inhibitors (MEKi) are notorious for causing papulopustular rash. Treatment recommendations from studies and expert panels include, amongst others, oral tetracyclines", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24422792"}, {"offsetInBeginSection": 185, "offsetInEndSection": 463, "text": "Minocycline, an oral tetracycline antibiotic, is recommended as treatment (and increasingly, for prevention) of the rash, though infection is seen in only one-third of the patients. Minocycline has additional anticancer properties such as poly(ADP-ribose) polymerase inhibition.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27833902"}, {"offsetInBeginSection": 131, "offsetInEndSection": 463, "text": "Its appearance and severity correlates with survival. Minocycline, an oral tetracycline antibiotic, is recommended as treatment (and increasingly, for prevention) of the rash, though infection is seen in only one-third of the patients. Minocycline has additional anticancer properties such as poly(ADP-ribose) polymerase inhibition.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27833902"}, {"offsetInBeginSection": 185, "offsetInEndSection": 366, "text": "Minocycline, an oral tetracycline antibiotic, is recommended as treatment (and increasingly, for prevention) of the rash, though infection is seen in only one-third of the patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27833902"}, {"offsetInBeginSection": 749, "offsetInEndSection": 1088, "text": "LTS: Seventeen patients (13 men, 4 women) were treated with rld-doxycycline while receiving EGFRi [monoclonal antibodies (mab) n = 8, tyrosine kinase inhibitors (TKi) n = 7] or MEKi (n = 2). In 47% (n = 8) the rash was reduced by at least one grade, in 29% (n = 5) the rash was stabilized, 24% (n = 4) did not profit from the treatment. Al", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24422792"}, {"offsetInBeginSection": 823, "offsetInEndSection": 1919, "text": "The goal of managing EGFR inhibitor-associated skin toxicity is to minimize the detrimental effects of the rash on patients' quality of life and treatment course without antagonizing the clinical efficacy of EGFR inhibitors. There is currently no evidence-based treatment guideline to prevent or treat the EGFR inhibitor-associated skin toxicities. Expert panels recommend a proactive, multidisciplinary approach that includes patient education and the use of a grade-based treatment algorithm. Elucidation of the mechanisms of EGFR inhibitor-associated skin toxicity and development of mechanism-based novel therapies are urgently needed. Preclinical data suggest topical application of a potent phosphatase inhibitor menadione (Vitamin K3) can rescue the inhibition of EGFR and downstream signaling molecules in the skin of mice receiving systemic EGFR inhibitor erlotinib or cetuximab. A randomized, double-blinded, placebo-controlled study has been initiated to evaluate the clinical efficacy of menadione topical cream, in the treatment or prevention of EGFR inhibitor-induced skin toxicity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19452131"}, {"offsetInBeginSection": 1799, "offsetInEndSection": 2059, "text": "g panitumumab, and six patients were using pertuzumab. In 22 patients, PPL side effects were observed in the skin; it was G1 in 19 patients and G2 in three patients. In seven patients who developed acneiform side effects, systemic doxycycline was used, and in ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33028137"}, {"offsetInBeginSection": 125, "offsetInEndSection": 452, "text": "tular rash. Treatment recommendations from studies and expert panels include, amongst others, oral tetracyclines. The efficacy of retarded low-dose doxycycline (rld-doxycycline), however, has not been investigated. The objective was to review the response and development of EGFRi- and MEKi-induced rash under therapy with rld-", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24422792"}, {"offsetInBeginSection": 959, "offsetInEndSection": 1115, "text": "Mild cases of acneiform eruption respond well to topical anti-inflammatory acne therapy, whereas tetracyclines are needed to treat moderate to severe cases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16012181"}, {"offsetInBeginSection": 201, "offsetInEndSection": 351, "text": "ng issues for the EGFR-TKI treatment, namely skin toxicity. Antibiotics and corticosteroids are usually used to treat the EGFR inhibitor-associated sk", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36165327"}, {"offsetInBeginSection": 115, "offsetInEndSection": 265, "text": "rapy of cancer. Its appearance and severity correlates with survival. Minocycline, an oral tetracycline antibiotic, is recommended as treatment (and i", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27833902"}, {"offsetInBeginSection": 261, "offsetInEndSection": 406, "text": "Antibiotics and corticosteroids are usually used to treat the EGFR inhibitor-associated skin rash, with prominent side effects over long-time use", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36165327"}, {"offsetInBeginSection": 706, "offsetInEndSection": 851, "text": "Early concurrent administration of minocycline is recommended in patients planned for EGFR therapy while awaiting trials proving this hypothesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27833902"}, {"offsetInBeginSection": 464, "offsetInEndSection": 705, "text": "It is proposed that such properties contribute to the efficacy of EGFR inhibitors and can also explain the positive correlation between grade of rash and survival as patients with higher grades of rash are more likely to receive minocycline.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27833902"}, {"offsetInBeginSection": 1201, "offsetInEndSection": 1351, "text": "itive Staphylococcus aureus in 2 patients. Combined doxycycline 100 mg daily and benzoyl peroxide was prescribed for 3 months and a favourable outcome", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16800173"}, {"offsetInBeginSection": 492, "offsetInEndSection": 612, "text": "algorithm has been proposed for management based on severity. However, treatment options for EGFR-inhibitor induced rash", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33026750"}, {"offsetInBeginSection": 17, "offsetInEndSection": 396, "text": "ncidence of epidermal growth factor receptor inhibitor (EGFRI)-induced papulopustular rash is 60-85%.OBJECTIVE: To investigate prophylactic topical treatment for EGFRI-induced rash.METHODS: A single-center, randomized, double-blind, placebo-controlled trial. Adult cancer patients initiating treatment with EGFRIs were randomized to receive facial topical treatment with chloramp", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33378750"}, {"offsetInBeginSection": 1262, "offsetInEndSection": 1402, "text": "Besides topical antibiotics and steroids, oral tetracyclines are the first choice in systemic treatment and can also be used as prophylaxis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34811916"}, {"offsetInBeginSection": 1092, "offsetInEndSection": 1192, "text": " II to grade I during cetuximab treatment.RESULTS: Our results showed that tetracycline treatment ma", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24748906"}, {"offsetInBeginSection": 1193, "offsetInEndSection": 1317, "text": " shorten the period needed to achieve improvement. Ketoconazole cream and a combination of oral tetracycline and topical ket", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24748906"}, {"offsetInBeginSection": 1027, "offsetInEndSection": 1160, "text": "To date, prophylactic systemic tetracycline and tetracycline class antibiotics have proven to be the most effective treatment regime.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24723942"}, {"offsetInBeginSection": 929, "offsetInEndSection": 1097, "text": "with EGFR inhibitors.RESULTS: Oral antibiotics had the greatest efficacy in preventing grade 2 or higher acneiform eruptions with a relative risk reduction of 40% (RR\u00a0=", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35352492"}, {"offsetInBeginSection": 1453, "offsetInEndSection": 1785, "text": "5, 95% CI .49-1.14, p\u00a0=\u00a0.18).CONCLUSIONS: The results of this meta-analysis reinforce the fact that oral tetracycline antibiotics are the most efficacious prophylactic option for acneiform eruptions in EGFR inhibitors. They should be offered to suitable patients commencing treatment and used with a general skin-care routine involv", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35352492"}, {"offsetInBeginSection": 536, "offsetInEndSection": 953, "text": "Depending on the particular EGFR inhibitor, an acneiform rash occurs in 30 to 90 % of patients. Severity, site, stage of eruptions and individual response influence the decision of treatment in the given case. It follows the forms of treatment for acne and rosacea, including topical and systemic antibiotics for their antimicrobial effect and anti-inflammatory effect, sometimes in combination with topical steroids.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20101558"}, {"offsetInBeginSection": 1092, "offsetInEndSection": 1317, "text": " II to grade I during cetuximab treatment.RESULTS: Our results showed that tetracycline treatment may shorten the period needed to achieve improvement. Ketoconazole cream and a combination of oral tetracycline and topical ket", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24748906"}, {"offsetInBeginSection": 1318, "offsetInEndSection": 1529, "text": "conazole also significantly shortened this period.CONCLUSION: The results of our short case study may indicate that a combitation therapy of oral tetracyclin and topical ketokonazole is most effective in the the", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24748906"}]}
+{"question_id": "660810a0fdcbea915f000005", "question": "Is MIRPE, also known as the Nuss procedure, considered to be an very invasive form of surgical treatment?", "answer": "The Nuss procedure , also called MIRPE OR Minimally Invasive Pectus Excavatum Repair is a minimally invasive surgical technique for repair of pectus excavatum.", "relevant_passage_ids": ["36935229", "36881966", "34743569", "16982197", "15111830", "23137116", "10693675", "19715130", "27458490", "35722532", "29473012", "33603601", "35455522", "30214110", "35817669", "37559617", "36967421", "33469524", "29078501", "31734479", "27407553", "15318043", "35096458", "23525153", "12368999", "16122489", "15943730", "37868874", "30935731", "16986397", "23217908", "31199434", "23788198", "26982189", "30278932", "30922685", "23464773", "29602550", "31529332", "18721589", "19632566", "20533731", "24822124", "36922280", "37279827", "29890147", "36452283"], "type": "yesno", "snippets": [{"offsetInBeginSection": 12, "offsetInEndSection": 211, "text": "We aimed to determine the longitudinal changes in pulmonary functions of adolescents with Pectus Excavatum who underwent the Nuss procedure, the minimally invasive repair of pectus excavatum (MIRPE).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36935229"}, {"offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "The minimally invasive repair of pectus excavatum (MIRPE), or Nuss procedure, is regarded as the gold standard technique for the treatment of symptomatic pectus excavatum", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36881966"}, {"offsetInBeginSection": 14, "offsetInEndSection": 201, "text": "Surgical correction of pectus excavatum by Nuss procedure, commonly referred to as minimally invasive repair of pectus excavatum (MIRPE), often results in significant postoperative pain. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34743569"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "The minimally invasive repair of pectus excavatum (MIRPE), or Nuss procedure, is regarded as the gold standard technique for the treatment of symptomatic pectus excavatum.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36881966"}, {"offsetInBeginSection": 0, "offsetInEndSection": 537, "text": "The minimally invasive repair of pectus excavatum (MIRPE), or Nuss procedure, is regarded as the gold standard technique for the treatment of symptomatic pectus excavatum. Minimally invasive repair of pectus excavatum is regarded as a low-risk operation with a reported life-threatening complication rate estimated at around 0.1%. Presented are three cases of right internal mammary artery injury (RIMA) after MIRPE resulting in massive hemorrhage in both the acute and chronic postoperative setting and subsequent management strategies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36881966"}, {"offsetInBeginSection": 0, "offsetInEndSection": 330, "text": "The minimally invasive repair of pectus excavatum (MIRPE), or Nuss procedure, is regarded as the gold standard technique for the treatment of symptomatic pectus excavatum. Minimally invasive repair of pectus excavatum is regarded as a low-risk operation with a reported life-threatening complication rate estimated at around 0.1%.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36881966"}, {"offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "INTRODUCTION: Surgical correction of pectus excavatum by Nuss procedure, commonly referred to as minimally invasive repair of pectus excavatum (MIRPE), often results in significant postoperative pain", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34743569"}, {"offsetInBeginSection": 0, "offsetInEndSection": 361, "text": "INTRODUCTION: Surgical correction of pectus excavatum by Nuss procedure, commonly referred to as minimally invasive repair of pectus excavatum (MIRPE), often results in significant postoperative pain. This study investigated whether adding intraoperative methadone would reduce the postoperative opioid requirement during admission for patients undergoing MIRPE", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34743569"}, {"offsetInBeginSection": 0, "offsetInEndSection": 464, "text": "INTRODUCTION: Surgical correction of pectus excavatum by Nuss procedure, commonly referred to as minimally invasive repair of pectus excavatum (MIRPE), often results in significant postoperative pain. This study investigated whether adding intraoperative methadone would reduce the postoperative opioid requirement during admission for patients undergoing MIRPE.METHODS: A retrospective cohort chart review was conducted for 40 MIRPE patients between 2018 and 2020", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34743569"}, {"offsetInBeginSection": 227, "offsetInEndSection": 531, "text": "The Nuss technique includes using temporary metallic bars without costochondral resection to correct the chest wall deformity. Modified MIRPE can be learned easily and performed safely with few complications. There are no reports of successful MIRPE in Iran, although the Ravitch technique is well known.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30214110"}, {"offsetInBeginSection": 854, "offsetInEndSection": 1317, "text": "However, the widespread use of the minimally invasive repair of pectus excavatum (MIRPE) procedure has been associated with a significant number of serious complications. Furthermore, several studies report near-fatal complications, not only during bar placement, but also during bar removal. This review focuses upon the most relevant modifications, including recent published surgical techniques of MIRPE, in order to describe current developments in the field.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35455522"}, {"offsetInBeginSection": 0, "offsetInEndSection": 418, "text": "INTRODUCTION: The Nuss procedure is suitable for prepubertal and early pubertal patients but can also be used in adult patients.AIM: To determine whether the minimally invasive technique (MIRPE) can also be performed successfully in adults.MATERIAL AND METHODS: Between July 2006 and January 2016, 836 patients (744 male, 92 female) underwent correction of pectus excavatum with the MIRPE technique at our institution.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27458490"}, {"offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Current Development of Minimally Invasive Repair of Pectus Excavatum (MIRPE).", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35455522"}, {"offsetInBeginSection": 854, "offsetInEndSection": 1024, "text": "However, the widespread use of the minimally invasive repair of pectus excavatum (MIRPE) procedure has been associated with a significant number of serious complications.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35455522"}, {"offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "BACKGROUND: Personal preliminary experience with Minimally Invasive Repair of Pectus Excavatum (MIRPE), \"Nuss\" procedure, using VATS is reported.METHODS: From January 2001 to February 2002, MIRPE has been performed on 5 patients (age range 13-18 y; mean 14.8 y).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15111830"}, {"offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Objectives: Since its introduction, the Nuss minimally invasive procedure for pectus excavatum (PE) repair (MIRPE) has become the method of choice.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35722532"}, {"offsetInBeginSection": 128, "offsetInEndSection": 231, "text": "In 1998, D. Nuss described a minimally invasive procedure for surgical repair of Pectus excavatum (PE).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35455522"}, {"offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Minimally invasive repair of pectus excavatum (MIRPE) technique (the Nuss procedure) is a minimally-invasive method that is commonly used in the treatment of pectus excavatum.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33603601"}, {"offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "INTRODUCTION: For one decade, the minimally invasive technique (MIRPE) of Nuss has been used in our Service as the elective technique for correction of Pectus Excavatum.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19715130"}, {"offsetInBeginSection": 477, "offsetInEndSection": 970, "text": "In the late 1990's, the operative approach was challenged with a new minimally invasive technique described by Dr. Donald Nuss. This approach utilizes thoracoscopic visualization with small incisions and placement of a temporary metal bar positioned behind the sternum for support it while the costal cartilages remodel. Since introduction, the minimally invasive repair of pectus excavatum (MIRPE) has become accepted in many centers as the procedure of choice for repair of pectus excavatum.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29078501"}, {"offsetInBeginSection": 69, "offsetInEndSection": 186, "text": "ll deformity. The minimally invasive repair of pectus excavatum (MIRPE) is the most commonly practiced method of surg", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31734479"}, {"offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "The technique of minimally invasive repair of pectus excavatum is a new operation that allows for repair of this deformity without any cartilage resection or sternal osteotomy. The procedure has revolutionized the management of pectus excavatum.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27407553"}, {"offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Surgical correction of pectus excavatum in children has gained new momentum since the introduction of the new minimally invasive repair by Nuss.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15318043"}, {"offsetInBeginSection": 574, "offsetInEndSection": 871, "text": "In the minimally invasive repair of pectus excavatum group, the children were younger (14.4 +/- 2.9 versus 17.8 +/- 3.2 years), had shorter operation times (53 +/- 18 versus 125 +/- 6 minutes), and had less blood loss (minimal versus 380 +/- 175 ml). No intraoperative complications were recorded.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15318043"}, {"offsetInBeginSection": 1515, "offsetInEndSection": 1650, "text": "Minimally invasive repair of pectus excavatum is a novel method with clear advantages, such as limited surgical trauma and small scars.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15318043"}, {"offsetInBeginSection": 29, "offsetInEndSection": 108, "text": " Nuss proposed minimally invasive repair of pectus excavatum (MIRPE) which did ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16982197"}, {"offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Objectives: Since its introduction, the Nuss minimally invasive procedure for pectus excavatum (PE) repair (MIRPE) has become the method of ch", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35722532"}, {"offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "The Nuss procedure is a minimally invasive surgical repair technique for pectus excavatum with fewer delayed complications compared to open procedures.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23525153"}, {"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Since the first description in 1998, the minimally invasive repair of pectus excavatum has gained increasing acceptance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12368999"}, {"offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "BACKGROUND: The Nuss procedure is a newly developed operative method for minimally invasive repair of pectus excavatum in pediatric patients. However, the surgical indication for this procedure has been extended into adu", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16122489"}, {"offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "BACKGROUND: The Nuss procedure is a new minimally invasive repair for pectus excavatum that was first publis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15943730"}, {"offsetInBeginSection": 503, "offsetInEndSection": 842, "text": "A technique for minimally invasive repair for pectus excavatum (MIRPE) was introduced with the concept of temporarily implanting metal bars to correct the deformity. This has rapidly become the standard of care for the pediatric and adolescent patients. The use of MIRPE in adults, however, has been slower to adopt and more controversial.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37868874"}, {"offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "PURPOSE: Minimally-invasive repair of pectus excavatum by the Nuss procedure is associated with significant postoperative pain, prolonged hospital stay, and high opiate req", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30935731"}, {"offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "BACKGROUND/PURPOSE: Since the first report in 1997 by Dr Nuss of the technique for minimally invasive repair of pectus excavatum (MIRPE), the popularity and demand for this operation has inc", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10693675"}, {"offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "Since 1996, the technique for minimally invasive repair of pectus excavatum (MIRPE) has gained increasing acceptance among pediatric patients. However, the feasibility of the operation and outcomes have not yet been evaluated in adult patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16986397"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "INTRODUCTION: For one decade, the minimally invasive technique (MIRPE) of Nuss has been used in our Service as the elective technique for correction o", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19715130"}, {"offsetInBeginSection": 42, "offsetInEndSection": 192, "text": " surgical procedure to correct pectus excavatum. Although it is a minimally invasive approach, a number of major early complications, such as heart pe", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23217908"}, {"offsetInBeginSection": 1525, "offsetInEndSection": 1675, "text": "ONCLUSIONS: MIRPE proposed by Nuss has all the features of a minimally invasive procedure and is straightforward. Better clinical results are achievab", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16982197"}, {"offsetInBeginSection": 24, "offsetInEndSection": 174, "text": "r of pectus excavatum (MIRPE) technique (the Nuss procedure) is a minimally-invasive method that is commonly used in the treatment of pectus excavatum", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33603601"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "OBJECTIVE: In 1998, Dr Donald Nuss proposed minimally invasive repair of pectus excavatum (MIRPE) which did not require the osteochondrous parts of th", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16982197"}, {"offsetInBeginSection": 93, "offsetInEndSection": 243, "text": "can also be used in adult patients.AIM: To determine whether the minimally invasive technique (MIRPE) can also be performed successfully in adults.MAT", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27458490"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "BACKGROUND: Despite advancements in minimally invasive repair of pectus excavatum (MIRPE), Nuss procedure, postoperative pain control remains challeng", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36967421"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Introduction \u2003Minimally invasive repair for pectus excavatum (MIRPE) is controversial in extremely severe cases of pectus excavatum (PE) and an open r", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29473012"}, {"offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "OBJECTIVES: Minimally invasive repair of pectus excavatum, the so-called Nuss procedure, has become a popular technique in r", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23788198"}, {"offsetInBeginSection": 2505, "offsetInEndSection": 2639, "text": "und abscess (1) and seroma (3).CONCLUSION: Minimally invasive pectus excavatum repair is an effective surgical technique for the treat", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26982189"}, {"offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "BACKGROUND: This study aimed to evaluate postoperative outcomes after minimally invasive repair of pectus excavatum (Nuss procedure) using video-assisted intercostal nerve cryoablation (INC) compared to thoracic ep", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30278932"}, {"offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "PURPOSE: The purpose of this study was to determine outcomes of an enhanced recovery pathway (ERP) for minimally invasive repair of pectus excavatum (MIRPE) at a high volume center, hypothesizing it is associated with decreased opioid requirement and shorter hospi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30922685"}, {"offsetInBeginSection": 1164, "offsetInEndSection": 1330, "text": "Nuss procedure has a series of advantages: minimally invasive surgical procedure reduced operative time, minimal blood loss and fast socio-professional reinstatement.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23464773"}, {"offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "OBJECTIVE: In 1998, Dr Donald Nuss proposed minimally invasive repair of pectus excavatum (MIRPE) which did not require the osteochondrous parts of the anterior chest wall to be resected", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16982197"}, {"offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "OBJECTIVE: To evaluate the routine use of the vacuum bell for elevating the sternum during minimally invasive repair of pectus excavatum (MIRPE) (the Nuss procedure)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23137116"}, {"offsetInBeginSection": 35, "offsetInEndSection": 185, "text": "treated with surgical repair in a procedure known as minimally invasive repair of pectus excavatum (MIRPE). MIRPE causes considerable postoperative pa", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37629283"}, {"offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Objectives: Minimal invasive repair of pectus excavatum (MIRPE) described by Nuss is the most popular correction nowadays of this deformity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33469524"}, {"offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "The aim of the review was to evaluate the routine use of sternal elevation techniques (SETs) during minimally invasive repair of pectus excavatum (MIRPE, the Nuss procedure).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31199434"}, {"offsetInBeginSection": 115, "offsetInEndSection": 265, "text": "lude Ravitch (costochondral resection) and Nuss (minimally invasive pectus repair of pectus excavatum [MIRPE]). The Nuss technique includes using temp", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30214110"}, {"offsetInBeginSection": 14, "offsetInEndSection": 167, "text": "e minimally invasive repair of pectus excavatum (MIRPE) has been widely accepted and has become a viable alternative to the open Ravitch technique. MIRPE", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29602550"}, {"offsetInBeginSection": 172, "offsetInEndSection": 537, "text": "Minimally invasive repair of pectus excavatum is regarded as a low-risk operation with a reported life-threatening complication rate estimated at around 0.1%. Presented are three cases of right internal mammary artery injury (RIMA) after MIRPE resulting in massive hemorrhage in both the acute and chronic postoperative setting and subsequent management strategies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36881966"}, {"offsetInBeginSection": 0, "offsetInEndSection": 417, "text": "INTRODUCTION: The Nuss procedure is suitable for prepubertal and early pubertal patients but can also be used in adult patients.AIM: To determine whether the minimally invasive technique (MIRPE) can also be performed successfully in adults.MATERIAL AND METHODS: Between July 2006 and January 2016, 836 patients (744 male, 92 female) underwent correction of pectus excavatum with the MIRPE technique at our institution", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27458490"}, {"offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "INTRODUCTION: The Nuss procedure is suitable for prepubertal and early pubertal patients but can also be used in adult patients.AIM: To determine whether the minimally invasive technique (MIRPE) can also be performed successfully in adults", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27458490"}, {"offsetInBeginSection": 172, "offsetInEndSection": 674, "text": "Minimally invasive repair of pectus excavatum is regarded as a low-risk operation with a reported life-threatening complication rate estimated at around 0.1%. Presented are three cases of right internal mammary artery injury (RIMA) after MIRPE resulting in massive hemorrhage in both the acute and chronic postoperative setting and subsequent management strategies. Exploratory thoracoscopy and angioembolization were utilized which achieved prompt hemostasis and allowed for complete patient recovery.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36881966"}, {"offsetInBeginSection": 854, "offsetInEndSection": 1146, "text": "However, the widespread use of the minimally invasive repair of pectus excavatum (MIRPE) procedure has been associated with a significant number of serious complications. Furthermore, several studies report near-fatal complications, not only during bar placement, but also during bar removal.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35455522"}, {"offsetInBeginSection": 14, "offsetInEndSection": 251, "text": "invasive repair of pectus excavatum (MIRPE) is widely accepted as a method of pectus excavatum (PE) repair. Repair is rarely performed in patients with a history of median sternotomy. A feared complication of this procedure is iatrogenic", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37559617"}, {"offsetInBeginSection": 10, "offsetInEndSection": 160, "text": ": Minimally invasive surgery (MIS) for Mirizzi syndrome (MS) remains a technically challenging procedure with a high open conversion rate. We critical", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31529332"}, {"offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Minimally invasive repair of pectus excavatum (Nuss) operation is the current choice of surgical treatment for pectus excavatum deformities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35096458"}, {"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "BACKGROUND: The Nuss operation, a minimally invasive repair of pectus excavatum, is considered the treatment of choice ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18721589"}, {"offsetInBeginSection": 1199, "offsetInEndSection": 1323, "text": "islocated during follow-up.CONCLUSIONS: Minimally invasive repair for pectus excavatum can be performed safely in adults, wi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18721589"}, {"offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "The minimally invasive approach for repair of pectus excavatum has become widely accepted by pediatric and thoracic surgeons primarily because of increased patient awareness and good long-term outcomes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19632566"}, {"offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "OBJECTIVE(S): Compared to the open surgical technique, the minimally invasive repair of pectus excavatum (MIRPE; Nuss procedure) is a thoracoscopic technique designed to minimize intraoperative ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35817669"}, {"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Minimally invasive surgery (Nuss procedure) is being accepted rapidly as a preferred method for pectus excavatum repair.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20533731"}, {"offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Nowadays the Nuss operation has been widely adopted as a minimally invasive procedure and standard surgical choice in pectus excavatum.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24822124"}, {"offsetInBeginSection": 0, "offsetInEndSection": 345, "text": "OBJECTIVE(S): Compared to the open surgical technique, the minimally invasive repair of pectus excavatum (MIRPE; Nuss procedure) is a thoracoscopic technique designed to minimize intraoperative tissue damage. It still causes severe postoperative pain due to the insertion and pressure of the retrosternal bar used to raise the sternum and stabil", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35817669"}, {"offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "INTRODUCTION: Surgical correction of pectus excavatum by Nuss procedure, commonly referred to as minimally invasive repair of pectus excavatum (MIRPE), often results in significant posto", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34743569"}, {"offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "BACKGROUND: Despite advancements in minimally invasive repair of pectus excavatum (MIRPE), Nuss procedure, postoperative pain control remains ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36967421"}, {"offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "INTRODUCTION: Surgical repair of pectus excavatum is a painful procedure requiring multimodal pain control with historically prolonged ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36922280"}, {"offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "BACKGROUND: Pain control after minimally invasive repair of pectus excavatum (MIRPE) can be challenging, especially in adult patients undergoing surg", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37279827"}, {"offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "BACKGROUND: Minimally invasive repair of pectus excavatum is a widely used technique for correction of pectus excavatum. Yet despite the advancement in the surgical techniques, it is still associated with various complications, including bar displacement leading to ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29890147"}, {"offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "Life-threatening complications (LTCs) and negative results of surgical treatments often go unreported. Minimally invasive repair of pectus excavatum (MIRPE) represents a procedure with a low incidence of adverse outcomes. However, 15 potentially fatal cases of MIRPE-related heart injury have been published.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36452283"}]}
+{"question_id": "66154a32fdcbea915f00004b", "question": "What are major complications of mastoiditis?", "answer": "The major complications of mastoiditis can be classified into extracranial, intratemporal, and intracranial complications. Extracranial complications include subperiosteal abscess, Bezold's abscess, and cervical abscess. Intratemporal complications include facial nerve palsy, labyrinthitis, and sigmoid sinus thrombosis. Intracranial complications are the most severe and can be life-threatening, including meningitis, brain abscess, subdural abscess, and epidural abscess. Other possible complications include hearing loss, vertigo, and neurological sequelae such as seizures and cerebral edema. Prompt diagnosis and aggressive treatment, including antibiotics and surgical interventions, are crucial to prevent these complications and improve outcomes in patients with mastoiditis.", "relevant_passage_ids": ["37056111", "31563751", "32073562"], "type": "list", "snippets": [{"offsetInBeginSection": 1008, "offsetInEndSection": 1029, "text": "subperiosteal abscess", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37056111"}, {"offsetInBeginSection": 1195, "offsetInEndSection": 1211, "text": "sinus thrombosis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31563751"}, {"offsetInBeginSection": 1217, "offsetInEndSection": 1233, "text": "cerebral abscess", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31563751"}, {"offsetInBeginSection": 1242, "offsetInEndSection": 1277, "text": "postauricular subperiosteal abscess", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31563751"}, {"offsetInBeginSection": 885, "offsetInEndSection": 906, "text": "subperiosteal abscess", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32073562"}, {"offsetInBeginSection": 908, "offsetInEndSection": 924, "text": "Bezold's abscess", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32073562"}, {"offsetInBeginSection": 962, "offsetInEndSection": 975, "text": "labyrinthitis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32073562"}, {"offsetInBeginSection": 927, "offsetInEndSection": 960, "text": "intratemporal (facial nerve palsy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32073562"}, {"offsetInBeginSection": 995, "offsetInEndSection": 1011, "text": "subdural abscess", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32073562"}]}
+{"question_id": "661c41d448a2c27714000009", "question": "Which DNA language models currently exist to model the human genome?", "answer": "Whereas protein language models have demonstrated remarkable efficacy in predicting the effects of missense variants, DNA counterparts have not yet achieved a similar competitive edge for genome-wide variant effect predictions, especially in complex genomes such as that of humans. To address this challenge, a number of DNA language models have been introduced such as the Genomic Pre-trained Network (GPN), DNABERT, HyenaDNA, and Nucleotide Transformer. These models can learn generalizable features from unlabeled genome data and can then be fine-tuned for downstream tasks such as identifying regulatory elements.", "relevant_passage_ids": ["37873118", "37883436", "33538820", "37426456", "36136096", "35536244", "36523764", "38089911", "37502861"], "type": "list", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 486, "text": "Whereas protein language models have demonstrated remarkable efficacy in predicting the effects of missense variants, DNA counterparts have not yet achieved a similar competitive edge for genome-wide variant effect predictions, especially in complex genomes such as that of humans. To address this challenge, we here introduce GPN-MSA, a novel framework for DNA language models that leverages whole-genome sequence alignments across multiple species and takes only a few hours to train.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37873118"}, {"offsetInBeginSection": 413, "offsetInEndSection": 1006, "text": "Inspired by recent progress in natural language processing, unsupervised pretraining on large protein sequence databases has proven successful in extracting complex information related to proteins. These models showcase their ability to learn variant effects in coding regions using an unsupervised approach. Expanding on this idea, we here introduce the Genomic Pre-trained Network (GPN), a model designed to learn genome-wide variant effects through unsupervised pretraining on genomic DNA sequences. Our model also successfully learns gene structure and DNA motifs without any supervision. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37883436"}, {"offsetInBeginSection": 346, "offsetInEndSection": 554, "text": "we developed a novel pre-trained bidirectional encoder representation, named DNABERT, to capture global and transferrable understanding of genomic DNA sequences based on up and downstream nucleotide contexts.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33538820"}, {"offsetInBeginSection": 12, "offsetInEndSection": 109, "text": "Deciphering the language of non-coding DNA is one of the fundamental problems in genome research.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33538820"}, {"offsetInBeginSection": 0, "offsetInEndSection": 348, "text": "Genomic (DNA) sequences encode an enormous amount of information for gene regulation and protein synthesis. Similar to natural language models, researchers have proposed foundation models in genomics to learn generalizable features from unlabeled genome data that can then be fine-tuned for downstream tasks such as identifying regulatory elements.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37426456"}, {"offsetInBeginSection": 997, "offsetInEndSection": 1280, "text": "Leveraging Hyena's new long-range capabilities, we present HyenaDNA, a genomic foundation model pretrained on the human reference genome with context lengths of up to 1 million tokens at the single nucleotide-level - an up to 500x increase over previous dense attention-based models.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37426456"}, {"offsetInBeginSection": 1556, "offsetInEndSection": 1752, "text": "On fine-tuned benchmarks from the Nucleotide Transformer, HyenaDNA reaches state-of-the-art (SotA) on 12 of 18 datasets using a model with orders of magnitude less parameters and pretraining data.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37426456"}, {"offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "BERT-5mC: an interpretable model for predicting 5-methylcytosine sites of DNA based on BERT.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38089911"}, {"offsetInBeginSection": 282, "offsetInEndSection": 485, "text": "To address this challenge, we here introduce GPN-MSA, a novel framework for DNA language models that leverages whole-genome sequence alignments across multiple species and takes only a few hours to train", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37873118"}, {"offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "GPN-MSA: an alignment-based DNA language model for genome-wide variant effect prediction.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37873118"}, {"offsetInBeginSection": 282, "offsetInEndSection": 486, "text": "To address this challenge, we here introduce GPN-MSA, a novel framework for DNA language models that leverages whole-genome sequence alignments across multiple species and takes only a few hours to train.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37873118"}, {"offsetInBeginSection": 281, "offsetInEndSection": 617, "text": "Here, we present LOGO (Language of Genome), a self-attention based contextualized pre-trained language model containing only two self-attention layers with 1 million parameters as a substantially light architecture that applies self-supervision techniques to learn bidirectional representations of the unlabelled human reference genome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35536244"}, {"offsetInBeginSection": 821, "offsetInEndSection": 1454, "text": "Recently, Hyena, a large language model based on implicit convolutions was shown to match attention in quality while allowing longer context lengths and lower time complexity. Leveraging Hyena's new long-range capabilities, we present HyenaDNA, a genomic foundation model pretrained on the human reference genome with context lengths of up to 1 million tokens at the single nucleotide-level - an up to 500x increase over previous dense attention-based models. HyenaDNA scales sub-quadratically in sequence length (training up to 160x faster than Transformer), uses single nucleotide tokens, and has full global context at each layer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37426456"}, {"offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "DNABERT: pre-trained Bidirectional Encoder Representations from Transformers model for DNA-language in genome.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33538820"}, {"offsetInBeginSection": 1562, "offsetInEndSection": 1825, "text": "We make a conceptual analogy between natural language and human genome and demonstrate LOGO is an accurate, fast, scalable, and robust framework to interpret non-coding regions for global sequence labeling as well as for variant prioritization at base-resolution.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35536244"}, {"offsetInBeginSection": 471, "offsetInEndSection": 551, "text": "TFBert treats DNA sequences as natural sentences and k-mer nucleotides as words.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36136096"}, {"offsetInBeginSection": 471, "offsetInEndSection": 686, "text": "TFBert treats DNA sequences as natural sentences and k-mer nucleotides as words. It can effectively extract upstream and downstream nucleotide context information by pre-training the 690 unlabeled ChIP-seq datasets.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36136096"}]}
+{"question_id": "661d1d2deac11fad33000015", "question": "What biomarkers are used for the identification of neonatal sepsis in low-income countries?", "answer": "CRP and PCT are considered to have high diagnostic value in identifying neonatal sepsis in low-income settings.", "relevant_passage_ids": ["36649385", "36467887"], "type": "list", "snippets": [{"offsetInBeginSection": 1182, "offsetInEndSection": 1396, "text": "CRP of \u226560\u2009mg/L (AUC 0.87, 95% CI 0.76 to 0.91) among 1339 neonates and PCT of \u22650.5\u2009ng/mL (AUC 0.87, 95% CI 0.70 to 0.92) among 617 neonates demonstrated the greatest discriminatory value for the diagnosis of neona", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36649385"}, {"offsetInBeginSection": 1474, "offsetInEndSection": 1546, "text": " PCT and CRP had good discriminatory value for neonatal sepsis in LMICs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36649385"}, {"offsetInBeginSection": 1433, "offsetInEndSection": 1579, "text": " reference standard in LMICs.CONCLUSIONS: PCT and CRP had good discriminatory value for neonatal sepsis in LMICs. ESR and WBC demonstrated poor di", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36649385"}]}
+{"question_id": "65cfdd9c1930410b13000027", "question": "What is the mechanism of action of Mirikizumab?", "answer": "Mirikizumab is a humanized IgG4 monoclonal antibody against the p19 subunit of IL-23.", "relevant_passage_ids": ["37465925", "37389706", "37379135", "37069321", "30734266", "31493397", "33105016", "32950748", "36881820", "37610533", "34748774", "36777368", "37714687", "35166398", "37249522", "35553661", "36777426", "37001911", "37594044", "32570252", "38034882"], "type": "summary", "snippets": [{"offsetInBeginSection": 289, "offsetInEndSection": 451, "text": "Mirikizumab is a humanized IgG4 monoclonal antibody against the p19 subunit of IL-23, dosed intravenously during induction and subcutaneously during maintenance. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37465925"}, {"offsetInBeginSection": 627, "offsetInEndSection": 700, "text": "Like other IL-23 antagonists, mirikizumab has a favorable safety profile.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37465925"}, {"offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Mirikizumab (Omvoh\u00ae), a humanized IgG4 anti-human IL-23p19 monoclonal antibody, is being developed by Eli Lilly and Company Ltd for the treatment of ulcerative colitis and Crohn's disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37389706"}, {"offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "BACKGROUND: Mirikizumab, a p19-directed antibody against interleukin-23, showed efficacy in the treatment of ulcerative colitis in a phase 2 trial.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37379135"}, {"offsetInBeginSection": 359, "offsetInEndSection": 736, "text": "An\u00a0increased understanding of these biological effects, particularly the pro-inflammatory effects mediated by IL-12 and IL-23, has led to the development of monoclonal antibodies that target a subunit common to IL-12 and IL-23 (p40; targeted by ustekinumab and briakinumab), or the IL-23-specific subunit (p19; targeted by risankizumab, guselkumab, brazikumab and mirikizumab).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37069321"}, {"offsetInBeginSection": 800, "offsetInEndSection": 974, "text": "Among the most promising biologics are interleukin (IL)-23p19 inhibitors (guselkumab, mirikizumab, and brazikumab), IL-6 inhibitors, and anti-adhesion molecules (ontamalimab)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37249522"}, {"offsetInBeginSection": 687, "offsetInEndSection": 1017, "text": "We reviewed and summarised available clinical trial data on the use of the IL-23 inhibitors risankizumab, brazikumab, mirikizumab, and guselkumab in the treatment of IBD, as well as the evidence from studies of these agents in IBD and other immune-mediated conditions which might inform prediction of response to IL-23 inhibition.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35553661"}, {"offsetInBeginSection": 289, "offsetInEndSection": 450, "text": "Mirikizumab is a humanized IgG4 monoclonal antibody against the p19 subunit of IL-23, dosed intravenously during induction and subcutaneously during maintenance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37465925"}, {"offsetInBeginSection": 289, "offsetInEndSection": 626, "text": "Mirikizumab is a humanized IgG4 monoclonal antibody against the p19 subunit of IL-23, dosed intravenously during induction and subcutaneously during maintenance. It is effective for the induction and maintenance of remission in moderately to severely active UC, including patients with prior failure of biological or tofacitinib therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37465925"}, {"offsetInBeginSection": 289, "offsetInEndSection": 700, "text": "Mirikizumab is a humanized IgG4 monoclonal antibody against the p19 subunit of IL-23, dosed intravenously during induction and subcutaneously during maintenance. It is effective for the induction and maintenance of remission in moderately to severely active UC, including patients with prior failure of biological or tofacitinib therapy. Like other IL-23 antagonists, mirikizumab has a favorable safety profile.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37465925"}, {"offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "INTRODUCTION: Mirikizumab, a monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, demonstrated efficacy and was well-tolerated in a phase 2 randomized clinical trial in patients with moderate-to-severe ulcerative colitis (UC) (NCT02589665)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36881820"}, {"offsetInBeginSection": 0, "offsetInEndSection": 376, "text": "INTRODUCTION: Mirikizumab, a monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, demonstrated efficacy and was well-tolerated in a phase 2 randomized clinical trial in patients with moderate-to-severe ulcerative colitis (UC) (NCT02589665). We explored gene expression changes in colonic tissue from study patients and their association with clinical outcomes", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36881820"}, {"offsetInBeginSection": 216, "offsetInEndSection": 626, "text": "The IL-23 pathway has emerged as an important therapeutic target for UC. Mirikizumab is a humanized IgG4 monoclonal antibody against the p19 subunit of IL-23, dosed intravenously during induction and subcutaneously during maintenance. It is effective for the induction and maintenance of remission in moderately to severely active UC, including patients with prior failure of biological or tofacitinib therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37465925"}, {"offsetInBeginSection": 1195, "offsetInEndSection": 1601, "text": "SIGNIFICANCE STATEMENT: This article describes the generation and characterization of mirikizumab, a high affinity, neutralizing IgG4 variant monoclonal antibody that is under development for the treatment of ulcerative colitis and Crohn's disease. Neutralization of interleukin (IL)-23 is achieved by preventing the binding of IL-23 p19 subunit to the IL-23 receptor and does not affect the IL-12 pathway.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37714687"}, {"offsetInBeginSection": 216, "offsetInEndSection": 450, "text": "The IL-23 pathway has emerged as an important therapeutic target for UC. Mirikizumab is a humanized IgG4 monoclonal antibody against the p19 subunit of IL-23, dosed intravenously during induction and subcutaneously during maintenance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37465925"}, {"offsetInBeginSection": 0, "offsetInEndSection": 474, "text": "INTRODUCTION: Mirikizumab, a monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, demonstrated efficacy and was well-tolerated in a phase 2 randomized clinical trial in patients with moderate-to-severe ulcerative colitis (UC) (NCT02589665). We explored gene expression changes in colonic tissue from study patients and their association with clinical outcomes.METHODS: Patients were randomized to receive intravenous placebo or 3 mirikizumab induction doses", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36881820"}, {"offsetInBeginSection": 336, "offsetInEndSection": 681, "text": "This study describes the generation and characterization of mirikizumab (miri), a humanized IgG4 monoclonal antibody directed against the p19 subunit of IL-23. Miri binds human and cynomolgus monkey IL-23 with high affinity and binds rabbit IL-23 weakly but does not bind to rodent IL-23 or the other IL-23 family members IL-12, IL-27, or IL-35.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37714687"}, {"offsetInBeginSection": 0, "offsetInEndSection": 578, "text": "BACKGROUND: Inhibiting interleukin (IL)-23 in patients with psoriasis has demonstrated high levels of skin clearance.OBJECTIVES: To investigate, in a phase II (AMAF; NCT02899988), multicentre, double-blind trial, the efficacy and safety of three doses of mirikizumab (LY3074828), a p19-directed IL-23 antibody, vs. placebo in patients with moderate-to-severe plaque psoriasis.METHODS: Adult patients were randomized 1 : 1 : 1 : 1 to receive placebo (n = 52), mirikizumab 30 mg (n = 51), mirikizumab 100 mg (n = 51) or mirikizumab 300 mg (n = 51) subcutaneously at weeks 0 and 8.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30734266"}, {"offsetInBeginSection": 336, "offsetInEndSection": 495, "text": "This study describes the generation and characterization of mirikizumab (miri), a humanized IgG4 monoclonal antibody directed against the p19 subunit of IL-23.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37714687"}, {"offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "INTRODUCTION: Mirikizumab, a monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, demonstrated efficacy and was well-tolerated in a phase 2 randomized clinical trial in patients with moderate-to-severe ulcerative colitis (UC) (NCT02589665).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36881820"}, {"offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Generation and Characterization of Mirikizumab, a Humanized Monoclonal Antibody Targeting the p19 Subunit of IL-23.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37714687"}, {"offsetInBeginSection": 94, "offsetInEndSection": 441, "text": "We investigated the effects of mirikizumab, a monoclonal antibody against the p19 subunit of interleukin 23, in a phase 2 study of patients with UC.METHODS: We performed a trial of the efficacy and safety of mirikizumab in patients with moderate to severely active UC, enrolling patients from 14 countries from January 2016 through September 2017.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31493397"}, {"offsetInBeginSection": 755, "offsetInEndSection": 932, "text": "Specific IL-23p19 antagonists are in development and promising results from phase II trials of mirikizumab and risankizumab underscore the potential for this class of treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33105016"}, {"offsetInBeginSection": 0, "offsetInEndSection": 736, "text": "Interleukin-12 (IL-12) and interleukin-23 (IL-23), which belong to the IL-12 family of cytokines, have a key role in intestinal homeostasis and inflammation and are implicated in the pathogenesis of inflammatory bowel disease. Upon their secretion by antigen-presenting cells, they exert both pro-inflammatory and anti-inflammatory receptor-mediated effects. An\u00a0increased understanding of these biological effects, particularly the pro-inflammatory effects mediated by IL-12 and IL-23, has led to the development of monoclonal antibodies that target a subunit common to IL-12 and IL-23 (p40; targeted by ustekinumab and briakinumab), or the IL-23-specific subunit (p19; targeted by risankizumab, guselkumab, brazikumab and mirikizumab).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37069321"}, {"offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "INTRODUCTION: Mirikizumab, an anti-interleukin-23p19 monoclonal antibody, demonstrated efficacy in phase 2 and 3 randomized clinical trials of patients with moderate-to-severe ulcerative", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37594044"}, {"offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "OBJECTIVE: Mirikizumab, a monoclonal antibody targeting the interleukin-23 p19 subunit, was effective in a Phase 2 study (NCT02589665) of moderately-to-severely active ulcerative co", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37001911"}, {"offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "INTRODUCTION: Mirikizumab, a monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, demonstrated efficacy and was well-tolerated in a phase 2 randomized clinical trial in patients with moderate-to-severe ulcerative colitis (UC) ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36881820"}, {"offsetInBeginSection": 444, "offsetInEndSection": 932, "text": "The interleukin (IL)-23 pathway plays a key role in IBD pathogenesis through promoting a pathological Th17 response. Targeting IL-23 is effective in the treatment of IBD. Ustekinumab, a monoclonal antibody targeting the shared p40 subunit of IL-12/23, is approved for treatment of moderate-to-severe CD and UC. Specific IL-23p19 antagonists are in development and promising results from phase II trials of mirikizumab and risankizumab underscore the potential for this class of treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33105016"}, {"offsetInBeginSection": 388, "offsetInEndSection": 734, "text": "kocyte trafficking. Besides tumor necrosis factor, interleukin (IL)-23 is a promising drug target, and antibodies for the combined inhibition of IL-23 and IL-12 (ustekinumab and briakinumab) or selective IL-23 inhibition (brazikumab, risankizumab, and mirikizumab) seem to be effective in Crohn's disease (CD) with emerging evidence also for ulce", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32570252"}, {"offsetInBeginSection": 148, "offsetInEndSection": 398, "text": "life (QoL). Mirikizumab, a humanized monoclonal antibody directed against the p19 subunit of IL-23, significantly reduced bowel urgency in a double-blind, randomized, placebo-controlled Phase 2 clinical trial in patients with moderate-to-severe UC (N", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36777426"}, {"offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "BACKGROUND & AIMS: Mirikizumab is an antibody against the p19 subunit of interleukin 23 that has demonstrated clinical efficacy and was well tolerated following 12 weeks of induction treatment", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32950748"}, {"offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "INTRODUCTION: Mirikizumab, an anti-interleukin-23p19 monoclonal antibody, demonstrated efficacy in phase 2 and 3 randomized clinical trials of patients with mode", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37594044"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "OBJECTIVE: Mirikizumab, a monoclonal antibody targeting the interleukin-23 p19 subunit, was effective in a Phase 2 study (N", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37001911"}, {"offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "INTRODUCTION: Mirikizumab, a monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, demonstrated efficacy and was well-tolerated in a phase 2 randomized ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36881820"}, {"offsetInBeginSection": 771, "offsetInEndSection": 1012, "text": "trasimod, ozanimod), anti-IL-23 agent (mirikizumab), anti-lymphocyte trafficking agents (ontamalimab, subcutaneous vedolizumab), JAK inhibitors (upadacitinib, filgotinib) and TLR9 agonist (cobitolimod). In Crohn's disease (CD), anti-IL-23 ag", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35166398"}, {"offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "BACKGROUND AND OBJECTIVE: Mirikizumab is a humanized anti-interleukin-23-p19 monoclonal antibody being developed for ulcerative colitis and Crohn's disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37610533"}, {"offsetInBeginSection": 0, "offsetInEndSection": 363, "text": "INTRODUCTION: Mirikizumab, an anti-interleukin-23p19 monoclonal antibody, demonstrated efficacy in phase 2 and 3 randomized clinical trials of patients with moderate-to-severe ulcerative colitis (UC). Previous results have shown that 12 weeks of mirikizumab treatment downregulated transcripts associated with UC disease activity and tumor necrosis factor inhibit", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37594044"}, {"offsetInBeginSection": 755, "offsetInEndSection": 931, "text": "Specific IL-23p19 antagonists are in development and promising results from phase II trials of mirikizumab and risankizumab underscore the potential for this class of treatment", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33105016"}, {"offsetInBeginSection": 660, "offsetInEndSection": 972, "text": "In ulcerative colitis (UC), phase 2b and/or phase 3 studies met primary endpoints for S1P receptor agonists (estrasimod, ozanimod), anti-IL-23 agent (mirikizumab), anti-lymphocyte trafficking agents (ontamalimab, subcutaneous vedolizumab), JAK inhibitors (upadacitinib, filgotinib) and TLR9 agonist (cobitolimod)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35166398"}, {"offsetInBeginSection": 336, "offsetInEndSection": 863, "text": "This study describes the generation and characterization of mirikizumab (miri), a humanized IgG4 monoclonal antibody directed against the p19 subunit of IL-23. Miri binds human and cynomolgus monkey IL-23 with high affinity and binds rabbit IL-23 weakly but does not bind to rodent IL-23 or the other IL-23 family members IL-12, IL-27, or IL-35. Miri effectively inhibits the interaction of IL-23 with its receptor, and potently blocks IL-23-induced IL-17 production in cell-based assays while preserving the function of IL-12.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37714687"}, {"offsetInBeginSection": 160, "offsetInEndSection": 681, "text": "IL-23 plays a key role in the differentiation and maintenance of T helper 17 cells, and deregulation of IL-23 can result in autoimmune pathologies of the skin, lungs, and gut. This study describes the generation and characterization of mirikizumab (miri), a humanized IgG4 monoclonal antibody directed against the p19 subunit of IL-23. Miri binds human and cynomolgus monkey IL-23 with high affinity and binds rabbit IL-23 weakly but does not bind to rodent IL-23 or the other IL-23 family members IL-12, IL-27, or IL-35.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37714687"}, {"offsetInBeginSection": 79, "offsetInEndSection": 169, "text": " Mirikizumab, a p19-directed anti-IL-23 antibody, demonstrates ulcerative colitis efficacy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36777368"}, {"offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "INTRODUCTION: Mirikizumab, an anti-interleukin-23p19 monoclonal antibody, demonstrated efficacy in phase 2 and 3 randomized clinical trials of patients with moderate-to-severe ulcerative colitis (UC)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37594044"}, {"offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "BACKGROUND: Mirikizumab, a p19-directed antibody against interleukin-23, showed efficacy in the treatment of ulcerative colitis in a phase 2 trial", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37379135"}, {"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "BACKGROUND AND OBJECTIVE: Mirikizumab is a humanized anti-interleukin-23-p19 monoclonal antibody being developed for ulcerative colitis and Crohn's disease", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37610533"}, {"offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "BACKGROUND: Mirikizumab is a humanized monoclonal antibody targeting interleukin 23p19 with demonstrated efficacy in psoriasis and ulcerative colitis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34748774"}, {"offsetInBeginSection": 93, "offsetInEndSection": 241, "text": " We investigated the effects of mirikizumab, a monoclonal antibody against the p19 subunit of interleukin 23, in a phase 2 study of patients with UC", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31493397"}, {"offsetInBeginSection": 396, "offsetInEndSection": 863, "text": "mirikizumab (miri), a humanized IgG4 monoclonal antibody directed against the p19 subunit of IL-23. Miri binds human and cynomolgus monkey IL-23 with high affinity and binds rabbit IL-23 weakly but does not bind to rodent IL-23 or the other IL-23 family members IL-12, IL-27, or IL-35. Miri effectively inhibits the interaction of IL-23 with its receptor, and potently blocks IL-23-induced IL-17 production in cell-based assays while preserving the function of IL-12.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37714687"}, {"offsetInBeginSection": 0, "offsetInEndSection": 477, "text": "Mirikizumab (Omvoh\u00ae), a humanized IgG4 anti-human IL-23p19 monoclonal antibody, is being developed by Eli Lilly and Company Ltd for the treatment of ulcerative colitis and Crohn's disease. Mirikizumab was approved in March 2023 in Japan for use as induction and maintenance therapy in patients with moderate to severe ulcerative colitis who have an inadequate response to conventional therapy or therapies and is the first IL-23p19 inhibitor to be approved for this indication.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37389706"}, {"offsetInBeginSection": 0, "offsetInEndSection": 440, "text": "BACKGROUND & AIMS: Interleukin 23 contributes to the pathogenesis of ulcerative colitis (UC). We investigated the effects of mirikizumab, a monoclonal antibody against the p19 subunit of interleukin 23, in a phase 2 study of patients with UC.METHODS: We performed a trial of the efficacy and safety of mirikizumab in patients with moderate to severely active UC, enrolling patients from 14 countries from January 2016 through September 2017", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31493397"}, {"offsetInBeginSection": 0, "offsetInEndSection": 753, "text": "Mirikizumab (Omvoh\u00ae), a humanized IgG4 anti-human IL-23p19 monoclonal antibody, is being developed by Eli Lilly and Company Ltd for the treatment of ulcerative colitis and Crohn's disease. Mirikizumab was approved in March 2023 in Japan for use as induction and maintenance therapy in patients with moderate to severe ulcerative colitis who have an inadequate response to conventional therapy or therapies and is the first IL-23p19 inhibitor to be approved for this indication. Mirikizumab was granted a positive opinion in the EU in March 2023 for the treatment of adult patients with moderately to severely active UC who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a biologic treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37389706"}, {"offsetInBeginSection": 0, "offsetInEndSection": 315, "text": "BACKGROUND AND OBJECTIVE: Mirikizumab is a humanized anti-interleukin-23-p19 monoclonal antibody being developed for ulcerative colitis and Crohn's disease. This analysis characterized mirikizumab pharmacokinetics using phase II and III trial data from patients with moderately to severely active ulcerative colitis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37610533"}, {"offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "BACKGROUND & AIMS: Interleukin 23 contributes to the pathogenesis of ulcerative colitis (UC). We investigated the effects of mirikizumab, a monoclonal antibody against the p19 subunit of interleukin 23, in a phase 2 study of patients with UC", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31493397"}, {"offsetInBeginSection": 0, "offsetInEndSection": 615, "text": "BACKGROUND AND OBJECTIVE: Mirikizumab is a humanized anti-interleukin-23-p19 monoclonal antibody being developed for ulcerative colitis and Crohn's disease. This analysis characterized mirikizumab pharmacokinetics using phase II and III trial data from patients with moderately to severely active ulcerative colitis.METHODS: Serum pharmacokinetic data in patients receiving mirikizumab 50-1000 mg intravenously every 4 weeks as induction treatment and mirikizumab 200 mg subcutaneously every 4 or 12 weeks as maintenance treatment across three trials (N = 1362) were analyzed using non-linear mixed-effects modeling", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37610533"}, {"offsetInBeginSection": 189, "offsetInEndSection": 477, "text": "Mirikizumab was approved in March 2023 in Japan for use as induction and maintenance therapy in patients with moderate to severe ulcerative colitis who have an inadequate response to conventional therapy or therapies and is the first IL-23p19 inhibitor to be approved for this indication.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37389706"}, {"offsetInBeginSection": 189, "offsetInEndSection": 753, "text": "Mirikizumab was approved in March 2023 in Japan for use as induction and maintenance therapy in patients with moderate to severe ulcerative colitis who have an inadequate response to conventional therapy or therapies and is the first IL-23p19 inhibitor to be approved for this indication. Mirikizumab was granted a positive opinion in the EU in March 2023 for the treatment of adult patients with moderately to severely active UC who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a biologic treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37389706"}, {"offsetInBeginSection": 0, "offsetInEndSection": 312, "text": "BACKGROUND: Mirikizumab, a p19-directed antibody against interleukin-23, showed efficacy in the treatment of ulcerative colitis in a phase 2 trial.METHODS: We conducted two phase 3, randomized, double-blind, placebo-controlled trials of mirikizumab in adults with moderately to severely active ulcerative colitis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37379135"}, {"offsetInBeginSection": 0, "offsetInEndSection": 470, "text": "INTRODUCTION: Mirikizumab, an anti-interleukin-23p19 monoclonal antibody, demonstrated efficacy in phase 2 and 3 randomized clinical trials of patients with moderate-to-severe ulcerative colitis (UC). Previous results have shown that 12 weeks of mirikizumab treatment downregulated transcripts associated with UC disease activity and tumor necrosis factor inhibitor resistance. We assessed week-52 gene expression from week-12 responders receiving mirikizumab or placebo", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37594044"}, {"offsetInBeginSection": 0, "offsetInEndSection": 376, "text": "INTRODUCTION: Mirikizumab, an anti-interleukin-23p19 monoclonal antibody, demonstrated efficacy in phase 2 and 3 randomized clinical trials of patients with moderate-to-severe ulcerative colitis (UC). Previous results have shown that 12 weeks of mirikizumab treatment downregulated transcripts associated with UC disease activity and tumor necrosis factor inhibitor resistance", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37594044"}, {"offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Background: Mirikizumab, an anti-IL-23p19 antibody, demonstrated efficacy in phase 3, randomized, double-blind, placebo-controlled LUCENT-1 (induction/NCT03518086) ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38034882"}, {"offsetInBeginSection": 628, "offsetInEndSection": 941, "text": " pertinent information.RESULTS: In ulcerative colitis (UC), phase 2b and/or phase 3 studies met primary endpoints for S1P receptor agonists (estrasimod, ozanimod), anti-IL-23 agent (mirikizumab), anti-lymphocyte trafficking agents (ontamalimab, subcutaneous vedolizumab), JAK inhibitors (upadacitinib, filgotinib)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35166398"}, {"offsetInBeginSection": 942, "offsetInEndSection": 1197, "text": "and TLR9 agonist (cobitolimod). In Crohn's disease (CD), anti-IL-23 agents (risankizumab, mirikizumab, guselkumab), JAK inhibitors (upadacitinib, filgotinib) and anti-lymphocyte trafficking agents (ontamalimab, etrolizumab) met primary endpoints in random", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35166398"}, {"offsetInBeginSection": 0, "offsetInEndSection": 313, "text": "BACKGROUND: Mirikizumab, a p19-directed antibody against interleukin-23, showed efficacy in the treatment of ulcerative colitis in a phase 2 trial.METHODS: We conducted two phase 3, randomized, double-blind, placebo-controlled trials of mirikizumab in adults with moderately to severely active ulcerative colitis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37379135"}, {"offsetInBeginSection": 1695, "offsetInEndSection": 1824, "text": "izumab responder DEGSEGs suggest a distinct molecular healing pathway associated with mirikizumab interleukin-23 inhibition. The ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37594044"}]}
+{"question_id": "66099c30fdcbea915f000024", "question": "What clinical indications does the self-expanding colon stent have in colorectal cancer patients?", "answer": "This technique can be used in the palliation of malignant colorectal obstruction, as a bridge to elective surgery for resectable colorectal cancers, palliation of extracolonic malignant obstruction, and for nonmalignant etiologies such as anastomotic strictures, Crohn's disease, radiation therapy, and diverticular diseases", "relevant_passage_ids": ["26064818", "26798442", "11089586", "29197194", "30550698", "31583324", "11182388", "20703837", "26691172", "21855868", "22761609", "24506142", "38050306", "33537495", "18443807", "30445358", "37138935", "15038322", "28325090", "31456127", "35601122", "26805137", "20213457", "36081551", "24696676", "28579348", "25309061", "33940240", "36220989", "22773238", "12833730", "30746374", "35066617", "37568537", "35000753", "33915760", "30652215", "25473154", "32583222"], "type": "list", "snippets": [{"offsetInBeginSection": 276, "offsetInEndSection": 600, "text": "This technique can be used in the palliation of malignant colorectal obstruction, as a bridge to elective surgery for resectable colorectal cancers, palliation of extracolonic malignant obstruction, and for nonmalignant etiologies such as anastomotic strictures, Crohn's disease, radiation therapy, and diverticular diseases", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26798442"}, {"offsetInBeginSection": 113, "offsetInEndSection": 361, "text": "Based on recent evidence, colorectal SEMS is now recommended for the palliation of patients with colonic obstruction from incurable colorectal cancer or extracolonic malignancy and also as a bridge to surgery in those who are a high surgical risk. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26064818"}, {"offsetInBeginSection": 1395, "offsetInEndSection": 1544, "text": "One week after endoscopic intestinal stent placement, the patient underwent radical left hemicolectomy for colon cancer and release of bowel adhesion", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38050306"}, {"offsetInBeginSection": 1339, "offsetInEndSection": 1513, "text": "The purpose of this review was to evaluate self-expanding metallic stent in the management of the obstruction of the colon due to the colorectal and extracolonic obstruction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26798442"}, {"offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Clinical outcomes and patency of self-expanding metal stents in patients with malignant colorectal obstruction: a prospective single center study.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18443807"}, {"offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Role of self expandable stents in management of colorectal cancers.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26798442"}, {"offsetInBeginSection": 116, "offsetInEndSection": 711, "text": "Self-expanding metallic stent placement for malignant colorectal obstruction has gained popularity as a safe and effective procedure for relieving obstruction. This technique can be used in the palliation of malignant colorectal obstruction, as a bridge to elective surgery for resectable colorectal cancers, palliation of extracolonic malignant obstruction, and for nonmalignant etiologies such as anastomotic strictures, Crohn's disease, radiation therapy, and diverticular diseases. Self-expanding metallic stent has its own advantages and disadvantages over the surgery in these indications.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26798442"}, {"offsetInBeginSection": 0, "offsetInEndSection": 968, "text": "BACKGROUND: The self-expandable metal stent (SEMS) can alleviate malignant colonic obstruction and avoid emergency decompressive surgery.OBJECTIVE: To document performance, safety, and effectiveness of colorectal stents used per local standards of practice in patients with malignant large-bowel obstruction to avoid palliative stoma surgery in incurable patients (PAL) and facilitate bowel decompression as a bridge to surgery for curable patients (BTS).DESIGN: Prospective clinical cohort study.SETTING: Two global registries with 39 academic and community centers.PATIENTS: This study involved 447 patients with malignant colonic obstruction who received stents (255 PAL, 182 BTS, 10 no indication specified).INTERVENTION: Colorectal through-the-scope SEMS placement.MAIN OUTCOME MEASUREMENTS: The primary endpoint was clinical success at 30 days, defined as the patient's ability to maintain bowel function without adverse events related to the procedure or stent.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21855868"}, {"offsetInBeginSection": 116, "offsetInEndSection": 275, "text": "Self-expanding metallic stent placement for malignant colorectal obstruction has gained popularity as a safe and effective procedure for relieving obstruction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26798442"}, {"offsetInBeginSection": 276, "offsetInEndSection": 601, "text": "This technique can be used in the palliation of malignant colorectal obstruction, as a bridge to elective surgery for resectable colorectal cancers, palliation of extracolonic malignant obstruction, and for nonmalignant etiologies such as anastomotic strictures, Crohn's disease, radiation therapy, and diverticular diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26798442"}, {"offsetInBeginSection": 1803, "offsetInEndSection": 2046, "text": "Only 3 of the 18 patients in the palliation group required the subsequent creation of stomas.CONCLUSION: The use of the self-expanding metallic stents can achieve rapid and effective nonsurgical means to relieve left-sided colonic obstruction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11089586"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Self-expandable metal stent (SEMS) placement is a minimally invasive option for achieving acute colonic decompression in obstructed colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20703837"}, {"offsetInBeginSection": 505, "offsetInEndSection": 647, "text": "Colonic stent placement also offers effective palliation of malignant colonic obstruction, although it carries risks of delayed complications.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20703837"}, {"offsetInBeginSection": 361, "offsetInEndSection": 1513, "text": "a bridge to elective surgery for resectable colorectal cancers, palliation of extracolonic malignant obstruction, and for nonmalignant etiologies such as anastomotic strictures, Crohn's disease, radiation therapy, and diverticular diseases. Self-expanding metallic stent has its own advantages and disadvantages over the surgery in these indications. During the insertion of the self-expanding metallic stent, and in the follow-up, short term and long term morbidities should be kept in mind. The most important complications of the stents are perforation, stent obstruction, stent migration, and bleeding. Additionally, given the high risk of perforation, if a patient is treated or being considered fortreatmentwith antiangiogenic agents such as bevacizumab, it is not recommended to use self-expanding metallic stent as a palliative treatment for obstruction. Therefore, there is a need for careful clinical evaluation for each patient who is a candidate for this procedure. The purpose of this review was to evaluate self-expanding metallic stent in the management of the obstruction of the colon due to the colorectal and extracolonic obstruction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26798442"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1191, "text": "BACKGROUND AND STUDY AIMS: Self-Expanding Metallic Stents (SEMS) are a surgery-sparing option for malignant colonic obstruction. They can be inserted as a \"bridge to surgery\" (BTS) for potentially curable disease, or as a palliative measure, thereby avoiding the higher morbidity and mortality associated with surgery. The objective of this study was to report our local experience of left-sided colonic stents.METHODS: Data on 49 patients was collected retrospectively from Oct 2008 to Nov 2014 at our cancer centre. This included demographics, baseline clinical characteristics, indications for SEMS placement (bridge to surgery/palliative), technical and clinical success, complications, and the mean patency of duration. Survival in both groups was also plotted on a Kaplan-Meier chart.RESULTS: A total of 49 patients with colorectal carcinoma (CRC) of the left side were enrolled. The mean age was 50 years (range 18-86). Ninety percent of patients had disease involving the rectum, sigmoid colon, or both. Forty-seven percent (n = 23) of patients had stent insertion as a BTS, whereas 53% (n = 26) had the procedure with palliative intent. Technical and clinical success rates were 96 ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26691172"}, {"offsetInBeginSection": 0, "offsetInEndSection": 404, "text": "BACKGROUND: Self-expandable metal stents (SEMS) have been used as a bridging or palliative treatment for malignant colorectal obstruction. Colonic obstruction also may arise from advanced extracolonic malignancy, but the clinical outcomes of stent placement for extracolonic malignancy are unclear. This study compared the clinical outcomes of SEMS between patients with colorectal cancer and those with ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22773238"}, {"offsetInBeginSection": 24, "offsetInEndSection": 1333, "text": "lacement of a self-expandable metal stent (SEMS) is a minimally invasive treatment for use in malignant and benign colonic obstruction. However, their widespread use is still limited with a nationwide analysis showing only 5.4% of patients with colon obstruction undergoing stent placement. This underutilization could be due to perceived increase risk of complications with stent placement.AIM: To review long- and short-term clinical success of SEMS use for colonic obstruction at our center.METHODS: We retrospectively reviewed all the patients who underwent colonic SEMS placement over a eighteen year period (August 2004 through August 2022) at our academic center. Demographics including age, gender, indication (malignant and benign), technical success, clinical success, complications (perforation, stent migration), mortality, and outcomes were recorded.RESULTS: Sixty three patients underwent colon SEMS over an 18-year period. Fifty-five cases were for malignant indications, 8 were for benign conditions. The benign strictures included diverticular disease stricturing (n = 4), fistula closure (n = 2), extrinsic fibroid compression (n = 1), and ischemic stricture (n = 1). Forty-three of the malignant cases were due to intrinsic obstruction from primary or recurrent colon cancer; 12 were from e", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37138935"}, {"offsetInBeginSection": 828, "offsetInEndSection": 987, "text": "(113 days versus 135 days, p > 0.09).CONCLUSION: Colorectal stenting for malignant disease in older patients is both safe and effective with comparative succes", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20213457"}, {"offsetInBeginSection": 68, "offsetInEndSection": 218, "text": "ructive colorectal cancers (CRC). SEMS placement has indicated in the palliation of malignant colorectal obstruc- tion, and bridge to elective surgery", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30550698"}, {"offsetInBeginSection": 314, "offsetInEndSection": 493, "text": "The European Society of Gastrointestinal Endoscopy (ESGE) recommends self-expandable metal stent (SEMS) as a bridge (two weeks) to surgery for left-sided obstructing colon cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36081551"}, {"offsetInBeginSection": 668, "offsetInEndSection": 806, "text": "Colonic stents have been shown to be effective and safe to treat obstruction from CRC, and are now the therapy of choice in this scenario.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25309061"}, {"offsetInBeginSection": 268, "offsetInEndSection": 396, "text": "The practice of placing a self-expandable metallic stent (SEMS) has dramatically increased as an effective palliative treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33537495"}, {"offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "BACKGROUND: Colonic stent placement can avoid urgent surgery for large bowel obstruction in select", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33940240"}, {"offsetInBeginSection": 1494, "offsetInEndSection": 1654, "text": "ortality and complications.CONCLUSION: Colonic stenting is increasingly utilized for malignant, left-sided bowel obstructions, and associated with lower ostomy ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36220989"}, {"offsetInBeginSection": 5, "offsetInEndSection": 165, "text": "UK cancer guidelines recommend patients with colonic obstruction due to suspected malignancy be considered for stenting with a self-expanding metal stent (SEMS)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24506142"}, {"offsetInBeginSection": 0, "offsetInEndSection": 337, "text": "INTRODUCTION: The use of self-expanding metal stents (SEMS) has been considered an effective and safe alternative to emergency surgery as bridge to surgery or for palliation in advanced colorectal cancer even though more recent data have raised concerns on both early and long-term outcomes when patients are treated with bridge to surge", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28325090"}, {"offsetInBeginSection": 277, "offsetInEndSection": 486, "text": "In this article the authors report on the placement of a self-expandable stent for decompression of a malignant colorectal obstruction, which allows elective one stage resection of the tumour affected segment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15038322"}, {"offsetInBeginSection": 0, "offsetInEndSection": 352, "text": "INTRODUCTION: The use of self-expanding metal stents (SEMS) has been considered an effective and safe alternative to emergency surgery as bridge to surgery or for palliation in advanced colorectal cancer even though more recent data have raised concerns on both early and long-term outcomes when patients are treated with bridge to surgery indications.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28325090"}, {"offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "BACKGROUND: Endoscopic placement of a self-expandable metal stent (SEMS) is a minimally invasive treatment for use in malignant and benign colonic obstruction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37138935"}, {"offsetInBeginSection": 11, "offsetInEndSection": 877, "text": " Self-expanding metal stents can alleviate malignant colonic obstruction in incurable patients and avoid palliative stoma surgery. Objective. Evaluate stent effectiveness and safety on palliation of patients with malignant colorectal strictures. Design. Two prospective, one Spanish and one global, multicenter studies. Settings. 39 centers (22 academic, 17 community hospitals) from 13 countries. Patients. A total of 257 patients were enrolled, and 255 patients were treated with a WallFlex uncovered enteral colonic stent. Follow-up was up to 12 months or until death or retreatment. Interventions(s). Self-expanding metal stent placement. Main Outcome Measures. Procedural success, clinical success, and safety. Results. Procedural success was 98.4% (251). Clinical success rates were 87.8% at 30 days, 89.7% at 3 months, 92.8% at 6 months, and 96% at 12 months.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22761609"}, {"offsetInBeginSection": 102, "offsetInEndSection": 253, "text": "SEMS placement has indicated in the palliation of malignant colorectal obstruc- tion, and bridge to elective surgery for resectable colorectal cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30550698"}, {"offsetInBeginSection": 89, "offsetInEndSection": 239, "text": " of intestinal obstruction by colorectal cancer, either as a bridge to surgery or terminal treatment. When SEMS are used for patients in the terminal ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26805137"}, {"offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "INTRODUCTION: The self-expanding metal stent (SEMS) has been used in malignant colorectal obstruction as a bridge to surgery or for palliative treatment", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30445358"}, {"offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Background and Aim: The present study aimed to compare the utility and safety of the colonic self-expandable metallic stent between patients with obstructive primary colorectal cancer who underwent chemotherapy or palliative treatment care and patients", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35601122"}, {"offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Colon stent self-expanding metallic stents(SEMS) are useful for obstructive colorectal cancers (CRC). SEMS placement has indicated in the palliation of malignant colorectal obstruc- tion, and bridge to elective surgery", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30550698"}, {"offsetInBeginSection": 134, "offsetInEndSection": 735, "text": "Self-expanding metal stents represent an established alternative to surgery for the palliation of unresectable carcinomas and currently allow a \"bridge-to-surgery\" strategy to relieve large bowel obstruction and optimise the patients' clinical conditions before elective oncologic resection. Additionally, intraluminal stents represent an appealing option to manage obstructing extracolonic tumours and selected patients with benign conditions such as refractory anastomotic strictures and post-surgical leaks.This educational paper reviews the technical features and current indications of colorectal", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31456127"}, {"offsetInBeginSection": 361, "offsetInEndSection": 1595, "text": "of colonic stents (self-expandable metallic stents) for MCO is a major and standard endoscopic treatment that has been available since 2012 in Japan. This review presents the current conditions and future prospects of this procedure based on the literature. The current indication of colonic stent placement is malignant colorectal stenosis. One of the purposes of using stents is palliative treatment; further, its advantages over emergency surgery with colostomy include avoidance of colostomy, relief of obstruction, shorter hospitalization, and better quality of life. In addition, stent placement can also be used as a bridge to surgery since the duration of the hospitalization is shorter and postoperative complications, colostomy rates, and mortality rates are lower with elective than with emergency surgery. Although recent studies have reported low complication rates related to colonic stents, complications may still occur, highlighting the importance of good preparation, adequate staffing, backup systems, and informed consent. The current major problem related to colonic stents is the lack of evidence on patients' long-term prognoses for bridge to surgery purposes, awaiting the results of ongoing clinical research.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31583324"}, {"offsetInBeginSection": 186, "offsetInEndSection": 1047, "text": " may be not a good choice. Here, we report the successful treatment of obstructing colonic cancer by combining self-expandable stent and neoadjuvant chemotherapy.CASE SUMMARY: The patient was a 72-year-old man who was admitted with a chief complaint of abdominal pain for more than 1 mo. Computed tomography (CT) scanning revealed that there was a mass in the descending colon, which led to intestinal obstruction. On admission, a series of therapeutic measures, such as fasting and water deprivation, gastrointestinal decompression, total parenteral nutrition, and octreotide acetate, were taken to improve the obstructive symptoms. At the same time, a self-expandable metal stent was successfully placed across the stenosis, and a biopsy was obtained and diagnosed as adenocarcinoma. CT scanning 14 d after insertion of the stent revealed that the intestine w", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30746374"}, {"offsetInBeginSection": 50, "offsetInEndSection": 1363, "text": "ing programs, the colorectal cancer occurs in 7-29% of cases with a bowel obstruction, needing an immediate decompression treatment by emergency surgery; unfortunately, the emergency surgery is characterized by high morbidity and mortality rates. The endoscopic placement of self-expandable metallic stents can be a useful alternative, allowing to decompress the acute obstruction in a short time, in order to correct dehydration, electrolytic imbalance and to improve the overall clinical conditions prior to adequately plan the intervention of elective surgery.AIM: The objective of our study was to evaluate the clinical success and potential complications related to the stent placement as \"bridge to surgery\".MATERIALS AND METHODS: Twenty-four patients with acute intestinal obstruction due to colorectal cancer were retrospectively observed in our Surgery Unit. They were selected only patients in whom technical success, defined as the correct placement of the stent, was recorded. All patients underwent a preoperative abdominal X-rays and whole body contrast- enhanced Computed Tomography (ceCT). Furthermore, an intraoperative fluoroscopy was also performed to obtain a better anatomical depiction of the lesions. The sites of obstruction were in the left colon (n=13) and in the proximal rectal tract (", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29197194"}, {"offsetInBeginSection": 0, "offsetInEndSection": 361, "text": "Colon stent self-expanding metallic stents(SEMS) are useful for obstructive colorectal cancers (CRC). SEMS placement has indicated in the palliation of malignant colorectal obstruc- tion, and bridge to elective surgery for resectable colorectal cancers. SEMS can reduce the risk of early complications, mortality, stoma creation rate, and shorten hospital stay.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30550698"}, {"offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "Colon stent self-expanding metallic stents(SEMS) are useful for obstructive colorectal cancers (CRC). SEMS placement has indicated in the palliation of malignant colorectal obstruc- tion, and bridge to elective surgery for resectable colorectal cancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30550698"}, {"offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "INTRODUCTION: The self-expanding metal stent (SEMS) has been used in malignant colorectal obstruction as a bridge to surgery or for palliative treatment. We report a case of obstructive descending colon diverticulitis in-stent restenosis, which is difficult to distinguish from colon cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30445358"}, {"offsetInBeginSection": 0, "offsetInEndSection": 360, "text": "INTRODUCTION: The self-expanding metal stent (SEMS) has been used in malignant colorectal obstruction as a bridge to surgery or for palliative treatment. We report a case of obstructive descending colon diverticulitis in-stent restenosis, which is difficult to distinguish from colon cancer.PRESENTATION OF CASE: A 48-year-old man presented with abdominal pain", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30445358"}, {"offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Colon stent self-expanding metallic stents(SEMS) are useful for obstructive colorectal cancers (CRC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30550698"}, {"offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Self-expanding metallic stent for unresectable obstructive colorectal cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30550698"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "PURPOSE: This report describes our experience with the use of self-expanding metallic stents (SEMS) in the management of obstructing colorectal cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11182388"}, {"offsetInBeginSection": 0, "offsetInEndSection": 337, "text": "PURPOSE: This report describes our experience with the use of self-expanding metallic stents (SEMS) in the management of obstructing colorectal cancer.METHODS: A retrospective chart review of all patients undergoing placement of SEMS between May 1997 and January 2000 was performed.RESULTS: Insertion of SEMS was attempted in 12 patients", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11182388"}, {"offsetInBeginSection": 276, "offsetInEndSection": 853, "text": "This technique can be used in the palliation of malignant colorectal obstruction, as a bridge to elective surgery for resectable colorectal cancers, palliation of extracolonic malignant obstruction, and for nonmalignant etiologies such as anastomotic strictures, Crohn's disease, radiation therapy, and diverticular diseases. Self-expanding metallic stent has its own advantages and disadvantages over the surgery in these indications. During the insertion of the self-expanding metallic stent, and in the follow-up, short term and long term morbidities should be kept in mind.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26798442"}, {"offsetInBeginSection": 166, "offsetInEndSection": 427, "text": "A colorectal stent can be used both for palliation and as a \"bridge to surgery\". Twenty-three patients with obstructive sigmoid or rectal cancer were selected for stenting. Self-expanding metal mesh stents were placed under endoscopic and flouroscopic guidance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12833730"}, {"offsetInBeginSection": 791, "offsetInEndSection": 1106, "text": "Stent migration was noted in four patients but symptomatic reobstruction did not occur, no patient needed later surgery. Colorectal stenting procedure is effective and safe and can be used in obstructing cancers both as a temporary relief before elective resection and as a definitive treatment in palliative cases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12833730"}, {"offsetInBeginSection": 276, "offsetInEndSection": 711, "text": "This technique can be used in the palliation of malignant colorectal obstruction, as a bridge to elective surgery for resectable colorectal cancers, palliation of extracolonic malignant obstruction, and for nonmalignant etiologies such as anastomotic strictures, Crohn's disease, radiation therapy, and diverticular diseases. Self-expanding metallic stent has its own advantages and disadvantages over the surgery in these indications.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26798442"}, {"offsetInBeginSection": 0, "offsetInEndSection": 821, "text": "Colorectal\u00a0cancer (CRC) is the third most common cancer and the second leading cause of\u00a0cancer\u00a0mortality\u00a0globally. Large bowel obstruction (occurring in 15-30% of patients with CRCs) accounts for approximately 80% of medical emergencies related to CRC. Currently, there is no standard treatment of this condition. The European Society of Gastrointestinal Endoscopy (ESGE) recommends self-expandable metal stent (SEMS) as a bridge (two weeks) to surgery for left-sided obstructing colon cancer. In the present report, we describe an 81-year-old male with colon cancer who underwent colon stent placement for 32 months, but later underwent radical resection. A follow-up of more than four-months revealed that his condition was normal. The history as well as application and advantages of SEMS are discussed in this report.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36081551"}, {"offsetInBeginSection": 12, "offsetInEndSection": 459, "text": "the efficacy and safety of colorectal stent placement for palliation remains insufficient. This single-arm, prospective, multicenter study with a WallFlex enteral colonic stent included 200 consecutive patients with malignant large bowl obstruction in the palliation cohort. The technical and clinical success, as well as stent patency and complications as short-term (\u22647 days) and long-term (>7 days) outcomes, of high axial force self-expandable", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37568537"}, {"offsetInBeginSection": 39, "offsetInEndSection": 1732, "text": "struction due to colorectal cancer occurs in 7-30% of cases and is an abdominal emergency that requires urgent decompression. The safety and oncological effect of self-expandable metal stents (SEMS) in these patients remains controversial. This study aimed to evaluate its impact on these variables and compare it with that of emergency surgery (ES).METHODS: Descriptive, retrospective and single-centre study, performed between 2008 and 2015, with follow-up until 2017. One hundred eleven patients with diagnosis of left malignant colonic obstruction were included and divided according to the treatment received: stent as bridge to surgery (SBTS group: 39), palliative stent (PS group: 30) and emergency surgery with curative (ECS group: 34) or palliative intent (EPS group: 8). Treatment was decided by the attending surgeon in charge.RESULTS: Technical and clinical general success rates for colorectal SEMS were 95.7% and 91.3%, respectively, with an associated morbimortality of 23.2%, which was higher in the PS group (p\u2009=\u20090.002). The SBTS group presented a higher laparoscopic approach and primary anastomosis (p\u2009<\u20090.001), as well as a lower colostomy rate than the ECS group (12.8% vs. 40%; p\u2009=\u20090.023). Postoperative morbidity and mortality were significantly lower in the SBTS group compared to the ECS group (41% vs. 67.6%; p\u2009=\u20090.025). Overall survival (OS) and disease-free survival (DFS) were similar between the analysed groups.CONCLUSION: Colonic stent placement is a safe and effective therapeutic alternative to emergency surgery in the management of left-sided malignant colonic obstruction in both curative and palliative fields. It presents a lower postoperative morbimorta", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35066617"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1020, "text": "BACKGROUND: Colonic stenting has emerged as preferred palliative treatment for left sided malignant obstructions. It shortens hospital stays, decreases healthcare cost, reduces permanent stoma rates, and expedites the start of chemotherapy. The role of stenting as a bridge-to-surgery remains unsettled.DATA SOURCE: For this paper the recommendations of the American and European society of gastroenterology and colorectal surgery were reviewed. We will discuss the benefits and risks of stenting in palliative setting and as bridge-to-surgery. Quality of life, hospital stay, and health care cost will also be considered.CONCLUSION: Non-traversable colon masses during endoscopy are considered a risk factor of development of intestinal obstruction but preventive stent placement in patients without obstructive symptoms is not recommended. The risk of technical or clinical failure is significant at 25%. If stent placement allows neoadjuvant chemotherapy, it may increase the rate of R0 resections. Perforations may r", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35000753"}, {"offsetInBeginSection": 807, "offsetInEndSection": 1083, "text": "In the setting of an acute bowel obstruction in patients with potentially resectable colon cancer, stents may be used to delay surgery and thus allow for decompression, adequate bowel preparation, and optimization of the patient's condition for curative surgical intervention.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25309061"}, {"offsetInBeginSection": 723, "offsetInEndSection": 1121, "text": "However, endoscopic stent used as a bridge to surgery is not yet widely adopted because the concern was raised about the long-term survival and cancer safety of this approach. The recent scientific evidence has shown that this approach improves the short-term outcomes, such as postoperative complications and the stoma rate, without differences in long-term outcomes compared to emergency surgery.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33915760"}, {"offsetInBeginSection": 703, "offsetInEndSection": 933, "text": "One of the purposes of using stents is palliative treatment; further, its advantages over emergency surgery with colostomy include avoidance of colostomy, relief of obstruction, shorter hospitalization, and better quality of life.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31583324"}, {"offsetInBeginSection": 934, "offsetInEndSection": 1178, "text": "In addition, stent placement can also be used as a bridge to surgery since the duration of the hospitalization is shorter and postoperative complications, colostomy rates, and mortality rates are lower with elective than with emergency surgery.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31583324"}, {"offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "INTRODUCTION: Stenting of obstructing colorectal cancers obviates the need for emergency surgery, reducing initial morbidity and mortality rate associated with emergency surgery and facilitates full staging of the neoplastic process with an opportunity to optimize the patien", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30652215"}, {"offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "BACKGROUND AND AIMS: Self-expandable metal stents are used increasingly in the treatment of obstructing colorectal cancer (CRC). Although endoscopic colon stenting is widely accepted in palliation, disagreement exists about its role i", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28579348"}, {"offsetInBeginSection": 119, "offsetInEndSection": 435, "text": "Because of poor medical condition and high incidence of post-surgical complications, there has been increasing use of self-expanding metal stents (SEMS) for the purpose of palliation or as a bridge to surgery with some benefits, including shorter hospital stays, lower rates of adverse events, and one-stage surgery.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25473154"}, {"offsetInBeginSection": 0, "offsetInEndSection": 533, "text": "For the 8-29% colorectal cancers that initially manifest with obstruction, emergency surgery (ES) was traditionally considered the only available therapy, despite high morbidity and mortality rates and the need for colostomy creation. More recently, malignant obstruction of the left colon can be temporized by endoscopic placement of a self-expanding metallic stent (SEMS), used as bridge to surgery (BTS), facilitating a laparoscopic approach and increasing the likelihood that a primary anastomosis instead of stoma would be used.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32583222"}, {"offsetInBeginSection": 14, "offsetInEndSection": 246, "text": "Colonic obstruction is one of the manifestations of colon cancer for which self-expanding metal stents (SEMS) have been effectively used, to restore the luminal patency either for palliative care or as a bridge to resective surgery.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24696676"}]}
+{"question_id": "661a624bfdcbea915f00005b", "question": "List the cells which have CD21 on the surface.", "answer": "CD21 is produced by B cells and follicular dendritic cells, where it binds cleavage products of the C3 complement protein.", "relevant_passage_ids": ["11367532", "28449602", "28061947", "27010233", "1688740", "9723706", "22899340", "9144490", "23178404", "29202042", "12905672", "38037221", "37983289", "1386409", "23266128", "1966579", "10809953", "7858501", "11312253", "11091285", "7614999", "18295335", "17096529", "25640655", "7690241", "1706386", "24218269", "33193306"], "type": "list", "snippets": [{"offsetInBeginSection": 120, "offsetInEndSection": 241, "text": "CD21 is produced by B cells and follicular dendritic cells, where it binds cleavage products of the C3 complement protein", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11367532"}, {"offsetInBeginSection": 243, "offsetInEndSection": 536, "text": "CD21 facilitates internalization of immune complexes by B cells to enhance antigen presentation. CD21, in association with CD19/CD81, also serves as a coaccessory activation complex with the B-cell antigen receptor, permitting a lower antigen concentration to achieve maximal B-cell activation", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11367532"}, {"offsetInBeginSection": 538, "offsetInEndSection": 671, "text": "CD21 traps immune complexes on the surface of follicular dendritic cells and displays them to activated B cells in germinal centers. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11367532"}, {"offsetInBeginSection": 167, "offsetInEndSection": 344, "text": "Recently, B-cell co-receptor markers (CD19, CD21, and CD81) and CD20, CD22, and CD27 deficiencies have been reported in relation with different primary immunodeficiency diseases", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28449602"}, {"offsetInBeginSection": 345, "offsetInEndSection": 469, "text": "classical B2 cells (CD19+IgMloIgDhiCD1d-CD21/35intCD5-CD11b-CD43-), but differed from them by the absence of B2 marker CD23.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28061947"}, {"offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "The complement receptor 2 (CR2, CD21) is part of a complex (CD21/CD19/CD81) acting as a co-receptor to the B cell receptor (BCR). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27010233"}, {"offsetInBeginSection": 1216, "offsetInEndSection": 1311, "text": "on and differentiation of the CD21(-/low) B cells comparable to CD21(+) CD27(+) memory B cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27010233"}, {"offsetInBeginSection": 2021, "offsetInEndSection": 2378, "text": "We observed a significant lower expression of CD9 and of CD81 at the surface of B lymphoblasts with a t(9;22)(BCR-ABL) in comparison with B lymphoblasts without any recurrent cytogenetic alteration (p\u2009=\u20090.0317 and p\u2009=\u20090.0011, respectively) and with B lymphoblasts harboring other cytogenetic recurrent abnormalities (p\u2009=\u20090.0032 and p\u2009<\u20090.0001, respectively)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38037221"}, {"offsetInBeginSection": 831, "offsetInEndSection": 1079, "text": "These infection-induced ELAs were defined by the presence of ER-TR7+ fibroblastic reticular cells, CD21/35+ follicular dendritic cells (FDCs), CXCR5+ PD1+ T follicular helper-like phenotype, GL7+ CD95+ GC-like B cells, and plasmablasts/plasma cells", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37983289"}, {"offsetInBeginSection": 1189, "offsetInEndSection": 1526, "text": "Nevertheless only B cells, but not CD4+ or CD8+ T cells, expressed detectable amounts of CD21 on their cell surface. Expression of the CD21 exon 11 has been reported being restricted to follicular dendritic cells only. To the contrary, we found that both purified B and T cell subpopulations expressed CD21 mRNA with and without exon 11.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9723706"}, {"offsetInBeginSection": 1110, "offsetInEndSection": 1407, "text": "B lymphocytes and CD4+ or CD8+ T cells expressed similar amounts of CD21 mRNA. Nevertheless only B cells, but not CD4+ or CD8+ T cells, expressed detectable amounts of CD21 on their cell surface. Expression of the CD21 exon 11 has been reported being restricted to follicular dendritic cells only.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9723706"}, {"offsetInBeginSection": 1189, "offsetInEndSection": 1407, "text": "Nevertheless only B cells, but not CD4+ or CD8+ T cells, expressed detectable amounts of CD21 on their cell surface. Expression of the CD21 exon 11 has been reported being restricted to follicular dendritic cells only.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9723706"}, {"offsetInBeginSection": 1110, "offsetInEndSection": 1305, "text": "B lymphocytes and CD4+ or CD8+ T cells expressed similar amounts of CD21 mRNA. Nevertheless only B cells, but not CD4+ or CD8+ T cells, expressed detectable amounts of CD21 on their cell surface.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9723706"}, {"offsetInBeginSection": 1189, "offsetInEndSection": 1305, "text": "Nevertheless only B cells, but not CD4+ or CD8+ T cells, expressed detectable amounts of CD21 on their cell surface.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9723706"}, {"offsetInBeginSection": 218, "offsetInEndSection": 374, "text": "Although CD21 is important, B cells that express low amounts or lack surface CD21 (CD21(-/low) ) are increased in conditions with chronic inflammation, e.g.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27010233"}, {"offsetInBeginSection": 420, "offsetInEndSection": 535, "text": "CD21 is primarily expressed on B lymphocytes and follicular dendritic cells, but has also been reported on T cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9723706"}, {"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Human B and T lymphocytes have similar amounts of CD21 mRNA, but differ in surface expression of the CD21 glycoprotein.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9723706"}, {"offsetInBeginSection": 420, "offsetInEndSection": 876, "text": "CD21 is primarily expressed on B lymphocytes and follicular dendritic cells, but has also been reported on T cells. We established a semi-quantitative PCR and compared the CD21 mRNA levels of B and T lymphocytes with the expression of the CD21 glycoprotein on the surface of the respective cells by flow cytometry. The B cell lines Raji and Ramos and the T cell lines Jurkat and Molt4 expressed equal amounts of CD21 mRNA, but differed in surface staining.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9723706"}, {"offsetInBeginSection": 218, "offsetInEndSection": 395, "text": "Although CD21 is important, B cells that express low amounts or lack surface CD21 (CD21(-/low) ) are increased in conditions with chronic inflammation, e.g. autoimmune diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27010233"}, {"offsetInBeginSection": 1110, "offsetInEndSection": 1188, "text": "B lymphocytes and CD4+ or CD8+ T cells expressed similar amounts of CD21 mRNA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9723706"}, {"offsetInBeginSection": 1306, "offsetInEndSection": 1407, "text": "Expression of the CD21 exon 11 has been reported being restricted to follicular dendritic cells only.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9723706"}, {"offsetInBeginSection": 735, "offsetInEndSection": 876, "text": "The B cell lines Raji and Ramos and the T cell lines Jurkat and Molt4 expressed equal amounts of CD21 mRNA, but differed in surface staining.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9723706"}, {"offsetInBeginSection": 446, "offsetInEndSection": 696, "text": "We report here that fluorescent liposomes carrying CD23 interact specifically with the cell-surface protein CD21, identified as the receptor for Epstein-Barr virus and the complement receptor-2 on B cells, some T cells and follicular dendritic cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1386409"}, {"offsetInBeginSection": 0, "offsetInEndSection": 535, "text": "CD21, the complement receptor type 2 (CR2), binds the complement fragments iC3b, C3dg and C3d, interacts with CD23 (the low-affinity receptor for IgE), and binds IFN-alpha. This 145 kDa glycoprotein merits particular interest because it plays a pivotal role in the activation and proliferation of B cells by lowering the signal threshold. In human disease CD21 is important as a receptor for Epstein-Barr virus and HIV. CD21 is primarily expressed on B lymphocytes and follicular dendritic cells, but has also been reported on T cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9723706"}, {"offsetInBeginSection": 138, "offsetInEndSection": 358, "text": "The primary function of complement, in this regard, is to opsonize antigen or immune complexes for uptake by complement receptor type 2 (CR2, CD21) expressed on B cells, follicular dendritic cells (FDC) and some T cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10809953"}, {"offsetInBeginSection": 0, "offsetInEndSection": 662, "text": "Follicular dendritic cells (FDC) are restricted to the B-cell regions of secondary lymphoid tissue and to non-Hodgkin's lymphomas derived from the follicular center or the mantle zone. With their cytoplasmic ramifications they form a dense network which contains the B-lymphocytes. In situ, FDC are only detectable at the ultrastructural level or when stained with anti FDC-reagents. On the surface of their dendritic extensions they express transferrin receptors (CD71), the B-cell epitope CD20, class II antigens, the myelomonocytic molecule CD14, the glycoprotein gp50 (CD40), and several receptors for components of the complement system (CD11b, CD21, CD35).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7858501"}, {"offsetInBeginSection": 0, "offsetInEndSection": 333, "text": "Complement receptors 1 and 2 (CR1/2 or CD35/CD21) recognize complement-opsonized antigens to initiate innate and adaptive immunity, respectively. CD35 stimulates phagocytosis on macrophages and antigen presentation on follicular dendritic cells (FDCs). CD21 helps activate B cells as part of the B cell coreceptor with CD19 and CD81.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29202042"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Expression of human complement receptor type 2 (CR2/CD21) is primarily restricted to mature B cells and follicular dendritic cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11312253"}, {"offsetInBeginSection": 170, "offsetInEndSection": 861, "text": "to study expression of CD21 and other surface markers in different cell lines. Special emphasis was placed on cell lines with a normally low expression of CD21, especially on T cell lines. After induction of EBNA2, a substantial increase in CD21 mRNA was observed, as well as increased production of membrane CD21. This was found not only in cell lines of B cell origin, but also in the T cell line Jurkat. The amount of CD21 was quantitated by means of a fluorescence immunoassay, and found to correlate with the presence of EBNA2 protein. A decrease in EBNA2 abundance was associated with complete loss of cell-associated CD21. As we could also detect large amounts of soluble CD21 (sCD21)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7614999"}, {"offsetInBeginSection": 0, "offsetInEndSection": 334, "text": "CD21, the receptor for the C3d complement fragment, has been reported to be the Epstein-Barr virus (EBV) receptor in B lymphocytes and cultured squamous epithelial cells. This receptor has previously been found to be expressed in the epithelia of nonocular mucosal-associated lymphoid tissues (MALT) which are also sites of persistent", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1966579"}, {"offsetInBeginSection": 564, "offsetInEndSection": 723, "text": "B cells expressing a mutant CD21 cytoplasmic domain with only three amino acids (KHR) showed increased CD21-shedding and required lower stimuli concentrations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18295335"}, {"offsetInBeginSection": 90, "offsetInEndSection": 155, "text": "CD21 receptor, a cell surface marker of malignant B cell lymphoma", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17096529"}, {"offsetInBeginSection": 207, "offsetInEndSection": 365, "text": "CR2 (CD21) cell surface protein was detected in normal quantities on peripheral B cells, but was almost absent on synovial B lymphocytes of the same patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11091285"}, {"offsetInBeginSection": 203, "offsetInEndSection": 353, "text": "CR signal transduction. CD21 also expresses on the surface of follicular dendritic cells, which mediates the long-term maintenance of antigens and is ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12905672"}, {"offsetInBeginSection": 1135, "offsetInEndSection": 1285, "text": " CD8+ T cells expressed similar amounts of CD21 mRNA. Nevertheless only B cells, but not CD4+ or CD8+ T cells, expressed detectable amounts of CD21 on", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9723706"}, {"offsetInBeginSection": 267, "offsetInEndSection": 417, "text": " secretion. We detected increased surface expression of CD21 on AchR specified B cells as well as decreased surface expression of CD21 on total B cell", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23266128"}, {"offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Complement receptor 2 (CR2/CD21) is predominantly expressed on the surface of mature B cells where it forms part of a coreceptor complex that functions, in part, to modulate B-cell receptor signal strength.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25640655"}, {"offsetInBeginSection": 0, "offsetInEndSection": 328, "text": "The complement receptor 2 (CR2; CD21), a 145,000 MW glycoprotein, has been useful as a marker of B lymphocyte maturation. It is expressed on the 1:13 monoclonal, EBV-transformed, B cell line which produces TNP-specific IgM-kappa and displays an in vitro capacity for differentiation. The line expresses the CD20+CD21+ phenotype.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1688740"}, {"offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The complement receptor 2 (CR2 or CD21) can be found in non-covalent association with the B lymphocyte specific CD19 complex at the surface of mature human B cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7690241"}, {"offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Expression of human complement receptor 2 (CR2, CD21, C3d,g/EBV receptor) is developmentally restricted on human B lymphocytes to cells of the late-pre and mature stages.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1706386"}, {"offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "The complement receptor 2 (Cr2) gene is exclusively expressed in B cells and follicular dendritic cells (FDC) in mice and in humans.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24218269"}, {"offsetInBeginSection": 536, "offsetInEndSection": 734, "text": "We established a semi-quantitative PCR and compared the CD21 mRNA levels of B and T lymphocytes with the expression of the CD21 glycoprotein on the surface of the respective cells by flow cytometry.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9723706"}, {"offsetInBeginSection": 227, "offsetInEndSection": 405, "text": "CD21 also expresses on the surface of follicular dendritic cells, which mediates the long-term maintenance of antigens and is indispensable for maintaining the memory of B cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12905672"}, {"offsetInBeginSection": 51, "offsetInEndSection": 201, "text": "4 are routinely used to detect CD21 orthologue on the surface of porcine B lymphocytes. Cross-reactive studies show that IAH-CC51 and B-Ly4 recognize ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23178404"}, {"offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "CD21 is a 145-kDa membrane glycoprotein mainly expressed on B cells and follicular dendritic cells, and is involved in B-cell activation, survival and proliferation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22899340"}, {"offsetInBeginSection": 538, "offsetInEndSection": 778, "text": "CD21 traps immune complexes on the surface of follicular dendritic cells and displays them to activated B cells in germinal centers. Much work has been conducted to determine the transcriptional control mechanisms dictating CD21 expression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11367532"}, {"offsetInBeginSection": 420, "offsetInEndSection": 734, "text": "CD21 is primarily expressed on B lymphocytes and follicular dendritic cells, but has also been reported on T cells. We established a semi-quantitative PCR and compared the CD21 mRNA levels of B and T lymphocytes with the expression of the CD21 glycoprotein on the surface of the respective cells by flow cytometry.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9723706"}, {"offsetInBeginSection": 1306, "offsetInEndSection": 1526, "text": "Expression of the CD21 exon 11 has been reported being restricted to follicular dendritic cells only. To the contrary, we found that both purified B and T cell subpopulations expressed CD21 mRNA with and without exon 11.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9723706"}, {"offsetInBeginSection": 120, "offsetInEndSection": 242, "text": "CD21 is produced by B cells and follicular dendritic cells, where it binds cleavage products of the C3 complement protein.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11367532"}, {"offsetInBeginSection": 0, "offsetInEndSection": 337, "text": "Human CD21low B cells are expanded in autoimmune (AI) diseases and display a unique phenotype with high expression of co-stimulatory molecules, compatible with a potential role as antigen-presenting cells (APCs). Thus, we addressed the co-stimulatory capacity of na\u00efve-like, IgM-memory, switched memory and CD27negIgDneg memory CD21low B", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33193306"}, {"offsetInBeginSection": 554, "offsetInEndSection": 696, "text": "CD21, identified as the receptor for Epstein-Barr virus and the complement receptor-2 on B cells, some T cells and follicular dendritic cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1386409"}, {"offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Murine CD21 gene products are expressed primarily on the surface of B lymphocytes and follicular dendritic cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9144490"}, {"offsetInBeginSection": 207, "offsetInEndSection": 367, "text": "CR2/CD21 expression is tightly regulated throughout B-cell development such that CR2/CD21 cannot be detected on pre-B or terminally differentiated plasma cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25640655"}]}
+{"question_id": "6616a250fdcbea915f000059", "question": "Do PPIs increase the risk of gastric cancer?", "answer": "Proton pump inhibitors have been associated with a higher risk of gastric cancer.", "relevant_passage_ids": ["34226290", "37505975"], "type": "yesno", "snippets": [{"offsetInBeginSection": 36, "offsetInEndSection": 118, "text": "users of proton pump inhibitors (PPIs) are at an increased risk of gastric cancer ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34226290"}, {"offsetInBeginSection": 1345, "offsetInEndSection": 1415, "text": "the use of PPIs is associated with an increased risk of gastric cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34226290"}, {"offsetInBeginSection": 1419, "offsetInEndSection": 1476, "text": "Higher GC rate was associated with omeprazole chronic use", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37505975"}, {"offsetInBeginSection": 166, "offsetInEndSection": 224, "text": "GC in elderly community-dwelling omeprazole chronic users ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37505975"}]}
+{"question_id": "661c414d48a2c27714000007", "question": "Can enhancers act as promoters?", "answer": "It is generally assumed that there is a clear distinction between promoters, which initiate transcription, and enhancers, which control the spatiotemporal expression. However, studies have unexpectedly shown that regulatory elements can have both enhancer and promoter functions.\nFor example, some enhancers (mainly bidirectional) can act as weak promoters, producing overlapping spatiotemporal expression. Conversely, bidirectional promoters often act as strong enhancers, while unidirectional promoters generally cannot.", "relevant_passage_ids": ["29378788", "31605096", "22264824", "8290549", "26948815", "26073855", "24178450", "29673772"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "Gene expression is regulated by promoters, which initiate transcription, and enhancers, which control their temporal and spatial activity. However, the discovery that mammalian enhancers also initiate transcription questions the inherent differences between enhancers and promoters.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29378788"}, {"offsetInBeginSection": 113, "offsetInEndSection": 374, "text": "Although diverse methodologies have been developed to identify enhancers and promoters, most have tacitly assumed that these elements are distinct. However, studies have unexpectedly shown that regulatory elements may have both enhancer and promoter functions. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31605096"}, {"offsetInBeginSection": 537, "offsetInEndSection": 752, "text": "define regulatory elements by accessible DNA and their non-mutually-exclusive abilities to drive transcription initiation (promoter activity) and/or to enhance transcription at other such regions (enhancer activity)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31605096"}, {"offsetInBeginSection": 1047, "offsetInEndSection": 1478, "text": "Some enhancers (mainly bidirectional) can act as weak promoters, producing overlapping spatio-temporal expression. Conversely, bidirectional promoters often act as strong enhancers, while unidirectional promoters generally cannot. The balance between enhancer and promoter activity is generally reflected in the levels and directionality of eRNA transcription and is likely an inherent sequence property of the elements themselves.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29378788"}, {"offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "Intragenic enhancers act as alternative promoters.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22264824"}, {"offsetInBeginSection": 664, "offsetInEndSection": 881, "text": "These data demonstrate functional relatedness between the promoter and enhancers, supporting the hypothesis that enhancers could have evolved from duplicated promoter domains that bind essential transcription factors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8290549"}, {"offsetInBeginSection": 1047, "offsetInEndSection": 1277, "text": "Some enhancers (mainly bidirectional) can act as weak promoters, producing overlapping spatio-temporal expression. Conversely, bidirectional promoters often act as strong enhancers, while unidirectional promoters generally cannot.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29378788"}, {"offsetInBeginSection": 286, "offsetInEndSection": 545, "text": "However, recent studies have revealed broad similarities between enhancers and promoters, blurring the distinction: active enhancers often initiate transcription, and some gene promoters have the potential to enhance transcriptional output of other promoters.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26073855"}]}
+{"question_id": "661d575eeac11fad33000020", "question": "How is pain treated in patients with Ehlers-Danlos Syndrome?", "answer": "Treatment of pain in Ehlers-Danlos Syndrome patients requires a multidisciplinary approach which includes physical therapy, psychotherapy, pharmacotherapy and interventional pain procedures such as trigger point injections, peripheral nerve block, radiofrequency ablation and peripheral nerve stimulation.", "relevant_passage_ids": ["36305215", "36124037", "28186390", "34124258", "30407326"], "type": "summary", "snippets": [{"offsetInBeginSection": 594, "offsetInEndSection": 920, "text": "Since hEDS\u00a0associated chronic pain is multifactorial in origin, treatment requires a multidisciplinary approach which includes physical therapy, psychotherapy, pharmacotherapy\u00a0and interventional pain procedures such as trigger point injections, peripheral nerve block, radiofrequency ablation\u00a0and peripheral nerve stimulation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36305215"}, {"offsetInBeginSection": 1824, "offsetInEndSection": 2146, "text": "EDS is a complex illness with a multitude of symptoms. As in our patients, EDS patients also suffer from panic and anxiety disorders that increase the burden of pain. Apart from optimization of medications, EDS patients are best managed by a multidisciplinary approach that includes pain education and life style changes. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30407326"}, {"offsetInBeginSection": 1011, "offsetInEndSection": 1338, "text": "The clinical results observed in our study seem to confirm the role of a specific neurocognitive rehabilitation program in the chronic pain management in the Ehlers-Danlos syndrome; the rehabilitation treatment should be tailored on patient problems and focused not only in the recovery of movement but also on pain perception.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34124258"}]}
+{"question_id": "65cfa6201930410b1300000e", "question": "Is Patisiran used for Transthyretin Cardiac Amyloidosis?", "answer": "Yes. Patisiran can be used for Transthyretin Cardiac Amyloidosis", "relevant_passage_ids": ["37288260", "36336119", "37599395", "37888916", "33841597", "37456349"], "type": "yesno", "snippets": [{"offsetInBeginSection": 829, "offsetInEndSection": 1134, "text": "The small interfering RNA (siRNA) patisiran and the antisense oligonucleotide (ASO) inotersen have been approved for the treatment of patients with hereditary ATTR polyneuropathy regardless of the presence of cardiac involvement, with patisiran also showing preliminary benefits on the cardiac phenotype. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37288260"}, {"offsetInBeginSection": 555, "offsetInEndSection": 675, "text": "New RNA-interfering drugs (such as patisiran) have been devised and are effective in the treatment of ATTRh amyloidosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36336119"}, {"offsetInBeginSection": 973, "offsetInEndSection": 1048, "text": "Patisiran should be considered in ATTRh cardiomyopathy with polyneuropathy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36336119"}, {"offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Aims: Novel ribonucleic acid interference (RNAi) therapeutics such as patisiran and inotersen have been shown to benefit neurologic disease course and quality of life in patients with hereditary transthyretin amyloidosis (ATTRv). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37599395"}, {"offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Patisiran Treatment in Patients with Transthyretin Cardiac Amyloidosis.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37888916"}, {"offsetInBeginSection": 2030, "offsetInEndSection": 2198, "text": "CONCLUSIONS: In this trial, administration of patisiran over a period of 12 months resulted in preserved functional capacity in patients with ATTR cardiac amyloidosis. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37888916"}, {"offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Patisiran for the Treatment of Transthyretin-mediated Amyloidosis with Cardiomyopathy.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37456349"}, {"offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Patisiran for advanced heart failure with hereditary transthyretin cardiac amyloidosis.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33841597"}, {"offsetInBeginSection": 351, "offsetInEndSection": 541, "text": "Patisiran might be a promising disease-modifying drug for hereditary transthyretin cardiac amyloidosis even in its advanced stage, although further evaluation in a large cohort is warranted.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33841597"}, {"offsetInBeginSection": 0, "offsetInEndSection": 541, "text": "We experienced a 78-year-old woman who was diagnosed with hereditary transthyretin cardiac amyloidosis and administered patisiran for advanced heart failure refractory to tafamidis. The levels of N-terminal pro B-type natriuretic peptide and left ventricular mass index decreased following the six-month patisiran treatment without any complications. Patisiran might be a promising disease-modifying drug for hereditary transthyretin cardiac amyloidosis even in its advanced stage, although further evaluation in a large cohort is warranted.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33841597"}, {"offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "We experienced a 78-year-old woman who was diagnosed with hereditary transthyretin cardiac amyloidosis and administered patisiran for advanced heart failure refractory to tafamidis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33841597"}, {"offsetInBeginSection": 0, "offsetInEndSection": 350, "text": "We experienced a 78-year-old woman who was diagnosed with hereditary transthyretin cardiac amyloidosis and administered patisiran for advanced heart failure refractory to tafamidis. The levels of N-terminal pro B-type natriuretic peptide and left ventricular mass index decreased following the six-month patisiran treatment without any complications.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33841597"}]}
+{"question_id": "65f77a32c4010b4d7800003a", "question": "What are the molecular mechanisms for secondary resistance to Bevacizumab in advanced colorectal cancer patients?", "answer": "Despite promising preclinical results, anti-angiogenic monotherapies led only to mild clinical benefits. The minimal benefits could be secondary to primary or acquired resistance, through the activation of alternative mechanisms that sustain tumor vascularization and growth. Mechanisms of resistance are categorized into VEGF-dependent alterations, non-VEGF pathways and stromal cell interactions. Resistance observed in several tumor types through alternative angiogenic \"escape\" pathways contributes to restoration of tumor growth and may induce progression, enhancement of invasion, and metastasis. Therefore, activation of major compensatory angiogenic pathways, sustaining tumor angiogenesis during VEGF blockade contributing to the recurrence of tumor growth overcome antiangiogenic strategies.", "relevant_passage_ids": ["32175278", "29184575", "30253191", "32087735", "19707427", "37610655", "37663749", "29670046", "37715566", "27527865", "32318348", "24143206", "26857924", "23323147", "27733559", "28736637", "23113577", "34616173", "21240464", "33099574", "37066085", "37744267"], "type": "list", "snippets": [{"offsetInBeginSection": 1022, "offsetInEndSection": 1420, "text": "Despite promising preclinical results, anti-angiogenic monotherapies led only to mild clinical benefits. The minimal benefits could be secondary to primary or acquired resistance, through the activation of alternative mechanisms that sustain tumor vascularization and growth. Mechanisms of resistance are categorized into VEGF-dependent alterations, non-VEGF pathways and stromal cell interactions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32175278"}, {"offsetInBeginSection": 666, "offsetInEndSection": 1072, "text": "The resistance observed in several tumor types through alternative angiogenic \"escape\" pathways contributes to restoration of tumor growth and may induce progression, enhancement of invasion, and metastasis. Therefore, activation of major compensatory angiogenic pathways, sustaining tumor angiogenesis during VEGF blockade contributing to the recurrence of tumor growth overcome antiangiogenic strategies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29184575"}, {"offsetInBeginSection": 297, "offsetInEndSection": 460, "text": "Bevacizumab resistance has been extensively studied at the molecular level, but no drug candidates have been developed for clinical use to overcome this resistance", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37715566"}, {"offsetInBeginSection": 1657, "offsetInEndSection": 2074, "text": "This metabolic mechanism of bevacizumab resistance mediated by the physical tumor microenvironment represents a potential therapeutic target for reversing drug resistance.SIGNIFICANCE: Extracellular matrix stiffening drives bevacizumab resistance by stimulating hepatic stellate cells to provide fuel for mCRC cells in the liver, indicating a potential metabolism-based therapeutic strategy for overcoming resistance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37610655"}, {"offsetInBeginSection": 0, "offsetInEndSection": 411, "text": "Vascular endothelial growth factor (VEGF) has become a major target in cancer treatment as it promotes tumor angiogenesis. Therapy with anti-VEGF antibody bevacizumab reportedly induces high levels of circulating VEGF which may potentially contribute to resistance. Based on animal or computational models, mechanisms of VEGF induction by bevacizumab have been proposed but not verified in the clinical setting.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27527865"}, {"offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Vascular endothelial growth factor (VEGF) has become a major target in cancer treatment as it promotes tumor angiogenesis. Therapy with anti-VEGF antibody bevacizumab reportedly induces high levels of circulating VEGF which may potentially contribute to resistance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27527865"}, {"offsetInBeginSection": 0, "offsetInEndSection": 453, "text": "Bevacizumab is an anti-VEGF monoclonal antibody that plays an important role in the combination treatment of advanced colorectal cancer. However, resistance remains a major hurdle limiting bevacizumab efficacy, highlighting the importance of identifying a mechanism of antiangiogenic therapy resistance. Here, we investigated biophysical properties of the extracellular matrix (ECM) related to metabolic processes and acquired resistance to bevacizumab.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37610655"}, {"offsetInBeginSection": 454, "offsetInEndSection": 846, "text": "Evaluation of paired pre- and posttreatment samples of liver metastases from 20 colorectal cancer patients treated with combination bevacizumab therapy, including 10 responders and 10 nonresponders, indicated that ECM deposition in liver metastases and a highly activated fatty acid oxidation (FAO) pathway were elevated in nonresponders after antiangiogenic therapy compared with responders.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37610655"}, {"offsetInBeginSection": 847, "offsetInEndSection": 1074, "text": "In mouse models of liver metastatic colorectal cancer (mCRC), anti-VEGF increased ECM deposition and FAO in colorectal cancer cells, and treatment with the FAO inhibitor etomoxir enhanced the efficacy of antiangiogenic therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37610655"}, {"offsetInBeginSection": 1511, "offsetInEndSection": 2061, "text": "Together, these results indicate that bevacizumab-induced ECM remodeling triggers lipid metabolic cross-talk between colon cancer cells and HSCs. This metabolic mechanism of bevacizumab resistance mediated by the physical tumor microenvironment represents a potential therapeutic target for reversing drug resistance.SIGNIFICANCE: Extracellular matrix stiffening drives bevacizumab resistance by stimulating hepatic stellate cells to provide fuel for mCRC cells in the liver, indicating a potential metabolism-based therapeutic strategy for overcomin", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37610655"}, {"offsetInBeginSection": 609, "offsetInEndSection": 707, "text": "The mechanism by which colorectal cancer may become resistant to bevacizumab is poorly understood.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19707427"}, {"offsetInBeginSection": 566, "offsetInEndSection": 810, "text": "ithout bevacizumab.RESULTS: In the discovery cohort, VEGF-C was increased prior to progression and at progression (+49% and +95%, respectively, p<0.01), consistent with previously reported elevations in PlGF. Levels of VEGF-D were increased (+2", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24143206"}, {"offsetInBeginSection": 811, "offsetInEndSection": 1101, "text": "%) at progression (p=0.05). In the validation cohort, samples obtained from patients after progression on a regimen with bevacizumab had higher levels of PlGF and VEGF-D (+43% and +6%, p=0.02, p=0.01, respectively) compared to untreated patients, but failed to validate the increase in VEGF", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24143206"}, {"offsetInBeginSection": 1102, "offsetInEndSection": 1287, "text": "C seen in the first cohort. Patients who progressed on chemotherapy with bevacizumab had significantly elevated levels of PlGF (+88%) but not VEGF-C and VEGF-D compared to patients trea", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24143206"}, {"offsetInBeginSection": 1391, "offsetInEndSection": 1686, "text": "ith a half-life of 6 weeks.CONCLUSIONS: Increases in PlGF and VEGF-D were observed after progression on chemotherapy with bevacizumab. These changes appear to be reversible after discontinuing therapy. These ligands are associated with resistance to bevacizumab-containing chemotherapy in mCRC, ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24143206"}, {"offsetInBeginSection": 973, "offsetInEndSection": 1304, "text": "receptor and the vascular endothelial growth factor have provided proof of principle that disruption of signal cascades in patients with colorectal cancer has therapeutic potential. This experience has also taught us that resistance to such rationally developed targeted therapeutic strategies is common. In this article, we review", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23323147"}, {"offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "Bevacizumab is an anti-VEGF monoclonal antibody that plays an important role in the combination treatment of advanced colorectal cancer. However, resistance remains a major hurdle limiting bevacizumab efficacy, highlighting the importance of identifying a mechanism of antiangiogenic therapy resistance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37610655"}, {"offsetInBeginSection": 673, "offsetInEndSection": 966, "text": "Although many types of VEGF pathway inhibitors can improve survival in most cancer patients, some patients have little or no beneficial effect from them. The primary or acquired resistance towards many oncological drugs, including anti-VEGF inhibitors, is a common problem in cancer treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29670046"}, {"offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "BACKGROUND: Bevacizumab, a monoclonal antibody against soluble VEGFA, is an approved and commonly administered anti-angiogenic drug in patients with metastasized colorectal cancer (mCRC). The survival benefit of anti-VEGF therapy in mCRC patients is limited to a few months, and acquired resistance mechanisms are larg", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32087735"}, {"offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "The survival benefit of anti-vascular endothelial growth factor (VEGF) therapy in metastatic colorectal cancer (mCRC) patients is limited to a few months because of acquired resistance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27733559"}, {"offsetInBeginSection": 62, "offsetInEndSection": 210, "text": "The majority of patients receiving targeted therapy or chemotherapy develop drug resistance, while its molecular mechanism remains to be elucidated.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32318348"}, {"offsetInBeginSection": 690, "offsetInEndSection": 897, "text": "Translational research for biomarker discovery and validation and further study into mechanisms of resistance are essential for future development and sustained benefit with this class of therapeutic agents.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23113577"}, {"offsetInBeginSection": 318, "offsetInEndSection": 577, "text": "The aim of the present work was to determine whether the expression of 26 miRNAs could be associated with the effectiveness of bevacizumab plus chemotherapy, with progression-free survival (PFS), and with overall survival (OS) in metastatic colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34616173"}, {"offsetInBeginSection": 900, "offsetInEndSection": 1170, "text": "We propose that down-regulation of ARHGAP6 and MMP15 transcripts indicates that tumors are sensitive to bevacizumab whereas inhibition of PKC\u03b4- or S6K-dependent signaling and up-regulation of TNFRS4 or MMP13 and MMP14 mark a developing resistance to bevacizumab therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21240464"}, {"offsetInBeginSection": 109, "offsetInEndSection": 325, "text": "advanced colorectal cancer. However, resistance remains a major hurdle limiting bevacizumab efficacy, highlighting the importance of identifying a mechanism of antiangiogenic therapy resistance. Here, we investigated", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37610655"}, {"offsetInBeginSection": 0, "offsetInEndSection": 413, "text": "Bevacizumab is the standard treatment for colorectal cancer (CRC) in the advanced stage. However, poor diagnosis identified due to the bevacizumab resistance in many CRC patients. Previous studies have found that CRC stem cells (CCSCs) and interleukin 22 (IL-22) are involved in the resistance of bevacizumab, however, the mechanism of remains unclear. In this study, we established the bevacizumab drug-resistant", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37663749"}, {"offsetInBeginSection": 54, "offsetInEndSection": 594, "text": "demonstrated to be dependent upon the PDGF-BB/PDGFR-\u03b2/Src/STAT3/VEGFA pathway in colorectal cancer (CRC). However, the ability of ETV5 to affect the efficacy of anti-angiogenic therapy in CRC requires further investigation. Gene set enrichment analysis (GSEA) and a series of experiments were performed to identify the critical candidate gene involved in Bevacizumab resistance. Furthermore, the ability of treatment targeting the candidate gene to enhance Bevacizumab sensitivity in vitro and in vivo was investigated. Our results revealed", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33099574"}, {"offsetInBeginSection": 49, "offsetInEndSection": 222, "text": "the effect of treatment with Bevacizumab on the gene expression profile of colorectal adenocarcinoma cells. The transcriptomic profile of Bevacizumab-adapted HCT-116 (Bev/A)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37066085"}, {"offsetInBeginSection": 150, "offsetInEndSection": 1202, "text": "the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways have led the way in colon cancer. Monoclonal antibodies (mAbs) such as bevacizumab, ramucirumab, cetuximab, and panitumumab, have improved progression free survival and overall survival (OS) for colorectal cancers and were quickly adopted. Human epidermal growth factor receptor 2 (HER2) has demonstrated significant benefit for gastroesophageal cancers and in the setting of HER2 amplification, trastuzumab in combination with chemotherapy has become the standard of care. However, responses have not been as durable nor as robust as once hoped. Mechanisms of resistance for each of these biologic compounds have been hypothesized and are in the process of being better elucidated. This review will approach the innate and acquired mechanisms of resistance of the above compounds. Additionally, we will explore some ongoing clinical trials to capitalize on the mechanisms of resistance in the hopes of retaining the promise of targeting these pathways.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28736637"}, {"offsetInBeginSection": 522, "offsetInEndSection": 918, "text": "In this study, 43 CRC tissues collected from patients who underwent treatment with first-line standard chemotherapeutic regimens in combination with bevacizumab were used to explore the correlation between FOXF1 expression and resistance to bevacizumab. In addition, FOXF1 regulated angiogenesis by inducing the transcription of vascular endothelial growth factor A1 (VEGFA) in vitro and in vivo.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30253191"}, {"offsetInBeginSection": 0, "offsetInEndSection": 397, "text": "Background: Although bevacizumab is an important treatment for metastatic colorectal cancer (CRC), not all patients with CRC benefit from it; in unselected patient populations, only modest survival benefits have been reported.Methods: We evaluated clinical outcomes in 110 patients using comprehensive molecular characterization to identify biomarkers for a response to bevacizumab-containing trea", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37744267"}, {"offsetInBeginSection": 967, "offsetInEndSection": 1176, "text": "This review summarizes the proposed alternative mechanisms of angiogenesis other than the VEGF pathway. These mechanisms are involved in the development of resistance to anti-VEGF therapies in cancer patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29670046"}, {"offsetInBeginSection": 1511, "offsetInEndSection": 1828, "text": "Together, these results indicate that bevacizumab-induced ECM remodeling triggers lipid metabolic cross-talk between colon cancer cells and HSCs. This metabolic mechanism of bevacizumab resistance mediated by the physical tumor microenvironment represents a potential therapeutic target for reversing drug resistance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37610655"}]}
+{"question_id": "661a6a67fdcbea915f00005d", "question": "Does early stage oral squamous cell carcinoma have  good survival rates?", "answer": "Oral squamous cell carcinoma (OSCC) is amongst the most common cancers, with more than 377,000 new cases worldwide each year. OSCC prognosis remains poor, related to cancer presentation at a late stage", "relevant_passage_ids": ["36688107", "37294162", "36891418", "37356209", "37779502", "38073011", "26306491", "26015702"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 350, "text": "Oral cavity squamous cell carcinoma (OCSCC) is a well-recognized malignancy of the head and neck. Studies on patients with early-stage oral cancer have shown that they develop locally recurring and/or regional lymph node metastasis, which results in disease-associated mortality. Thus, early-stage oral cancer does not always present good prognoses. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36688107"}, {"offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Oral squamous cell carcinoma (OSCC) is amongst the most common cancers, with more than 377,000 new cases worldwide each year. OSCC prognosis remains poor, related to cancer presentation at a late stage,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37294162"}, {"offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "The cumulative survival for all stages in oral squamous cell cancers (OSCC) in the world remains poor despite the advances in management", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36891418"}, {"offsetInBeginSection": 12, "offsetInEndSection": 250, "text": "Oral squamous cell carcinoma (OSCC) is frequently diagnosed at an advanced stage, with the five-year survival rate varying around 50%, however, ifs the sooner OSCC in early-stage is treated, the lower the chances of recurrence and death. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37356209"}, {"offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Oral squamous cell carcinoma (OSCC) is treated based on the TNM staging. However, early T-stage OSCC still exhibits substantial nodal metastasis and death rates", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37779502"}, {"offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "The oral squamous cell carcinoma (OSCC) 5\u2009year survival rate of 41% has marginally improved in the last few years, with less than a 1% improvement per year from 2005 to 2017, with higher survival rates when detected at early stages", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38073011"}, {"offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "BACKGROUND: Oral squamous cell carcinoma (OSCC) is frequently diagnosed at an advanced stage, with the five-year survival rate varying around 50%, however, ifs the sooner OSCC in early-stage is treated, the lower the chances of recurrence and death.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37356209"}, {"offsetInBeginSection": 280, "offsetInEndSection": 349, "text": "Thus, early-stage oral cancer does not always present good prognoses.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36688107"}, {"offsetInBeginSection": 98, "offsetInEndSection": 279, "text": "Studies on patients with early-stage oral cancer have shown that they develop locally recurring and/or regional lymph node metastasis, which results in disease-associated mortality.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36688107"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "BACKGROUND: Oral squamous cell carcinoma (OSCC) is associated with a poor 5-year survival rate.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26306491"}, {"offsetInBeginSection": 269, "offsetInEndSection": 386, "text": "mortality. Thus, early-stage oral cancer does not always present good prognoses. The present study aimed to determine", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36688107"}, {"offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "BACKGROUND: Oral squamous cell carcinoma (OSCC) is associated with a poor 5-year survival rate. In general, patients diagnosed with small tumors have a fairly good prognosis, but some small tumors have an aggressive behavior leading to ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26306491"}, {"offsetInBeginSection": 256, "offsetInEndSection": 406, "text": "e-associated mortality. Thus, early-stage oral cancer does not always present good prognoses. The present study aimed to determine the efficacy of usi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36688107"}, {"offsetInBeginSection": 0, "offsetInEndSection": 309, "text": "BACKGROUND: Oral squamous cell carcinoma (OSCC) is associated with a poor 5-year survival rate. In general, patients diagnosed with small tumors have a fairly good prognosis, but some small tumors have an aggressive behavior leading to early death. There are at present no reliable prognostic biomarkers for o", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26306491"}, {"offsetInBeginSection": 99, "offsetInEndSection": 197, "text": "In spite of major advances in diagnosis and treatment of OSCC, survival rates, have remained poor.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26015702"}, {"offsetInBeginSection": 32, "offsetInEndSection": 1470, "text": "stages in oral squamous cell cancers (OSCC) in the world remains poor despite the advances in management; hence, we conducted this study to evaluate the survival outcomes. This is a retrospective review and analysis of treatment, follow-up and survival records of 249 OSCC patients treated in our department from April 2010 to April 2014. Telephonic interviews were conducted for survival details for some patients who had not reported. Survival analysis was done using the Kaplan-Meier analysis, comparisons were done using log-rank test and multivariate analysis was conducted using the Cox proportional hazard model to find different variables (site, age, sex, stage and treatment) affecting overall survival (OS)/disease-free survival (DFS). Two-year and 5-year DFS for OSCC were observed to be 72.3% and 58.3% with mean survival of 63.17\u00a0months (95% CI: 58.342-68.002). Similarly, OS at 2\u00a0years and 5\u00a0years were 84.3% and 55.9% with mean survival of 65.143\u00a0months (95% CI: 60.143-69.601). Tumour site, patient age, stage of disease and treatment modality had a statistically significant hazardous effect on the overall and disease-free survival rates. The significant influence of age, site of tumour, stage of disease and modality of treatment required based on the clinic-pathologic risk factors on prognosis emphasizes the importance of early diagnosis through regular screening and early treatment which can be ensured with early", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36891418"}]}
+{"question_id": "65f85fdbc4010b4d78000054", "question": "What is the technique of choice to perform a caesarean section?", "answer": "Low transverse incision", "relevant_passage_ids": ["32760792", "3497629"], "type": "factoid", "snippets": [{"offsetInBeginSection": 146, "offsetInEndSection": 233, "text": "Usually laparotomy followed by hysterotomy with a low transverse incision is preferable", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32760792"}, {"offsetInBeginSection": 293, "offsetInEndSection": 660, "text": "There are indications when the preferred lower segment Caesarean section with a transverse incision should be avoided in the interest of the mother and baby. A low vertical incision has more advantages and less dangers than a classical fundal incision. It is prudent to defer the decision regarding the type of incision until the uterus is inspected intraoperatively.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3497629"}, {"offsetInBeginSection": 293, "offsetInEndSection": 545, "text": "There are indications when the preferred lower segment Caesarean section with a transverse incision should be avoided in the interest of the mother and baby. A low vertical incision has more advantages and less dangers than a classical fundal incision.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3497629"}, {"offsetInBeginSection": 293, "offsetInEndSection": 450, "text": "There are indications when the preferred lower segment Caesarean section with a transverse incision should be avoided in the interest of the mother and baby.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3497629"}, {"offsetInBeginSection": 160, "offsetInEndSection": 545, "text": "All the others were the standard transverse lower segment operation except for 1 which was a postmortem classical Caesarean section. There are indications when the preferred lower segment Caesarean section with a transverse incision should be avoided in the interest of the mother and baby. A low vertical incision has more advantages and less dangers than a classical fundal incision.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3497629"}, {"offsetInBeginSection": 0, "offsetInEndSection": 450, "text": "Eleven of the 3,420 Caesarean sections performed in Westmead Hospital, Sydney during a 6-year period from 1979 to 1985 were by a low vertical uterine incision. All the others were the standard transverse lower segment operation except for 1 which was a postmortem classical Caesarean section. There are indications when the preferred lower segment Caesarean section with a transverse incision should be avoided in the interest of the mother and baby.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3497629"}, {"offsetInBeginSection": 0, "offsetInEndSection": 292, "text": "Eleven of the 3,420 Caesarean sections performed in Westmead Hospital, Sydney during a 6-year period from 1979 to 1985 were by a low vertical uterine incision. All the others were the standard transverse lower segment operation except for 1 which was a postmortem classical Caesarean section.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3497629"}]}
+{"question_id": "661d9e79fe9d0b3967000001", "question": "Which cell states can exist in melanomas?", "answer": "In melanoma, cells can switch between a melanocytic (MEL) and a mesenchymal-like (MES) state and present themselves with different responses to therapy. Scattered evidence has also indicated the existence of additional intermediate state(s).", "relevant_passage_ids": ["34874265", "32753671", "32732264", "34529939", "35810190", "37268606", "37788736"], "type": "list", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Melanoma cells can switch between a melanocytic and a mesenchymal-like state. Scattered evidence indicates that additional intermediate state(s) may exist.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32753671"}, {"offsetInBeginSection": 0, "offsetInEndSection": 354, "text": "Understanding how enhancers drive cell-type specificity and efficiently identifying them is essential for the development of innovative therapeutic strategies. In melanoma, the melanocytic (MEL) and the mesenchymal-like (MES) states present themselves with different responses to therapy, making the identification of specific enhancers highly relevant. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34874265"}, {"offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Melanoma cells can switch between a melanocytic and a mesenchymal-like state.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32753671"}, {"offsetInBeginSection": 954, "offsetInEndSection": 1136, "text": "Taken together, these analyses indicate that an intermediate state exists and is driven by a distinct and stable 'mixed' GRN rather than being a symbiotic heterogeneous mix of cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32753671"}, {"offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Melanoma exhibits numerous transcriptional cell states including neural crest-like cells as well as pigmented melanocytic cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37268606"}, {"offsetInBeginSection": 378, "offsetInEndSection": 548, "text": "Although each culture exhibited a unique transcriptome, we identified shared GRNs that underlie the extreme melanocytic and mesenchymal states and the intermediate state.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32753671"}, {"offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Robust gene expression programs underlie recurrent cell states and phenotype switching in melanoma.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32753671"}, {"offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Melanoma cells display distinct intrinsic phenotypic states.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35810190"}, {"offsetInBeginSection": 160, "offsetInEndSection": 353, "text": "In melanoma, the melanocytic (MEL) and the mesenchymal-like (MES) states present themselves with different responses to therapy, making the identification of specific enhancers highly relevant.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34874265"}, {"offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Melanomas can have multiple coexisting cell states, including proliferative (PRO) versus invasive (INV) subpopulations that represent a \"go or grow\" trade-off; however, how these populations interact is poorly understood.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34529939"}]}
+{"question_id": "661d1c3ceac11fad33000012", "question": "Are there any molecular signatures identified for the differentiation between bacterial and viral infections?", "answer": "Yes, there have been identified molecular signatures that can differentiate between bacterial and viral infections.", "relevant_passage_ids": ["34166284", "27552617", "31631046", "28588308", "23858444", "33808774", "25785720", "34828783", "33008730", "36543100", "36543117", "34912024", "29700762", "34768022", "37890901", "33938716", "35184750", "29795312", "30619110", "37597512"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "A Novel 29-Messenger RNA Host-Response Assay From Whole Blood Accurately Identifies Bacterial and Viral Infections in Patients Presenting to the Emergency Department With Suspected Infections", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34166284"}, {"offsetInBeginSection": 1666, "offsetInEndSection": 1760, "text": "IMX-BVN-2 demonstrated accuracy for detecting both viral infections and bacterial infections. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34166284"}, {"offsetInBeginSection": 1230, "offsetInEndSection": 1652, "text": "The IMX-BVN-2 bacterial score showed an area under the receiver operating curve for adjudicated bacterial versus ruled out bacterial infection of 0.90 (95% CI, 0.85-0.95) compared with 0.89 (95% CI, 0.84-0.94) for procalcitonin with procalcitonin being used in the adjudication. The IMX-BVN-2 viral score area under the receiver operating curve for adjudicated versus ruled out viral infection was 0.83 (95% CI, 0.77-0.89)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34166284"}, {"offsetInBeginSection": 275, "offsetInEndSection": 507, "text": "We aimed to develop and prospectively validate a new, 29-messenger RNA blood-based host-response classifier Inflammatix Bacterial Viral Non-Infected version 2 (IMX-BVN-2) to determine the likelihood of bacterial and viral infections", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34166284"}, {"offsetInBeginSection": 1615, "offsetInEndSection": 1747, "text": "This is the first review on the use of transcript RNA signatures in febrile children to distinguish viral from bacterial infections.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34912024"}, {"offsetInBeginSection": 793, "offsetInEndSection": 1355, "text": "Transcript host-RNA signatures are a new tool used to differentiate viral from bacterial infections by analyzing the transcriptional biosignatures of RNA in host leukocytes. In this systematic review, we evaluate the efficacy and the possible application of this new diagnostic method in febrile children, along with challenges in its implementation. Our review support the growing evidence that the application of these new tools can improve the characterization of the spectrum of bacterial and viral infections and optimize the use of antibiotics in children.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34912024"}, {"offsetInBeginSection": 825, "offsetInEndSection": 1207, "text": "LTS: Signature performance varied widely, with median AUCs ranging from 0.55 to 0.96 for bacterial classification and 0.69-0.97 for viral classification. Signature size varied (1-398 genes), with smaller signatures generally performing more poorly (P < 0.04). Viral infection was easier to diagnose than bacterial infection (84% vs. 79% overall accuracy, respectively; P < .001). Ho", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35184750"}, {"offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Systematic comparison of published host gene expression signatures for bacterial/viral discrimination.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35184750"}, {"offsetInBeginSection": 1499, "offsetInEndSection": 1861, "text": "The signature performed consistently across different patient subgroups and detected bacterial immune responses in viral PCR-positive patients.CONCLUSIONS: The findings validate the high diagnostic performance of the TRAIL/IP-10/CRP signature in a broad paediatric cohort, and support its potential to reduce antibiotic overuse in children with viral infections.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34768022"}, {"offsetInBeginSection": 1687, "offsetInEndSection": 1847, "text": "The host-protein signature demonstrated superior diagnostic performance in differentiating viral from bacterial respiratory infections and fever without source.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29700762"}, {"offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "A host-protein signature is superior to other biomarkers for differentiating between bacterial and viral disease in patients with respiratory infection and fever without source: a prospective observational study.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29700762"}, {"offsetInBeginSection": 62, "offsetInEndSection": 280, "text": "A new 8-gene blood RNA signature to discriminate bacterial and viral infections extends our focus hitherto on the case mix from the US and Europe to include that of low- and middle-income countries.1 Challenges remain.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36543100"}, {"offsetInBeginSection": 1031, "offsetInEndSection": 1188, "text": "The 8-gene signature meets the target product profile proposed by the World Health Organization and others for distinguishing bacterial and viral infections.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36543117"}, {"offsetInBeginSection": 578, "offsetInEndSection": 844, "text": "Using these 69 datasets, we identify an 8-gene signature to distinguish intracellular or extracellular bacterial infections from viral infections with an area under the receiver operating characteristic curve (AUROC)\u00a0>\u00a00.91 (85.9% specificity and 90.2% sensitivity).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36543117"}, {"offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "A novel host-proteome signature for distinguishing between acute bacterial and viral infections.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25785720"}, {"offsetInBeginSection": 2883, "offsetInEndSection": 3236, "text": "Of the children in the indeterminate groups, 46.3% (63/136) were classified as having bacterial infection, although 94.9% (129/136) received antibiotic treatment.CONCLUSIONS AND RELEVANCE: This study provides preliminary data regarding test accuracy of a 2-transcript host RNA signature discriminating bacterial from viral infection in febrile children.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27552617"}, {"offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Recently, a biomarker signature consisting of 2-transcript host RNAs was proposed for discriminating bacterial from viral infections in febrile children.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29795312"}, {"offsetInBeginSection": 1048, "offsetInEndSection": 1320, "text": "tory diseases (n\u2009=\u200948) and on published gene expression datasets.EXPOSURES: A 2-transcript RNA expression signature distinguishing bacterial infection from viral infection was evaluated against clinical and microbiological diagnosis.MAIN OUTCOMES AND MEASURES: Definite ba", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27552617"}, {"offsetInBeginSection": 342, "offsetInEndSection": 1798, "text": "validated recently for differentiating bacterial from viral disease. However, a focused head-to-head comparison of its diagnostic performance against other biomarker candidates for this indication was lacking in patients with respiratory infection and fever without source. We compared the signature to other biomarkers and prediction rules using specimens collected prospectively at two secondary medical centers from children and adults. Inclusion criteria included fever >\u200937.5\u00a0\u00b0C, symptom duration \u2264\u200912\u00a0days, and presentation with respiratory infection or fever without source. Comparator method was based on expert panel adjudication. Signature and biomarker cutoffs and prediction rules were predefined. Of 493 potentially eligible patients, 314 were assigned unanimous expert panel diagnosis and also had sufficient specimen volume. The resulting cohort comprised 175 (56%) viral and 139 (44%) bacterial infections. Signature sensitivity 93.5% (95% CI 89.1-97.9%), specificity 94.3% (95% CI 90.7-98.0%), or both were significantly higher (all p values <\u20090.01) than for CRP, procalcitonin, interleukin-6, human neutrophil lipocalin, white blood cell count, absolute neutrophil count, and prediction rules. Signature identified as viral 50/57 viral patients prescribed antibiotics, suggesting potential to reduce antibiotic overuse by 88%. The host-protein signature demonstrated superior diagnostic performance in differentiating viral from bacterial", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29700762"}, {"offsetInBeginSection": 30, "offsetInEndSection": 1879, "text": "infections (ARIs) are the leading indication for antibacterial prescriptions despite a viral etiology in the majority of cases. The lack of available diagnostics to discriminate viral and bacterial etiologies contributes to this discordance. Recent efforts have focused on the host response as a source for novel diagnostic targets although none have explored the ability of host-derived microRNAs (miRNA) to discriminate between these etiologies. Methods: In this study, we compared host-derived miRNAs and mRNAs from human H3N2 influenza challenge subjects to those from patients with Streptococcus pneumoniae pneumonia. Sparse logistic regression models were used to generate miRNA signatures diagnostic of ARI etiologies. Generalized linear modeling of mRNAs to identify differentially expressed (DE) genes allowed analysis of potential miRNA:mRNA relationships. High likelihood miRNA:mRNA interactions were examined using binding target prediction and negative correlation to further explore potential changes in pathway regulation in response to infection. Results: The resultant miRNA signatures were highly accurate in discriminating ARI etiologies. Mean accuracy was 100% [88.8-100; 95% Confidence Interval (CI)] in discriminating the healthy state from S. pneumoniae pneumonia and 91.3% (72.0-98.9; 95% CI) in discriminating S. pneumoniae pneumonia from influenza infection. Subsequent differential mRNA gene expression analysis revealed alterations in regulatory networks consistent with known biology including immune cell activation and host response to viral infection. Negative correlation network analysis of miRNA:mRNA interactions revealed connections to pathways with known immunobiology such as interferon regulation and MAP kinase signaling. Conclusion: We have developed novel human host-response miRNA signatures for bacterial", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30619110"}, {"offsetInBeginSection": 181, "offsetInEndSection": 701, "text": "bacteria and viruses. We hypothesized that a blood-based transcriptional signature could be discovered indicating a host systemic response to viral infection. Previous work identified host transcriptional signatures to individual viruses including influenza, respiratory syncytial virus and dengue, but the generality of these signatures across all viral infection types has not been established. Based on 44 publicly available datasets and two clinical studies of our own design, we discovered and validated a four-gene", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28588308"}, {"offsetInBeginSection": 1422, "offsetInEndSection": 2122, "text": "in viral infected patients. We further developed a multi-protein signature using logistic-regression on half of the patients and validated it on the remaining half. The signature with the highest precision included both viral- and bacterial-induced proteins: TRAIL, Interferon gamma-induced protein-10, and CRP (AUC of 0.94; 95% CI, 0.92 to 0.96). The signature was superior to any of the individual proteins (P<0.001), as well as routinely used clinical parameters and their combinations (P<0.001). It remained robust across different physiological systems, times from symptom onset, and pathogens (AUCs 0.87-1.0). The accurate differential diagnosis provided by this novel combination of viral- and", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25785720"}, {"offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Identification of a Minimal 3-Transcript Signature to Differentiate Viral from Bacterial Infection from Best Genome-Wide Host RNA Biomarkers: A Multi-Cohort Analysis.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33808774"}, {"offsetInBeginSection": 690, "offsetInEndSection": 840, "text": "tion, definite viral infection, or indeterminate infection. RNA expression signatures distinguishing definite bacterial from viral infection were iden", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27552617"}, {"offsetInBeginSection": 733, "offsetInEndSection": 883, "text": " on costs, antibiotic resistance, and pediatric microbiota. Transcript host-RNA signatures are a new tool used to differentiate viral from bacterial i", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34912024"}, {"offsetInBeginSection": 274, "offsetInEndSection": 972, "text": "with bacterial or viral infections representing a broad spectrum of biological, clinical, and technical heterogeneity, we show current host-response-based gene signatures have lower accuracy to distinguish intracellular bacterial infections from viral infections than extracellular bacterial infections. Using these 69 datasets, we identify an 8-gene signature to distinguish intracellular or extracellular bacterial infections from viral infections with an area under the receiver operating characteristic curve (AUROC)\u00a0>\u00a00.91 (85.9% specificity and 90.2% sensitivity). In prospective cohorts from Nepal and Laos, the 8-gene classifier distinguished bacterial infections from viral infections with", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36543117"}, {"offsetInBeginSection": 1615, "offsetInEndSection": 1906, "text": "This is the first review on the use of transcript RNA signatures in febrile children to distinguish viral from bacterial infections. Our review identified a wide variability of target populations and gold standards used to define sepsis and SBIs, limiting the generalization of our findings.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34912024"}, {"offsetInBeginSection": 698, "offsetInEndSection": 966, "text": "This approach has an adverse effect on costs, antibiotic resistance, and pediatric microbiota. Transcript host-RNA signatures are a new tool used to differentiate viral from bacterial infections by analyzing the transcriptional biosignatures of RNA in host leukocytes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34912024"}, {"offsetInBeginSection": 698, "offsetInEndSection": 1143, "text": "This approach has an adverse effect on costs, antibiotic resistance, and pediatric microbiota. Transcript host-RNA signatures are a new tool used to differentiate viral from bacterial infections by analyzing the transcriptional biosignatures of RNA in host leukocytes. In this systematic review, we evaluate the efficacy and the possible application of this new diagnostic method in febrile children, along with challenges in its implementation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34912024"}, {"offsetInBeginSection": 502, "offsetInEndSection": 966, "text": "On the other hand, this may lead to overuse of empiric antibiotic therapies, particularly for specific subgroups of patients, such as infants younger than 90 days of life or neutropenic patients. This approach has an adverse effect on costs, antibiotic resistance, and pediatric microbiota. Transcript host-RNA signatures are a new tool used to differentiate viral from bacterial infections by analyzing the transcriptional biosignatures of RNA in host leukocytes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34912024"}, {"offsetInBeginSection": 1356, "offsetInEndSection": 1747, "text": "IMPACT: Transcript host RNA signatures may allow to better characterize the spectrum of viral, bacterial, and inflammatory illnesses in febrile children and can be used with traditional diagnostic methods to determine if and when to start antibiotic therapy. This is the first review on the use of transcript RNA signatures in febrile children to distinguish viral from bacterial infections.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34912024"}, {"offsetInBeginSection": 231, "offsetInEndSection": 419, "text": " treatment. As an alternative to pathogen detection, host gene expression signatures in blood have shown promise in discriminating several infectious and inflammatory diseases in a dichoto", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37597512"}]}
+{"question_id": "65d1369c1930410b1300003b", "question": "What are active ingredients of Xacduro?", "answer": "Sulbactam and durlobactam are active ingredients of XACDURO. It is a co-packaged antibacterial product that has been developed by Entasis Therapeutics Inc. for the treatment of infections caused by Acinetobacter baumannii-calcoaceticus complex.", "relevant_passage_ids": ["37523122"], "type": "list", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Sulbactam/durlobactam (XACDURO\u00ae), is a co-packaged antibacterial product that has been developed by Entasis Therapeutics Inc. for the treatment of infections caused by Acinetobacter baumannii-calcoaceticus complex (ABC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37523122"}]}
+{"question_id": "66099967fdcbea915f000018", "question": "What is the faster length time for oxaliplatin infusion?", "answer": "Infusing oxaliplatin at a rate of 1 mg/m(2)/min does not increase the rate of hypersentitivity reactions and does not compromise patient safety. This infusion rate is safe for use in routine practice.", "relevant_passage_ids": ["27072569", "32451327", "37525581", "19622596", "19238627", "16088232", "10668856", "17450468", "14755010"], "type": "factoid", "snippets": [{"offsetInBeginSection": 1411, "offsetInEndSection": 1590, "text": " Infusing oxaliplatin at a rate of 1 mg/m(2)/min does not increase the rate of HSRs and does not compromise patient safety. This infusion rate is safe for use in routine practice.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27072569"}, {"offsetInBeginSection": 694, "offsetInEndSection": 864, "text": "e then instituted a new policy to infuse all nonresearch doses of oxaliplatin at a set rate of 1 mg/m(2)/min (85 mg/m(2) given over 85 min; 68 mg/m(2) over 68 min, etc). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27072569"}, {"offsetInBeginSection": 694, "offsetInEndSection": 937, "text": "e then instituted a new policy to infuse all nonresearch doses of oxaliplatin at a set rate of 1 mg/m(2)/min (85 mg/m(2) given over 85 min; 68 mg/m(2) over 68 min, etc). The incidence of HSRs with the new infusion rate was actively monitored.R", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27072569"}, {"offsetInBeginSection": 0, "offsetInEndSection": 460, "text": "PURPOSE: Oxaliplatin at a dose of 85 mg/m(2) traditionally has been administered over 120 min in the standard FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin) regimen. CapeOx (capecitabine plus oxaliplatin), in which the dose of oxaliplatin is 130 mg/m(2), has also been infused over 120 min. Maintenance of a prolonged infusion time has been largely based on the concern for a potential hypersensitivity reaction (HSR) if administered too quickly", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27072569"}, {"offsetInBeginSection": 694, "offsetInEndSection": 1098, "text": "e then instituted a new policy to infuse all nonresearch doses of oxaliplatin at a set rate of 1 mg/m(2)/min (85 mg/m(2) given over 85 min; 68 mg/m(2) over 68 min, etc). The incidence of HSRs with the new infusion rate was actively monitored.RESULTS: Of 2,097 patients who previously received oxaliplatin over 120 min, 1,936 received a dose of 85 mg/m(2) (\u00b1 10%), and 161 received a dose of 130 mg/m(2). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27072569"}, {"offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "PURPOSE: Oxaliplatin at a dose of 85 mg/m(2) traditionally has been administered over 120 min in the standard FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin) regimen", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27072569"}, {"offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "PURPOSE: Oxaliplatin at a dose of 85 mg/m(2) traditionally has been administered over 120 min in the standard FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin) regimen.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27072569"}, {"offsetInBeginSection": 1323, "offsetInEndSection": 1534, "text": "The incidence of HSRs in patients treated at this fixed infusion rate was 8%.CONCLUSION: Infusing oxaliplatin at a rate of 1 mg/m(2)/min does not increase the rate of HSRs and does not compromise patient safety.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27072569"}, {"offsetInBeginSection": 0, "offsetInEndSection": 648, "text": "OBJECTIVES: The aim of the study was to define the feasibility and efficacy of Xelox (capecitabine and oxaliplatin) administered through a new and original schedule in advanced pretreated colorectal cancer (CRC) patients.METHODS: 36 metastatic CRC patients resistant at least to a previous 5-fluorouracil- and irinotecan-based chemotherapy line were included in the study.TREATMENT: Oxaliplatin 70 mg/m2 as continuous infusion for 12 h (8.00 a.m. to 8.00 p.m.) on days 1, 8 plus chronomodulated capecitabine 1,750 mg/m2/day per os (8.00 a.m. 25% of total dose; 6.00 p.m. 25% of total dose; 11.00 p.m. 50% of total dose), on days 1-14 every 21 days.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16088232"}, {"offsetInBeginSection": 990, "offsetInEndSection": 1315, "text": "Rapid-rate oxaliplatin was not associated with increased HSR or difference in toxicity requiring dose reduction, delayed dose, or slowed infusion rate, but was associated with increased rate of permanent discontinuation of oxaliplatin, 7.8% and 1.1% in the rapid-rate group and standard-rate groups, respectively (p\u2009=\u20090.032).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37525581"}, {"offsetInBeginSection": 239, "offsetInEndSection": 409, "text": "We evaluated the safety outcomes of rapid administration of oxaliplatin compared to standard infusion.METHODS: We performed a retrospective, cohort study by chart review.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37525581"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1553, "text": "PURPOSE: Oxaliplatin at a dose of 85 mg/m(2) traditionally has been administered over 120 min in the standard FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin) regimen. CapeOx (capecitabine plus oxaliplatin), in which the dose of oxaliplatin is 130 mg/m(2), has also been infused over 120 min. Maintenance of a prolonged infusion time has been largely based on the concern for a potential hypersensitivity reaction (HSR) if administered too quickly.METHODS: We first performed a retrospective review of our institutional experience to assess whether HSR rates were similar in FOLFOX and CapeOx by using computerized pharmacy records between January 1, 2011, and December 31, 2013. We then instituted a new policy to infuse all nonresearch doses of oxaliplatin at a set rate of 1 mg/m(2)/min (85 mg/m(2) given over 85 min; 68 mg/m(2) over 68 min, etc). The incidence of HSRs with the new infusion rate was actively monitored.RESULTS: Of 2,097 patients who previously received oxaliplatin over 120 min, 1,936 received a dose of 85 mg/m(2) (\u00b1 10%), and 161 received a dose of 130 mg/m(2). The incidence of HSRs in the 85 mg/m(2) group was 11% versus 7% in the 130 mg/m(2) group (P = .13). Then between December 1, 2014, and June 4, 2015, 667 patients received oxaliplatin at a rate of 1 mg/m(2)/min for all doses. The incidence of HSRs in patients treated at this fixed infusion rate was 8%.CONCLUSION: Infusing oxaliplatin at a rate of 1 mg/m(2)/min does not increase the rate of HSRs and does not compromise patient safety. This infusion rate", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27072569"}, {"offsetInBeginSection": 150, "offsetInEndSection": 392, "text": "mens may be infused over a rapid rate of 85\u2005min instead of the standard time of 120\u2005min. We evaluated the safety outcomes of rapid administration of oxaliplatin compared to standard infusion.METHODS: We performed a retrospective, cohort study", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37525581"}, {"offsetInBeginSection": 113, "offsetInEndSection": 414, "text": " A known side effect of oxaliplatin administration via a peripheral vein is infusion-related pain. In this retrospective cohort study we compared the incidence of infusion-related pain in patients treated with oxaliplatin with or without simultaneous fluid infusion (FI) (800\u2009mL glucose 5% in 2\u2009hours)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32451327"}]}
+{"question_id": "661be55f48a2c27714000003", "question": "What disease is treated by Callosotomy", "answer": "Corpus callosotomy (CC) is a surgical palliative procedure done for a selected group of patients with drug-resistant epilepsy (DRE) to stop drop attacks.", "relevant_passage_ids": ["36435385", "36637309", "37303192", "31140570", "18759631", "20384766", "10449075", "17521926", "22681320", "25692412", "18539083", "32305273", "35033693", "32280261", "31835250", "27237542", "27010176", "31042603", "36347391", "36114075", "35716888", "37770691", "36682756", "11455228", "32889189", "7754863", "37766507", "35770757", "35713776", "35498367", "23948796", "7806786", "36600777", "16552568", "27923529", "8029136", "32652281", "19702730", "25284034", "2124757", "10612336", "21628134", "35241305", "18799327", "35091359", "30153937", "30579267", "14698693"], "type": "factoid", "snippets": [{"offsetInBeginSection": 12, "offsetInEndSection": 177, "text": "Corpus callosotomy (CC) is a surgical palliative procedure done for a selected group of patients with drug resistant epilepsy (DRE) to stop drop attacks and prevent ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36435385"}, {"offsetInBeginSection": 12, "offsetInEndSection": 166, "text": "Corpus callosotomy (CC) is a palliative neurosurgical procedure for patients with intractable epilepsy and without resectable focal epileptogenic lesions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36637309"}, {"offsetInBeginSection": 11, "offsetInEndSection": 253, "text": "Corpus callosotomy (CC) is a palliative surgical intervention for patients with medically refractory epilepsy that has evolved in recent years to include a less-invasive alternative with the use of laser interstitial thermal therapy (LITT). L", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37303192"}, {"offsetInBeginSection": 504, "offsetInEndSection": 779, "text": "This review describes feline epilepsy syndrome and epilepsy-related pathology, and discusses the indications for and availability of neurosurgery, including lesionectomy, temporal lobectomy with hippocampectomy, and corpus callosotomy, for cats with different epilepsy types.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36347391"}, {"offsetInBeginSection": 849, "offsetInEndSection": 970, "text": "In dogs with drug-resistant epilepsy, corpus callosotomy is available as a disconnection surgery for generalized epilepsy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35716888"}, {"offsetInBeginSection": 0, "offsetInEndSection": 595, "text": "Corpus callosotomy (CC) is an effective surgical treatment for medically resistant generalized or multifocal epilepsy (MRE). The premise of CC extrapolates from the observation that the corpus callosum is the predominant commissural pathway that allows spread and synchroneity of epileptogenic activity between the hemispheres. Candidacy for CC is typically reserved for patients seeking palliative epilepsy treatment with the goal of reducing the frequency of drop attacks, although reduction of other seizure semiologies (absence, complex partial seizures, and tonic-clonic) has been observed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37770691"}, {"offsetInBeginSection": 0, "offsetInEndSection": 327, "text": "Corpus callosotomy (CC) is an effective surgical treatment for medically resistant generalized or multifocal epilepsy (MRE). The premise of CC extrapolates from the observation that the corpus callosum is the predominant commissural pathway that allows spread and synchroneity of epileptogenic activity between the hemispheres.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37770691"}, {"offsetInBeginSection": 167, "offsetInEndSection": 658, "text": "The rationale for this procedure is based on the hypothesis that the corpus callosum is a critical pathway for interhemispheric spread of epileptic activity. Efficacy and relatively low permanent morbidity in corpus callosotomy for medically intractable epilepsy have been demonstrated by more than six decades of experience. Callosotomy best ameliorates drop attacks (tonic and atonic seizures), though tonic-clonic, absence, and frontal lobe complex partial seizures often respond as well.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18539083"}, {"offsetInBeginSection": 0, "offsetInEndSection": 492, "text": "Corpus callosotomy is a palliative surgical procedure that is suitable for some patients with intractable seizures who are not candidates for focal resective surgery. The rationale for this procedure is based on the hypothesis that the corpus callosum is a critical pathway for interhemispheric spread of epileptic activity. Efficacy and relatively low permanent morbidity in corpus callosotomy for medically intractable epilepsy have been demonstrated by more than six decades of experience.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18539083"}, {"offsetInBeginSection": 0, "offsetInEndSection": 324, "text": "Corpus callosotomy is a palliative surgical procedure that is suitable for some patients with intractable seizures who are not candidates for focal resective surgery. The rationale for this procedure is based on the hypothesis that the corpus callosum is a critical pathway for interhemispheric spread of epileptic activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18539083"}, {"offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "Corpus callosotomy, first used in the management of epilepsy by William P. van Wagenen in 1940, was for years a contentious procedure. Two decades later, Nobel Laureate Roger W. Sperry's split-brain studies inspired surgeons to reexamine the role of corpus callosotomy in the control of epileptic seizures.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32889189"}, {"offsetInBeginSection": 0, "offsetInEndSection": 437, "text": "Corpus callosotomy, first used in the management of epilepsy by William P. van Wagenen in 1940, was for years a contentious procedure. Two decades later, Nobel Laureate Roger W. Sperry's split-brain studies inspired surgeons to reexamine the role of corpus callosotomy in the control of epileptic seizures. In 1962, Joseph Bogen and Philip Vogel performed complete corpus callosotomies in patients with a history of generalized seizures.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32889189"}, {"offsetInBeginSection": 325, "offsetInEndSection": 734, "text": "Efficacy and relatively low permanent morbidity in corpus callosotomy for medically intractable epilepsy have been demonstrated by more than six decades of experience. Callosotomy best ameliorates drop attacks (tonic and atonic seizures), though tonic-clonic, absence, and frontal lobe complex partial seizures often respond as well. In addition to seizure reduction, behavior and quality of life may improve.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18539083"}, {"offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Corpus callosotomy is a palliative surgical procedure that is suitable for some patients with intractable seizures who are not candidates for focal resective surgery.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18539083"}, {"offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Corpus callosotomy (CC) is an effective surgical treatment for medically resistant generalized or multifocal epilepsy (MRE).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37770691"}, {"offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "OBJECTIVE: Corpus callosotomy (CC) is an important treatment for atonic seizures in patients with generalized or multifocal drug-resistant epilepsy (DRE).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37766507"}, {"offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Corpus Callosotomy Is a Safe and Effective Procedure for Medically Resistant Epilepsy.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37770691"}, {"offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Corpus callosotomy is among the oldest surgeries performed for drug-resistant epilepsy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35033693"}, {"offsetInBeginSection": 857, "offsetInEndSection": 1268, "text": "Two patients with epilepsy with myoclonic absences with atonia underwent corpus callosotomy; one patient was seizurefree eight months after surgery and the other had greater than 50% seizure reduction over a five-month period.SIGNIFICANCE: Phenotypic heterogeneity was evident based on seizure semiologies, comorbidities, seizure frequency and response to anti-seizure medications and non-medication treatments.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35770757"}, {"offsetInBeginSection": 0, "offsetInEndSection": 631, "text": "Background: Whether epilepsy surgery, such as corpus callosotomy is effective in patients with pediatric intractable epilepsy with mitochondrial dysfunction is controversial, and there is a paucity of literature on this issue.Objective: This study aimed to assess and describe the effective application of corpus callosotomy for treating pediatric patients with intractable epilepsy with mitochondrial dysfunction in a single institution in Korea.Methods: This was a retrospective study of pediatric patients with intractable epilepsy and mitochondrial dysfunction who underwent corpus callosotomy in a single tertiary care center.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35498367"}, {"offsetInBeginSection": 328, "offsetInEndSection": 595, "text": "Candidacy for CC is typically reserved for patients seeking palliative epilepsy treatment with the goal of reducing the frequency of drop attacks, although reduction of other seizure semiologies (absence, complex partial seizures, and tonic-clonic) has been observed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37770691"}, {"offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "PURPOSE OF REVIEW: To summarize current evidence and recent developments in the surgical treatment of drug-resistant generalized epilepsy.RECENT FINDINGS: Current surgical treatments of drug-resistant generalized epilepsy include vagus nerve stimulation (VNS), deep brain stimulation (DBS) and corpus callosotomy (CC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35713776"}, {"offsetInBeginSection": 259, "offsetInEndSection": 681, "text": "Optimal treatment of seizures in AS remains undetermined.METHODS: We report a series of four patients with Aicardi syndrome who underwent surgical management of their epilepsy including two with corpus callosotomy (CC) of a partial corpus callosum and three with vagus nerve stimulator implantation.RESULTS: Seizure outcome was variable and ranged from near complete resolution of seizures to worsening of seizure profile.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23948796"}, {"offsetInBeginSection": 0, "offsetInEndSection": 497, "text": "Although corpus callosotomy has been used since 1940 to treat severe, medically intractable seizure disorders, controversy remains as to when, or even if, the surgery should be performed. Unlike other types of surgical therapy of epilepsy where the epileptic focus is identified and removed, corpus callosotomy is used to interrupt the propagation of epileptic discharges. The procedure is primarily used in patients with secondarily generalized seizures in whom focal resections are not possible.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7806786"}, {"offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "OBJECTIVE: Corpus callosotomy is a palliative procedure that is effective at reducing seizure burden in patients with medically refractor", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31835250"}, {"offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "Background: Medically refractory epilepsy constitutes up to one-third of the epilepsy pediatric patients. Corpus callosotomy (CC) has been used for the treatment of medically refractory epilepsy in children with atonic seizures and generalized tonic-clonic (GT", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36600777"}, {"offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "OBJECTIVE: Corpus callosotomy is a palliative neurosurgical treatment for patients with either generalized or multifocal refractory epilepsy and injurious dr", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27237542"}, {"offsetInBeginSection": 0, "offsetInEndSection": 355, "text": "Although many patients with medically refractory focal epilepsy are candidates for resective surgery, patients with multifocal epilepsy and symptomatic generalized epilepsy remain difficult to treat medically and surgically. Corpus callosotomy has been utilized since 1940 for the treatment of seizures, with reports of efficacy in multiple seizure types.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20384766"}, {"offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "OBJECTIVE: Corpus callosotomy is a surgical option for medically uncontrolled generalized epilepsy in appropriat", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10449075"}, {"offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Corpus callosotomy is a palliative therapy for refractory epilepsy, including West syndrome, without a resectable epileptic focus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27923529"}, {"offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "INTRODUCTION: Corpus callosotomy (CCT) is a palliative procedure to treat injurious drop attacks or multifocal/generalized seizures in which resection of the epileptogenic focus is", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32280261"}, {"offsetInBeginSection": 67, "offsetInEndSection": 516, "text": "This review focuses on the significance of CC for seizure disorders, the role of CC in seizure spread and the surgical disruption of callosal fibers (callosotomy) for treatment of patients with drug-resistant epilepsy.METHODS: Personal experience/extensive literature review.RESULTS: Structural CC pathologies comprise developmental abnormalities, callosal involvement in identified disorders, transient imaging findings and microstructural changes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27010176"}, {"offsetInBeginSection": 586, "offsetInEndSection": 906, "text": "In so doing, we also review the literature with regard to the neurosurgical management of these unique patients.CONCLUSIONS: For the subset of children who present with partial, rather than complete, agenesis of the corpus callosum, corpus callosotomy should be considered as a treatment option to reduce seizure burden.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32652281"}, {"offsetInBeginSection": 7, "offsetInEndSection": 127, "text": "VE: Corpus callosotomy is a palliative procedure that is effective at reducing seizure burden in patients with medically", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31835250"}, {"offsetInBeginSection": 197, "offsetInEndSection": 337, "text": "low morbidity. Callosotomy is a more ambitious procedure, with a higher risk of complications but greater likelihood of seizure improvement.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19702730"}, {"offsetInBeginSection": 7, "offsetInEndSection": 324, "text": "CTION: Corpus callosotomy (CCT) is a palliative procedure to treat injurious drop attacks or multifocal/generalized seizures in which resection of the epileptogenic focus is not feasible. We are presenting our experience in treating intractable epilepsy patients by CCT procedures.METHODS: We observed 16 patients who", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32280261"}, {"offsetInBeginSection": 7, "offsetInEndSection": 158, "text": " Although corpus callosotomy has been used effectively since the late 1930s to treat severe, medically intractable seizure disorders, particularly aton", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18759631"}, {"offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "OBJECT: Corpus callosotomy is usually intended to alleviate-not to achieve total control of-epileptic seizures. A few patients experience complete seizure control after callosotomy, but the associated clinical factors are ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22681320"}, {"offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "OBJECT: Although corpus callosotomy has been used effectively since the late 1930s to treat severe, medically intractable seizure disorders, particularly atonic or drop-attack ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18759631"}, {"offsetInBeginSection": 493, "offsetInEndSection": 658, "text": "Callosotomy best ameliorates drop attacks (tonic and atonic seizures), though tonic-clonic, absence, and frontal lobe complex partial seizures often respond as well.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18539083"}, {"offsetInBeginSection": 944, "offsetInEndSection": 1149, "text": "Corpus callosotomy is a palliative surgical approach that aims at controlling potentially injurious seizures, for example, atonic or drop seizures, by preventing the bilateral spread of epileptic activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25284034"}, {"offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Corpus callosotomy is a palliative surgical option for patients with refractory epilepsy and frequent drop attacks, decreasing seizure frequency and severity by disconnecting the cerebral hemispheres.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32305273"}, {"offsetInBeginSection": 822, "offsetInEndSection": 909, "text": "corpus callosotomies frequently reduce the number and severity of generalized seizures.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2124757"}, {"offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Corpus callosotomy has a long history as a palliative treatment for intractable epilepsy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17521926"}, {"offsetInBeginSection": 7, "offsetInEndSection": 157, "text": "UND: Callosotomy represents a palliative procedure for intractable multifocal epilepsy. The extent of callosotomy and the benefits of adding anterior ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31140570"}, {"offsetInBeginSection": 12, "offsetInEndSection": 162, "text": "orpus callosotomy is a surgical option for medically uncontrolled generalized epilepsy in appropriate patients. Because numerous complications related", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10449075"}, {"offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "Gamma knife radiosurgery is a minimally invasive procedure which can be used for patients with intractable epilepsies as an alternative for surgical corpus callosotomy. We report a 13-year-old boy with intractable epilepsy who underwent radiosurgical callosotomy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21628134"}, {"offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Although corpus callosotomy has been used since 1940 to treat severe, medically intractable seizure disorders, controversy remains as to when, or even if, the surgery should be performed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7806786"}, {"offsetInBeginSection": 225, "offsetInEndSection": 355, "text": "Corpus callosotomy has been utilized since 1940 for the treatment of seizures, with reports of efficacy in multiple seizure types.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20384766"}, {"offsetInBeginSection": 823, "offsetInEndSection": 989, "text": "Because the seizures were intractable, a corpus callosotomy was performed at 16\u00a0years along with a concurrent brain biopsy from the bilateral lateral frontal cortices", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35241305"}, {"offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Callosotomy is widely used today as a treatment option for medically refractory epilepsy in patients with generalized or unknown-onset seizures.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36682756"}, {"offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "INTRODUCTION: Corpus callosotomy (CCT) is a palliative procedure to treat injurious drop attacks or multifocal/generalized seizures in which resection of the epileptogenic focus is not feasible.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32280261"}, {"offsetInBeginSection": 479, "offsetInEndSection": 959, "text": "The aim of this study is to evaluate the outcome of corpus callosotomy for the treatment of childhood onset medically intractable epilepsy in a developing pediatric epilepsy surgery center.METHOD: We report 16 patients who underwent two thirds anterior corpus callosotomy for treatment of refractory seizures in childhood.RESULTS: All patients had drop attacks or multiple types of seizures, yet some showed focal onset with secondary generalization on electroencephalogram (EEG).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16552568"}, {"offsetInBeginSection": 1092, "offsetInEndSection": 1338, "text": "Overall 11/16 (69%) of our patients improved significantly after anterior callosotomy.CONCLUSION: Corpus callosotomy remains to be a fairly good choice of surgical treatment for childhood onset medically intractable epilepsy in selected patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16552568"}, {"offsetInBeginSection": 375, "offsetInEndSection": 658, "text": "Here, we present a case of DEE with early childhood onset caused by anATP1A3variant that was effectively treated using corpus callosotomy (CC).CASE PRESENTATION: At the age of 3\u00a0years, the patient developed epileptic spasms, complicated by generalized and focal aware tonic seizures.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36114075"}, {"offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "INTRODUCTION: Corpus callosotomy (CCT) is a palliative procedure to treat injurious drop attacks or multifocal/generalized seizures in which resection of the epileptogenic focus is not feasible", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32280261"}, {"offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Corpus callosotomy, first used in the management of epilepsy by William P. van Wagenen in 1940, was for years a contentious procedure.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32889189"}, {"offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "OBJECTIVE: Corpus callosotomy is a surgical option for medically uncontrolled generalized epilepsy in appropriate patients", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10449075"}, {"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Corpus callosotomy is an effective neurosurgical procedure for children with intractable atonic or drop attack seizures.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11455228"}, {"offsetInBeginSection": 675, "offsetInEndSection": 838, "text": "THODS: The authors retrospectively reviewed all patients treated for medically refractory epilepsy by corpus callosotomy, either partial or completion, with LITT. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31835250"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "The authors present palliative therapy of severe epilepsy, i.e. callosotomy. Experimental studies and numerous clinical trials indicate possible use o", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8029136"}, {"offsetInBeginSection": 1328, "offsetInEndSection": 1804, "text": "From this paper the following conclusions can be drawn: a) epileptic patients with severe drug-resistant epilepsy due to bihemispheric cortical dysplasias are good candidates for callosotomy, b) one-stage extensive anterior callosotomy sparing the splenium is the procedure of choice, c) associated severe mental retardation seems to contra-indicate callosotomy, d) the neurophysiological study of the IHT can yield information on the functional status of the corpus callosum.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7754863"}, {"offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "PURPOSE: Corpus callosotomy can be an effective surgical treatment for medically intractable generalized seizures, particularly for drop attacks", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18799327"}, {"offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Callosotomy is widely used today as a treatment option for medically refractory epilepsy in patients with", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36682756"}, {"offsetInBeginSection": 7, "offsetInEndSection": 114, "text": ": Corpus callosotomy is a palliative surgical procedure for patients with drug-resistant epilepsy and suffe", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35091359"}, {"offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Callosotomy is a palliative surgery method for selected individuals with severe, drug-resistant epilepsy. The aim of this retrospective study", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30153937"}, {"offsetInBeginSection": 369, "offsetInEndSection": 993, "text": "ity. Corpus callosotomy (CC) is used in patients with drug-resistant epilepsy who are not candidates for either excisional epilepsy surgery or neurostimulation. We report the application of the standard complete callosotomy to control medically refractory status epilepticus in a patient with PME.CASE DESCRIPTION: A 16-year-old boy was referred to the emergency department with generalized tonic-clonic seizures. He was known to have PME since 5 years earlier, with frequent generalized seizures requiring hospitalization and reloading of the drugs. The patient was discussed by the epilepsy surgery working group, and corp", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31042603"}, {"offsetInBeginSection": 116, "offsetInEndSection": 546, "text": " The purpose of this review is to summarize the studies of callosotomy in the past years as a treatment for severe drug-resistant epilepsy with traumatizing drop attacks, mostly in children and also in some adults. The aim is also to discuss knowledge gaps and suggest how these could be addressed.RECENT FINDINGS: Lately, a number of callosotomy series, mostly retrospective and single center, have included 289 operated patients", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25692412"}, {"offsetInBeginSection": 116, "offsetInEndSection": 413, "text": " The purpose of this review is to summarize the studies of callosotomy in the past years as a treatment for severe drug-resistant epilepsy with traumatizing drop attacks, mostly in children and also in some adults. The aim is also to discuss knowledge gaps and suggest how these could be addressed", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25692412"}, {"offsetInBeginSection": 116, "offsetInEndSection": 329, "text": " The purpose of this review is to summarize the studies of callosotomy in the past years as a treatment for severe drug-resistant epilepsy with traumatizing drop attacks, mostly in children and also in some adults", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25692412"}, {"offsetInBeginSection": 735, "offsetInEndSection": 831, "text": "Hence, callosotomy is justified as a therapy for appropriate patients with intractable epilepsy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18539083"}, {"offsetInBeginSection": 0, "offsetInEndSection": 413, "text": "PURPOSE OF REVIEW: Corpus callosotomy is a palliative surgical treatment modality that has gone in and out of favor. The purpose of this review is to summarize the studies of callosotomy in the past years as a treatment for severe drug-resistant epilepsy with traumatizing drop attacks, mostly in children and also in some adults. The aim is also to discuss knowledge gaps and suggest how these could be addressed", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25692412"}, {"offsetInBeginSection": 0, "offsetInEndSection": 329, "text": "PURPOSE OF REVIEW: Corpus callosotomy is a palliative surgical treatment modality that has gone in and out of favor. The purpose of this review is to summarize the studies of callosotomy in the past years as a treatment for severe drug-resistant epilepsy with traumatizing drop attacks, mostly in children and also in some adults", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25692412"}, {"offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "[Callosotomy in treatment of severe epilepsy].", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8029136"}, {"offsetInBeginSection": 0, "offsetInEndSection": 45, "text": "Callosotomy for epilepsy after West syndrome.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10612336"}, {"offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "The authors present palliative therapy of severe epilepsy, i.e. callosotomy. Experimental studies and numerous clinical trials indicate possible use of this technique.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8029136"}, {"offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "The authors present palliative therapy of severe epilepsy, i.e. callosotomy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8029136"}, {"offsetInBeginSection": 270, "offsetInEndSection": 555, "text": "The authors discuss own experience with 8 epileptic patients refractory to preservative therapies. These patients were treated surgically with anterior callosotomy. Small number of patients and relatively short period of the follow-up do not allow more general conclusions to be drawn.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8029136"}, {"offsetInBeginSection": 270, "offsetInEndSection": 434, "text": "The authors discuss own experience with 8 epileptic patients refractory to preservative therapies. These patients were treated surgically with anterior callosotomy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8029136"}, {"offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Corpus callosotomy has been used as a form of surgical palliation for patients suffering from medically refractory generalized seizures, including drop attacks.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30579267"}, {"offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "OBJECT: Although corpus callosotomy has been used effectively since the late 1930s to treat severe, medically intractable seizure disorders, particularly atonic or drop-attack seizures, controversy remains as to when, how, and how much surgery should be pe", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18759631"}, {"offsetInBeginSection": 477, "offsetInEndSection": 666, "text": "Callosotomy remains an effective technique to treat atonic, tonic, and tonic-clonic seizures, especially in patients with symptomatic generalized epilepsies such as Lennox-Gastaut syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14698693"}]}
+{"question_id": "6614fe3dfdcbea915f000045", "question": "Is there an approved vaccine to prevent Zika virus infection during pregnancy?", "answer": "No, there is no approved vaccine to prevent Zika virus (ZIKV) infection during pregnancy. Although different types of vaccine antigens have been investigated, none have been licensed for use in humans. Researchers are actively working on developing effective vaccines against ZIKV, including novel recombinant virus-like particles (VLPs). However, the development process is challenging due to concerns about cross-reactions with other flaviviruses, safety during pregnancy, and evaluating efficacy in clinical trials. Currently, there is no vaccine or drug approved for preventing ZIKV infection during pregnancy, highlighting the need for continued research and development in this area.", "relevant_passage_ids": ["36690159", "36762592", "37058415"], "type": "yesno", "snippets": [{"offsetInBeginSection": 130, "offsetInEndSection": 177, "text": "a safe and effective vaccine is urgently needed", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36690159"}, {"offsetInBeginSection": 391, "offsetInEndSection": 600, "text": "update on the clinical progress on leading mRNA vaccine candidates against different viruses that include influenza viruses, human immunodeficiency virus 1, respiratory syncytial virus, Nipah virus, Zika virus", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36762592"}, {"offsetInBeginSection": 1139, "offsetInEndSection": 1249, "text": "Immunization with the AAV VLP displaying one of the mimotopes induced antibodies that recognized ZIKV and DENV", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37058415"}, {"offsetInBeginSection": 407, "offsetInEndSection": 544, "text": "envelope dimer epitope (EDE), which induces neutralizing antibodies that do not elicit ADE, to design a vaccine against both flaviviruses", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37058415"}]}
+{"question_id": "661c416048a2c27714000008", "question": "What are eRNAs and what is their function?", "answer": "Enhancer RNAs (eRNAs) are non-coding RNA molecules produced by the transcription of DNA cis-acting elements called enhancers. eRNAs are relatively short-lived RNA species that are transcribed at very high rates but also quickly degraded. Nevertheless, eRNAs are deeply intertwined within enhancer regulatory networks and are implicated in a number of transcriptional control mechanisms. Recent studies revealed that the transcription of eRNAs may be a biological marker of enhancer activity that can participate in the regulation of coding gene transcription.", "relevant_passage_ids": ["36909657", "37537618", "36039999", "29138457", "32568241", "34731149", "33408781", "30026829", "35454885", "31594934", "35170113", "33235186", "36923642", "33034351", "33568070", "31106290", "35508485", "34551433", "34073237", "32888773", "31791217", "31916476", "36287118", "37266452", "25263592", "25561718", "24674738", "28599852", "29951530", "34016622", "37294799", "34321580", "35600050", "34612730", "33870423", "28533025", "34539983", "28936977", "24962887", "25810254", "35064362", "32579929", "30862109", "28891741", "36232885", "35135243", "33083767", "29449408"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Enhancer RNAs (eRNAs) are non-coding RNAs produced from transcriptional enhancers that are highly correlated with their activities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36909657"}, {"offsetInBeginSection": 396, "offsetInEndSection": 692, "text": "eRNAs are non-coding RNA molecules produced by the transcription of DNA cis-acting elements, enhancer fragments. Recent studies revealed that the transcription of eRNAs may be a biological marker responding to enhancer activity that can participate in the regulation of coding gene transcription.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37537618"}, {"offsetInBeginSection": 124, "offsetInEndSection": 558, "text": "Over the last decade, the transcription of enhancer RNAs (eRNAs) - nascent RNAs transcribed from active enhancers - has emerged as a key factor regulating enhancer activity. eRNAs are relatively short-lived RNA species that are transcribed at very high rates but also quickly degraded. Nevertheless, eRNAs are deeply intertwined within enhancer regulatory networks and are implicated in a number of transcriptional control mechanisms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36039999"}, {"offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "Enhancer RNAs (eRNAs) are non-coding RNAs (ncRNAs) transcribed in enhancer regions. They play an important role in transcriptional regulation, mainly during cellular differentiation. eRNAs are tightly tissue- and cell-type specific and are induced by specific stimuli, activating promoters of target genes in turn.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35454885"}, {"offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Enhancer RNAs (eRNAs) are non-coding RNAs (ncRNAs) transcribed in enhancer regions. They play an important role in transcriptional regulation, mainly during cellular differentiation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35454885"}, {"offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Enhancer RNAs (eRNAs) are non-coding RNAs (ncRNAs) transcribed in enhancer regions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35454885"}, {"offsetInBeginSection": 288, "offsetInEndSection": 692, "text": "The discovery of enhancer RNAs (eRNAs) in 2010 has further broadened the range of non-coding RNAs revealed. eRNAs are non-coding RNA molecules produced by the transcription of DNA cis-acting elements, enhancer fragments. Recent studies revealed that the transcription of eRNAs may be a biological marker responding to enhancer activity that can participate in the regulation of coding gene transcription.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37537618"}, {"offsetInBeginSection": 288, "offsetInEndSection": 508, "text": "The discovery of enhancer RNAs (eRNAs) in 2010 has further broadened the range of non-coding RNAs revealed. eRNAs are non-coding RNA molecules produced by the transcription of DNA cis-acting elements, enhancer fragments.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37537618"}, {"offsetInBeginSection": 124, "offsetInEndSection": 409, "text": "Over the last decade, the transcription of enhancer RNAs (eRNAs) - nascent RNAs transcribed from active enhancers - has emerged as a key factor regulating enhancer activity. eRNAs are relatively short-lived RNA species that are transcribed at very high rates but also quickly degraded.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36039999"}, {"offsetInBeginSection": 0, "offsetInEndSection": 504, "text": "A large portion of the human genome is transcribed into RNAs without known protein-coding functions, far outnumbering coding transcription units. Extensive studies of long noncoding RNAs (lncRNAs) have clearly demonstrated that they can play critical roles in regulating gene expression, development, and diseases, acting both as transcriptional activators and repressors. More recently, enhancers have been found to be broadly transcribed, resulting in the production of enhancer-derived RNAs, or eRNAs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24674738"}, {"offsetInBeginSection": 0, "offsetInEndSection": 409, "text": "Enhancers confer precise spatiotemporal patterns of gene expression in response to developmental and environmental stimuli. Over the last decade, the transcription of enhancer RNAs (eRNAs) - nascent RNAs transcribed from active enhancers - has emerged as a key factor regulating enhancer activity. eRNAs are relatively short-lived RNA species that are transcribed at very high rates but also quickly degraded.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36039999"}, {"offsetInBeginSection": 598, "offsetInEndSection": 800, "text": "Although some believe that eRNAs are merely transcriptional byproducts, many studies have demonstrated that eRNAs execute crucial tasks in regulating chromatin conformation and transcription activation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33034351"}, {"offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Enhancers are cis-acting elements that control the transcription of target genes and are transcribed into a class of noncoding RNAs (ncRNAs) termed enhancer RNAs (eRNAs).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34612730"}, {"offsetInBeginSection": 612, "offsetInEndSection": 864, "text": "We focus here on studies using cloned eRNAs to study their function as transcripts, revealing roles for eRNAs in enhancer-promoter looping, recruiting transcriptional machinery, and facilitating RNA polymerase pause-release to regulate gene expression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32888773"}, {"offsetInBeginSection": 308, "offsetInEndSection": 439, "text": "In recent years, emerging evidence suggests that active enhancers are bidirectionally transcribed to produce enhancer RNAs (eRNAs).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33034351"}, {"offsetInBeginSection": 733, "offsetInEndSection": 890, "text": "We conclude that eRNAs are active molecules, transcriptional regulators, and partners of NamiRNAs, rather than mere RNAs produced during enhancer activation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33568070"}, {"offsetInBeginSection": 286, "offsetInEndSection": 409, "text": "Meanwhile, activated enhancers produce endogenous non-coding RNAs (named enhancer RNAs, eRNAs) to activate gene expression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33568070"}, {"offsetInBeginSection": 373, "offsetInEndSection": 504, "text": "More recently, enhancers have been found to be broadly transcribed, resulting in the production of enhancer-derived RNAs, or eRNAs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24674738"}, {"offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Enhancers play a central role in the transcriptional regulation of metazoans. Almost a decade ago, the discovery of their pervasive transcription into noncoding RNAs, termed enhancer RNAs (eRNAs), opened a whole new field of study.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31106290"}, {"offsetInBeginSection": 232, "offsetInEndSection": 361, "text": "The presence of eRNAs correlates with enhancer activity; however, whether they act as functional molecules remains controversial.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31106290"}, {"offsetInBeginSection": 362, "offsetInEndSection": 586, "text": "Here we review direct experimental evidence supporting a functional role of eRNAs in transcription and provide a general pipeline that could help in the design of experimental approaches to investigate the function of eRNAs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31106290"}, {"offsetInBeginSection": 413, "offsetInEndSection": 570, "text": "These eRNAs can promote enhancer-promoter (E-P) looping formation by binding to other protein factors or propel expression of downstream protein-coding gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29951530"}, {"offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Since the discovery that many transcriptional enhancers are transcribed into long noncoding RNAs termed \"enhancer RNAs\" (eRNAs), their putative role in enhancer function has been debated.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25810254"}, {"offsetInBeginSection": 188, "offsetInEndSection": 432, "text": "Very recent evidence has indicted that some eRNAs play a role in initiating or activating transcription, possibly by helping recruit and/or stabilize binding of the general transcription machinery to the proximal promoter of their target genes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25810254"}, {"offsetInBeginSection": 190, "offsetInEndSection": 280, "text": "eRNAs in different direction are functional or merely a reflection of enhancer activation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33408781"}, {"offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "The function of enhancer RNAs (eRNAs) in transcriptional regulation remains obscure.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32579929"}, {"offsetInBeginSection": 125, "offsetInEndSection": 254, "text": "A subclass of lncRNAs, termed enhancer RNAs (eRNAs), are derived from enhancer regions and could contribute to enhancer function.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30862109"}, {"offsetInBeginSection": 494, "offsetInEndSection": 619, "text": "eRNAs play roles in the initiation or stabilization of enhancer-promoter looping, and promote the expression of target genes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28936977"}, {"offsetInBeginSection": 660, "offsetInEndSection": 769, "text": "eRNAs have crucial roles in biological processes, such as development and disease initiation and progression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28936977"}, {"offsetInBeginSection": 102, "offsetInEndSection": 231, "text": "Enhancer RNAs (eRNAs) are derived from the transcription of enhancers and has attracted increasing attention in cancers recently.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33870423"}, {"offsetInBeginSection": 396, "offsetInEndSection": 508, "text": "eRNAs are non-coding RNA molecules produced by the transcription of DNA cis-acting elements, enhancer fragments.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37537618"}, {"offsetInBeginSection": 248, "offsetInEndSection": 338, "text": "Recent studies have shown that enhancers are transcribed to produce enhancer RNAs (eRNAs).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32888773"}, {"offsetInBeginSection": 886, "offsetInEndSection": 1071, "text": "The results suggest a functional role for eRNAs as regulatory molecules that are able to stimulate the activity of a key epigenetic regulatory enzyme, thereby promoting gene expression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28891741"}, {"offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Enhancer RNAs (eRNAs) are long non-coding RNAs that originate from enhancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35508485"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Enhancer RNAs (eRNAs) are a novel class of non-coding RNA (ncRNA) molecules transcribed from the DNA sequences of enhancer regions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29138457"}, {"offsetInBeginSection": 100, "offsetInEndSection": 318, "text": "Recent studies have shown that enhancers can act as transcriptional units for the production of enhancer RNAs (eRNAs), which are hallmarks of activity enhancers and are involved in the regulation of gene transcription.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30026829"}, {"offsetInBeginSection": 22, "offsetInEndSection": 328, "text": "(eRNAs) are a group of RNAs transcribed by RNA polymerase II from the domain of transcription enhancers, a major type of cis-regulatory elements in the genome. The correlation between eRNA production and enhancer activity has stimulated studies on the potential role of eRNAs in transcriptional regulation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28533025"}, {"offsetInBeginSection": 284, "offsetInEndSection": 623, "text": "are referred to as eRNAs. Studies have demonstrated that eRNA transcripts can play significant roles in gene regulation in both physiology and disease. Commonly used methods to investigate the function of eRNAs are constrained to \"loss-of-function\" approaches by knockdown of eRNAs, or by chemical inhibition of the enhancer transcription.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32568241"}, {"offsetInBeginSection": 84, "offsetInEndSection": 454, "text": "They play an important role in transcriptional regulation, mainly during cellular differentiation. eRNAs are tightly tissue- and cell-type specific and are induced by specific stimuli, activating promoters of target genes in turn. eRNAs usually have a very short half-life but in some cases, once activated, they can be stably expressed and acquire additional functions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35454885"}, {"offsetInBeginSection": 84, "offsetInEndSection": 314, "text": "They play an important role in transcriptional regulation, mainly during cellular differentiation. eRNAs are tightly tissue- and cell-type specific and are induced by specific stimuli, activating promoters of target genes in turn.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35454885"}, {"offsetInBeginSection": 183, "offsetInEndSection": 454, "text": "eRNAs are tightly tissue- and cell-type specific and are induced by specific stimuli, activating promoters of target genes in turn. eRNAs usually have a very short half-life but in some cases, once activated, they can be stably expressed and acquire additional functions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35454885"}, {"offsetInBeginSection": 100, "offsetInEndSection": 538, "text": "Recent studies have shown that enhancers can act as transcriptional units for the production of enhancer RNAs (eRNAs), which are hallmarks of activity enhancers and are involved in the regulation of gene transcription. The in-depth study of eRNAs is of great significance for us to better understand enhancer function and transcriptional regulation in various diseases. Therefore, eRNAs may be a potential therapeutic target for diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30026829"}, {"offsetInBeginSection": 183, "offsetInEndSection": 649, "text": "eRNAs are tightly tissue- and cell-type specific and are induced by specific stimuli, activating promoters of target genes in turn. eRNAs usually have a very short half-life but in some cases, once activated, they can be stably expressed and acquire additional functions. Due to their critical role, eRNAs are often dysregulated in cancer and growing number of interactions with chromatin modifiers, transcription factors, and splicing machinery have been described.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35454885"}, {"offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "MOTIVATION: Enhancers are vital cis-regulatory elements that regulate gene expression. Enhancer RNAs (eRNAs), a type of long noncoding RNAs, are transcribed from enhancer regions in the genome. The tissue-specific expression of eRNAs is crucial in the regulation of gene expression and cancer development", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37294799"}, {"offsetInBeginSection": 91, "offsetInEndSection": 460, "text": "Long non-coding RNAs (lncRNAs) are transcripts of >200 nucleotides and are best known for their ability to regulate gene expression. Enhancer RNAs (eRNAs) are subclass of lncRNAs that are synthesized from enhancer regions and have also been shown to coordinate gene expression. The biological function and significance of most lncRNAs and eRNAs remain to be determined.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36923642"}, {"offsetInBeginSection": 0, "offsetInEndSection": 358, "text": "Enhancers are key cis-acting gene regulatory elements in eukaryotes, which can effectively promote the expression of target genes. Emerging evidence showed that enhancers in activation state could be transcribed to enhancer RNAs (eRNAs), the processes of which are regulated by various signaling systems and actions of signal-dependent transcription factors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28936977"}, {"offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Enhancer RNAs (eRNAs) are a class of non-coding RNAs transcribed from enhancers. As the markers of active enhancers, eRNAs play important roles in gene regulation and are associated with various complex traits and characteristics.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34551433"}, {"offsetInBeginSection": 507, "offsetInEndSection": 652, "text": "eRNAs can not only increase enhancer activity by promoting the formation of enhancer-promoter loops but also regulate transcriptional activation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34612730"}, {"offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Enhancers are critical genomic elements that can cooperate with promoters to regulate gene transcription in both normal and cancer cells. Recent studies reveal that enhancer regions are transcribed to produce a class of noncoding RNAs referred to as enhancer RNAs (eRNAs).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34073237"}, {"offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Enhancer RNAs (eRNAs) are a subset of long noncoding RNA generated from genomic enhancers: they are thought to act as potent promoters of the expression of nearby genes through interaction with the transcriptional and epigenomic machineries.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33083767"}, {"offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Recent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25561718"}, {"offsetInBeginSection": 611, "offsetInEndSection": 709, "text": "eRNAs may then facilitate enhancer-promoter interaction or activate promoter-driven transcription.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25561718"}, {"offsetInBeginSection": 295, "offsetInEndSection": 460, "text": "Emerging studies, showing that eRNAs function in controlling mRNA transcription, challenge the idea that enhancers are merely sites of transcription factor assembly.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25561718"}, {"offsetInBeginSection": 509, "offsetInEndSection": 692, "text": "Recent studies revealed that the transcription of eRNAs may be a biological marker responding to enhancer activity that can participate in the regulation of coding gene transcription.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37537618"}]}
+{"question_id": "661d20b7eac11fad33000016", "question": "Can cytomegalovirus (CMV) be transmitted via breast milk to premature infants?", "answer": "Yes, CMV can be transmitted via breastfeeding/breast milk.", "relevant_passage_ids": ["20670291", "21164427", "9469396", "25675905", "24172840", "17661570", "12193509", "12777549", "16470162", "26512588", "37182845", "36890689", "30474531", "32662174", "33670693", "16790732", "17118633", "26968830", "27257513", "33325402", "23016620", "14762453", "27328166", "28093696", "30338856", "35454995", "34840311"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1070, "offsetInEndSection": 1239, "text": "The current data report low rates of symptomatic disease after transmission of HCMV via breast milk to the preterm infant without evidence of certain long-term sequelae.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20670291"}, {"offsetInBeginSection": 455, "offsetInEndSection": 715, "text": "Twenty-six studies were included for analysis. Maternal HCMV-IgG-positivity was reported to be in the range 51.6-100% (median 81.6%), HCMV-IgG detection in breast milk in the range 67-97.2% (median 80%) and HCMV-positivity of the infants in the range 5.7-58.6%", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20670291"}, {"offsetInBeginSection": 717, "offsetInEndSection": 832, "text": "Symptomatic HCMV disease occurred in 0-34.5% (median 3.7%) and severe sepsis-like syndrome in 0-13.8% (median 0.7%)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20670291"}, {"offsetInBeginSection": 834, "offsetInEndSection": 1068, "text": "Data on long-term outcome of preterm infants with symptomatic HCMV infection revealed a low risk for mild neurological and cognitive sequelae, without hearing impairment. Recommendations for high-risk preterm infants diverged markedly", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20670291"}, {"offsetInBeginSection": 14, "offsetInEndSection": 157, "text": "Although breast milk is considered the optimal nutrition for infants, it is also the primary cause of postnatal cytomegalovirus (CMV) infection", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37182845"}, {"offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Cytomegalovirus (CMV) may transmit perinatally or from breast milk. The risk for development of symptomatic CMV disease in very-low-birth-weight premature infants after transmission from maternal breast milk is not clear.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24172840"}, {"offsetInBeginSection": 0, "offsetInEndSection": 352, "text": "Cytomegalovirus (CMV) may transmit perinatally or from breast milk. The risk for development of symptomatic CMV disease in very-low-birth-weight premature infants after transmission from maternal breast milk is not clear. There are scarce data in the literature about congenital CMV infection in multiple pregnancies, being mostly with twin gestations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24172840"}, {"offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "Human cytomegalovirus (HCMV) can be transmitted through breast milk to neonates. Although healthy full-term infants rarely develop symptoms of CMV infection; premature or low-birth-weight infants can experience symptomatic infection that is occasionally severe.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17661570"}, {"offsetInBeginSection": 0, "offsetInEndSection": 498, "text": "Human cytomegalovirus (HCMV) can be transmitted through breast milk to neonates. Although healthy full-term infants rarely develop symptoms of CMV infection; premature or low-birth-weight infants can experience symptomatic infection that is occasionally severe. There is limited information on the long-term effects of postnatal CMV infection in premature infants, suggesting that these infants do not develop cognitive function delays or hearing loss, although those with intrapartum infection do.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17661570"}, {"offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Cytomegalovirus (CMV) may transmit perinatally or from breast milk.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24172840"}, {"offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Human cytomegalovirus (HCMV) can be transmitted through breast milk to neonates.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17661570"}, {"offsetInBeginSection": 906, "offsetInEndSection": 1349, "text": "Although acquisition of cytomegalovirus by this route is seldom of consequence in healthy term infants, cytomegalovirus infections in low-birth-weight premature infants have been demonstrated to cause symptomatic illness, including hepatitis, neutropenia, thrombocytopenia, and a 'sepsis-like' state.SUMMARY: Cytomegalovirus is commonly shed in human milk, and cytomegalovirus-seropositive women can transmit this infection via breast-feeding.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16470162"}, {"offsetInBeginSection": 1328, "offsetInEndSection": 1624, "text": "However, 5 extremely low birth weight infants (gestational age, 24.4 +/- 0.5 weeks) were infected at an age of 4 to 7 weeks; 4 of these infants had marked symptoms of an acute CMV infection.CONCLUSION: In mothers of preterm infants a high incidence of CMV excretion into breast milk was detected.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9469396"}, {"offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "There is evidence that CMV is commonly present in breast milk and is often transmitted to babies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12193509"}, {"offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Approximately 15% of preterm infants may develop postnatal cytomegalovirus (CMV) infection from seropositive mothers via breast milk and are at risk for neurological sequelae in childhood.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26512588"}, {"offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Perinatal transmission of human cytomegalovirus (HCMV) infection in very low birth weight (VLBW) premature infants can lead to serious clinical symptoms and it has ben increasingly recognized that breast milk is the most frequent route of transmission.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23016620"}, {"offsetInBeginSection": 430, "offsetInEndSection": 556, "text": "The majority of HCMV seropositive mothers shed the virus into their breast milk and can transmit infection to their offspring.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23016620"}, {"offsetInBeginSection": 6, "offsetInEndSection": 167, "text": "cytomegalovirus (HCMV) can be transmitted through breast milk to neonates. Although healthy full-term infants rarely develop symptoms of CMV infection; premature", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17661570"}, {"offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "Cytomegalovirus (CMV) may transmit perinatally or from breast milk. The risk for development of symptomatic CMV disease in very-low-birth-weight premature infants after transmission from maternal breast milk is not clear. There are scarce data in the literature", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24172840"}, {"offsetInBeginSection": 0, "offsetInEndSection": 393, "text": "OBJECTIVE: Preterm infants are at greater risk of symptomatic cytomegalovirus (CMV) infection than term infants. Breast milk is the main source of perinatal CMV infections. This study evaluated the kinetics of CMV load in breast milk and the rate of postnatal CMV transmission via breast milk from mothers to their preterm infants.METHODS: This was a prospective study of 30 mothers and their ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12777549"}, {"offsetInBeginSection": 27, "offsetInEndSection": 1339, "text": "nonfrozen, fresh breast milk from mothers with positive cytomegalovirus (CMV) serology was initially contraindicated to very low-birth-weight infants because of the risk of milk-acquired CMV infection. Recently, the severity of this infection was increasingly discussed and the international guidelines now differ. Since 2012, the American Academy of Pediatrics has recommended nutrition through raw breast milk for all preterm infants. Case\u2003We report the case of an infant born prematurely at 27 weeks and 4 days and fed with raw breastmilk from day 12 of life (D12). He presented with a late-onset of CMV infection from D39. The CMV polymerase chain reaction (PCR), negative on D3, was strongly positive on D49, as well as the PCR on breast milk. He had CMV-specific immunoglobulin (Ig) M while his mother had only CMV-specific IgG. On D52, he deteriorated further with septic shock, and a fatal cardiac arrest on D54. His twin presented an asymptomatic CMV infection. The autopsy and histological examination showed evidence of numerous organ damage caused by CMV (with differences compared with congenital infection) but no evidence of bacterial infection. Conclusion\u2003Although rare, postnatal CMV infections transmitted by raw breast milk given to very low-birthweight infants can have dramatic consequences.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27257513"}, {"offsetInBeginSection": 563, "offsetInEndSection": 1563, "text": "CMV infection. Post-natal CMV (pCMV) infection is most commonly transmitted by breast-feeding, and in full-term infants is of little consequence. However, in preterm, very-low birthweight (VLBW) infants (<1500\u2009g), pCMV can result in a severe sepsis-like syndrome, with wide-ranging end-organ disease manifestations. Although such short-term complications are well recognized among clinicians caring for premature infants, the long-term risks with respect to adverse neurodevelopmental outcomes remain controversial. In this review, we provide an overview of the clinical manifestations of breast milk-acquired pCMV infection. In particular, we summarize studies that have examined-sometimes with conflicting conclusions-the risks of long-term adverse neurodevelopmental outcome in VLBW infants that acquire pCMV from breast milk. We highlight proposed preventive strategies and antiviral interventions, and offer recommendations for high-priority areas for future basic science and clinical research.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32662174"}, {"offsetInBeginSection": 120, "offsetInEndSection": 463, "text": "Mothers of these infants often experience difficulties in establishing and maintaining lactation. The majority of women excrete cytomegalovirus (CMV) in their breast milk. CMV transmitted through maternal milk could cause symptomatic infection in preterm infants presenting as a sepsis like syndrome, pneumonitis, hepatopathy or enterocolitis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27328166"}, {"offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "OBJECTIVE: Preterm infants are at greater risk of symptomatic cytomegalovirus (CMV) infection than term infants. Breast milk is the main source of perinatal CMV ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12777549"}, {"offsetInBeginSection": 280, "offsetInEndSection": 469, "text": "Vertical CMV transmission may occur in utero, during birth, and by breast feeding. Usually, a CMV infection transmitted via breast milk is symptomatic only in very immature preterm infants.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28093696"}, {"offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Cytomegalovirus (CMV) in breast milk is transmitted to infants and may be associated with disease especially in preterm infants.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14762453"}, {"offsetInBeginSection": 194, "offsetInEndSection": 352, "text": "lovirus infection. One route by which cytomegalovirus infections are acquired in newborns is via consumption of breast milk from cytomegalovirus-seropositive,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16470162"}, {"offsetInBeginSection": 1423, "offsetInEndSection": 1573, "text": "atients were CMV DNA negative.CONCLUSION: CMV is principally transmitted through breast milk in VLBWIs. The risk of TT-CMV seems to be extremely low w", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30338856"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "BACKGROUND: Breast milk is the primary source of cytomegalovirus (CMV) transmission to newborns and premature infants. The role of cell-free milk whey", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25675905"}, {"offsetInBeginSection": 812, "offsetInEndSection": 962, "text": "At our institutes, we mainly use frozen-thawed breast milk. We found low CMV transmission rates even in extremely premature infants, and the CMV-posit", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21164427"}, {"offsetInBeginSection": 1388, "offsetInEndSection": 1538, "text": "he results indicate that the pathogenic CMV strain was transmitted through breast milk, which is consistent with the claims that transfusion-transmitt", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26968830"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Postnatally acquired cytomegalovirus (CMV) is commonly acquired via breast milk, with premature infants more frequently developing symptoms of CMV inf", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33325402"}, {"offsetInBeginSection": 218, "offsetInEndSection": 463, "text": "The majority of women excrete cytomegalovirus (CMV) in their breast milk. CMV transmitted through maternal milk could cause symptomatic infection in preterm infants presenting as a sepsis like syndrome, pneumonitis, hepatopathy or enterocolitis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27328166"}, {"offsetInBeginSection": 0, "offsetInEndSection": 292, "text": "Freezing human milk is recommended to inactivate cytomegalovirus (CMV). A case of a preterm infant exclusively receiving frozen breast milk from his CMV seropositive mother showed that storage of breast milk for two months at -20 degrees C did not prevent symptomatic postnatal CMV infection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16790732"}, {"offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Cytomegalovirus (CMV) may transmit perinatally or from breast milk", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24172840"}, {"offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Human cytomegalovirus (HCMV) can be transmitted through breast milk to neonates", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17661570"}, {"offsetInBeginSection": 1587, "offsetInEndSection": 1920, "text": "None of the infants had CMV-related death or permanent sensorineural hearing loss.Transmission of CMV from seropositive mother via breast milk to preterm infants does not appear at this time to have major adverse effects on clinical outcomes, growth, neurodevelopmental status, and hearing function at 12 and 24 months corrected age.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26512588"}, {"offsetInBeginSection": 218, "offsetInEndSection": 618, "text": "The majority of women excrete cytomegalovirus (CMV) in their breast milk. CMV transmitted through maternal milk could cause symptomatic infection in preterm infants presenting as a sepsis like syndrome, pneumonitis, hepatopathy or enterocolitis. Routine freezing of maternal milk decreases the CMV load in breast milk and is used in some neonatal centers to reduce CMV transmission to preterm infants", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27328166"}, {"offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Postnatally acquired cytomegalovirus (CMV) is commonly acquired via breast milk, with premature infants more frequently developing symptoms of CMV infection in comparison to term infants.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33325402"}, {"offsetInBeginSection": 86, "offsetInEndSection": 236, "text": "ns. Postnatal CMV is mainly transmitted via breast milk and blood transfusions. Frozen-thawed breast milk is used to prevent postnatal CMV infection. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36890689"}, {"offsetInBeginSection": 10, "offsetInEndSection": 150, "text": ": Postnatal infection with cytomegalovirus (CMV) in very-preterm and very-low-birth-weight infants, transmitted through breast milk (BM), is", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34840311"}, {"offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Cytomegalovirus (CMV) is able to replicate in the breast milk of lactating mothers and thus the offspring might be affected by mild to severe symptoms of postnatal CMV disease in case of prematurity; not", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35454995"}, {"offsetInBeginSection": 0, "offsetInEndSection": 648, "text": "Breast Milk (BM) is the best source of nutrition for newborns, especially if premature. In fact, its beneficial impact on short- and the long-term neonatal outcome has was deeply described. Unfortunately, BM could not be always so safe, especially due to the possible presence of maternal viruses that can be shed and transferred to the breastfed neonate. Among these, Cytomegalovirus (CMV) can potentially lead to a serious and acute illness, mostly in case of low gestational age. Some studies also report the association of CMV-acquired infection to an increased risk of structural and functional brain modifications and neurological impairment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30474531"}, {"offsetInBeginSection": 17, "offsetInEndSection": 765, "text": "recommended for all neonates due to a known variety of beneficial effects, but infants can be infected by cell-associated bacteria and viruses from breast milk, such as cytomegalovirus (CMV). The majority of CMV-seropositive breastfeeding women have a viral, self-restricted reactivation, can shed the virus in the milk for about 12 weeks after delivery, and can transmit the infection to their offspring. Post-natal CMV-infected term infants are mainly asymptomatic, while very low birth weight (VLBW, <1500 g) and extremely low birth weight (ELBW, <1000 g) infants may present with severe disease, short-term sequelae ranging from abnormalities in laboratory indexes to sepsis-like syndrome, and long-term sequelae such as developmental problems.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33670693"}, {"offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "INTRODUCTION: Although breast milk is considered the optimal nutrition for infants, it is also the primary cause of postnatal cytomegalovirus (CMV) infe", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37182845"}, {"offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "There is evidence that CMV is commonly present in breast milk and is often transmitted to babies. CMV infection acquired postnatally can cause serious disease in very premature babies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12193509"}, {"offsetInBeginSection": 105, "offsetInEndSection": 201, "text": "The transmission of CMV through breastmilk from mothers to preterm infants is frequent (15-20%).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17118633"}, {"offsetInBeginSection": 1301, "offsetInEndSection": 1479, "text": "However, they had no clinical symptoms of CMV infection.CONCLUSIONS: Despite the high rate of CMV DNA in breast milk, symptomatic infections in the preterm infants did not occur.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12777549"}]}
+{"question_id": "65cfcb4c1930410b13000017", "question": "What enzymes are inhibited by Vorasidenib?", "answer": "Vorasidenib (AG-881) is a first-in-class, brain-penetrant, dual inhibitor of the mutant IDH1 and mutant IDH2 enzymes.", "relevant_passage_ids": ["36698225", "36453510", "37272516", "37276325", "37812369", "34078652", "32071674", "33982420", "36823302", "27355333"], "type": "list", "snippets": [{"offsetInBeginSection": 135, "offsetInEndSection": 241, "text": "Few inhibitors, such as ivosidenib and vorasidenib, have been identified as selective inhibitors of mIDH1.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36698225"}, {"offsetInBeginSection": 302, "offsetInEndSection": 530, "text": "OBJECTIVE: Vorasidenib (AG-881) has recently been reported as a promising dual inhibitor of mutant isocitrate dehydrogenase 1 and 2 with the ability to penetrate the blood-brain barrier towards the treatment of low-grade glioma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36453510"}, {"offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37272516"}, {"offsetInBeginSection": 149, "offsetInEndSection": 279, "text": "Vorasidenib, an oral brain-penetrant inhibitor of mutant IDH1 and IDH2 enzymes, showed preliminary activity in IDH-mutant gliomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37272516"}, {"offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "According to the phase III INDIGO trial, vorasidenib, an IDH1/2 inhibitor, significantly benefited adults with IDH1/2-mutant low-grade gliomas, reducing progression risk and delaying the need for chemoradiotherapy. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37276325"}, {"offsetInBeginSection": 546, "offsetInEndSection": 828, "text": "Nonetheless, advances have been made with the IDH1/2 inhibitor vorasidenib for IDH-mutant grade 2 gliomas, the combination of dabrafenib and trametinib for BRAFV600E mutated gliomas, and the therapies for subsets of patients with fusions and H3K27M-altered diffuse midline gliomas. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37812369"}, {"offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Vorasidenib, a Dual Inhibitor of Mutant IDH1/2, in Recurrent or Progressive Glioma; Results of a First-in-Human Phase I Trial.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34078652"}, {"offsetInBeginSection": 317, "offsetInEndSection": 434, "text": "Vorasidenib (AG-881) is a first-in-class, brain-penetrant, dual inhibitor of the mutant IDH1 and mutant IDH2 enzymes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34078652"}, {"offsetInBeginSection": 546, "offsetInEndSection": 826, "text": "Nonetheless, advances have been made with the IDH1/2 inhibitor vorasidenib for IDH-mutant grade 2 gliomas, the combination of dabrafenib and trametinib for BRAFV600E mutated gliomas, and the therapies for subsets of patients with fusions and H3K27M-altered diffuse midline gliomas", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37812369"}, {"offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "According to the phase III INDIGO trial, vorasidenib, an IDH1/2 inhibitor, significantly benefited adults with IDH1/2-mutant low-grade gliomas, reducing progression risk and delaying the need for chemoradiotherapy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37276325"}, {"offsetInBeginSection": 313, "offsetInEndSection": 529, "text": "Vorasidenib (AG-881) has recently been reported as a promising dual inhibitor of mutant isocitrate dehydrogenase 1 and 2 with the ability to penetrate the blood-brain barrier towards the treatment of low-grade glioma", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36453510"}, {"offsetInBeginSection": 316, "offsetInEndSection": 692, "text": " Vorasidenib (AG-881) is a first-in-class, brain-penetrant, dual inhibitor of the mutant IDH1 and mutant IDH2 enzymes.PATIENTS AND METHODS: We conducted a multicenter, open-label, phase I, dose-escalation study of vorasidenib in 93 patients with mutant IDH1/2 (mIDH1/2) solid tumors, including 52 patients with glioma that had recurred or progressed following standard therapy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34078652"}, {"offsetInBeginSection": 211, "offsetInEndSection": 433, "text": " The majority of LGGs harbor mutations in the genes encoding isocitrate dehydrogenase 1 or 2 (IDH1/IDH2). Vorasidenib (AG-881) is a first-in-class, brain-penetrant, dual inhibitor of the mutant IDH1 and mutant IDH2 enzymes", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34078652"}, {"offsetInBeginSection": 148, "offsetInEndSection": 553, "text": " Vorasidenib, an oral brain-penetrant inhibitor of mutant IDH1 and IDH2 enzymes, showed preliminary activity in IDH-mutant gliomas.METHODS: In a double-blind, phase 3 trial, we randomly assigned patients with residual or recurrent grade 2 IDH-mutant glioma who had undergone no previous treatment other than surgery to receive either oral vorasidenib (40 mg once daily) or matched placebo in 28-day cycles", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37272516"}, {"offsetInBeginSection": 211, "offsetInEndSection": 692, "text": " The majority of LGGs harbor mutations in the genes encoding isocitrate dehydrogenase 1 or 2 (IDH1/IDH2). Vorasidenib (AG-881) is a first-in-class, brain-penetrant, dual inhibitor of the mutant IDH1 and mutant IDH2 enzymes.PATIENTS AND METHODS: We conducted a multicenter, open-label, phase I, dose-escalation study of vorasidenib in 93 patients with mutant IDH1/2 (mIDH1/2) solid tumors, including 52 patients with glioma that had recurred or progressed following standard therapy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34078652"}, {"offsetInBeginSection": 316, "offsetInEndSection": 802, "text": " Vorasidenib (AG-881) is a first-in-class, brain-penetrant, dual inhibitor of the mutant IDH1 and mutant IDH2 enzymes.PATIENTS AND METHODS: We conducted a multicenter, open-label, phase I, dose-escalation study of vorasidenib in 93 patients with mutant IDH1/2 (mIDH1/2) solid tumors, including 52 patients with glioma that had recurred or progressed following standard therapy. Vorasidenib was administered orally, once daily, in 28-day cycles until progression or unacceptable toxicity", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34078652"}, {"offsetInBeginSection": 148, "offsetInEndSection": 687, "text": " Vorasidenib, an oral brain-penetrant inhibitor of mutant IDH1 and IDH2 enzymes, showed preliminary activity in IDH-mutant gliomas.METHODS: In a double-blind, phase 3 trial, we randomly assigned patients with residual or recurrent grade 2 IDH-mutant glioma who had undergone no previous treatment other than surgery to receive either oral vorasidenib (40 mg once daily) or matched placebo in 28-day cycles. The primary end point was imaging-based progression-free survival according to blinded assessment by an independent review committee", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37272516"}, {"offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "BACKGROUND: Isocitrate dehydrogenase (IDH)-mutant grade 2 gliomas are malignant brain tumors that cause considerable disability and premature death. Vorasidenib, an oral brain-penetrant inhibitor of mutant IDH1 and IDH2 enzymes, showed preliminary activity in IDH-mutant gliomas", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37272516"}, {"offsetInBeginSection": 0, "offsetInEndSection": 530, "text": "BACKGROUND: Heterozygous mutations in the cytoplasmic and mitochondrial isoforms of isocitrate dehydrogenase enzymes 1 and 2 subtypes have been extensively exploited as viable druggable targets, as they decrease the affinity of isocitrate and higher affinity of D-2-hydroxyglutarate, an oncometabolite.OBJECTIVE: Vorasidenib (AG-881) has recently been reported as a promising dual inhibitor of mutant isocitrate dehydrogenase 1 and 2 with the ability to penetrate the blood-brain barrier towards the treatment of low-grade glioma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36453510"}, {"offsetInBeginSection": 702, "offsetInEndSection": 840, "text": "Vorasidenib represents a novel dual mIDH1/2 inhibitor and is currently in clinical development for the treatment of low-grade mIDH glioma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32071674"}, {"offsetInBeginSection": 317, "offsetInEndSection": 693, "text": "Vorasidenib (AG-881) is a first-in-class, brain-penetrant, dual inhibitor of the mutant IDH1 and mutant IDH2 enzymes.PATIENTS AND METHODS: We conducted a multicenter, open-label, phase I, dose-escalation study of vorasidenib in 93 patients with mutant IDH1/2 (mIDH1/2) solid tumors, including 52 patients with glioma that had recurred or progressed following standard therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34078652"}, {"offsetInBeginSection": 263, "offsetInEndSection": 393, "text": "Herein, we describe the discovery of vorasidenib (AG-881), a potent, oral, brain-penetrant dual inhibitor of both mIDH1 and mIDH2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32071674"}, {"offsetInBeginSection": 149, "offsetInEndSection": 554, "text": "Vorasidenib, an oral brain-penetrant inhibitor of mutant IDH1 and IDH2 enzymes, showed preliminary activity in IDH-mutant gliomas.METHODS: In a double-blind, phase 3 trial, we randomly assigned patients with residual or recurrent grade 2 IDH-mutant glioma who had undergone no previous treatment other than surgery to receive either oral vorasidenib (40 mg once daily) or matched placebo in 28-day cycles.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37272516"}, {"offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Vorasidenib (AG-881): A First-in-Class, Brain-Penetrant Dual Inhibitor of Mutant IDH1 and 2 for Treatment of Glioma.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32071674"}, {"offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "According to the phase III INDIGO trial, vorasidenib, an IDH1/2 inhibitor, significantly benefited adults with IDH1/2-mutant low-grade gliomas, reducing progression risk and delaying the need for chemoradiotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37276325"}, {"offsetInBeginSection": 0, "offsetInEndSection": 508, "text": "BACKGROUND: Heterozygous mutations in the cytoplasmic and mitochondrial isoforms of isocitrate dehydrogenase enzymes 1 and 2 subtypes have been extensively exploited as viable druggable targets, as they decrease the affinity of isocitrate and higher affinity of D-2-hydroxyglutarate, an oncometabolite.OBJECTIVE: Vorasidenib (AG-881) has recently been reported as a promising dual inhibitor of mutant isocitrate dehydrogenase 1 and 2 with the ability to penetrate the blood-brain barrier towards the treatmen", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36453510"}, {"offsetInBeginSection": 801, "offsetInEndSection": 993, "text": "s. Current targeted inhibitors of IDH1 (AG120, IDH305), IDH2 (AG221), and pan-IDH1/2 (AG881) selectively inhibit mutant IDH protein and induce cell differentiation in in vitro and in vivo mode", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27355333"}, {"offsetInBeginSection": 263, "offsetInEndSection": 392, "text": "Herein, we describe the discovery of vorasidenib (AG-881), a potent, oral, brain-penetrant dual inhibitor of both mIDH1 and mIDH2", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32071674"}, {"offsetInBeginSection": 274, "offsetInEndSection": 1113, "text": "ocitrate dehydrogenase 1 or 2 (IDH1/IDH2). Vorasidenib (AG-881) is a first-in-class, brain-penetrant, dual inhibitor of the mutant IDH1 and mutant IDH2 enzymes.PATIENTS AND METHODS: We conducted a multicenter, open-label, phase I, dose-escalation study of vorasidenib in 93 patients with mutant IDH1/2 (mIDH1/2) solid tumors, including 52 patients with glioma that had recurred or progressed following standard therapy. Vorasidenib was administered orally, once daily, in 28-day cycles until progression or unacceptable toxicity. Enrollment is complete; this trial is registered with ClinicalTrials.gov, NCT02481154.RESULTS: Vorasidenib showed a favorable safety profile in the glioma cohort. Dose-limiting toxicities of elevated transaminases occurred at doses \u2265100 mg and were reversible. The protocol-defined objective response rate per", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34078652"}, {"offsetInBeginSection": 272, "offsetInEndSection": 1071, "text": "yglutarate, an oncometabolite.OBJECTIVE: Vorasidenib (AG-881) has recently been reported as a promising dual inhibitor of mutant isocitrate dehydrogenase 1 and 2 with the ability to penetrate the blood-brain barrier towards the treatment of low-grade glioma. In order to combat drug resistance and toxicity levels, this compelled us to further investigate this substance as a basis for the creation of potential selective inhibitors of mutant isocitrate dehydrogenases 1 and 2.METHODS: By employing a wide range of computational techniques, binding moieties of AG-881 that contributed towards its selective binding to isocitrate dehydrogenase enzymes 1 and 2 were identified and subsequently used to generate pharmacophore models for the screening of potential inhibitor drugs that were further asse", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36453510"}, {"offsetInBeginSection": 46, "offsetInEndSection": 393, "text": "(mIDH) 1 and 2 cancer-associated enzymes prevent the accumulation of the oncometabolite d-2-hydroxyglutarate (2-HG) and are under clinical investigation for the treatment of several cancers harboring an IDH mutation. Herein, we describe the discovery of vorasidenib (AG-881), a potent, oral, brain-penetrant dual inhibitor of both mIDH1 and mIDH2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32071674"}, {"offsetInBeginSection": 41, "offsetInEndSection": 358, "text": "vorasidenib, an IDH1/2 inhibitor, significantly benefited adults with IDH1/2-mutant low-grade gliomas, reducing progression risk and delaying the need for chemoradiotherapy. Meanwhile, in a pediatric low-grade glioma cohort of FIREFLY-1, a phase II trial, robust responses to the type II pan-RAF inhibitor tovorafenib", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37276325"}, {"offsetInBeginSection": 533, "offsetInEndSection": 662, "text": "terogeneity. Nonetheless, advances have been made with the IDH1/2 inhibitor vorasidenib for IDH-mutant grade 2 gliomas, the combi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37812369"}, {"offsetInBeginSection": 136, "offsetInEndSection": 286, "text": "ature death. Vorasidenib, an oral brain-penetrant inhibitor of mutant IDH1 and IDH2 enzymes, showed preliminary activity in IDH-mutant gliomas.METHODS", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37272516"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "According to the phase III INDIGO trial, vorasidenib, an IDH1/2 inhibitor, significantly benefited adults with IDH1/2-mutant low-grade gliomas, reduci", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37276325"}, {"offsetInBeginSection": 41, "offsetInEndSection": 73, "text": "vorasidenib, an IDH1/2 inhibitor", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37276325"}, {"offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Recently, Vorasidenib (AG-881) has been reported as a therapeutic alternative that exerts potent dual inhibitory activity against mIDH1/2 towards the treatment of low-grade glioma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33982420"}, {"offsetInBeginSection": 304, "offsetInEndSection": 531, "text": "JECTIVE: Vorasidenib (AG-881) has recently been reported as a promising dual inhibitor of mutant isocitrate dehydrogenase 1 and 2 with the ability to penetrate the blood-brain barrier towards the treatment of low-grade glioma. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36453510"}, {"offsetInBeginSection": 263, "offsetInEndSection": 533, "text": "Herein, we describe the discovery of vorasidenib (AG-881), a potent, oral, brain-penetrant dual inhibitor of both mIDH1 and mIDH2. X-ray cocrystal structures allowed us to characterize the compound binding site, leading to an understanding of the dual mutant inhibition.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32071674"}, {"offsetInBeginSection": 263, "offsetInEndSection": 701, "text": "Herein, we describe the discovery of vorasidenib (AG-881), a potent, oral, brain-penetrant dual inhibitor of both mIDH1 and mIDH2. X-ray cocrystal structures allowed us to characterize the compound binding site, leading to an understanding of the dual mutant inhibition. Furthermore, vorasidenib penetrates the brain of several preclinical species and inhibits 2-HG production in glioma tissue by >97% in an orthotopic glioma mouse model.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32071674"}, {"offsetInBeginSection": 0, "offsetInEndSection": 553, "text": "BACKGROUND: Isocitrate dehydrogenase (IDH)-mutant grade 2 gliomas are malignant brain tumors that cause considerable disability and premature death. Vorasidenib, an oral brain-penetrant inhibitor of mutant IDH1 and IDH2 enzymes, showed preliminary activity in IDH-mutant gliomas.METHODS: In a double-blind, phase 3 trial, we randomly assigned patients with residual or recurrent grade 2 IDH-mutant glioma who had undergone no previous treatment other than surgery to receive either oral vorasidenib (40 mg once daily) or matched placebo in 28-day cycles", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37272516"}, {"offsetInBeginSection": 546, "offsetInEndSection": 827, "text": "Nonetheless, advances have been made with the IDH1/2 inhibitor vorasidenib for IDH-mutant grade 2 gliomas, the combination of dabrafenib and trametinib for BRAFV600E mutated gliomas, and the therapies for subsets of patients with fusions and H3K27M-altered diffuse midline gliomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37812369"}]}
+{"question_id": "66099a03fdcbea915f00001d", "question": "From what age is it recommended to start population screening for colorectal cancer?", "answer": "The US Preventive Services Task Force Recommendation Statement recommends screening for colorectal cancer in all adults aged 50 to 75 years. (A recommendation)", "relevant_passage_ids": ["34003218", "32029430", "27304597", "22393133", "22832797", "34035123", "34962727", "34794803", "34794816", "33533190", "31210710", "31279992", "34929223", "21737316", "29458155", "36403728", "16776889", "12473428", "22692444", "34630894", "35936740", "36399147", "32968365", "32095167", "33769894", "33919428", "29846947", "32740330", "31419895", "29846942", "22803015", "29508157", "37752872", "36475122", "16453208", "35367029", "35131739", "9654708", "35501176", "33734405"], "type": "factoid", "snippets": [{"offsetInBeginSection": 2296, "offsetInEndSection": 2404, "text": "The USPSTF recommends screening for colorectal cancer in all adults aged 50 to 75 years. (A recommendation) ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34003218"}, {"offsetInBeginSection": 0, "offsetInEndSection": 339, "text": "Colorectal cancer is a growing burden in adults less than 50 years old. In 2018, the American Cancer Society published a guideline update recommending a reduction in the colorectal cancer screening start age for average-risk individuals from 50 to 45. Implementing these recommendations would have important implications for public health.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32029430"}, {"offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "Colorectal cancer is a growing burden in adults less than 50 years old. In 2018, the American Cancer Society published a guideline update recommending a reduction in the colorectal cancer screening start age for average-risk individuals from 50 to 45.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32029430"}, {"offsetInBeginSection": 72, "offsetInEndSection": 339, "text": "In 2018, the American Cancer Society published a guideline update recommending a reduction in the colorectal cancer screening start age for average-risk individuals from 50 to 45. Implementing these recommendations would have important implications for public health.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32029430"}, {"offsetInBeginSection": 72, "offsetInEndSection": 487, "text": "In 2018, the American Cancer Society published a guideline update recommending a reduction in the colorectal cancer screening start age for average-risk individuals from 50 to 45. Implementing these recommendations would have important implications for public health. However, the approximate number of people impacted by this change, the average-risk population ages 45-49, is not well-described in the literature.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32029430"}, {"offsetInBeginSection": 72, "offsetInEndSection": 251, "text": "In 2018, the American Cancer Society published a guideline update recommending a reduction in the colorectal cancer screening start age for average-risk individuals from 50 to 45.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32029430"}, {"offsetInBeginSection": 1001, "offsetInEndSection": 1235, "text": "Within this population, we estimated the number of screening-eligible individuals by subtracting those with previous colorectal cancer screening (45- to 49-year-old) or up to date with colorectal cancer screening (50- to 74-year-old).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32029430"}, {"offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Estimating the Screening-Eligible Population Size, Ages 45-74, at Average Risk to Develop Colorectal Cancer in the United States.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32029430"}, {"offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Colorectal cancer incidence and mortality in patients younger than 50 years are increasing, but screening before the age of 50 is not offered in Europe.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31210710"}, {"offsetInBeginSection": 0, "offsetInEndSection": 747, "text": "This document is a focused update to the 2017 colorectal cancer (CRC) screening recommendations from the U.S. Multi-Society Task Force on Colorectal Cancer, which represents the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. This update is restricted to addressing the age to start and stop CRC screening in average-risk individuals and the recommended screening modalities. Although there is no literature demonstrating that CRC screening in individuals under age 50 improves health outcomes such as CRC incidence or CRC-related mortality, sufficient data support the U.S. Multi-Society Task Force to suggest average-risk CRC screening begin at age 45.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34794803"}, {"offsetInBeginSection": 0, "offsetInEndSection": 747, "text": "This document is a focused update to the 2017 colorectal cancer (CRC) screening recommendations from the U.S. Multi-Society Task Force on Colorectal Cancer, which represents the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. This update is restricted to addressing the age to start and stop CRC screening in average-risk individuals and the recommended screening modalities. Although there is no literature demonstrating that CRC screening in individuals under age 50 improves health outcomes such as CRC incidence or CRC-related mortality, sufficient data support the U.S. Multi-Society Task Force to suggest average-risk CRC screening begin at age 45.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34794816"}, {"offsetInBeginSection": 469, "offsetInEndSection": 747, "text": "Although there is no literature demonstrating that CRC screening in individuals under age 50 improves health outcomes such as CRC incidence or CRC-related mortality, sufficient data support the U.S. Multi-Society Task Force to suggest average-risk CRC screening begin at age 45.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34794803"}, {"offsetInBeginSection": 748, "offsetInEndSection": 1083, "text": "This recommendation is based on the increasing disease burden among individuals under age 50, emerging data that the prevalence of advanced colorectal neoplasia in individuals ages 45 to 49 approaches rates in individuals 50 to 59, and modeling studies that demonstrate the benefits of screening outweigh the potential harms and costs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34794803"}, {"offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "ABSTRACT: The US Preventive Services Task Force recently expanded its colorectal cancer screening recommendations to start screening adults with average risk profile at age 45.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36399147"}, {"offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "The United States Preventive Services Task Force (USPSTF) recently issued an updated recommendation for population-based colorectal cancer (CRC) screening starting at age 45, due to a sustained increase in the incidence of early-age-at-onset CRC (eoCRC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34929223"}, {"offsetInBeginSection": 534, "offsetInEndSection": 646, "text": "new screening recommendations have recently lowered the age for screening average-risk individuals from 50 to 45", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32968365"}, {"offsetInBeginSection": 1311, "offsetInEndSection": 1700, "text": "Although Multi-Society Task Force (MSTF) and American College of Physicians (ACP) recommend initiating screening colonoscopy at age 50 years in all individuals except African Americans who should begin screening colonoscopy at age 45 years, the American Cancer Society (ACS) recommends initiating screening colonoscopy at age 45 years in all individuals irrespective of race and ethnicity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32095167"}, {"offsetInBeginSection": 531, "offsetInEndSection": 655, "text": "ning.METHODS AND MATERIALS: Screening strategies were simulated for individuals without CRC at age 40 and screened from ages", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33769894"}, {"offsetInBeginSection": 120, "offsetInEndSection": 649, "text": "Organized screening programs targeting Canadians aged 50 to 74 at average risk of developing the disease have contributed to decreased rates of CRC, improved patient outcomes and reduced healthcare costs. However, data shows that recent incidence reductions are unique to the screening-age population, while rates in people under-50 are on the rise. Similar incidence patterns in the United States prompted the American Cancer Society and U.S. Preventive Services Task Force to recommend screening begin at age 45 rather than 50.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33919428"}, {"offsetInBeginSection": 1973, "offsetInEndSection": 2248, "text": " G-score ranged from 0.59 to 0.60. Although screening is recommended to begin at age 50 years for individuals with no family history of CRC, starting ages calculated based on combined E-score and G-score differed by 12 years for men and 14 for women, for\u00a0individuals with the", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29458155"}, {"offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "The U.S. Preventive Services Task Force issued new guidelines in May that recommend screening for colorectal cancer starting at age 45, rather than 50 as previously advised.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34035123"}, {"offsetInBeginSection": 753, "offsetInEndSection": 879, "text": "Results from modeling analyses identified efficient and model-recommendable strategies that started screening at age 45 years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29846947"}, {"offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "INTRODUCTION: Colorectal cancer (CRC) screening generally starts screening by the age of 50 based on guidelines. Lately however, a U.S. guideline recommended to start CRC screening from age 45 and, very recently, two studies were published that addressed young-onset in Eu", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31279992"}, {"offsetInBeginSection": 166, "offsetInEndSection": 487, "text": "the colorectal cancer screening start age for average-risk individuals from 50 to 45. Implementing these recommendations would have important implications for public health. However, the approximate number of people impacted by this change, the average-risk population ages 45-49, is not well-described in the literature.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32029430"}, {"offsetInBeginSection": 0, "offsetInEndSection": 886, "text": "ABSTRACT: Colorectal cancer (CRC) ranks third in both cancer diagnoses and cancer-related deaths in men and women in the United States. Fortunately, both incidence and deaths have declined due to the increased use of CRC screening to find and remove precancerous polyps and to diagnose CRC at earlier, more treatable stages. Deaths from CRC have shifted to a new demographic, with a recent increase in incidence of 2% per year in people younger than 55 years. The American Cancer Society has issued a qualified recommendation that screening start at the age of 45 years because of this increase in early-onset CRC. There are multiple CRC screening test options. Professional organizations vary in their screening guidelines, but regardless of these differences, screening has been shown to save lives. Currently, one out of every three adults aged 50-75 years are not screened as recomm", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32740330"}, {"offsetInBeginSection": 1593, "offsetInEndSection": 1804, "text": "hrough the age of 75 years.CONCLUSIONS: Microsimulation modeling suggests that CRC screening should be considered from the age of 45 years for blacks and for whites if the lifetime risk has increased proportiona", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29846942"}, {"offsetInBeginSection": 67, "offsetInEndSection": 247, "text": " in Canada. Screening guidelines recommend that first-time screening should occur at 50 years of age for average-risk individuals and at 40 years of age for those with a family his", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22803015"}, {"offsetInBeginSection": 115, "offsetInEndSection": 265, "text": "tely however, a U.S. guideline recommended to start CRC screening from age 45 and, very recently, two studies were published that addressed young-onse", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31279992"}, {"offsetInBeginSection": 670, "offsetInEndSection": 820, "text": "lti-Society Task Force to suggest average-risk CRC screening begin at age 45. This recommendation is based on the increasing disease burden among indi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34962727"}, {"offsetInBeginSection": 670, "offsetInEndSection": 820, "text": "lti-Society Task Force to suggest average-risk CRC screening begin at age 45. This recommendation is based on the increasing disease burden among indi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34794803"}, {"offsetInBeginSection": 670, "offsetInEndSection": 820, "text": "lti-Society Task Force to suggest average-risk CRC screening begin at age 45. This recommendation is based on the increasing disease burden among indi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34794816"}, {"offsetInBeginSection": 5, "offsetInEndSection": 170, "text": "The United States Preventive Services Taskforce (USPSTF) recently recommended lowering the age for average-risk colorectal cancer (CRC) screening from 50 to 45\u2009years", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37752872"}, {"offsetInBeginSection": 1262, "offsetInEndSection": 1399, "text": "Ninety-seven percent believe that colorectal cancer screening for asymptomatic average-risk patients aged 45 years and older is effective", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36475122"}, {"offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "AIMS: While most guidelines still recommend colorectal cancer (CRC) screening initiation at age 50\u00a0years in average-risk individuals, guideline-creating bodies are starting to lower the recommended age of initiation to 45\u00a0years to mitigate the trend of increasing CRC rates in younger populations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33769894"}, {"offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "BACKGROUND: It is strongly recommended that adults aged 50-75 years be screened for colorectal cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34088751"}, {"offsetInBeginSection": 177, "offsetInEndSection": 390, "text": " Via the colorectal cancer screening program, all average-risk individuals in the 50-74-year age group are invited every 2\u00a0years to do a guaiac-based or, since April 2015, an immunochemical fecal occult blood test", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29508157"}, {"offsetInBeginSection": 74, "offsetInEndSection": 283, "text": "recommend screening for colorectal cancer starting at age 45, rather than 50 as previously advised. The lower-age recommendation comes in response to a worrying uptick in diagnoses among middle-aged Americans.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34035123"}, {"offsetInBeginSection": 60, "offsetInEndSection": 298, "text": "anded its colorectal cancer screening recommendations to start screening adults with average risk profile at age 45. In the face of rising healthcare costs, limited medical resources, and in order to facilitate shared decision-making conv", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36399147"}, {"offsetInBeginSection": 721, "offsetInEndSection": 1312, "text": "screening begin at age 45. This recommendation is based on the increasing disease burden among individuals under age 50, emerging data that the prevalence of advanced colorectal neoplasia in individuals ages 45 to 49 approaches rates in individuals 50 to 59, and modeling studies that demonstrate the benefits of screening outweigh the potential harms and costs. For individuals ages 76 to 85, the decision to start or continue screening should be individualized and based on prior screening history, life expectancy, CRC risk, and personal preference. Screening is not recommended after age", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34794803"}, {"offsetInBeginSection": 721, "offsetInEndSection": 1312, "text": "screening begin at age 45. This recommendation is based on the increasing disease burden among individuals under age 50, emerging data that the prevalence of advanced colorectal neoplasia in individuals ages 45 to 49 approaches rates in individuals 50 to 59, and modeling studies that demonstrate the benefits of screening outweigh the potential harms and costs. For individuals ages 76 to 85, the decision to start or continue screening should be individualized and based on prior screening history, life expectancy, CRC risk, and personal preference. Screening is not recommended after age", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34794816"}, {"offsetInBeginSection": 721, "offsetInEndSection": 1312, "text": "screening begin at age 45. This recommendation is based on the increasing disease burden among individuals under age 50, emerging data that the prevalence of advanced colorectal neoplasia in individuals ages 45 to 49 approaches rates in individuals 50 to 59, and modeling studies that demonstrate the benefits of screening outweigh the potential harms and costs. For individuals ages 76 to 85, the decision to start or continue screening should be individualized and based on prior screening history, life expectancy, CRC risk, and personal preference. Screening is not recommended after age", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34962727"}, {"offsetInBeginSection": 32, "offsetInEndSection": 757, "text": "ts-all approach to colorectal cancer (CRC) screening that does not account for CRC risk factors is not conducive to personalized screening. On the basis of the principle of equal management of equal risks, we aimed to tailor and validate risk-adapted starting ages of CRC screening for individuals with different CRC risk factors.METHODS: A multi-center community-based population cohort (N\u00a0= 3,165,088) was used to evaluate the starting age of CRC screening with comprehensive consideration of risk factors. Age-specific 10-year cumulative risk curves were used to determine when individuals at greater risk for CRC reached the same risk level as the 50-year-old general population, which is currently the recommended starti", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36403728"}, {"offsetInBeginSection": 0, "offsetInEndSection": 747, "text": "This document is a focused update to the 2017 colorectal cancer (CRC) screening recommendations from the U.S. Multi-Society Task Force on Colorectal Cancer, which represents the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. This update is restricted to addressing the age to start and stop CRC screening in average-risk individuals and the recommended screening modalities. Although there is no literature demonstrating that CRC screening in individuals under age 50 improves health outcomes such as CRC incidence or CRC-related mortality, sufficient data support the U.S. Multi-Society Task Force to suggest average-risk CRC screening begin at age 45.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34962727"}, {"offsetInBeginSection": 748, "offsetInEndSection": 1316, "text": "This recommendation is based on the increasing disease burden among individuals under age 50, emerging data that the prevalence of advanced colorectal neoplasia in individuals ages 45 to 49 approaches rates in individuals 50 to 59, and modeling studies that demonstrate the benefits of screening outweigh the potential harms and costs. For individuals ages 76 to 85, the decision to start or continue screening should be individualized and based on prior screening history, life expectancy, CRC risk, and personal preference. Screening is not recommended after age\u00a085.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34794803"}, {"offsetInBeginSection": 488, "offsetInEndSection": 1235, "text": "Here, we provide methodology to conservatively estimate the average-risk and screening-eligible population in the United States, including those who would be impacted by a lowered colorectal cancer screening start age. Using multiple data sources, we estimated the current average-risk population by subtracting individuals with symptomatic colorectal cancer, with a family history of colorectal cancer, and with inflammatory bowel disease and hereditary nonpolyposis colorectal cancer from the total population. Within this population, we estimated the number of screening-eligible individuals by subtracting those with previous colorectal cancer screening (45- to 49-year-old) or up to date with colorectal cancer screening (50- to 74-year-old).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32029430"}, {"offsetInBeginSection": 614, "offsetInEndSection": 1145, "text": "for Colorectal Cancer recommended screening to commence at 45 years for NHB; this recommendation was supplanted by data showing an increase in early-onset CRCs in non-Hispanic Whites approaching the under-50-year rates observed for NHB. Subsequently the American Cancer Society and the USPSTF recommended that the entire average-risk population move to commence CRC screening at 45 years. Implementing screening in 45-49-year-olds has its challenges as younger groups compared with older groups participate less in preventive care.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35936740"}, {"offsetInBeginSection": 198, "offsetInEndSection": 252, "text": "the screening age for colorectal cancer from 50 to 45.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35131739"}, {"offsetInBeginSection": 10, "offsetInEndSection": 1174, "text": ": Screening for early detection of colorectal cancer (CRC), adenomatous polyps, and precancerous lesions can reduce mortality. This review aimed to illustrate methods, guidelines, and clinical utility of CRC screening programs.METHODS: Literature search of PubMed and Scopus electronic databases was independently performed by two authors in September 2021. Articles discussing CRC screening methods and updated guidelines were reviewed.RESULTS: After reviewing the full text of 55 studies, it was found that the screening tests for CRC are divided into stool-based, endoscopic, and molecular. All CRC screening guidelines recommend screening starting at age 45-50, but vary regarding screening methods, frequency, and timing of screening discontinuation. Controversies include clinical benefits of screening the elderly and discontinuation of screening. Effective screening barriers involve patient- and healthcare-related factors.CONCLUSION: Overall, screening should start at age 45-50 for average-risk individuals. Colonoscopy and FIT tests are standard modalities recommended for regular screening. Increasing public awareness of the importance of screening a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35367029"}, {"offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "People at average risk for colorectal cancer (asymptomatic, age > or = 45 years, no risk factors) are offered fecal occult blood testing each year and sigmoidoscopy every five years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9654708"}, {"offsetInBeginSection": 1261, "offsetInEndSection": 1387, "text": "age of 45 years for blacks. When CRC risk was assumed to be increased, the models recommended starting at the age of 45 years,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29846942"}, {"offsetInBeginSection": 1166, "offsetInEndSection": 1600, "text": "Similar benefits of sex-stratification are found at other FIT thresholds, but become negligible if mean screening start age is reduced to 50.CONCLUSION: Where resources are constrained and it is not feasible to screen everyone from the age of 50, starting screening earlier in men than women is likely to be more cost-effective and gain more health benefits overall than strategies where men and women start screening at the same age.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33533190"}, {"offsetInBeginSection": 1058, "offsetInEndSection": 1307, "text": "The ACS recommends that adults aged 45 years and older with an average risk of CRC undergo regular screening with either a high-sensitivity stool-based test or a structural (visual) examination, depending on patient preference and test availability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29846947"}, {"offsetInBeginSection": 1446, "offsetInEndSection": 1633, "text": "The recommendation to begin screening at age 45 years is a qualified recommendation. The recommendation for regular screening in adults aged 50 years and older is a strong recommendation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29846947"}, {"offsetInBeginSection": 137, "offsetInEndSection": 324, "text": "2021 US Preventive Service Task Force (USPSTF) guidelines and available evidence support routine screening from ages 45 to 75, and individualized consideration of screening ages 76 to 85.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35501176"}, {"offsetInBeginSection": 614, "offsetInEndSection": 852, "text": " (response rate, 61.9%).RESULTS: The most commonly recommended starting age for colorectal cancer screening and polyp diagnosis was 50 years old in the average risk group, and 40 years old in groups who had a family history of colon cance", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22832797"}, {"offsetInBeginSection": 1423, "offsetInEndSection": 1685, "text": "% to 0.03%, Ptrend < .001). When using age 45\u2009years as the benchmark to start screening, individuals with risk scores of 0-2, 3, 4, 5, and 6-8 attained the threshold CRC risk level (10-year cumulative risk of 0.47%) at age 51 years, 48 years, 45 years, 42 years,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33734405"}]}
+{"question_id": "65f03bf8c4010b4d78000003", "question": "What is acupotomy?", "answer": "Acupotomy is a modern type of acupuncture that uses a blade-needle combined with a flat surgical scalpel at its tip.", "relevant_passage_ids": ["37123050", "36050272", "32280270", "31393365", "31383431"], "type": "summary", "snippets": [{"offsetInBeginSection": 186, "offsetInEndSection": 302, "text": "Acupotomy, as one kind acupuncture that has flat knife-shaped tip, has been widely used for treating shoulder pain. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37123050"}, {"offsetInBeginSection": 11, "offsetInEndSection": 91, "text": "Acupotomy is a modern acupuncture method that includes modern surgical methods. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36050272"}, {"offsetInBeginSection": 12, "offsetInEndSection": 212, "text": "Acupotomy, which involves the addition of a scalpel function to the conventional acupuncture treatment, has recently been applied as a conservative treatment method for lumbar disc herniation (LDH). T", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32280270"}, {"offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "BACKGROUND AND PURPOSE: Acupotomy is a modern type of acupuncture that uses a blade-needle combined with a flat surgical scalpel at its tip.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31383431"}, {"offsetInBeginSection": 376, "offsetInEndSection": 695, "text": "Conversely, acupotomy is a minimally invasive technique that combines the effects of conventional acupuncture with micro-incision, which may offer an alternative to surgery for the treatment of LSS. This review was conducted to investigate and critically review the current evidence on the efficacy and safety of acupot", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31393365"}, {"offsetInBeginSection": 175, "offsetInEndSection": 290, "text": "ic burden. Acupotomy, as one kind acupuncture that has flat knife-shaped tip, has been widely used for treating sho", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37123050"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "BACKGROUND: Acupotomy, which involves the addition of a scalpel function to the conventional acupuncture treatment, has recently been applied as a con", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32280270"}, {"offsetInBeginSection": 0, "offsetInEndSection": 363, "text": "BACKGROUND AND PURPOSE: Acupotomy is a modern type of acupuncture that uses a blade-needle combined with a flat surgical scalpel at its tip. This study was conducted to summarize and critically evaluate the current evidence on acupotomy.MATERIALS AND METHODS: All relevant studies up to February 19, 2019, were included, through comprehensive searches in 11 elect", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31383431"}]}
+{"question_id": "660d7324fdcbea915f000040", "question": "How many people affected by Parkinson's Disease develop dementia?", "answer": "Approximately a quarter of people affected by Parkinson's disease develop Parkinsonn's disease dementia.", "relevant_passage_ids": ["34896923"], "type": "factoid", "snippets": [{"offsetInBeginSection": 747, "offsetInEndSection": 793, "text": "The global pooled dementia frequency was 26.3%", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34896923"}, {"offsetInBeginSection": 1245, "offsetInEndSection": 1313, "text": "approximately one-quarter of the PD patients were diagnosed with PDD", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34896923"}]}
+{"question_id": "661c3d1448a2c27714000005", "question": "What chromatin signatures are characteristic of active enhancers?", "answer": "Enhancers are cis-regulatory elements that can stimulate gene expression from long distances and drive precise spatiotemporal gene expression profiles during development. Active enhancers display specific chromatin signatures including histone H3 lysine 27 acetylation (H3K27ac) and histone H3 lysine 4 mono-methylation (H3K4me1). These features are modified upon developmental cues which impacts their activity.", "relevant_passage_ids": ["36602897", "22593555", "22421546", "21160473", "23880941", "17277777", "28981749", "37024579", "24599251", "21632746", "38011682", "33034351", "37312570", "31944157", "34309923", "21106759", "34195788", "24038352", "33623376", "36823213", "35580127", "35121725", "32616859", "29498679", "30858345", "27089178", "26957309", "23739122", "27792455"], "type": "list", "snippets": [{"offsetInBeginSection": 317, "offsetInEndSection": 513, "text": "Drosophila embryos suggest that active enhancers form part of a defined chromatin landscape marked by histone H3 lysine 4 mono-methylation (H3K4me1) and histone H3 lysine 27 acetylation (H3K27ac).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22593555"}, {"offsetInBeginSection": 0, "offsetInEndSection": 449, "text": "Enhancers are cis-regulatory elements that can stimulate gene expression from distance, and drive precise spatiotemporal gene expression profiles during development. Functional enhancers display specific features including an open chromatin conformation, Histone H3 lysine 27 acetylation, Histone H3 lysine 4 mono-methylation enrichment, and enhancer RNAs production. These features are modified upon developmental cues which impacts their activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36602897"}, {"offsetInBeginSection": 452, "offsetInEndSection": 1339, "text": "The coexistence of high mono-methylation and low tri-methylation levels of lysine 4 of histone H3 is considered a signature of enhancers, but a comprehensive view of histone modifications associated to enhancers is still lacking. By combining chromatin immunoprecipitation (ChIP) with mass spectrometry, we investigated cis-regulatory regions in macrophages to comprehensively identify histone marks specifically associated with enhancers, and to profile their dynamics after transcriptional activation elicited by an inflammatory stimulation. The intersection of the proteomics data with ChIP-seq and RNA-seq analyses revealed the existence of novel subpopulations of enhancers, marked by specific histone modification signatures: specifically, H3K4me1/K36me2 marks transcribed enhancers, while H3K4me1/K36me3 and H3K4me1/K79me2 combinations mark distinct classes of intronic enhancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28981749"}, {"offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Histone H3K4me1 and H3K27ac are enhancer-specific modifications and are required for enhancers to activate transcription of target genes. However, the reciprocal effects of these histone modifications on each other and their roles in enhancers are not clear.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34309923"}, {"offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Histone H3K4me1 and H3K27ac are enhancer-specific modifications and are required for enhancers to activate transcription of target genes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34309923"}, {"offsetInBeginSection": 452, "offsetInEndSection": 995, "text": "The coexistence of high mono-methylation and low tri-methylation levels of lysine 4 of histone H3 is considered a signature of enhancers, but a comprehensive view of histone modifications associated to enhancers is still lacking. By combining chromatin immunoprecipitation (ChIP) with mass spectrometry, we investigated cis-regulatory regions in macrophages to comprehensively identify histone marks specifically associated with enhancers, and to profile their dynamics after transcriptional activation elicited by an inflammatory stimulation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28981749"}, {"offsetInBeginSection": 0, "offsetInEndSection": 519, "text": "Histone H3K4me1 and H3K27ac are enhancer-specific modifications and are required for enhancers to activate transcription of target genes. However, the reciprocal effects of these histone modifications on each other and their roles in enhancers are not clear. Here to comparatively analyze the role of these modifications, we inhibited H3K4me1 and H3K27ac by deleting the SET domains of histone methyltransferases MLL3 and MLL4 and the HAT domain of histone acetyltransferase p300, respectively, in erythroid K562 cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34309923"}, {"offsetInBeginSection": 999, "offsetInEndSection": 1220, "text": "We describe a chromatin state signature associated with active developmental enhancers, defined by high levels of H3K27ac marking, nucleosome displacement, hypersensitivity to sonication, and strong depletion of H3K27me3.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22421546"}, {"offsetInBeginSection": 166, "offsetInEndSection": 367, "text": "Functional enhancers display specific features including an open chromatin conformation, Histone H3 lysine 27 acetylation, Histone H3 lysine 4 mono-methylation enrichment, and enhancer RNAs production.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36602897"}, {"offsetInBeginSection": 245, "offsetInEndSection": 394, "text": "H3K27ac is a characteristic marker for identifying active enhancers and even indicates chromatin accessibility associated with super-enhancers (SEs).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35121725"}, {"offsetInBeginSection": 819, "offsetInEndSection": 990, "text": "While mono-methylation of H3K4 (H3K4me1) is located preferentially at active enhancers, tri-methylation (H3K4me3) is a mark found at open and potentially active promoters.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29498679"}, {"offsetInBeginSection": 261, "offsetInEndSection": 513, "text": "Studies performed on mammalian embryonic stem cells and Drosophila embryos suggest that active enhancers form part of a defined chromatin landscape marked by histone H3 lysine 4 mono-methylation (H3K4me1) and histone H3 lysine 27 acetylation (H3K27ac).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22593555"}, {"offsetInBeginSection": 347, "offsetInEndSection": 484, "text": "H2BNTac prominently marks candidate active enhancers and a subset of promoters and discriminates them from ubiquitously active promoters.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37024579"}, {"offsetInBeginSection": 231, "offsetInEndSection": 346, "text": "Here we establish histone H2B N-terminus multisite lysine acetylation (H2BNTac) as a signature of active enhancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37024579"}, {"offsetInBeginSection": 438, "offsetInEndSection": 651, "text": "Genome-wide analyses have revealed chromatin signatures of enhancers, such as the enrichment for monomethylation of histone H3 lysine 4 (H3K4me1) and the acetylation or methylation of histone H3 lysine 27 (H3K27).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24599251"}, {"offsetInBeginSection": 287, "offsetInEndSection": 412, "text": "Individual chromatin marks, such as H3K27ac and H3K27me3, have been identified to distinguish active from inactive enhancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24038352"}, {"offsetInBeginSection": 511, "offsetInEndSection": 758, "text": "In general, transcription start sites of actively transcribed genes are marked by trimethylated H3K4 (H3K4me3) and acetylated H3K27 (H3K27ac), and active enhancers can be identified by enrichments of both monomethylated H3K4 (H3K4me1) and H3K27ac.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23739122"}, {"offsetInBeginSection": 718, "offsetInEndSection": 842, "text": "We find that histone H3K27ac distinguishes active enhancers from inactive/poised enhancer elements containing H3K4me1 alone.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21106759"}, {"offsetInBeginSection": 135, "offsetInEndSection": 307, "text": "Specific histone modifications, such as monomethylation on histone H3 lysine 4 (H3K4me1) and H3K27ac, have been widely used to assign enhancer regions in mammalian genomes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33034351"}, {"offsetInBeginSection": 101, "offsetInEndSection": 284, "text": "Co-occurrence of acetylation of histone H3 at lysine 27 (H3K27ac) and mono methylation of histone H3 at lysine 4 (H3K4me1) has been widely used for identification of active enhancers.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27792455"}]}
+{"question_id": "661d4fabeac11fad3300001c", "question": "What are the types of Ehlers-Danlos Syndrome?", "answer": "There are 13 recognized subtypes: classical, classical-like, cardiac-valvular, vascular, hypermobile, arthrochlasia, dermosparaxis, kyphoscoliotic, brittle cornea syndrome, spondylodysplastic, musculocontractural, myopathic, and periodontal.", "relevant_passage_ids": ["33437956", "10906878", "9762220", "20847697", "34807421", "17487505", "16638060", "28306225", "32732924", "21966332", "34807422", "32162201", "33498938", "36727144", "37214418", "30858776", "35396906", "30983397", "34437011", "962660", "7944780", "23762718", "29709596", "7455751", "34927503", "19818579", "7352721", "26919608", "28866967", "11642233", "28306229", "30759870"], "type": "list", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 344, "text": "Ehlers-Danlos Syndrome (EDS) is a family of multisystemic hereditary connective tissue disorders now comprised of 13 recognized subtypes, classical, classical-like, cardiac-valvular, vascular, hypermobile, arthrochlasia, dermosparaxis, kyphoscoliotic, brittle cornea syndrome, spondylodysplastic, musculocontractural, myopathic, and periodontal", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33437956"}, {"offsetInBeginSection": 0, "offsetInEndSection": 420, "text": "Ehlers-Danlos Syndrome (EDS) is a family of multisystemic hereditary connective tissue disorders now comprised of 13 recognized subtypes, classical, classical-like, cardiac-valvular, vascular, hypermobile, arthrochlasia, dermosparaxis, kyphoscoliotic, brittle cornea syndrome, spondylodysplastic, musculocontractural, myopathic, and periodontal, as designated by the most recent 2017 International classification system.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33437956"}, {"offsetInBeginSection": 0, "offsetInEndSection": 617, "text": "Ehlers-Danlos Syndrome (EDS) is a family of multisystemic hereditary connective tissue disorders now comprised of 13 recognized subtypes, classical, classical-like, cardiac-valvular, vascular, hypermobile, arthrochlasia, dermosparaxis, kyphoscoliotic, brittle cornea syndrome, spondylodysplastic, musculocontractural, myopathic, and periodontal, as designated by the most recent 2017 International classification system. Clinical presentation of this disease can range from mild manifestations including skin hyperextensibility and joint hypermobility, to more severe complications such as vascular and organ rupture.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33437956"}, {"offsetInBeginSection": 0, "offsetInEndSection": 751, "text": "Ehlers-Danlos Syndrome (EDS) is a family of multisystemic hereditary connective tissue disorders now comprised of 13 recognized subtypes, classical, classical-like, cardiac-valvular, vascular, hypermobile, arthrochlasia, dermosparaxis, kyphoscoliotic, brittle cornea syndrome, spondylodysplastic, musculocontractural, myopathic, and periodontal, as designated by the most recent 2017 International classification system. Clinical presentation of this disease can range from mild manifestations including skin hyperextensibility and joint hypermobility, to more severe complications such as vascular and organ rupture. While there may be accompanying inflammation in some of the subtypes of EDS, the pathogenic mechanisms have not been clearly defined.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33437956"}, {"offsetInBeginSection": 0, "offsetInEndSection": 486, "text": "PURPOSE OF REVIEW: To summarize the bone findings, mainly bone mass and fracture risk, in Ehlers-Danlos syndromes (EDS).RECENT FINDINGS: Low bone mineral density and fractures seem to be frequent in some of the rare EDS types (kyphoscoliotic, arthrochalasia, spondylodysplastic, and classic-like EDS). For the more prevalent hypermobile and classic EDS types, some case-control studies found mildly decreased bone mineral density, but it was not clear that fracture rates were increased", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32162201"}, {"offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "PURPOSE OF REVIEW: To summarize the bone findings, mainly bone mass and fracture risk, in Ehlers-Danlos syndromes (EDS).RECENT FINDINGS: Low bone mineral density and fractures seem to be frequent in some of the rare EDS types (kyphoscoliotic, arthrochalasia, spondylodysplastic, and classic-like EDS)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32162201"}, {"offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "We report an extremely rare case of combined classical and periodontal Ehlers-Danlos syndrome (EDS) with early severe periodontitis and a generalized lack of attached gingiva. A German family with classical EDS was investigated by physical and dental evaluation and exome and Sanger sequencing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33498938"}, {"offsetInBeginSection": 0, "offsetInEndSection": 417, "text": "We report an extremely rare case of combined classical and periodontal Ehlers-Danlos syndrome (EDS) with early severe periodontitis and a generalized lack of attached gingiva. A German family with classical EDS was investigated by physical and dental evaluation and exome and Sanger sequencing. Due to the specific periodontal phenotype in the affected child, an additional diagnosis of periodontal EDS was suspected.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33498938"}, {"offsetInBeginSection": 221, "offsetInEndSection": 922, "text": "The main forms are classical, hypermobile, vascular, kyphoscoliotic A/B, arthrochalasis A/B and dermatosparaxis types.PATIENTS AND METHODS: We report our experience in diagnosis and classification of Ehlers-Danlos-syndrome, especially with the combination of clinical and morphological criteria, at the Department of Dermatology of the University of Heidelberg with more than 600 patients between 1984 and 2004.RESULTS: We classified those types of EDS which are characterized by regular and characteristic ultrastructural changes in the dermal components, primarily collagen, including the classical, hypermobile and vascular types as well as the less-common arthrochalasis and dermatosparaxis types.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16638060"}, {"offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "INTRODUCTION: The Ehlers-Danlos syndrome (EDS) is a non-inflammatory, heritable connective tissue disorder divided into 13 types according to the 2017 International Classification of the Ehlers-Dan", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30858776"}, {"offsetInBeginSection": 182, "offsetInEndSection": 435, "text": "Fourteen subtypes of Ehlers-Danlos Syndrome (EDS) have been described, each with characteristic phenotypes and associated genes. Pathogenic variants in COL5A1 and COL5A2 cause the classical EDS subtypes. Pathogenic variants in COL3A1 cause vascular EDS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35396906"}, {"offsetInBeginSection": 772, "offsetInEndSection": 983, "text": "The novel international nosology of Ehlers-Danlos syndromes published in 2017 delineates 13 clinical subtypes, describes their genetic background and defines major and minor diagnostic criteria for each subtype.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30983397"}, {"offsetInBeginSection": 224, "offsetInEndSection": 390, "text": "In the Villefranche Nosology, six subtypes were recognized: The classical, hypermobile, vascular, kyphoscoliotic, arthrochalasis, and dermatosparaxis subtypes of EDS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28306225"}, {"offsetInBeginSection": 458, "offsetInEndSection": 638, "text": "Types include classical EDS (EDS I/II), hypermobility EDS (EDS III), vascular EDS (EDS IV), kyphoscoliosis EDS (EDS VI), arthrochalasia (EDS VIIA, B) and Dermatospraxis (EDS VIIC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23762718"}, {"offsetInBeginSection": 85, "offsetInEndSection": 402, "text": "the Ehlers-Danlos syndrome type VI. Previously reported cases of the Ehlers-Danlos syndrome type VI showed a deficiency of lysyl hydroxylase in cultured fibroblasts. Assays of cultured skin fibroblasts from these two boys yielded normal activity of this enzyme, suggesting that there are two variants of this disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/962660"}, {"offsetInBeginSection": 63, "offsetInEndSection": 171, "text": "itted to patients with Ehlers-Danlos syndrome hypermobile type (hEDS), what symptoms they perceive as having", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34927503"}, {"offsetInBeginSection": 34, "offsetInEndSection": 179, "text": "permobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT) commonly suffer from pain. How this hereditary connective tissue dis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26919608"}, {"offsetInBeginSection": 20, "offsetInEndSection": 152, "text": "Syndrome/Ehlers-Danlos Syndrome-Hypermobility Type (JHS/EDS-HT) is a complex and multisystemic condition which significantly impacts", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28866967"}, {"offsetInBeginSection": 307, "offsetInEndSection": 456, "text": "In this chapter, we discuss two types of EDS that are associated with proteoglycan abnormalities: spondylodysplastic EDS and musculocontractural EDS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34807422"}, {"offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Two patients were treated emergently for impending ruptured thoracic aortic aneurysms caused by type IV Ehlers-Danlos syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7944780"}, {"offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Retroperitoneal hemorrhagic bleeding is a known manifestation of Type-IV Ehlers-Danlos Syndrome that is caused by loss-of-function mutations of the pro-alpha-1 chains of type III pro-collagen (COL3A1) resulting in vascular fragility.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21966332"}, {"offsetInBeginSection": 213, "offsetInEndSection": 363, "text": "gility. The main forms are classical, hypermobile, vascular, kyphoscoliotic A/B, arthrochalasis A/B and dermatosparaxis types.PATIENTS AND METHODS: We", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16638060"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "The vascular type of Ehlers-Danlos syndrome (type IV) is an infrequent disease caused by heterozygous germline mutations in the procollagen 3A gene (C", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17487505"}, {"offsetInBeginSection": 15, "offsetInEndSection": 165, "text": "yndrome is a rare inherited disease of connective tissue. Patients with type IV Ehlers-Danlos syndrome are likely to present with arterial disorders s", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19818579"}, {"offsetInBeginSection": 465, "offsetInEndSection": 631, "text": "The 2017 International Classification of Ehlers-Danlos syndromes and related disorders identifies 13 clinical types due to deleterious variants in 19 different genes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34807421"}, {"offsetInBeginSection": 0, "offsetInEndSection": 320, "text": "INTRODUCTION: Ehlers-Danlos syndrome is a well classified connective tissue disorder recognized by its features of hyperextensibility of joints and hyperelasticity of the skin. However, the rare vascular type (Ehlers-Danlos type IV) is more difficult to identify in the absence, rarity, or subtlety of the classical phys", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34437011"}, {"offsetInBeginSection": 0, "offsetInEndSection": 436, "text": "Classic Ehlers-Danlos syndrome is a heritable connective tissue disorder characterized by skin hyperextensibility, fragile and soft skin, delayed wound healing with formation of atrophic scars, easy bruising, and generalized joint hypermobility. It comprises Ehlers-Danlos syndrome type I and Ehlers-Danlos syndrome type II, but it is now apparent that these form a continuum of clinical findings and differ only in phenotypic severity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20847697"}, {"offsetInBeginSection": 0, "offsetInEndSection": 983, "text": "In this review article, the authors summarize the clinical aspects of the novel classification of Ehlers-Danlos syndrome, which is a group of rare, hereditary connective tissue disorders. The leading symptom of the Ehlers-Danlos syndrome group is joint hypermobility, skin hyperextensibility and generalized tissue fragility. Ehlers-Danlos syndrome displays a high clinical and genetic heterogeneity and harbors many multidisciplinary properties. Certain subtypes only affect the quality of life, while other forms may lead to severe, even fatal vascular or intestinal complications. Last year, based on the data of various international genotype-phenotype correlation studies of large populations, a new classification of the syndrome's clinical subtypes was introduced. The novel international nosology of Ehlers-Danlos syndromes published in 2017 delineates 13 clinical subtypes, describes their genetic background and defines major and minor diagnostic criteria for each subtype.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30983397"}, {"offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "The Ehlers-Danlos Syndromes (EDS), a group of hereditary connective tissue disorders, were classified into 13 subtypes in the 2017 International Classification", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37214418"}, {"offsetInBeginSection": 468, "offsetInEndSection": 775, "text": "THODS: We screened serum samples from 151 patients with the classic, hypermobility, or vascular types of the Ehlers-Danlos syndrome; 75 patients with psoriasis; 93 patients with rheumatoid arthritis; and 21 healthy persons for the presence of tenascin-X and tenascin-C by enzyme-linked immunosorbent assay. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11642233"}, {"offsetInBeginSection": 230, "offsetInEndSection": 380, "text": "usive disease. Fibroblast cultures excluded Ehlers-Danlos syndrome types IV and VII. Literature review suggests this may represent a previously uniden", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14666965"}, {"offsetInBeginSection": 220, "offsetInEndSection": 338, "text": " The main forms are classical, hypermobile, vascular, kyphoscoliotic A/B, arthrochalasis A/B and dermatosparaxis types", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16638060"}, {"offsetInBeginSection": 898, "offsetInEndSection": 1048, "text": "reful cardiovascular evaluation. Conversely, Ehlers-Danlos syndrome types I and III should be excluded in patients with mitral or tricuspid valve prol", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7352721"}, {"offsetInBeginSection": 40, "offsetInEndSection": 190, "text": "t has been called either fragilitas oculi or the Ehlers-Danlos syndrome type VI. Previously reported cases of the Ehlers-Danlos syndrome type VI showe", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/962660"}, {"offsetInBeginSection": 0, "offsetInEndSection": 484, "text": "The Ehlers-Danlos syndromes (EDS) are a heterogeneous group of hereditary disorders of connective tissue, with common features including joint hypermobility, soft and hyperextensible skin, abnormal wound healing and easy bruising. Fourteen different types of EDS are recognized, of which the molecular cause is known for 13 types. These types are caused by variants in 20 different genes, the majority of which encode the fibrillar collagen types I, III and V, modifying or processing", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32732924"}, {"offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "Ehlers-Danlos Syndrome (EDS) is a family of multisystemic hereditary connective tissue disorders now comprised of 13 recognized subtypes, classical, classical-like, cardiac-valvular, vascular, hypermobile, arthrochlasia, dermosparaxis, kyphoscoliotic, brittle", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33437956"}, {"offsetInBeginSection": 753, "offsetInEndSection": 1145, "text": "Fifty-eight patients had Ehlers-Danlos syndrome Types I, II, III, or IV and form the study cohort. Among these four types, there were no significant differences in history of joint dislocation, swelling, or types of orthopaedic surgical procedures experienced. Thirty patients with Type III Ehlers-Danlos syndrome reported joint pain more frequently than did patients with Types I, II, or IV.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10906878"}, {"offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "Ehlers-Danlos syndrome denotes a group of inherited connective tissue diseases comprising nine types. Type IV Ehlers-Danlos syndrome is the most life-threatening form. It is characterized by a type III collagen deficiency resulting in arterial fragility and death from vascular rupture or bowel perforation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9762220"}, {"offsetInBeginSection": 753, "offsetInEndSection": 1013, "text": "Fifty-eight patients had Ehlers-Danlos syndrome Types I, II, III, or IV and form the study cohort. Among these four types, there were no significant differences in history of joint dislocation, swelling, or types of orthopaedic surgical procedures experienced.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10906878"}, {"offsetInBeginSection": 104, "offsetInEndSection": 286, "text": "Of the six subtypes of Ehlers-Danlos syndrome, which can usually be clinically differentiated, only types 1 and 4 appear to be associated with a substantial risk of arterial rupture.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7455751"}, {"offsetInBeginSection": 102, "offsetInEndSection": 307, "text": "Type IV Ehlers-Danlos syndrome is the most life-threatening form. It is characterized by a type III collagen deficiency resulting in arterial fragility and death from vascular rupture or bowel perforation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9762220"}, {"offsetInBeginSection": 1452, "offsetInEndSection": 1630, "text": "Contrary to most previous reports, the patients in this study showed that Type III Ehlers-Danlos syndrome was the most debilitating form with respect to musculoskeletal function.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10906878"}, {"offsetInBeginSection": 102, "offsetInEndSection": 354, "text": "Type IV Ehlers-Danlos syndrome is the most life-threatening form. It is characterized by a type III collagen deficiency resulting in arterial fragility and death from vascular rupture or bowel perforation. This disease involves a col 3A1 gene mutation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9762220"}, {"offsetInBeginSection": 168, "offsetInEndSection": 433, "text": "It is characterized by a type III collagen deficiency resulting in arterial fragility and death from vascular rupture or bowel perforation. This disease involves a col 3A1 gene mutation. We report the case of a 44 year-old woman with type IV Ehlers-Danlos syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9762220"}, {"offsetInBeginSection": 355, "offsetInEndSection": 519, "text": "We report the case of a 44 year-old woman with type IV Ehlers-Danlos syndrome. The medical history of our patient included bowel necrosis and two vascular ruptures.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9762220"}, {"offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Ehlers-Danlos syndrome denotes a group of inherited connective tissue diseases comprising nine types. Type IV Ehlers-Danlos syndrome is the most life-threatening form.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9762220"}, {"offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "We have described a patient with type 4 Ehlers-Danlos syndrome who died of a ruptured pulmonary artery. Of the six subtypes of Ehlers-Danlos syndrome, which can usually be clinically differentiated, only types 1 and 4 appear to be associated with a substantial risk of arterial rupture.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7455751"}, {"offsetInBeginSection": 182, "offsetInEndSection": 310, "text": "Fourteen subtypes of Ehlers-Danlos Syndrome (EDS) have been described, each with characteristic phenotypes and associated genes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35396906"}, {"offsetInBeginSection": 662, "offsetInEndSection": 763, "text": "The International EDS Consortium proposes a revised EDS classification, which recognizes 13 subtypes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28306229"}, {"offsetInBeginSection": 0, "offsetInEndSection": 329, "text": "Ehlers-Danlos syndrome (EDS) comprises clinically heterogeneous connective tissue disorders with diverse molecular etiologies. The 2017 International Classification for EDS recognized 13 distinct subtypes caused by pathogenic variants in 19 genes mainly encoding fibrillar collagens and collagen-modifying or processing proteins.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30759870"}, {"offsetInBeginSection": 231, "offsetInEndSection": 330, "text": "Fourteen different types of EDS are recognized, of which the molecular cause is known for 13 types.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32732924"}, {"offsetInBeginSection": 127, "offsetInEndSection": 329, "text": "The 2017 International Classification for EDS recognized 13 distinct subtypes caused by pathogenic variants in 19 genes mainly encoding fibrillar collagens and collagen-modifying or processing proteins.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30759870"}, {"offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "The Ehlers-Danlos Syndromes (EDS), a group of hereditary connective tissue disorders, were classified into 13 subtypes in the 2017 International Classification.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37214418"}, {"offsetInBeginSection": 157, "offsetInEndSection": 236, "text": "EDS is classified into 13 subtypes according to the most recent classification.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36727144"}, {"offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "The Ehlers-Danlos Syndromes comprise a heterogeneous group of rare monogenic conditions that are characterized by joint hypermobility, skin and vascular fragility and generalized connective tissue friability. The latest classification recognizes 13 clinical subtypes, with mutations identified in 19 different genes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29709596"}]}
+{"question_id": "65cfe0381930410b13000029", "question": "Can tacrolimus increase risk of Posterior Reversible Encephalopathy Syndrome?", "answer": "Yes. Tacrolimus is associated with increase risk of Posterior Reversible Encephalopathy Syndrome.", "relevant_passage_ids": ["36728342", "36398875", "35469414", "36329183", "37120321", "35990782", "30602365", "24405697", "23290027", "29993355", "23331314", "24678391", "19096887", "23460378", "35074159", "20171145", "30506735", "12823354", "28190435"], "type": "yesno", "snippets": [{"offsetInBeginSection": 168, "offsetInEndSection": 439, "text": "This study investigated tacrolimus PK in a 2-year-old post-renal transplant patient and a known CYP3A5 expresser who developed posterior reversible encephalopathy syndrome (PRES) and had significantly elevated tacrolimus blood concentrations during tacrolimus treatment. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36728342"}, {"offsetInBeginSection": 1636, "offsetInEndSection": 1836, "text": "CONCLUSIONS: This is the first report to demonstrate acutely decreased tacrolimus clearance in PRES, likely caused by the downregulation of metabolizing enzymes in response to inflammatory cytokines. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36728342"}, {"offsetInBeginSection": 1073, "offsetInEndSection": 1157, "text": "CONCLUSION: Renal insufficiency and high tacrolimus levels are associated with PRES.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36398875"}, {"offsetInBeginSection": 345, "offsetInEndSection": 502, "text": "We present a clinical case in the field of liver transplantation where tacrolimus neurotoxicity may play a relevant role in the development of this syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35469414"}, {"offsetInBeginSection": 1269, "offsetInEndSection": 1469, "text": "The main drug classes involved were antineoplastic and immunomodulating agents and the drugs with the greatest number of cases were tacrolimus, cyclosporin, bevacizumab, methotrexate, and vincristine.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36329183"}, {"offsetInBeginSection": 281, "offsetInEndSection": 452, "text": "Neurologic side effects attributed to tacrolimus include headaches, posterior reversible encephalopathy syndrome (PRES), or reversible cerebral vasospasm syndrome (RCVS). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37120321"}, {"offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Late presentation of posterior reversible encephalopathy syndrome following liver transplantation in the setting of tacrolimus and cannabis use.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35990782"}, {"offsetInBeginSection": 281, "offsetInEndSection": 450, "text": "Neurologic side effects attributed to tacrolimus include headaches, posterior reversible encephalopathy syndrome (PRES), or reversible cerebral vasospasm syndrome (RCVS)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37120321"}, {"offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Model-Informed Estimation of Acutely Decreased Tacrolimus Clearance and Subsequent Dose Individualization in a Pediatric Renal Transplant Patient With Posterior Reversible Encephalopathy Syndrome.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36728342"}, {"offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "We report on tacrolimus-associated posterior reversible encephalopathy syndrome with the previously unreported finding of leptomeningeal enhancement occurring separate from the site of parenchymal magnetic resonance signal abnormality.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23290027"}, {"offsetInBeginSection": 871, "offsetInEndSection": 1074, "text": "In these patients, the tacrolimus dose is reduced or discontinued. In transplant patients with neurologic symptoms, the possibility of posterior reversible encephalopathy syndrome should be kept in mind.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29993355"}, {"offsetInBeginSection": 0, "offsetInEndSection": 422, "text": "We report on tacrolimus-associated posterior reversible encephalopathy syndrome with the previously unreported finding of leptomeningeal enhancement occurring separate from the site of parenchymal magnetic resonance signal abnormality. Recognition of this atypical finding as a noninfectious cause of leptomeningeal enhancement may assist those caring for patients affected by posterior reversible encephalopathy syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23290027"}, {"offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Isolated leptomeningeal enhancement in tacrolimus-associated posterior reversible encephalopathy syndrome.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23290027"}, {"offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Tacrolimus associated posterior reversible encephalopathy syndrome - a case series and review.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24678391"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "PRES (posterior reversible encephalopathy syndrome), a rare complication of tacrolimus therapy.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19096887"}, {"offsetInBeginSection": 847, "offsetInEndSection": 1015, "text": "The focus of this review is to enhance clinical recognition of PRES as it is related to an adverse effect of Tacrolimus in the setting of hematopoietic transplantation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24678391"}, {"offsetInBeginSection": 702, "offsetInEndSection": 846, "text": "We report three cases of PRES in patients with acute myeloid leukemia (AML) placed on tacrolimus after receiving a bone marrow transplant (BMT).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24678391"}, {"offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "A Late Complication Occurring Due to Tacrolimus After Liver Transplant: Posterior Reversible Encephalopathy Syndrome.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29993355"}, {"offsetInBeginSection": 1444, "offsetInEndSection": 1731, "text": "This report highlights tacrolimus as a potential trigger of posterior reversible encephalopathy syndrome and may inform clinical decisions regarding tacrolimus administration in liver transplant recipients with preexisting or newly developed posterior reversible encephalopathy syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30602365"}, {"offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Tacrolimus-associated posterior reversible encephalopathy syndrome (PRES) is a potential complication of allogeneic stem cell transplant (SCT).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23460378"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1481, "text": "Posterior reversible encephalopathy syndrome (PRES) is a disorder characterized by gray and white matter abnormalities in the temporal, parietal, and occipital lobes of the brain. Its etiology has been attributed to renal failure, immunosuppressive drugs such as cyclosporine and tacrolimus, and other potential entities leading to acute hypertension. Clinical findings include headaches, altered mental status, seizures, visual changes, and focal neurologic deficits. We report the case of a child who developed PRES with intracerebral and subarachnoid hemorrhages associated with tacrolimus exposure 10 days after heart transplantation for restrictive cardiomyopathy. The patient initially presented with complex partial seizures, headache, agitation, and hypertension. Head MRI was suggestive of PRES along with intracerebral and subarachnoid hemorrhages. Tacrolimus was discontinued and blood pressure was controlled. The patient's encephalopathy resolved, but he has had ongoing neurologic symptoms secondary to hemorrhage. Generally, PRES is less common in children than in the adult population and is a rare complication of calcineurin inhibitors (CNI). Presentation with secondary hemorrhage also can occur. In children receiving CNIs presenting with new neurologic symptoms, PRES should be considered as prompt discontinuation of the offending agent can induce resolution of symptoms. Children can develop hemorrhage in the context of PRES, leading to increased morbidity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23331314"}, {"offsetInBeginSection": 70, "offsetInEndSection": 345, "text": "From April 1998 to December 2001, we identified 10 patients (six women, four men) who developed 11 episodes of tacrolimus-associated posterior reversible encephalopathy syndrome (PRES) after allogeneic haematopoietic stem cell transplantation for haematological malignancies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12823354"}, {"offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Tacrolimus-associated posterior reversible encephalopathy syndrome after allogeneic haematopoietic stem cell transplantation.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12823354"}, {"offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "BACKGROUND: Tacrolimus-related neurotoxicity is a serious complication. Posterior reversible encephalopathy syndrome, which is severe neuroto", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35074159"}, {"offsetInBeginSection": 0, "offsetInEndSection": 717, "text": "Tacrolimus is an immunosuppressive drug mainly used to lower the risk of transplant rejection in individuals who are post solid organ or hematopoietic transplantation. It is a macrolide which reduces peptidyl-propyl isomerase activity and inhibits calcineurin, thus inhibiting T-lymphocyte signal transduction and interleukin-2 (IL-2) transcription. It has been associated with Posterior Reversible Encephalopathy Syndrome (PRES), a disease of sudden onset that can present as a host of different symptoms, depending on the affected area of the brain. While infectious causes of encephalopathy must always be entertained, the differential diagnosis should also include PRES in the appropriate context. We report three", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24678391"}, {"offsetInBeginSection": 0, "offsetInEndSection": 604, "text": "Posterior reversible encephalopathy syndrome (PRES) is a disorder characterized by gray and white matter abnormalities in the temporal, parietal, and occipital lobes of the brain. Its etiology has been attributed to renal failure, immunosuppressive drugs such as cyclosporine and tacrolimus, and other potential entities leading to acute hypertension. Clinical findings include headaches, altered mental status, seizures, visual changes, and focal neurologic deficits. We report the case of a child who developed PRES with intracerebral and subarachnoid hemorrhages associated with tacrolimus exposure 10", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23331314"}, {"offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is an increasingly recognized serious complication of cyclosporine A (CSA) and tacrolimus (TAC) use in hematopoietic cell transplantation (HCT)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30506735"}, {"offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Alternative tacrolimus and sirolimus regimen associated with rapid resolution of posterior reversible encephalopathy syndrome after lung transplantation.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24405697"}, {"offsetInBeginSection": 474, "offsetInEndSection": 754, "text": "Drug neurotoxicity accounts for a significant proportion of complications, with posterior reversible leukoencephalopathy syndrome, primarily associated with calcineurin inhibitors (i.e., cyclosporine and tacrolimus), being prominent as a cause of seizures and neurologic deficits.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28190435"}, {"offsetInBeginSection": 281, "offsetInEndSection": 451, "text": "Neurologic side effects attributed to tacrolimus include headaches, posterior reversible encephalopathy syndrome (PRES), or reversible cerebral vasospasm syndrome (RCVS).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37120321"}, {"offsetInBeginSection": 1399, "offsetInEndSection": 1549, "text": "c vessels and subsequent hepatic infarction. This report highlights tacrolimus as a potential trigger of posterior reversible encephalopathy syndrome ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30602365"}, {"offsetInBeginSection": 532, "offsetInEndSection": 937, "text": "Causative factors include hypertensive encephalopathy, renal failure, preeclampsia, autoimmune conditions, and the use of cytotoxic or immunosuppressive agents. Rare cases of posterior reversible encephalopathy syndrome due to treatment with tacrolimus, an immunosuppressive agent commonly used after organ transplant, have been reported. In these patients, the tacrolimus dose is reduced or discontinued.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29993355"}, {"offsetInBeginSection": 0, "offsetInEndSection": 351, "text": "Posterior reversible encephalopathy syndrome (PRES) is a disorder characterized by gray and white matter abnormalities in the temporal, parietal, and occipital lobes of the brain. Its etiology has been attributed to renal failure, immunosuppressive drugs such as cyclosporine and tacrolimus, and other potential entities leading to acute hypertension.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23331314"}, {"offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Posterior reversible encephalopathy syndrome (PRES) is known to occur after solid organ transplantation, and is caused by immunosuppressive agents such as tacrolimus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20171145"}]}
+{"question_id": "660999e7fdcbea915f00001c", "question": "What is the most effective immunotherapy regimen in patients with MSI-H advanced colorectal cancer?", "answer": "Nivolumab plus ipilimumab demonstrated high response rates, encouraging progression-free survival and OS at 12 months, manageable safety, and meaningful improvements in key patient-reported outcomes. Indirect comparisons suggest combination therapy provides improved efficacy relative to anti-programmed death-1 monotherapy and has a favorable benefit-risk profile. Nivolumab plus ipilimumab provides a promising new treatment option for patients with dMMR/MSI-H mCRC.", "relevant_passage_ids": ["29355075", "35340168", "35433988", "36528470", "35340169", "34431576", "35371084", "37246506", "36217119", "38091773", "31322663", "31383813", "31139574", "33846198", "34970153", "33264544", "37821934", "33183114", "36111897", "35958603", "36998297", "34775366", "36896306", "33671871", "34391139", "33537496", "37259600", "30343509", "37569431", "35720492", "37114536", "31079031", "32090113", "33563194", "32160138", "35351582", "37668816", "31147488", "33812497"], "type": "factoid", "snippets": [{"offsetInBeginSection": 1607, "offsetInEndSection": 2075, "text": "Nivolumab plus ipilimumab demonstrated high response rates, encouraging progression-free survival and OS at 12 months, manageable safety, and meaningful improvements in key patient-reported outcomes. Indirect comparisons suggest combination therapy provides improved efficacy relative to anti-programmed death-1 monotherapy and has a favorable benefit-risk profile. Nivolumab plus ipilimumab provides a promising new treatment option for patients with dMMR/MSI-H mCRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29355075"}, {"offsetInBeginSection": 12, "offsetInEndSection": 273, "text": "To determine the clinical predictors of response rate, progression-free survival (PFS), and overall survival (OS) to pembrolizumab in advanced or recurrent, mismatch repair deficient (MMRd) or Microsatellite Instability-High (MSI-H) endometrial adenocarcinomas.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38091773"}, {"offsetInBeginSection": 1255, "offsetInEndSection": 1490, "text": "Conclusion: For patients with MSI-H/dMMR advanced colorectal cancer, reserving pembrolizumab for second-line line use is dominated by its first-line use, and first-line use of pembrolizumab is cost-effective compared with chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34970153"}, {"offsetInBeginSection": 0, "offsetInEndSection": 682, "text": "Background: Pembrolizumab is a guideline-recommended, both first- and second-line treatment option for microsatellite-instability-high (MSI-H)/mismatch repair-deficient (dMMR)advanced colorectal cancer patients. The aim of the present study is to investigates the health and economic outcomes of three treatment strategies with or without pembrolizumab in MSI-H/dMMR advanced colorectal cancer to define the best treatment strategy from the perspective of the US payer. Methods: A microsimulation model was developed to estimate the cost and effectiveness of three treatment strategies: 1) pembrolizumab used as first-line, 2) pembrolizumab used as second-line and, 3) chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34970153"}, {"offsetInBeginSection": 0, "offsetInEndSection": 469, "text": "Background: Pembrolizumab is a guideline-recommended, both first- and second-line treatment option for microsatellite-instability-high (MSI-H)/mismatch repair-deficient (dMMR)advanced colorectal cancer patients. The aim of the present study is to investigates the health and economic outcomes of three treatment strategies with or without pembrolizumab in MSI-H/dMMR advanced colorectal cancer to define the best treatment strategy from the perspective of the US payer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34970153"}, {"offsetInBeginSection": 1468, "offsetInEndSection": 1653, "text": "Approval of pembrolizumab is likely to change the treatment paradigm for first-line treatment with MSI-H advanced colorectal cancer given the study results and different safety profile.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33846198"}, {"offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Background: Pembrolizumab is a guideline-recommended, both first- and second-line treatment option for microsatellite-instability-high (MSI-H)/mismatch repair-deficient (dMMR)advanced colorectal cancer patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34970153"}, {"offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "The FDA approved pembrolizumab on June 29, 2020, for the treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) colorectal cancer with no prior systemic treatment for advanced disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33846198"}, {"offsetInBeginSection": 359, "offsetInEndSection": 864, "text": "The 2015 KEYNOTE-016 trial identified MSI-H/dMMR as a biomarker indicative of immunotherapy efficacy, and pointed to the potential use of immune checkpoint inhibitors (ICIs). In 2017, the FDA approved two ICIs (pembrolizumab and nivolumab) for treatment of MSI-H/dMMR metastatic CRC (mCRC). In 2018, the CheckMate-142 trial demonstrated successful treatment of mCRC based on \"double immunity\" provided by nivolumab with ipilimumab, a regimen that may become a standard first-line treatment for MSI-H mCRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35371084"}, {"offsetInBeginSection": 2117, "offsetInEndSection": 2319, "text": "Combination therapy (e.g., nivolumab with low-dose ipilimumab) has demonstrated numerically higher response rates and improved long-term clinical benefit relative to anti-programmed death-1 monotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31383813"}, {"offsetInBeginSection": 218, "offsetInEndSection": 489, "text": "The use of immunotherapy, like nivolumab and pembrolizumab (which are monoclonal antibodies against programmed cell death 1) has shown prosperous outcomes in a group of CRC patients who represent mismatch-repair-deficient and microsatellite instability-high (dMMR-MSI-H).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34775366"}, {"offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Nivolumab (NIVO) plus low-dose ipilimumab (IPI) has shown a promising survival benefit in first-line treatment of microsatellite instability-high (MSI-H) colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33671871"}, {"offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "An Investigator-Initiated Phase 2 Study of Nivolumab Plus Low-Dose Ipilimumab as First-Line Therapy for Microsatellite Instability-High Advanced Gastric or Esophagogastric Junction Cancer (NO LIMIT, WJOG13320G/CA209-7W7).", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33671871"}, {"offsetInBeginSection": 92, "offsetInEndSection": 788, "text": "bility-high (dMMR/MSI-H) colorectal cancer exhibits better immune activity, and patients with dMMR/MSI-H colorectal cancer benefit from immunotherapy with programmed death-1 (PD-1)/PD-1 ligand (PD-L1) inhibitors and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibitors as a first-line treatment. However, for microsatellite-stable (MSS) colorectal cancer, which accounts for the majority of the cases of colorectal cancer, immunotherapy has yielded little success, especially in cases of patients with advanced colorectal cancer in whom multiple lines of chemotherapy have failed. Hence, safe and effective targeted treatment strategies are urgently needed to achieve greater survival ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35433988"}, {"offsetInBeginSection": 8, "offsetInEndSection": 1307, "text": "the recent advances in the systemic treatment of metastatic colorectal cancer (mCRC), prognostic outcomes have remained to be poor. Thus, what is needed is an innovative treatment approach. Immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) have exhibited a durable response and dominated the treatment of various tumor types. However, in mCRC, the clinical benefit is limited in patients with deficient mismatch repair (dMMR)/high levels of microsatellite instability (MSI-H), comprising approximately 5% of mCRC cases, and some do not respond to ICI treatment. Thus, further research is needed to identify predictive biomarkers. The most urgent need is developing effective immunotherapy for patients with proficient mismatch repair (pMMR)/microsatellite stable (MSS) cancer, which comprises 95% of mCRC cases. Tumors with the pMMR/MSS phenotype often exhibit a lower tumor mutation burden and fewer tumor-infiltrating lymphocytes than dMMR/MSI-H, leading to immune tolerance and evasion in the tumor microenvironment. Therefore, a number of investigative studies aimed at overcoming tumor resistance in current immunotherapy approaches are underway. A better understanding on the complexity and diversity of the immune system's", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33537496"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1802, "text": "Patients with locally advanced colorectal cancer (LACRC) have a high risk of recurrence and metastasis, although neoadjuvant therapy may provide some benefit. However, patients with high microsatellite instability/deficient mismatch repair (MSI-H/dMMR) LACRC receive little benefit from neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant chemotherapy (nCT). The 2015 KEYNOTE-016 trial identified MSI-H/dMMR as a biomarker indicative of immunotherapy efficacy, and pointed to the potential use of immune checkpoint inhibitors (ICIs). In 2017, the FDA approved two ICIs (pembrolizumab and nivolumab) for treatment of MSI-H/dMMR metastatic CRC (mCRC). In 2018, the CheckMate-142 trial demonstrated successful treatment of mCRC based on \"double immunity\" provided by nivolumab with ipilimumab, a regimen that may become a standard first-line treatment for MSI-H mCRC. In 2018, the FDA approved nivolumab alone or with ipilimumab for patients who progressed to MSI-H/dMMR mCRC after standard chemotherapy. The FDA then approved pembrolizumab alone as a first-line treatment for patients with MSI-H/dMMR CRC that was unresectable or metastatic. There is now interest in using these drugs in neoadjuvant immunotherapy (nIT) for patients with MSI-H/dMMR non-mCRC. In 2020, the NICHE trial marked the start of using nIT for CRC. This novel treatment of MSI-H/dMMR LACRC may change the approaches used for neoadjuvant therapy of other cancers. Our review of immunotherapy for CRC covers diagnosis and treatment, clinical prognostic characteristics, the mechanism of nIT, analysis of completed prospective and retrospective studies, and ongoing clinical trials, and the clinical practice of using nIT for MSI-H/dMMR LACRC. Our team also proposes a new organ-preservation strategy for patients with MSI-H/dMMR low", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35371084"}, {"offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "OBJECTIVE: The immune checkpoint inhibitor pembrolizumab has recently been recognized as a standard treatment regimen for patients with metastatic colorectal cancer and the microsatellite-instability-high/mismatch repair-deficien", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37259600"}, {"offsetInBeginSection": 1097, "offsetInEndSection": 1391, "text": "ess ratios (ICERs).RESULTS: Ipilimumab with nivolumab was the most effective strategy (10.69 life-years and 9.25 QALYs for the third line; 10.69 life-years and 9.44 QALYs for the first line) in comparison with nivolumab (8.21 life-years and 6.76 QALYs for the third line; 8.21 life-years and 7.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30343509"}, {"offsetInBeginSection": 0, "offsetInEndSection": 521, "text": "DNA mismatch repair deficient (dMMR) and microsatellite instable (MSI) metastatic colorectal cancer (mCRC) can be successfully treated with FDA- and EMA-approved immune checkpoint inhibitors (ICI) pembrolizumab and nivolumab (as single agents targeting the anti-programmed cell death protein-1 (PD-1)) or combinations of a PD-1 inhibitor with ipilimumab, a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)-targeting antibody. The best treatment strategy beyond progression on single-agent ICI therapy remains unclear.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37569431"}, {"offsetInBeginSection": 559, "offsetInEndSection": 732, "text": "The success of KEYNOTE-177 study has changed the guidelines with pembrolizumab becoming a standard treatment in the first-line treatment of MSI-H advanced colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35340169"}, {"offsetInBeginSection": 0, "offsetInEndSection": 825, "text": "Immunotherapy has revolutionized the treatment landscape in a number of solid tumors. In colorectal cancer, evidence suggests that microsatellite high (MSI-H) tumors are the most responsive to immune checkpoint blockade due to increased neo-antigen load and a favorable tumor microenvironment. Indeed, Pembrolizumab now represents a first-line option in such patients. However, MSI-H tumors represent the minority and a proportion of patients' progress despite initially responding. Trials are investigating different immunotherapy combinatorial strategies to enhance immune response in less immunogenic colorectal tumors. Such strategies include dual immune checkpoint blockade, combining immune checkpoint inhibitors with other treatment modalities such as radiotherapy, chemotherapy or other biological or targeted agents.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33563194"}, {"offsetInBeginSection": 121, "offsetInEndSection": 862, "text": "immunotherapy has become widely recognized as a new standard treatment for cancers including microsatellite instability-high (MSI-H) colorectal cancer. Immune checkpoint inhibitors such as pembrolizumab and nivolumab (anti-PD-1 antibodies) that act in the effector phase of T cells and ipilimumab (anti-CTLA-4 antibody) that acts mainly in the priming phase are now in clinical use. These antibodies have shown therapeutic efficacy in MSI colorectal cancer patients who have failed to respond to existing standard therapies. Pembrolizumab is also strongly recommended as first-line therapy for MSI-H metastatic colorectal cancer. Therefore, the MSI status and tumor mutation burden of the tumor should be clarified before starting treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36998297"}, {"offsetInBeginSection": 0, "offsetInEndSection": 656, "text": "Immunotherapy has recently become a major treatment modality for several types of solid tumours, achieving remarkable and long-lasting remissions. In metastatic colorectal cancer patients (mCRC), immune checkpoint inhibitors (ICIs) were found to be effective as treatment for deficient mismatch repair (dMMR)/ microsatellite instability high (MSI-H) tumours and received regulatory approval for this indication. However, mCRC is a complex disease and dMMR/MSI-H tumours represent a minority of the cases; therefore, new strategies are needed to extend the benefits of immunotherapy to a larger population of patients. This review explores the immunological", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34391139"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1408, "text": "Colorectal cancer (CRC) remains a leading cause of cancer-related deaths in the United States. Although immunotherapy has dramatically changed the landscape of treatment for many advanced cancers, the benefit in CRC has thus far been limited to patients with microsatellite instability high (MSI-H):DNA mismatch repair-deficient (dMMR) tumors. Recent studies in the refractory CRC setting have led to US Food and Drug Administration approvals for pembrolizumab as well as nivolumab (with or without ipilimumab) for tumors harboring an MSI-H:dMMR molecular profile. Several randomized controlled trials are underway to move immunotherapy into the frontline for metastatic cancer (with or without chemotherapy) and the adjuvant setting. Awareness of these studies is critical given the relatively low incidence (approximately 3%-5%) of MSI-H:dMMR in advanced or metastatic CRC to support study completion, because the results could be potentially practice changing. The real challenge in this disease is related to demonstrating the benefit of immunotherapy for the vast majority of patients with CRC not harboring MSI-H:dMMR. Given the rapid pace of scientific changes, this article provides a narrative review regarding the current landscape of immunotherapy for CRC. Particular attention is paid to the currently available data that inform today's clinical practice along with upcoming randomized controlled", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31322663"}, {"offsetInBeginSection": 196, "offsetInEndSection": 1760, "text": "metastatic colorectal cancer (mCRC). As a result of their dramatic and durable response rates in patients with chemorefractory, mismatch repair-deficient-microsatellite instability-high (dMMR-MSI-H) mCRC, ICIs have become potential alternatives to classical systemic therapies. The anti-programmed death-1 (PD-1) agents, Pembrolizumab and Nivolumab, have been granted FDA approval for this subset of patients. Unfortunately, however, not all CRC cases with the dMMR-MSI-H phenotype respond well to ICIs, and ongoing studies are currently exploring biomarkers that can predict good response to them. Another challenge lies in developing novel treatment strategies for the subset of patients with the mismatch repair-proficient-microsatellite instability-low (pMMR-MSI-L) phenotype that comprises 95% of all mCRC cases in whom treatment with currently approved ICIs has been largely unsuccessful. Approaches aiming at overcoming the resistance of tumors in this subset of patients are being developed including combining different checkpoint inhibitors with either chemotherapy, anti-angiogenic agents, cancer vaccines, adoptive cell transfer (ACT), or bispecific T-cell (BTC) antibodies. This review describes the rationale behind using immunotherapeutics in CRC. It sheds light on the progress made in the use of immunotherapy in the treatment of patients with dMMR-MSI-H CRC. It also discusses emerging approaches and proposes potential strategies for targeting the immune microenvironment in patients with pMMR-MSI-L CRC tumors in an attempt to complement immune", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32090113"}, {"offsetInBeginSection": 406, "offsetInEndSection": 1212, "text": "The advent of PD-1 antibodies has significantly improved the prognosis and changed treatment landscape in this population, not only achieving good outcomes in late-line therapy, but also significantly outperforming traditional chemotherapy combined with targeted therapy in first-line therapy. How to overcome primary and secondary drug resistance is a key issue in improving the outcome of MSI-H metastatic colorectal cancer, and commonly used approaches include changing chemotherapy regimens, combining with other immunotherapies, combining with anti-angiogenesis, and local treatments (surgery, radiotherapy, or interventional therapy). It is worth noting that immunotherapy has certain lifelong or even lethal toxicity, and the indications for neoadjuvant immunotherapy must be evaluated with caution.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35340168"}, {"offsetInBeginSection": 1313, "offsetInEndSection": 1813, "text": "TS: Immune checkpoint inhibitors are more active in treatment-na\u00efve patients than in patients with refractory high-grade microsatellite instability (MSI-H)/deficiency in mismatch repair (dMMR) colorectal cancer. Standard neoadjuvant chemoradiation is less effective in MSI-H/dMMR rectal cancer patients than in patients with proficient mismatch repair. A young patient with Lynch syndrome and MSI-H/dMMR locally advanced rectal cancer refused chemoradiation in order to preserve his fertility. After ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34431576"}, {"offsetInBeginSection": 0, "offsetInEndSection": 499, "text": "Recent studies have identified durable responses with the use of immune checkpoint inhibitors in patients with mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (CRC). The dramatic improvement in clinical outcomes led to the US Food and Drug Administration approval of pembrolizumab, nivolumab, and nivolumab in combination with ipilimumab in metastatic patients with MSI-H/MMR-D CRC who previously experienced progression on cytotoxic therapies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32160138"}, {"offsetInBeginSection": 585, "offsetInEndSection": 837, "text": "In subsequent lines, both these immunotherapeutic regimens (e.g., pembrolizumab and nivolumab+/-ipilimumab) as well as dostarlimab-gxly are currently recommended for patients with dMMR/MSI-H chemo-resistant mCRC who have not previously received an ICI.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35351582"}, {"offsetInBeginSection": 542, "offsetInEndSection": 827, "text": "For metastatic colorectal cancer, pembrolizumab and nivolumab, with or without ipilimumab, are recommended for chemotherapy-refractory patients, and pembrolizumab is recommended for chemotherapy-naive patients with mismatch repair deficiency and microsatellite instability-high tumors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37668816"}, {"offsetInBeginSection": 148, "offsetInEndSection": 532, "text": "e outcomes. In CheckMate 142, nivolumab (3 mg/kg) plus low-dose ipilimumab (1 mg/kg) provided durable clinical benefit (objective response rate [ORR] 55%, median duration of response not reached, 12-month overall survival [OS] rate 85%) and manageable safety for previously treated microsatellite instability-high and/or mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal ca", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31147488"}, {"offsetInBeginSection": 1605, "offsetInEndSection": 1970, "text": "n Nivolumab plus ipilimumab demonstrated high response rates, encouraging progression-free survival and OS at 12 months, manageable safety, and meaningful improvements in key patient-reported outcomes. Indirect comparisons suggest combination therapy provides improved efficacy relative to anti-programmed death-1 monotherapy and has a favorable benefit-risk profil", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29355075"}, {"offsetInBeginSection": 3648, "offsetInEndSection": 4022, "text": "48 [95% CI 0\u00b733-0\u00b769]; one-sided nominal p<0\u00b70001).INTERPRETATION: Pembrolizumab monotherapy led to clinically meaningful improvements in HRQOL compared with chemotherapy in patients with previously untreated microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer. These data, along with the previously reported clinical benefits, support ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33812497"}]}
+{"question_id": "661c03c848a2c27714000004", "question": "What is the function of the paraoxonase (PON) multigene family?", "answer": "The paraoxonase (PON) gene family includes three proteins, PON1, PON2 and PON3. PON1 and PON3 are both associated with high-density lipoprotein (HDL) particles and exert anti-oxidant and anti-inflammatory properties. PON(s) acts as important guardians against cellular damage from toxic agents, such as organophosphates, oxidized lipids in the plasma low-density lipoproteins", "relevant_passage_ids": ["14551701", "15607899", "11918623", "8661009", "32487820", "29170064", "31816846", "24903163", "29308836", "15993332", "31052559", "27578362", "19359600", "33374313", "20582942", "15613429", "25953737", "25887882", "31366068", "27238723", "21867409", "28889264", "33348669", "27771368", "19942738", "20535264", "36140402", "20705007", "30241945", "37108044", "19226538", "33562328", "33831384", "33260536", "22824324", "20122908"], "type": "summary", "snippets": [{"offsetInBeginSection": 413, "offsetInEndSection": 574, "text": " PON(s) acts as important guardians against cellular damage from toxic agents, such as organophosphates, oxidized lipids in the plasma low-density lipoproteins. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14551701"}, {"offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Epidemiologic, genetic, and biochemical studies support an antiatherogenic role for paraoxonase (", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15607899"}, {"offsetInBeginSection": 12, "offsetInEndSection": 132, "text": "Paraoxonase is a serum enzyme, which prevents oxidation of low-density lipoprotein (LDL) by hydrolyzing lipid peroxides.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11918623"}, {"offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "A physiological role for paraoxonase (PON1) is still uncertain, but it catalyzes the hydrolysis of toxic organophosphates.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8661009"}, {"offsetInBeginSection": 19, "offsetInEndSection": 186, "text": "Studies have shown the three-member paraoxonase (PON) multigene family to be involved in the development of a large variety of diseases with an inflammatory component.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32487820"}, {"offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "The paraoxonase (PON) gene family includes three proteins, PON1, PON2 and PON3. PON1 and PON3 are both associated with high-density lipoprotein (HDL) particles and exert anti-oxidant and anti-inflammatory properties", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29170064"}, {"offsetInBeginSection": 218, "offsetInEndSection": 319, "text": "The paraoxonase (PON) gene cluster (PC) protects against atherosclerosis and coronary artery diseases", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27578362"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "The paraoxonase (PON) gene cluster consists of the PON1, PON2, and PON3 genes, each of which can individually inhibit atherogenesis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19359600"}, {"offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "Paraoxonase, an enzyme associated with high-density lipoprotein (HDL-PON), exerts a protective effect against oxidative damage of circulating cells and lipoproteins, modulates the susceptibility of HDL to atherogenic modifications such as glycation and homocysteinylation, and even exerts an antiinflammatory role.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15613429"}, {"offsetInBeginSection": 0, "offsetInEndSection": 475, "text": "Paraoxonase, an enzyme associated with high-density lipoprotein (HDL-PON), exerts a protective effect against oxidative damage of circulating cells and lipoproteins, modulates the susceptibility of HDL to atherogenic modifications such as glycation and homocysteinylation, and even exerts an antiinflammatory role. The aim of the present study was to investigate the relationship between lipoprotein oxidative stress and the activity of HDL-PON in healthy and obese subjects.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15613429"}, {"offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "The paraoxonase (PON) family is composed of 3 proteins (PON1, PON2, and PON3), each of which plays a crucial role in the body, displaying antioxidant, anti-inflammatory, and antiatherosclerotic properties.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25953737"}, {"offsetInBeginSection": 0, "offsetInEndSection": 690, "text": "Paraoxonase, an enzyme associated with high-density lipoprotein (HDL-PON), exerts a protective effect against oxidative damage of circulating cells and lipoproteins, modulates the susceptibility of HDL to atherogenic modifications such as glycation and homocysteinylation, and even exerts an antiinflammatory role. The aim of the present study was to investigate the relationship between lipoprotein oxidative stress and the activity of HDL-PON in healthy and obese subjects. Therefore, the activity of HDL-PON and the levels of lipid hydroperoxides in HDL and low-density lipoprotein (LDL) isolated from plasma of obese females (n = 12) and age-sex-matched controls (n = 31) were compared.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15613429"}, {"offsetInBeginSection": 0, "offsetInEndSection": 333, "text": "The paraoxonase (PON) family is composed of 3 proteins (PON1, PON2, and PON3), each of which plays a crucial role in the body, displaying antioxidant, anti-inflammatory, and antiatherosclerotic properties. The activities and properties of PON proteins can be modulated by a number of environmental factors, including cigarette smoke.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25953737"}, {"offsetInBeginSection": 0, "offsetInEndSection": 335, "text": "The human body has biological redox systems capable of preventing or mitigating the damage caused by increased oxidative stress throughout life. One of them are the paraoxonase (PON) enzymes. The PONs genetic cluster is made up of three members (PON1, PON2, PON3) that share a structural homology, located adjacent to chromosome seven.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33374313"}, {"offsetInBeginSection": 0, "offsetInEndSection": 519, "text": "The paraoxonase (PON) family is composed of 3 proteins (PON1, PON2, and PON3), each of which plays a crucial role in the body, displaying antioxidant, anti-inflammatory, and antiatherosclerotic properties. The activities and properties of PON proteins can be modulated by a number of environmental factors, including cigarette smoke. In the present article, a review of existing literature is employed to analyze both the direct and the indirect impact of cigarette smoking on the activity of members of the PON family.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25953737"}, {"offsetInBeginSection": 825, "offsetInEndSection": 923, "text": "Paraoxonase 2 (PON2) possesses antiatherogenic properties and is associated with lower ROS levels.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29308836"}, {"offsetInBeginSection": 421, "offsetInEndSection": 599, "text": "The two other members of the PON gene family, namely, PON2 and PON3, have also been reported to possess antioxidant properties and may exhibit antiatherogenic capacities as well.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15607899"}, {"offsetInBeginSection": 0, "offsetInEndSection": 752, "text": "The paraoxonase (PON) gene family includes three proteins, PON1, PON2 and PON3. PON1 and PON3 are both associated with high-density lipoprotein (HDL) particles and exert anti-oxidant and anti-inflammatory properties. PON2 and PON3 are intracellular enzymes which modulate mitochondrial superoxide anion production and endoplasmic reticulum (ER) stress-induced apoptosis. The pleiotropic roles exerted by PONs have been mainly investigated in cardiovascular and neurodegenerative diseases. In recent years, overexpression of PON2 and PON3 has been observed in cancer cells and it has been proposed that both enzymes could be involved in tumor survival and stress resistance. Moreover, a lower activity of serum PON1 has been reported in cancer patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29170064"}, {"offsetInBeginSection": 207, "offsetInEndSection": 622, "text": "the Paraoxonase multigene family (PON1, PON2, PON3) has been shown to play an important role in pathogenesis of cardiovascular disorders including coronary artery disease (CAD). The PON genes are clustered in tandem on the long arm of human chromosome 7 (q21, 22). All of them have been shown to act as antioxidants. Of them, PON3 is the least studied member as its exact physiological substrate is still not clear.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31816846"}, {"offsetInBeginSection": 0, "offsetInEndSection": 709, "text": "Extract: Owing to their detoxifying functions, and roles in drug metabolism as well as the prevention of atherosclerosis, mammalian or serum paraoxonases (PONs) are an intriguing subject of research and a prime therapeutic and engineering target. Initially identified in mammals, PON and PON-related genes have now been found in fowls, zebra fish, and even in invertebrates such as C. elegans. The more closely-related PON genes are divided into three classes or sub-families: PON1, PON2 and PON3, that share 60-70% sequence identity. PONs are calcium-dependent hydrolases that catalyze the hydrolysis of a broad range of esters and lactones. PON1, which is by far the most investigated member of this family,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20705007"}, {"offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "A physiological role for paraoxonase (PON1) is still uncertain, but it catalyzes the hydrolysis of toxic organophosphates. Evidence that the human genome contains two PON1-like genes, designated PON2 and PON3, is presented here. Human PON1 and PON2 each have nine exons,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8661009"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1085, "text": "Paraoxonase-1 (PON1), an esterase/lactonase primarily associated with plasma high-density lipoprotein (HDL), was the first member of this family of enzymes to be characterized. Its name was derived from its ability to hydrolyze paraoxon, the toxic metabolite of the insecticide parathion. Related enzymes PON2 and PON3 were named from their evolutionary relationship with PON1. Mice with each PON gene knocked out were generated at UCLA and have been key for elucidating their roles in organophosphorus (OP) metabolism, cardiovascular disease, innate immunity, obesity, and cancer. PON1 status, determined with two-substrate analyses, reveals an individual's functional Q192R genotype and activity levels. The three-dimensional structure for a chimeric PON1 has been useful for understanding the structural properties of PON1 and for engineering PON1 as a catalytic scavenger of OP compounds. All three PONs hydrolyze microbial N-acyl homoserine lactone quorum sensing factors, quenching Pseudomonas aeruginosa's pathogenesis. All three PONs modulate oxidative stress and inflammation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27238723"}, {"offsetInBeginSection": 0, "offsetInEndSection": 370, "text": "The paraoxonase (PON) gene family includes three proteins, PON1, PON2 and PON3. PON1 and PON3 are both associated with high-density lipoprotein (HDL) particles and exert anti-oxidant and anti-inflammatory properties. PON2 and PON3 are intracellular enzymes which modulate mitochondrial superoxide anion production and endoplasmic reticulum (ER) stress-induced apoptosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29170064"}, {"offsetInBeginSection": 0, "offsetInEndSection": 844, "text": "The paraoxonases (PONs) are a three-gene family which includes PON1, PON2, and PON3. PON1 and PON3 are synthesized primarily in the liver and a portion is secreted in the plasma, where they are associated with high-density lipoproteins (HDLs), while PON2 is an intracellular enzyme, expressed in most tissues and organs, including the brain. PON1 received its name from its ability to hydrolyze paraoxon, the active metabolite of the organophosphorus (OP) insecticide parathion, and also more efficiently hydrolyzes the active metabolites of several other OPs. PON2 and PON3 do not have OP-esterase activity, but all PONs are lactonases and are capable of hydrolyzing a variety of lactones, including certain drugs, endogenous compounds, and quorum-sensing signals of pathogenic bacteria. In addition, all PONs exert potent antioxidant effects.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28889264"}, {"offsetInBeginSection": 0, "offsetInEndSection": 955, "text": "Paraoxonase (PON) is a group of proteins present in three forms (PON1, PON2, PON3) encoded by genes PON1, PON2, and PON3. PON1 and PON3 are plasma enzymes, structurally and functionally related to HDL, while PON2 is characterized by an intracellular location. Many polymorphisms of PON have been observed. The most widely and accurately described is the single nucleotide polymorphism, which impacts the conversion of glutamine (Q) to arginine (R) and has the effect of altering the hydrolytic activity of the PON1 form. Each PON form plays an important role in the human body, and they exhibit antioxidant, antiatherosclerotic, and anti-inflammatory influences. The PON family inhibits LDL oxidative modification and suppresses the differentiation of monocytes into macrophages, which is the first stage in the development of atherosclerosis. Furthermore, PON1 prevents the accumulation of oxidized LDL and stimulates cholesterol efflux from macrophages.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25887882"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1157, "text": "In humans, three paraoxonase (PON1, PON2, and PON3) genes are clustered on chromosome 7\u00a0at a locus that spans a distance around 170\u00a0kb. These genes are highly homologous to each other and have a similar protein structural organization. PON2 is the intracellular enzyme, which is expressed in many tissues and organs, while two other members of PON gene family are produced by liver and associate with high density lipoprotein (HDL). The lactonase activity is the ancestral. Besides lactones and organic phosphates, PONs can hydrolyze and therefore detoxify oxidized low density lipoprotein and homocysteine thiolactone, i.e. two cytotoxic compounds with a strong proatherogenic action. Indeed, PONs possess numerous atheroprotective properties, which include antioxidant activity, anti-inflammatory action, preserving HDL function, stimulation of cholesterol efflux, anti-apoptosis, anti-thrombosis, and anti-adhesion. PON genetic polymorphisms contribute to susceptibility/protection from atherosclerosis-related diseases. The bright antiatherogenic activity of the PON cluster makes it a promising target for the development of new therapeutic strategies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27771368"}, {"offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Paraoxonases (PONs) i.e. PON1, PON2, PON3 are basically lactonases. Of these, PON1 in addition has an efficient esterase activity and can hydrolyze organophosphates.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19942738"}, {"offsetInBeginSection": 166, "offsetInEndSection": 281, "text": "The PONs prevent low density lipoprotein cholesterol (LDL-C) from peroxidation, thereby preventing atherosclerosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19942738"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "The involvement of paraoxonase family in antiathrogenesis has recently attracted attention of many researchers to these enzymes. Type 1 paraoxonase (P", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19062578"}, {"offsetInBeginSection": 43, "offsetInEndSection": 193, "text": " genes (PON1/2/3) that are believed to be involved in the protection against oxidative stress. PON1 and PON3 are circulating in serum attached to high", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15993332"}, {"offsetInBeginSection": 16, "offsetInEndSection": 166, "text": "ON 1) is a high-density lipoprotein (HDL)-associated enzyme with antioxidant function protecting low-density lipoprotein (LDL) from oxidation. PON 1 h", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19226538"}, {"offsetInBeginSection": 521, "offsetInEndSection": 662, "text": "Each PON form plays an important role in the human body, and they exhibit antioxidant, antiatherosclerotic, and anti-inflammatory influences.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25887882"}, {"offsetInBeginSection": 663, "offsetInEndSection": 843, "text": "The PON family inhibits LDL oxidative modification and suppresses the differentiation of monocytes into macrophages, which is the first stage in the development of atherosclerosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25887882"}, {"offsetInBeginSection": 0, "offsetInEndSection": 402, "text": "Paraoxonase (PON) is an aryldialkylphosphatase, which reversibly binds and hydrolyzes organophosphates. The PON family has three members (PON1, PON2 and PON3); they share structural properties and enzymatic activities. PON1 is shown to reside over high density lipoprotein (HDL) and has both antioxidant and antiatherogenic functions. Function of PON2 and PON3 are speculative and still under research.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20535264"}, {"offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "The paraoxonase (PON) family contains three genes (PON1/2/3) that are believed to be involved in the protection against oxidative stress. PON1 and PON3 are circulating in serum attached to high-density lipoprotein fraction (HDL), whereas PON2 is ubiquitously expressed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15993332"}, {"offsetInBeginSection": 80, "offsetInEndSection": 370, "text": "PON1 and PON3 are both associated with high-density lipoprotein (HDL) particles and exert anti-oxidant and anti-inflammatory properties. PON2 and PON3 are intracellular enzymes which modulate mitochondrial superoxide anion production and endoplasmic reticulum (ER) stress-induced apoptosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29170064"}, {"offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "A physiological role for paraoxonase (PON1) is still uncertain, but it catalyzes the hydrolysis of toxic organophosphates. Evidence that the human genome contains two PON1-like genes, designated PON2 and PON3, is presented here.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8661009"}, {"offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Paraoxonase-1 (PON-1) is a hydrolytic enzyme associated with HDL, contributing to its anti-inflammatory, antioxidant, and anti-atherogenic properties", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36140402"}, {"offsetInBeginSection": 134, "offsetInEndSection": 241, "text": "Paraoxonases (PON) are a family (PON-1, PON-2, PON-3) of antioxidant enzymes with anti-inflammatory action.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31366068"}, {"offsetInBeginSection": 477, "offsetInEndSection": 657, "text": "Animal studies show a critical role for PON enzymes, especially PON1 in protecting against cardiovascular diseases and related disorders, including diabetes and metabolic syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24903163"}, {"offsetInBeginSection": 41, "offsetInEndSection": 191, "text": "ee genes (PON1/2/3) that are believed to be involved in the protection against oxidative stress. PON1 and PON3 are circulating in serum attached to hi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15993332"}, {"offsetInBeginSection": 37, "offsetInEndSection": 187, "text": "se genes (PON1, PON2, and PON3) have roles in preventing lipid oxidation and detoxifying organophosphates. Recent reports describe a genetic associati", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20582942"}, {"offsetInBeginSection": 333, "offsetInEndSection": 1030, "text": "and production of reactive oxygen species (ROS) and free radicals. The paraoxonase (PON) gene family is composed of three members (PON1, PON2, PON3) that share considerable structural homology and are located adjacently on chromosome 7 in humans. The most studied member product is PON1, a protein associated with high-density lipoprotein with paraoxonase/esterase activity. Nevertheless, all the three proteins prevent oxidative stress. The major aim of this review is to highlight the importance of the role of PON enzymes in the aging process, and in the development of the main diseases present in the elderly: cardiovascular disease, diabetes mellitus, neurodegenerative diseases, and cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31052559"}, {"offsetInBeginSection": 6, "offsetInEndSection": 950, "text": "paraoxonase-1 (PON1) is the most studied member of the group of paraoxonases (PONs). This enzyme possesses three enzymatic activities: lactonase, arylesterase, and paraoxonase activity. PON1 and its isoforms play an important role in drug metabolism as well as in the prevention of cardiovascular and neurodegenerative diseases. Although all three members of the PON family have the same origin and very similar amino acid sequences, they have different functions and are found in different locations. PONs exhibit substrate promiscuity, and their true physiological substrates are still not known. However, possible substrates include homocysteine thiolactone, an analogue of natural quorum-sensing molecules, and the recently discovered derivatives of arachidonic acid-bioactive \u03b4-lactones. Directed evolution, site-directed mutagenesis, and kinetic studies provide comprehensive insights into the active site and catalytic mechanism of PON1.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33348669"}, {"offsetInBeginSection": 0, "offsetInEndSection": 635, "text": "PON1, PON2, and PON3 belong to a family of lactone hydrolyzing enzymes endowed with various substrate specificities. Among PONs, PON2 shows the highest hydrolytic activity toward many acyl-homoserine lactones (acyl-HL) involved in bacterial quorum-sensing signaling. Accordingly, defense against pathogens, such as Brevundimonas aeruginosa (B. aeruginosa), was postulated to be the principal function of PON2. However, recent findings have highlighted the importance of PON2 in oxidative stress control, inhibition of apoptosis, and the progression of various types of malignancies. This review focuses on all of these aspects of PON2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33562328"}, {"offsetInBeginSection": 134, "offsetInEndSection": 426, "text": "Paraoxonases (PON) are a family (PON-1, PON-2, PON-3) of antioxidant enzymes with anti-inflammatory action. Here, for the first time, we described PON-1 activities and PON-1, PON-2, PON-3 polymorphisms in patients with sickle cell disease, homozygous for HbSS, compared with healthy controls.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31366068"}, {"offsetInBeginSection": 134, "offsetInEndSection": 483, "text": "Paraoxonases (PON) are a family (PON-1, PON-2, PON-3) of antioxidant enzymes with anti-inflammatory action. Here, for the first time, we described PON-1 activities and PON-1, PON-2, PON-3 polymorphisms in patients with sickle cell disease, homozygous for HbSS, compared with healthy controls. (2) Methods: The groups were matched for age and gender.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31366068"}, {"offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Paraoxonase-1 (PON-1), a calcium ion-dependent high-density lipoprotein (HDL)-associated enzyme, has been proposed as a negative acute phase reactant biomarker in animal and human adult studies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33831384"}, {"offsetInBeginSection": 0, "offsetInEndSection": 312, "text": "Paraoxonase-1 (PON-1), a calcium ion-dependent high-density lipoprotein (HDL)-associated enzyme, has been proposed as a negative acute phase reactant biomarker in animal and human adult studies. The aim of this study was to evaluate the value of PON-1 activity in the diagnosis and monitoring of neonatal sepsis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33831384"}, {"offsetInBeginSection": 0, "offsetInEndSection": 437, "text": "Paraoxonase-1 (PON-1), a calcium ion-dependent high-density lipoprotein (HDL)-associated enzyme, has been proposed as a negative acute phase reactant biomarker in animal and human adult studies. The aim of this study was to evaluate the value of PON-1 activity in the diagnosis and monitoring of neonatal sepsis. Serum PON-1 activity, as paraoxonase and arylesterase, was prospectively studied in 48 septic neonates and matched controls.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33831384"}, {"offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "(1) Background: Oxidative stress, chronic inflammation, vasoocclusion, and free iron are all features present in sickle cell disease. Paraoxonases (PON) are a family (PON-1, PON-2, PON-3) of antioxidant enzymes with anti-inflammatory action.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31366068"}, {"offsetInBeginSection": 0, "offsetInEndSection": 331, "text": "A physiological role for paraoxonase (PON1) is still uncertain, but it catalyzes the hydrolysis of toxic organophosphates. Evidence that the human genome contains two PON1-like genes, designated PON2 and PON3, is presented here. Human PON1 and PON2 each have nine exons, and the exon/intron junctions occur at equivalent positions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8661009"}, {"offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Paraoxonase 1 (PON 1) is a high-density lipoprotein (HDL)-associated enzyme with antioxidant function protecting low-density lipoprotein (LDL) from oxidation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19226538"}, {"offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "Paraoxonase 1 (PON 1) is a high-density lipoprotein (HDL)-associated enzyme with antioxidant function protecting low-density lipoprotein (LDL) from oxidation. PON 1 has two amino acid polymorphisms in coding region; L/M 55 and Q/R 192. These polymorphisms modulate paraoxonase activity of the enzyme.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19226538"}, {"offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Paraoxonase enzymes serve as an important physiological redox system that participates in the protection against cellular injury caused by oxidative stress. The PON enzymes family", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37108044"}, {"offsetInBeginSection": 0, "offsetInEndSection": 879, "text": "High-density lipoprotein (HDL), in addition to promoting reverse cholesterol transport, possesses anti-inflammatory, antioxidative, and antithrombotic activities. Paraoxonase 1 (PON1), carried on HDL in the blood, can contribute to these antiatherogenic activities. The PON1-Q192R polymorphism involves a change from glutamine (Q variant) to arginine (R variant) at position 192 of the PON1 protein and affects its enzymatic activity. The molecular basis of PON1 association with cardiovascular and neurological diseases is not fully understood. To get insight into the function of PON1 in human disease, we examined how genetic attenuation of PON1 levels/activity affect plasma proteomes of mice and humans. Healthy participants (48.9 years old, 50% women) were randomly recruited from the Pozna\u0144 population. Four-month-old Pon1-/- (n = 17) and Pon1+/+ (n = 8) mice (50% female)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33260536"}, {"offsetInBeginSection": 152, "offsetInEndSection": 390, "text": "All PON proteins share considerable structural homology and have the capacity to protect cells from oxidative stress; therefore, they have been implicated in the pathogenesis of several inflammatory diseases, particularly atherosclerosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22824324"}, {"offsetInBeginSection": 413, "offsetInEndSection": 770, "text": " Each PON member has high catalytic activity toward corresponding artificial organophosphate, and all exhibit activities to lactones. Therefore, all three members of the family are regarded as lactonases. Under physiological conditions, they act to degrade metabolites of polyunsaturated fatty acids and homocysteine (Hcy) thiolactone, among other compounds", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21867409"}, {"offsetInBeginSection": 771, "offsetInEndSection": 996, "text": " By detoxifying both oxidized low-density lipoprotein and Hcy thiolactone, PONs protect against atherosclerosis and coronary artery diseases, as has been illustrated by many types of in vitro and in vivo experimental evidence", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21867409"}, {"offsetInBeginSection": 329, "offsetInEndSection": 631, "text": "We have established that all three PONs are lactonases/lactonyzing enzymes with overlapping, but also distinct substrate specificity. Dihydrocoumarin (DHC), long chain fatty acid lactones and acylhomoserine lactones (AHLs) are hydrolyzed by all three PONs and likely represent their natural substrates.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20122908"}, {"offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Paraoxonase (PON) is an aryldialkylphosphatase, which reversibly binds and hydrolyzes organophosphates. The PON family has three members (PON1, PON2 and PON3); they share structural properties and enzymatic activities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20535264"}, {"offsetInBeginSection": 413, "offsetInEndSection": 616, "text": " Each PON member has high catalytic activity toward corresponding artificial organophosphate, and all exhibit activities to lactones. Therefore, all three members of the family are regarded as lactonases", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21867409"}, {"offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "The mammalian paraoxonases (PONs 1, 2 and 3) are a family of esterases that are highly conserved within and between species. They exhibit antioxidant and anti-inflammatory activities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30241945"}]}
+{"question_id": "660d1285fdcbea915f000036", "question": "Inflammatory breast cancer is the most aggressive form of breast cancer.", "answer": "According to the provided abstracts, inflammatory breast cancer (IBC) is indeed considered the most aggressive form of breast cancer. This is supported by multiple studies that highlight its distinct clinical features and poorer prognosis compared to non-inflammatory breast cancer. The abstracts suggest that IBC is characterized by a higher frequency of somatic mutations, including TP53, PIK3CA, and ERBB2, as well as upregulated inflammatory signaling pathways, such as NF-\u03baB activation and excessive IL-6 production. Additionally, the role of the tumor microenvironment, including tumor-associated macrophages, infiltrating lymphocytes, and cancer stem cells, is thought to contribute to the aggressive behavior of IBC. Overall, the collective evidence from these abstracts confirms that IBC is a highly aggressive and distinct form of breast cancer.", "relevant_passage_ids": ["34973083", "33845027"], "type": "yesno", "snippets": [{"offsetInBeginSection": 9, "offsetInEndSection": 84, "text": "Inflammatory breast cancer is a deadly and aggressive type of breast cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34973083"}, {"offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Inflammatory breast cancer is a rare and aggressive malignancy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33845027"}, {"offsetInBeginSection": 690, "offsetInEndSection": 765, "text": "rapid onset of <3 months; and pathologic confirmation of invasive carcinoma", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33845027"}]}
+{"question_id": "661dc376fe9d0b3967000002", "question": "Is the majority of genetic variation present in the coding regions of the genome?", "answer": "Recent advancements in genomics involving individuals from different races and geographical locations have led to the identification of thousands of common as well as rare genetic variants and copy number variations (CNVs). These studies have surprisingly revealed that the majority of genetic variation is not present within the coding region but rather in the non-coding region of the genome.", "relevant_passage_ids": ["32472759", "30370373", "24667321", "27270572", "35850704", "28797091", "29325625", "25764334", "30619888", "27471964", "37372336", "24661571"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 435, "text": "Latest advancements in genomics involving individuals from different races and geographical locations has led to the identification of thousands of common as well as rare genetic variants and copy number variations (CNVs). These studies have surprisingly revealed that the majority of genetic variation is not present within the coding region but rather in the non-coding region of the genome, which is also termed as \"Medical Genome\".", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32472759"}, {"offsetInBeginSection": 0, "offsetInEndSection": 312, "text": "It has been found that the majority of disease-associated genetic variants identified by genome-wide association studies are located outside of protein-coding regions, where they seem to affect regions that control transcription (promoters, enhancers) and non-coding RNAs that also can influence gene expression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24667321"}, {"offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "The vast majority of somatic variants in cancer genomes occur in non-coding regions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30370373"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Almost 90\u00a0% of disease-associated genetic variants found using genome wide association studies (GWAS) are located in non-coding regions of the genome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27270572"}, {"offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "There is broad agreement that genetic mutations occurring outside of the protein-coding regions play a key role in human disease. Despite this consensus, we are not yet capable of discerning which portions of non-coding sequence are important in the context of human disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28797091"}, {"offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "The vast majority of somatic variants in cancer genomes occur in non-coding regions. However, progress in cancer genomics in the past decade has been mostly focused on coding regions, largely due to the prohibitive cost of whole genome sequencing (WGS).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30370373"}, {"offsetInBeginSection": 223, "offsetInEndSection": 435, "text": "These studies have surprisingly revealed that the majority of genetic variation is not present within the coding region but rather in the non-coding region of the genome, which is also termed as \"Medical Genome\".", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32472759"}, {"offsetInBeginSection": 327, "offsetInEndSection": 737, "text": "Most of what we know about genetic contributions to disease so far comes from analysis of mutations in protein-coding genes. Since most genetic variation lies in nonprotein-coding regions of the genome whose presumed function is entirely regulatory, understanding gene regulation in a cell type and developmental state-specific manner will be important to connect human genetic variation to disease mechanisms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29325625"}, {"offsetInBeginSection": 789, "offsetInEndSection": 906, "text": "Non-coding regions displayed greater genetic variation compared to coding regions, with a few highly variable regions", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37372336"}, {"offsetInBeginSection": 375, "offsetInEndSection": 562, "text": "However, the vast majority of sequence variants map to non-coding intergenic and intronic regions, and it has been much more challenging to assess the functional nature of these variants.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24661571"}]}
+{"question_id": "661d6252eac11fad33000025", "question": "What is the cause of autosomal dominant Polycystic Kidney Disease?", "answer": "Autosomal dominant polycystic kidney disease (ADPKD) is caused primarily by mutations in the PKD1 gene or PKD2 gene.", "relevant_passage_ids": ["37468838", "37598857", "31160911", "36469907", "21115670", "22508176", "25491204", "34542828", "37028763", "36035467", "23496908", "29633482", "29860066", "17100995", "31056860", "27016049", "10602361", "18947299", "21392578", "26718059", "9889186", "29767557", "11336705", "10322638", "26788466", "37664187", "30644092", "22383692", "15775720", "10655152", "27067213", "24374109", "31668373", "30792735", "20219615"], "type": "factoid", "snippets": [{"offsetInBeginSection": 12, "offsetInEndSection": 167, "text": "Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenic multisystem disease caused primarily by mutations in the PKD1 gene or PKD2 gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37468838"}, {"offsetInBeginSection": 0, "offsetInEndSection": 627, "text": "Autosomal dominant polycystic kidney disease (ADPKD), the most common inherited kidney disorder, is caused by mutations in PKD1 or PKD2. The molecular diagnosis of ADPKD is complicated by extensive allelic heterogeneity and particularly by the presence of six highly homologous sequences of PKD1 exons 1-33. Here, we screened PKD1 and PKD2 for both conventional mutations and gross genomic rearrangements in up to 700 unrelated ADPKD patients--the largest patient cohort to date--by means of direct sequencing, followed by quantitative fluorescent multiplex polymerase chain reaction or array-comparative genomic hybridization.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22508176"}, {"offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic renal disorder with an incidence of 1:1000. Mutations in two genes (PKD1 and PKD2) have been identified as causative. Eighty-five percent of patients with ADPKD carry their mutation in the PKD1 gene", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21115670"}, {"offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic renal disorder with an incidence of 1:1000. Mutations in two genes (PKD1 and PKD2) have been identified as causative", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21115670"}, {"offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Novel PKD1 and PKD2 mutations in autosomal dominant polycystic kidney disease (ADPKD).", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21115670"}, {"offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Autosomal dominant polycystic kidney disease (ADPKD) resulting from pathogenic variants in PKD1 and PKD2 is the most common form of PKD, but other genetic causes tied to primary cilia function have been identified.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37598857"}, {"offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Autosomal dominant polycystic kidney disease is caused by mutations in PKD1 or PKD2 genes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37028763"}, {"offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in the PKD1 or PKD2 gene which encodes membrane receptor PKD1 and cation channel PKD2, respectively.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36035467"}, {"offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder. It is caused by mutations in the PKD1 and PKD2 genes, and manifests as progressive cyst growth and renal enlargement, resulting in re", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25491204"}, {"offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is a systemic, irreversible, genetic condition caused by mutations in the PKD1 and ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36469907"}, {"offsetInBeginSection": 0, "offsetInEndSection": 348, "text": "BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of inherited kidney disease that results in renal failure. ADPKD is a systemic disorder with cysts and connective tissue abnormalities involving many organs. ADPKD caused by mutations in PKD1 gene is significantly more severe than the cases caused by PKD2 gen", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23496908"}, {"offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "AIM: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease in humans and is caused by mutations in the PKD1 or PKD2 ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29633482"}, {"offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "Autosomal Dominant Polycystic Kidney Disease (ADPKD), the most frequent genetic disorder of the kidneys, is characterized by a typical presenting symptoms include cysts development in different organs and a non-cysts manifestations. ADPKD is caused by mutations in PKD1 or PKD2 genes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29860066"}, {"offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Autosomal dominant polycystic kidney disease (ADPKD) is genetically heterogeneous and is caused by mutations in the PKD1 or PKD2 genes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17100995"}, {"offsetInBeginSection": 78, "offsetInEndSection": 221, "text": "ey disease. The main mutational genes causing autosomal dominant polycystic kidney disease (ADPKD) are PKD1 and PKD2 as well as some rare patho", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31056860"}, {"offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Autosomal Dominant Polycystic Kidney Disease (ADPKD), a common inherited disease leading to progressive renal failure, can be caused by a mutation in either the PKD1 or PKD2 gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10602361"}, {"offsetInBeginSection": 66, "offsetInEndSection": 226, "text": "The most common form, autosomal dominant polycystic kidney disease (ADPKD), is a disorder most often diagnosed in adults and caused by mutation in PKD1 or PKD2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18947299"}, {"offsetInBeginSection": 0, "offsetInEndSection": 326, "text": "Autosomal dominant polycystic kidney disease (ADPKD) is a common, monogenic multi-systemic disorder characterized by the development of renal cysts and various extrarenal manifestations. Worldwide, it is a common cause of end-stage renal disease. ADPKD is caused by mutation in either one of two principal genes, PKD1 and PKD2", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21392578"}, {"offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Autosomal-dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 and PKD2 and is characterized by proliferation of renal tubular epithelium and progressive chronic kidney disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26718059"}, {"offsetInBeginSection": 162, "offsetInEndSection": 312, "text": "sease include autosomal dominant polycystic kidney diseases (caused by mutations in PKD1 or PKD2), autosomal recessive polycystic kidney disease, tube", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27016049"}, {"offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Most cases of autosomal dominant polycystic kidney disease (ADPKD) are the result of mutations in the PKD1 gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9889186"}, {"offsetInBeginSection": 144, "offsetInEndSection": 222, "text": "Mutations in PKD1 lead to autosomal dominant polycystic kidney disease (ADPKD)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29767557"}, {"offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "The PKD1 gene accounts for 85% of autosomal dominant polycystic kidney disease (ADPKD), the most common human genetic disorder.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11336705"}, {"offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Mutations in the PKD1 gene cause the majority of cases of autosomal dominant polycystic kidney disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10322638"}, {"offsetInBeginSection": 252, "offsetInEndSection": 399, "text": "Approximately 85% of ADPKD cases are caused by mutations in the PKD1 gene, while mutations in the PKD2 gene account for the remaining 15% of cases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26788466"}, {"offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "OBJECTIVE: Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by the pathogenic mutation of PKD1 or PKD2 gene and usually affects bilateral kidneys.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34542828"}, {"offsetInBeginSection": 114, "offsetInEndSection": 426, "text": "Some of the inherited causes of cystic kidney disease include autosomal dominant polycystic kidney diseases (caused by mutations in PKD1 or PKD2), autosomal recessive polycystic kidney disease, tuberous sclerosis complex, von Hippel-Lindau disease, oral-facial-digital syndrome type I, and Hadju-Cheney syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27016049"}, {"offsetInBeginSection": 0, "offsetInEndSection": 497, "text": "Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic inherited renal cystic disease that occurs in different races worldwide. It is characterized by the development of a multitude of renal cysts, which leads to massive enlargement of the kidney and often to renal failure in adulthood. ADPKD is caused by a mutation in PKD1 or PKD2 genes encoding the proteins polycystin-1 and polycystin-2, respectively. Recent studies showed that cyst formation and growth result from deregulation", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30644092"}, {"offsetInBeginSection": 0, "offsetInEndSection": 330, "text": "ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is a systemic, irreversible, genetic condition caused by mutations in the PKD1 and PKD2 genes, and the most common form of inherited kidney disease in the United States, affecting more than 600,000 individuals. Because the condition is autosomal dominant, there is a ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36469907"}, {"offsetInBeginSection": 151, "offsetInEndSection": 555, "text": "Autosomal Dominant Polycystic Kidney Disease (ADPKD), one of the most common genetic kidney diseases. Approaches including both phenotype first and genotype first allows some interesting and informative observations within this disease population. PKD1 and PKD2 are the most frequent genetic causes of ADPKD accounting for 78% and 15% respectively, whilst around 7-8% of cases have an alternative genetic", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37664187"}, {"offsetInBeginSection": 247, "offsetInEndSection": 480, "text": "ADPKD is caused by mutation in either one of two principal genes, PKD1 and PKD2, but has large phenotypic variability among affected individuals, attributable to PKD genic and allelic variability and, possibly, modifier gene effects.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21392578"}, {"offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Mutations in two large multi-exon genes, PKD1 and PKD2, cause autosomal dominant polycystic kidney disease (ADPKD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22383692"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in two genes, PKD1 and PKD2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15775720"}, {"offsetInBeginSection": 145, "offsetInEndSection": 247, "text": "ADPKD is a heterogeneous human disease resulting from mutations in either of two genes, PKD1 and PKD2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10655152"}, {"offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 and PKD2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24374109"}, {"offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic renal disorder with an incidence of 1:1000. Mutations in two genes (PKD1 and PKD2) have been identified a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21115670"}, {"offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 or PKD2, the genes encoding polycystin 1 (PC1) and polycystin 2 (PC2), respectively.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31668373"}, {"offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "Autosomal Dominant Polycystic Kidney Disease (ADPKD) typically results from a mutation in the PKD1 and PKD2 genes, which code for polycystin-1 (PC1) and polycystin-2 (PC2), respectively. Mutations in these genes promote renal cystic dysplasia and are a significant cause of End-Stage Kidney Disease (ESKD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30792735"}, {"offsetInBeginSection": 129, "offsetInEndSection": 263, "text": "The understanding of the pathogenesis of ADPKD has advanced significantly since the discovery of the 2 causative genes, PKD1 and PKD2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20219615"}]}
+{"question_id": "65d1300e1930410b13000033", "question": "Is zilucoplan effective for myasthenia gravis?", "answer": "Yes. Zilucoplan is effective and approved for myasthenia gravis.", "relevant_passage_ids": ["37059508", "37204031", "38093160", "33792453"], "type": "yesno", "snippets": [{"offsetInBeginSection": 2570, "offsetInEndSection": 2928, "text": "INTERPRETATION: Zilucoplan treatment showed rapid and clinically meaningful improvements in myasthenia gravis-specific efficacy outcomes, had a favourable safety profile, and was well tolerated, with no major safety findings. Zilucoplan is a new potential treatment option for a broad population of patients with AChR-positive generalised myasthenia gravis. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37059508"}, {"offsetInBeginSection": 0, "offsetInEndSection": 850, "text": "Zilucoplan (Zilbrysq\u00ae) is a subcutaneously administered macrocyclic peptide inhibitor of complement component 5 (C5 inhibitor) being developed by UCB for the treatment of generalised myasthenia gravis (gMG). Zilucoplan received its first approval, in Japan, in September 2023 for the treatment of gMG in adult patients who inadequately respond to steroids or other immunosuppressants and are positive for anti-acetylcholine receptor (AChR) antibodies. Subsequently, zilucoplan was approved in the USA in October 2023 for the treatment of gMG in adult patients who are anti-AChR antibody positive and in the EU in December 2023 as an add-on to standard therapy for the treatment of gMG in adult patients who are anti-AChR antibody positive. Zilucoplan is also currently under regulatory review in Australia and Canada for use in the treatment of gMG. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38093160"}, {"offsetInBeginSection": 2586, "offsetInEndSection": 2794, "text": "Zilucoplan treatment showed rapid and clinically meaningful improvements in myasthenia gravis-specific efficacy outcomes, had a favourable safety profile, and was well tolerated, with no major safety findings", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37059508"}, {"offsetInBeginSection": 2576, "offsetInEndSection": 2932, "text": "RETATION: Zilucoplan treatment showed rapid and clinically meaningful improvements in myasthenia gravis-specific efficacy outcomes, had a favourable safety profile, and was well tolerated, with no major safety findings. Zilucoplan is a new potential treatment option for a broad population of patients with AChR-positive generalised myasthenia gravis. The ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37059508"}, {"offsetInBeginSection": 2576, "offsetInEndSection": 2800, "text": "RETATION: Zilucoplan treatment showed rapid and clinically meaningful improvements in myasthenia gravis-specific efficacy outcomes, had a favourable safety profile, and was well tolerated, with no major safety findings. Zilu", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37059508"}, {"offsetInBeginSection": 2576, "offsetInEndSection": 3040, "text": "RETATION: Zilucoplan treatment showed rapid and clinically meaningful improvements in myasthenia gravis-specific efficacy outcomes, had a favourable safety profile, and was well tolerated, with no major safety findings. Zilucoplan is a new potential treatment option for a broad population of patients with AChR-positive generalised myasthenia gravis. The long-term safety and efficacy of zilucoplan is being assessed in an ongoing open-label extension study.FUNDI", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37059508"}, {"offsetInBeginSection": 707, "offsetInEndSection": 1101, "text": "Zilucoplan is a small, subcutaneously administered, macrocyclic peptide that inhibits cleavage of complement component C5 and the subsequent formation of the membrane attack complex.EXPERT OPINION: In a randomized, double-blind, placebo-controlled, phase 2 clinical trial, zilucoplan demonstrated clinically meaningful complement inhibition in patients with acetylcholine receptor-positive gMG.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33792453"}]}
+{"question_id": "65f77618c4010b4d7800002e", "question": "Which are the clinical indications for the use of Raltitrexed in patients with colorectal cancer?", "answer": "Raltitrexed ('Tomudex') monotherapy is a conveniently administered alternative to 5-fluorouracil (5-FU) in the first-line treatment of advanced colorectal cancer (CRC),", "relevant_passage_ids": ["12056700", "10645208", "12044507", "11038040", "24093908", "11872339", "33268287", "23583220", "8936802", "10645206", "9528843", "9530547", "10573207", "15991972", "9579853", "9376633", "20080456", "18462574", "32588749", "11269736", "24388340", "10660737", "12449732", "11459994", "35837190", "34470724", "16556086", "12530045", "24869761", "33830591"], "type": "list", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Raltitrexed ('Tomudex') monotherapy is a conveniently administered alternative to 5-fluorouracil (5-FU) in the first-line treatment of advanced colorectal cancer (CRC),", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12056700"}, {"offsetInBeginSection": 1626, "offsetInEndSection": 1812, "text": "Prescription should be individualized and adapted to liver biology (irinotecan), kidney function (capecitabine and raltitrexed) and cardiovascular status (bevacizumab, 5-FU, capecitabin)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20080456"}, {"offsetInBeginSection": 12, "offsetInEndSection": 306, "text": "To evaluate three technologies for the management of advanced colorectal cancer: (1) first-line irinotecan combination [with 5-fluorouracil (5-FU)] or second-line monotherapy; (2) first- or second-line oxaliplatin combination (again, with 5-FU); and (3) raltitrexed, where 5-FU is inappropriate", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18462574"}, {"offsetInBeginSection": 1041, "offsetInEndSection": 1197, "text": "These results suggest that raltitrexed provides an effective and convenient treatment for patients with advanced and previously untreated colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10660737"}, {"offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Raltitrexed-based chemotherapy for advanced colorectal cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24388340"}, {"offsetInBeginSection": 0, "offsetInEndSection": 33, "text": "Raltitrexed in colorectal cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8936802"}, {"offsetInBeginSection": 990, "offsetInEndSection": 1197, "text": "Only one death was associated with drug treatment. These results suggest that raltitrexed provides an effective and convenient treatment for patients with advanced and previously untreated colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10660737"}, {"offsetInBeginSection": 932, "offsetInEndSection": 1197, "text": "These adverse reactions were considered to be manageable. Only one death was associated with drug treatment. These results suggest that raltitrexed provides an effective and convenient treatment for patients with advanced and previously untreated colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10660737"}, {"offsetInBeginSection": 324, "offsetInEndSection": 657, "text": "[symbol: see text] Raltitrexed (Tomudex-Zeneca), a new class of cytotoxic drug introduced last year, is claimed to simplify treatment and be as effective as one established fluorouracil regimen while causing less toxicity. We review raltitrexed and assess its place in the treatment of patients in whom colorectal cancer is advanced.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8936802"}, {"offsetInBeginSection": 0, "offsetInEndSection": 330, "text": "AIMS: To evaluate the efficiency and safety profile of raltitrexed-based chemotherapy in the treatment of advanced colorectal cancer.METHODS: An electronic search was undertaken to identify randomized controlled trials comparing raltitrexed-based regimen to 5-fluorouracil-based regimen in patients with advanced colorectal cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24388340"}, {"offsetInBeginSection": 0, "offsetInEndSection": 408, "text": "AIMS: To evaluate the efficiency and safety profile of raltitrexed-based chemotherapy in the treatment of advanced colorectal cancer.METHODS: An electronic search was undertaken to identify randomized controlled trials comparing raltitrexed-based regimen to 5-fluorouracil-based regimen in patients with advanced colorectal cancer. The outcomes included overall survival, overall response rate and toxicities", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24388340"}, {"offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "AIMS: To evaluate the efficiency and safety profile of raltitrexed-based chemotherapy in the treatment of advanced colorectal cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24388340"}, {"offsetInBeginSection": 1708, "offsetInEndSection": 1983, "text": "Thus, with its similar efficacy to fluorouracil-based regimens, convenient administration schedule and favourable tolerability profile, raltitrexed provides clinicians with a worthwhile alternative to fluorouracil-based treatment for patients with advanced colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9530547"}, {"offsetInBeginSection": 1727, "offsetInEndSection": 1854, "text": "In conclusion, raltitrexed is an active, convenient and low toxicity treatment for the elderly with advanced colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12044507"}, {"offsetInBeginSection": 392, "offsetInEndSection": 637, "text": "Phase III studies in patients with advanced colorectal cancer indicate similar efficacy with raltitrexed monotherapy and combination therapy with 5-fluorouracil + low or high dose leucovorin (5-FU + LV) (Mayo or Machover regimens, respectively).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15991972"}, {"offsetInBeginSection": 0, "offsetInEndSection": 309, "text": "Following the demonstration of efficacy, tolerability and quality-of-life benefits of raltitrexed ('Tomudex'), principally in advanced colorectal but also in other cancers, an extensive evaluation of combination therapy with other agents in patients with colorectal and other tumour types is being undertaken.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9579853"}, {"offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Raltitrexed ('Tomudex') monotherapy is a conveniently administered alternative to 5-fluorouracil (5-FU) in the first-line treatment of advanced colorectal cancer (CRC)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12056700"}, {"offsetInBeginSection": 10, "offsetInEndSection": 323, "text": "the demonstration of efficacy, tolerability and quality-of-life benefits of raltitrexed ('Tomudex'), principally in advanced colorectal but also in other cancers, an extensive evaluation of combination therapy with other agents in patients with colorectal and other tumour types is being undertaken. This work has", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9579853"}, {"offsetInBeginSection": 868, "offsetInEndSection": 1286, "text": "used in monotherapy. These results suggest a role for raltitrexed within combination regimens in colorectal cancer therapy, as well as other tumors such as head and neck cancer. A further potential application of raltitrexed in combination therapies is within multidisciplinary chemo-radiotherapy strategies, mainly in rectal cancer. Phase II studies are planned/ongoing to investigate these interesting possibilities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11459994"}, {"offsetInBeginSection": 102, "offsetInEndSection": 518, "text": "adiotherapy and chemotherapy. Raltitrexed ('Tomudex') is a specific thymidylate synthase inhibitor with a convenient administration schedule, acceptable and manageable toxicity, radiosensitising properties, and proven efficacy in the treatment of advanced colorectal cancer. It may, therefore, offer advantages compared with standard 5-FU chemotherapy regimens used in colorectal cancer. The aim of this phase I, dos", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11038040"}, {"offsetInBeginSection": 0, "offsetInEndSection": 462, "text": "Raltitrexed (Tomudex) is a new specific, mixed non-competitive inhibitor of thymidylate synthase indicated for use in the therapy of advanced colorectal cancer. Phase I and II studies defined a maximum tolerated dose of 3.0 mg/m(2) administered as a 15-min i.v. infusion every 3 weeks: this dose proved active in a range of malignancies, but most significantly in advanced colorectal cancer. Phase III studies in patients with advanced colorectal cancer indicate", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15991972"}, {"offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Raltitrexed ('Tomudex') monotherapy is a conveniently administered alternative to 5-fluorouracil (5-FU) in the first-line treatment of advanced colorectal cancer (CRC), and", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12056700"}, {"offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "PURPOSE: We have recently evaluated the combination of raltitrexed, levofolinic acid (LFA) and 5-fluorouracil (5-FU) in advanced head and neck and colorectal cancer, and we have shown that this combination is well tolerated and has clinical activity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11269736"}, {"offsetInBeginSection": 0, "offsetInEndSection": 397, "text": "Raltitrexed (Tomudex), a novel folate-based inhibitor of thymidylate synthase, has demonstrated anti-tumour efficacy comparable with 5-fluorouracil and leucovorin in patients with advanced colorectal cancer (CRC). This phase II study was conducted to evaluate the anti-timor efficacy and tolerability of raltitrexed in patients with advanced CRC who had received one previous chemotherapy regimen.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10573207"}, {"offsetInBeginSection": 1672, "offsetInEndSection": 1816, "text": "itabine due to cardiac history. Raltitrexed is therefore a suitable option for patients with fluoropyrimidine-induced cardiotoxicity or signific", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23583220"}, {"offsetInBeginSection": 2046, "offsetInEndSection": 2198, "text": "Raltitrexed in patients with colorectal cancer who were previously treated with fluoropyrimidine-based systemic therapy is effective and well-tolerated.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33268287"}, {"offsetInBeginSection": 1021, "offsetInEndSection": 1304, "text": "Considering the chemotherapy regimen, TOMOX was significantly associated with better PFS and OS compared to TOMIRI and raltitrexed alone.CONCLUSIONS: In patients with mCRC not eligible for fluoropyrimidines, first-line raltitrexed-based chemotherapy had an acceptable safety profile.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34470724"}, {"offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Raltitrexed (Tomudex), a novel folate-based inhibitor of thymidylate synthase, has demonstrated anti-tumour efficacy comparable with 5-fluorouracil and leucovorin in patients with advanced colorectal cancer (CRC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10573207"}, {"offsetInBeginSection": 34, "offsetInEndSection": 295, "text": "ned with S-1 and raltitrexed demonstrated positive antitumor efficacy and acceptable toxicity. This combination might represent a treatment option for refractory metastatic colorectal cancer.BACKGROUND: In patients with metastatic colorectal cancer (mCRC) refra", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33830591"}, {"offsetInBeginSection": 6, "offsetInEndSection": 407, "text": "ound: Local recurrence of colorectal cancer is associated with poor prognosis and quality of life. For patients not eligible for curative surgery, chemoradiation could be a promising therapeutic option, but there is no consensus yet for the concurrent chemotherapy regimen. This study evaluated the effects and safety of intensity-modulated radiation therapy (IMRT) when administered concurrently with", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35837190"}, {"offsetInBeginSection": 0, "offsetInEndSection": 591, "text": "BACKGROUND: Use of fluoropyrimidine-based therapy in patients with metastatic colorectal cancer is associated with significant toxicities. This study aimed to assess the safety and efficacy of raltitrexed use in patients with metastatic colorectal cancer who developed significant toxicities after fluoropyrimidine-based treatment.PATIENTS AND METHODS: We identified patients with metastatic colorectal cancer who were treated with raltitrexed-based systemic therapy after developing serious adverse events with fluoropyrimidine-based treatment in a large Canadian province from 2004 to 2018", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33268287"}, {"offsetInBeginSection": 0, "offsetInEndSection": 330, "text": "BACKGROUND: Use of fluoropyrimidine-based therapy in patients with metastatic colorectal cancer is associated with significant toxicities. This study aimed to assess the safety and efficacy of raltitrexed use in patients with metastatic colorectal cancer who developed significant toxicities after fluoropyrimidine-based treatment", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33268287"}, {"offsetInBeginSection": 275, "offsetInEndSection": 403, "text": "ath. Raltitrexed is indicated for palliative treatment of advanced CRC where 5-fluorouracil (5-FU) is not tolerated or inappropr", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23583220"}, {"offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "Raltitrexed is a thymidylate synthase inhibitor belonging to the antimetabolite class of cytotoxic drugs. It is also effective in colorectal cancer (CRC) both as a single agent and in combination with other drugs, in particular in those patients with cardiologic risk factors or previous cardiotoxicity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24869761"}, {"offsetInBeginSection": 412, "offsetInEndSection": 635, "text": "Although some of these new agents, such as raltitrexed, oxaliplatin and irinotecan, are active in colorectal cancer, single-agent therapy as first-line treatment has failed to demonstrate a substantial increase in survival.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10645206"}]}
+{"question_id": "661bdc9148a2c27714000001", "question": "Please list the findings in lateral medullary (Wallenberg) syndrome", "answer": "the lateral medullary (Wallenberg) syndrome, focuses on ocular lateropulsion, saccadic dysmetria, and the ocular tilt reaction.", "relevant_passage_ids": ["37275090", "32655466", "32539005", "34979701", "34373821", "36923779", "36993088", "29404361", "26350694", "8263550", "34705083", "7316726", "36367000", "24626124"], "type": "list", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 594, "text": "Wallenberg syndrome, or lateral medullar syndrome, is the clinical presentation of the infarct in the territory of posterior inferior cerebellar artery. Its signs and symptoms include vertigo, nystagmus, diplopia, ipsilateral Horner syndrome, facial ruddiness and dry skin, dysphonia, dysphagia, dysarthria, ipsilateral loss of gag reflex, ipsilateral ataxia, ipsilateral impaired taste, ipsilateral facial pain and paresthesia, decreased ipsilateral blink reflex, contralateral hypoalgesia and thermoanaesthesia in the trunk and limbs; and ipsilateral facial hypoalgesia and thermoanaesthesia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32539005"}, {"offsetInBeginSection": 12, "offsetInEndSection": 146, "text": "Lateral medullary stroke (LMS) results in a characteristic pattern of brainstem signs including ocular motor and vestibular deficits. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32655466"}, {"offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "Lateral medullary syndrome/Wallenberg syndrome, is a neurological disorder occurring due to ischemia in the lateral part of medullary oblongata resulting in wide range of symptoms. Dysphagia is usually exhibited in severe and persistent form in LMS. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37275090"}, {"offsetInBeginSection": 0, "offsetInEndSection": 313, "text": "Thirteen patients with Wallenberg's lateral medullary syndrome (WLMS) were studied. Clinical and magnetic resonance imaging (MRI) evidence demonstrated infarction in the dorsolateral medulla which produced loss of pain and temperature sensation on one side of the face ipsilateral to the lesion in seven patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8263550"}, {"offsetInBeginSection": 0, "offsetInEndSection": 367, "text": "BACKGROUND: Various sensory impairments have been reported in patients with lateral medullary syndrome, also known as Wallenberg syndrome. The typical sensory impairments experienced by patients with this condition are ipsilateral facial and contralateral trunk and limb thermal hypesthesia and hypoalgesia. Tactile (light touch) sensation is not generally diminished", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26350694"}, {"offsetInBeginSection": 1240, "offsetInEndSection": 1488, "text": "cal Discussion: LMS (Wallenberg syndrome) is one of the brainstem stroke syndromes caused by occlusion of PICA. Vertigo, vomiting, dysphagia, dysarthria, ipsilateral ataxia, Horner's syndrome, and contralateral hemiparesis define this syndrome. Bra", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36923779"}, {"offsetInBeginSection": 1240, "offsetInEndSection": 1554, "text": "cal Discussion: LMS (Wallenberg syndrome) is one of the brainstem stroke syndromes caused by occlusion of PICA. Vertigo, vomiting, dysphagia, dysarthria, ipsilateral ataxia, Horner's syndrome, and contralateral hemiparesis define this syndrome. Brain MRI is necessary for diagnosis alongside clinical syndrome.Conc", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36923779"}, {"offsetInBeginSection": 1191, "offsetInEndSection": 1486, "text": " was discharged for physical rehabilitation.Clinical Discussion: LMS (Wallenberg syndrome) is one of the brainstem stroke syndromes caused by occlusion of PICA. Vertigo, vomiting, dysphagia, dysarthria, ipsilateral ataxia, Horner's syndrome, and contralateral hemiparesis define this syndrome. B", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36923779"}, {"offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "BACKGROUND: Various sensory impairments have been reported in patients with lateral medullary syndrome, also known as Wallenberg syndrome. The typical sensory impairments experienced by patients with this condition are ipsilateral facial and contralateral trunk and limb thermal hypesthesia and hypoalgesia", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26350694"}, {"offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "Lateral medullary syndrome (LMS) is a less common form of a brainstem stroke. It is the result of occlusion of the posterior inferior cerebellar artery (PICA). It is caused by atherosclerosis, thrombosis, or emboli from another source.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36923779"}, {"offsetInBeginSection": 0, "offsetInEndSection": 333, "text": "Lateral medullary syndrome (LMS), also known as Wallenberg's syndrome, PICA syndrome, results from occlusion of the posterior inferior cerebellar artery, with associated infarction of parts of medulla oblongata, and cerebellum on the ipsilateral side. It often manifests as various patterns of sensory, motor, and autonomic deficits.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29404361"}, {"offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Lateral medullary syndrome/Wallenberg syndrome, is a neurological disorder occurring due to ischemia in the lateral part of medullary oblongata resulting in wide range of symptoms. Dysphagia is usually exhibited in severe and persistent form in LMS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37275090"}, {"offsetInBeginSection": 261, "offsetInEndSection": 503, "text": "The most pathognomonic symptoms of LMS includes pain and temperature deficits on ipsilateral facial side and contralateral side of rest of the body, ipsilateral ataxia, vertigo, nystagmus, dysphagia, hoarseness, hiccups and Horner's syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36993088"}, {"offsetInBeginSection": 149, "offsetInEndSection": 418, "text": "The diagnosis of Wallenberg's syndrome is justified when the classic symptoms are apparent (Horner's syndrome, nystagmus, dysphonia and dysphagia, ataxia, ipsilateral sensory impairment of the face and contralateral elsewhere, and accompanying vegetative disturbances).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7316726"}, {"offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Lateral medullary syndrome/Wallenberg syndrome is a stroke in the lateral medulla with symptoms often including dysphagia and dysphonia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34705083"}, {"offsetInBeginSection": 251, "offsetInEndSection": 370, "text": "The triad of Horner's syndrome, ipsilateral ataxia, and ipsilateral hyperalgesia clinically identify patients with LMS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34979701"}, {"offsetInBeginSection": 88, "offsetInEndSection": 342, "text": "Lateral medullary syndrome results in damage to the corresponding cranial nerve nuclei and the nucleus tractus solitarius, with vertigo, ipsilateral ataxia, crossed sensory disturbances, Horner's sign, bulbar palsy, and other underlying symptoms or signs", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36367000"}, {"offsetInBeginSection": 0, "offsetInEndSection": 324, "text": "Lateral medullary syndrome/Wallenberg syndrome, is a neurological disorder occurring due to ischemia in the lateral part of medullary oblongata resulting in wide range of symptoms. Dysphagia is usually exhibited in severe and persistent form in LMS. Hence timely intervention is mandatory before the patient further worsens.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37275090"}, {"offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Patients with lateral medullary syndrome classically present with crossed hemisensory disturbance, ipsilateral Horner syndrome, and cerebellar signs, all of which are attributable to infarction of the lateral medulla.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24626124"}]}
+{"question_id": "6614fb7bfdcbea915f000044", "question": "What are the new treatments for cystic fibrosis?", "answer": "CFTR (cystic fibrosis transmembrane conductance) modulators: ivacaftor, lumacaftor, tezacaftor, elexacaftor. Administered as triple therapy: elexacaftor, tezacaftor and ivacaftor (ETI).", "relevant_passage_ids": ["31899933", "35125294", "36986509"], "type": "summary", "snippets": [{"offsetInBeginSection": 402, "offsetInEndSection": 489, "text": "For patients with common mutations like F508del, CFTR modulators are life transforming ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31899933"}, {"offsetInBeginSection": 123, "offsetInEndSection": 200, "text": "disease-modifying triple combination therapy ivacaftor/tezacaftor/elexacaftor", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35125294"}, {"offsetInBeginSection": 155, "offsetInEndSection": 216, "text": "CF transmembrane conductance regulator (CFTR) modulator drugs", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36986509"}, {"offsetInBeginSection": 355, "offsetInEndSection": 498, "text": "These drugs consist of the potentiator ivacaftor (VX-770) and the correctors lumacaftor (VX-809), tezacaftor (VX-661), and elexacaftor (VX-445)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36986509"}, {"offsetInBeginSection": 519, "offsetInEndSection": 683, "text": "triple combination of CFTR modulators composed of elexacaftor, tezacaftor, and ivacaftor (ETI) represents a life-changing therapy for the majority of PwCF worldwide", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36986509"}]}
+{"question_id": "661c424588784bab31000001", "question": "By which method do micro RNAs (miRNAs) primarily aid in transcriptional and post-transcriptional regulation?", "answer": "Micro RNAs (miRNAs) are small non-coding RNAs that regulate gene expression by binding to mRNA and mediating its degradation or inhibiting translation.", "relevant_passage_ids": ["37505443", "32949853", "20545570", "23447695", "28602827", "20940025", "30374521", "11896390", "26673698", "23445489", "38075204", "35247033", "33381822", "24367289", "20036482", "25086339", "21832809", "18333757", "26257769", "22622804", "36316086", "34432271", "36040583", "19112830", "31752361", "16957368", "17507929", "27754357", "25914709", "26662984", "27525292", "17538623", "37958433", "29187891", "21893463", "29989022", "37397550", "22336708", "29471827", "19800023", "17127242", "21807045", "26616332", "31179855", "36069329", "34979040", "29959194", "30333195", "36552307", "29058542", "18533097", "20371515", "19841878", "24075926", "26308709", "21532838", "23559250", "24938790", "34155810", "28837599", "19643113", "26761000"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Small non-coding RNAs (miRNAs) regulate gene expression by binding to mRNA and mediating its degradation or inhibiting translation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37505443"}, {"offsetInBeginSection": 252, "offsetInEndSection": 409, "text": "MicroRNAs (miRNAs) are small non-coding RNAs mediating gene expression at the post-transcriptional level through mRNA degradation or translational repression", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32949853"}, {"offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Micro-RNAs (miRNAs) play a crucial role in post-transcriptional gene regulation by pairing with target mRNAs to repress protein production. It has been shown that over one-third of human genes are targeted by miRNA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21832809"}, {"offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Micro-RNAs (miRNAs) play a crucial role in post-transcriptional gene regulation by pairing with target mRNAs to repress protein production.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21832809"}, {"offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Micro RNAs (miRNAs) are a recently discovered class of small, non-coding RNAs with the function of post-transcriptional gene expression regulation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20940025"}, {"offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "MicroRNAs (miRNAs) play a major role in the post-transcriptional regulation of target genes, especially in development and differentiation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26673698"}, {"offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "MicroRNAs (miRNAs) are small non-coding RNAs (sncRNAs) that function in post-transcriptional gene regulation through imperfect base pairing with mRNA targets which results in inhibition of translation and typically destabilization of bound transcripts.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36316086"}, {"offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "MicroRNA (miRNA) is a small, non-coding RNA molecule (~22 nucleotides) that acts as a post-transcriptional gene regulator, primarily by inhibiting the translation of target mRNA transcripts or affecting cell mRNA stability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36040583"}, {"offsetInBeginSection": 0, "offsetInEndSection": 563, "text": "Although initially believed to act exclusively as translational repressors, microRNAs (miRNAs) are now known to target complementary messenger RNA (mRNA) transcripts for either translational repression or cleavage via the RNA-induced silencing complex (RISC) ([1], reviewed in ref. 2). The current model postulates that mature miRNAs are incorporated into the RISC, bind target mRNAs based on complementarity, and guide cleavage of mRNA targets with perfect or nearly perfect complementarity and translational repression of targets with lower complementarity (2).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16957368"}, {"offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "MicroRNAs (miRNAs) are a class of small RNAs that act post-transcriptionally to regulate messenger RNA stability and translation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17507929"}, {"offsetInBeginSection": 729, "offsetInEndSection": 866, "text": "miRNAs act as post-transcriptional regulators of their messenger RNA (mRNA) targets via mRNA degradation and/or translational repression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27754357"}, {"offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "MicroRNAs (miRNAs) are short (~22 nucleotides) single-stranded RNA molecules that primarily function to negatively regulate gene expression at the post-transcriptional level.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26662984"}, {"offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "MicroRNAs (MiRNAs) are small, non-coding RNA molecules that function in RNA silencing and post-transcriptional regulation of gene expression", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37958433"}, {"offsetInBeginSection": 0, "offsetInEndSection": 406, "text": "MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression in animals and in plants. In recent years, miRNAs have been shown to be important biological molecules for regulating various cellular functions. miRNAs function post-transcriptionally usually by base-pairing to the mRNA 3'-untranslated regions of the mRNAs and repress protein synthesis by mechanisms that are not fully understood.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22622804"}, {"offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "MicroRNA (miRNA) is a small non-coding RNA with an established function to regulate genes at the post-transcriptional level leading to suppression or degradation of its messenger RNA expression (mRNA).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29989022"}, {"offsetInBeginSection": 0, "offsetInEndSection": 342, "text": "MicroRNAs (miRNAs) are small non-coding single-stranded RNAs of about 22 nucleotides in length that act as post-transcriptional regulators of gene expression. Depending on the complementarity between miRNA and target mRNA, cleavage, destabilization, or translational suppression of mRNA occurs within the RISC (RNA-induced silencing complex).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37397550"}, {"offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "microRNAs (miRNAs), defined as 21-24 nucleotide non-coding RNAs, are important regulators of gene expression. Initially, the functions of miRNAs were recognized as post-transcriptional regulators on mRNAs that result in mRNA degradation and/or translational repression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22336708"}, {"offsetInBeginSection": 105, "offsetInEndSection": 194, "text": "MiRNAs regulate gene expression by inhibiting protein translation from the messenger RNA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21893463"}, {"offsetInBeginSection": 97, "offsetInEndSection": 285, "text": "Generally, miRNAs that are 20-24 nucleotides long bind to specific complementary transcripts, attenuating gene expression at the post-transcriptional level or via translational inhibition.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25914709"}, {"offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "MicroRNAs (miRNAs) are important regulators of gene expression that bind complementary target mRNAs and repress their expression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30333195"}, {"offsetInBeginSection": 0, "offsetInEndSection": 347, "text": "MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by degrading their RNA targets or by repressing the translation of messenger RNAs (mRNAs). Initially thought to primarily target the 3' untranslated region (3'UTR) of mRNAs, miRNAs have since been shown to also target the 5'UTR and coding sequence (CDS).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26257769"}, {"offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by degrading their RNA targets or by repressing the translation of messenger RNAs (mRNAs).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26257769"}, {"offsetInBeginSection": 0, "offsetInEndSection": 452, "text": "Post-transcriptional regulation of messenger RNAs (mRNAs) (i.e., mechanisms that control translation, stability and localization) is a critical focal point in spatiotemporal regulation of gene expression in response to changes in environmental conditions. The human genome encodes ~\u20092000 microRNAs (miRNAs), each of which could control the expression of hundreds of protein-coding mRNAs by inducing translational repression and/or promoting mRNA decay.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35247033"}, {"offsetInBeginSection": 143, "offsetInEndSection": 213, "text": "miRNAs degrade or repress target mRNAs by targeting the 3' UTR region.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29058542"}, {"offsetInBeginSection": 396, "offsetInEndSection": 471, "text": "miRNAs modulate gene expression by affecting mRNA translation or stability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18533097"}, {"offsetInBeginSection": 114, "offsetInEndSection": 245, "text": "miRNAs act by binding to the 3' untranslated region (3'UTR) of an mRNA, affecting the stability and translation of the target mRNA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20371515"}, {"offsetInBeginSection": 514, "offsetInEndSection": 644, "text": "miRNAs regulate gene expression at the post-transcriptional level, through both translational inhibition and mRNA destabilization.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19841878"}, {"offsetInBeginSection": 258, "offsetInEndSection": 553, "text": "miRNAs are incorporated into the RNA-induced silencing complexes (RISCs) that contain Argonaute (AGO) family proteins and guide RISC to target RNAs via complementary base pairing, leading to post-transcriptional gene silencing by a combination of translation inhibition and mRNA destabilization.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26308709"}, {"offsetInBeginSection": 1003, "offsetInEndSection": 1199, "text": "The degree and nature of the complementarity between the microRNA and target determine the gene silencing mechanism, slicer-dependent mRNA degradation or slicer-independent translation inhibition.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21532838"}, {"offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "MicroRNAs (miRNAs) control gene expression through both translational repression and degradation of target messenger RNAs (mRNAs).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23559250"}, {"offsetInBeginSection": 162, "offsetInEndSection": 351, "text": "To repress gene expression, miRNAs are packaged into RNA-induced silencing complexes (RISCs) that target mRNAs for degradation and/or translational repression in a sequence-specific manner.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24938790"}, {"offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "MicroRNAs (miRNAs) are major post-transcriptional regulators of gene expression. They base pair with the complementary target mRNA at the 3'UTR and modulate cellular processes by repressing the mRNA translation or degrading the mRNA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34155810"}, {"offsetInBeginSection": 805, "offsetInEndSection": 965, "text": "MicroRNAs (miRNAs) have emerged as a class of post-transcriptional regulators that control gene expression through translational repression or mRNA degradation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28837599"}, {"offsetInBeginSection": 142, "offsetInEndSection": 256, "text": "There are two main outcomes for the transcripts targeted by miRNAs: mRNA degradation and translational repression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19643113"}]}
+{"question_id": "661d6473eac11fad33000027", "question": "What is the cause of Autosomal Recessive Polycystic Kidney Disease?", "answer": "The cause of Autosomal Recessive Polycystic Kidney Disease is mutations in the polycystic kidney and hepatic disease 1 (PKHD1) gene.", "relevant_passage_ids": ["37456659"], "type": "factoid", "snippets": [{"offsetInBeginSection": 11, "offsetInEndSection": 154, "text": "Variants of the polycystic kidney and hepatic disease 1 (PKHD1) gene are associated with autosomal recessive polycystic kidney disease (ARPKD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37456659"}]}
+{"question_id": "65cf98431930410b1300000b", "question": "What are the targets of Tarlatamab?", "answer": "Tarlatamab is a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 and CD3. It showed promising antitumor activity in a phase 1 trial in patients with previously treated small-cell lung cancer.", "relevant_passage_ids": ["36351060", "36689692", "37355629", "37861218", "37877814"], "type": "list", "snippets": [{"offsetInBeginSection": 427, "offsetInEndSection": 679, "text": "In multiple patient-derived xenograft models, AMG 757 (tarlatamab), a half-life-extended bispecific T-cell engager (BiTE) immunotherapy that redirects CD3-positive T cells to kill DLL3-expressing cells, exhibited potent and durable antitumor activity. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36351060"}, {"offsetInBeginSection": 157, "offsetInEndSection": 282, "text": "Tarlatamab (AMG 757), a bispecific T-cell engager molecule, binds both DLL3 and CD3 leading to T-cellb-mediated tumor lysis. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36689692"}, {"offsetInBeginSection": 1067, "offsetInEndSection": 1307, "text": "We then review preclinical and clinical data for several DLL3-targeting agents that are currently in development, including the TCE molecules-tarlatamab (formerly known as AMG 757), BI 764532, and HPN328-and the CAR T-cell therapy AMG\u00a0119. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37355629"}, {"offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "BACKGROUND: Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 and CD3, showed promising antitumor activity in a phase 1 trial in patients with previously treated small-cell lung cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37861218"}, {"offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Tarlatamab, an investigational bispecific T-cell engager molecule that targets the cell surface protein delta-like ligand 3, has shown promising activity in patients with small cell lung cancer whose disease had progressed after receiving another therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37877814"}, {"offsetInBeginSection": 0, "offsetInEndSection": 443, "text": "BACKGROUND: Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 and CD3, showed promising antitumor activity in a phase 1 trial in patients with previously treated small-cell lung cancer.METHODS: In this phase 2 trial, we evaluated the antitumor activity and safety of tarlatamab, administered intravenously every 2 weeks at a dose of 10 mg or 100 mg, in patients with previously treated small-cell lung cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37861218"}, {"offsetInBeginSection": 157, "offsetInEndSection": 281, "text": "Tarlatamab (AMG 757), a bispecific T-cell engager molecule, binds both DLL3 and CD3 leading to T-cellb-mediated tumor lysis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36689692"}, {"offsetInBeginSection": 473, "offsetInEndSection": 628, "text": "AMG 757 (tarlatamab), a half-life-extended bispecific T-cell engager (BiTE) immunotherapy that redirects CD3-positive T cells to kill DLL3-expressing cells", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36351060"}, {"offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "BACKGROUND: Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 and CD3, showed promising antitumor activity in a phase 1 trial in patients with previously treated small-cell ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37861218"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "BACKGROUND: Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 and CD3, showed promising antitumor activity in a phas", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37861218"}, {"offsetInBeginSection": 16, "offsetInEndSection": 1360, "text": "ell lung cancer (SCLC) is an aggressive malignancy with limited treatments. Delta-like ligand 3 (DLL3) is aberrantly expressed in most SCLC. Tarlatamab (AMG 757), a bispecific T-cell engager molecule, binds both DLL3 and CD3 leading to T-cellb-mediated tumor lysis. Herein, we report phase I results of tarlatamab in patients with SCLC.PATIENTS AND METHODS: This study evaluated tarlatamab in patients with relapsed/refractory SCLC. The primary end point was safety. Secondary end points included antitumor activity by modified RECIST 1.1, overall survival, and pharmacokinetics.RESULTS: By July 19, 2022, 107 patients received tarlatamab in dose exploration (0.003 to 100 mg; n = 73) and expansion (100 mg; n = 34) cohorts. Median prior lines of anticancer therapy were 2 (range, 1-6); 49.5% received antiprogrammed death-1/programmed death ligand-1 therapy. Any-grade treatment-related adverse events occurred in 97 patients (90.7%) and grade b % 3 in 33 patients (30.8%). One patient (1%) had grade 5 pneumonitis. Cytokine release syndrome was the most common treatment-related adverse event, occurring in 56 patients (52%) including grade 3 in one patient (1%). Maximum tolerated dose was not reached. Objective response rate was 23.4% (95% CI, 15.7 to 32.5) including two complete and 23 partial responses. The median duration of response ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36689692"}, {"offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "BACKGROUND: Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 and CD3, showed promising antitumor activity in a phase 1 trial in patients with previously treated small-cell lung cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37861218"}, {"offsetInBeginSection": 0, "offsetInEndSection": 645, "text": "BACKGROUND: Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 and CD3, showed promising antitumor activity in a phase 1 trial in patients with previously treated small-cell lung cancer.METHODS: In this phase 2 trial, we evaluated the antitumor activity and safety of tarlatamab, administered intravenously every 2 weeks at a dose of 10 mg or 100 mg, in patients with previously treated small-cell lung cancer. The primary end point was objective response (complete or partial response), as assessed by blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37861218"}, {"offsetInBeginSection": 0, "offsetInEndSection": 442, "text": "BACKGROUND: Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 and CD3, showed promising antitumor activity in a phase 1 trial in patients with previously treated small-cell lung cancer.METHODS: In this phase 2 trial, we evaluated the antitumor activity and safety of tarlatamab, administered intravenously every 2 weeks at a dose of 10 mg or 100 mg, in patients with previously treated small-cell lung cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37861218"}, {"offsetInBeginSection": 156, "offsetInEndSection": 447, "text": " Tarlatamab (AMG 757), a bispecific T-cell engager molecule, binds both DLL3 and CD3 leading to T-cellb-mediated tumor lysis. Herein, we report phase I results of tarlatamab in patients with SCLC.PATIENTS AND METHODS: This study evaluated tarlatamab in patients with relapsed/refractory SCLC", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36689692"}, {"offsetInBeginSection": 156, "offsetInEndSection": 351, "text": " Tarlatamab (AMG 757), a bispecific T-cell engager molecule, binds both DLL3 and CD3 leading to T-cellb-mediated tumor lysis. Herein, we report phase I results of tarlatamab in patients with SCLC", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36689692"}, {"offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "PURPOSE: Small-cell lung cancer (SCLC) is an aggressive malignancy with limited treatments. Delta-like ligand 3 (DLL3) is aberrantly expressed in most SCLC. Tarlatamab (AMG 757), a bispecific T-cell engager molecule, binds both DLL3 and CD3 leading to T-cellb-mediated tumor lysis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36689692"}]}
+{"question_id": "65f77465c4010b4d78000028", "question": "Is liquid biopsy a cost-effective technique in general population screening for colorectal cancer?", "answer": "The inclusion of liquid biopsy as a first- or second-line screening strategy was not cost-effective at its current cost and screening performance.", "relevant_passage_ids": ["37971743", "35740615", "30268335", "36056434", "19574924", "19048626", "25468258", "26135268", "23796793"], "type": "yesno", "snippets": [{"offsetInBeginSection": 2360, "offsetInEndSection": 2507, "text": "the inclusion of liquid biopsy as a first- or second-line screening strategy was not cost-effective at its current cost and screening performance. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971743"}, {"offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Cost-Effectiveness of Liquid Biopsy for Colorectal Cancer Screening in Patients Who Are Unscreened.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971743"}, {"offsetInBeginSection": 12, "offsetInEndSection": 136, "text": "Analysis of circulating free DNA (cfDNA) is a promising tool for personalized management of colorectal cancer (CRC) patients", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36056434"}, {"offsetInBeginSection": 2162, "offsetInEndSection": 2517, "text": "and Relevance: In this economic evaluation of liquid biopsy for colorectal cancer screening, colonoscopy was a cost-effective strategy for colorectal cancer screening in the general population, and the inclusion of liquid biopsy as a first- or second-line screening strategy was not cost-effective at its current cost and screening performance. Liquid bio", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971743"}, {"offsetInBeginSection": 133, "offsetInEndSection": 387, "text": " Liquid biopsy tests are in development for cancer early detection, but it is unclear whether they are cost-effective for colorectal cancer screening.Objective: To estimate the cost-effectiveness of liquid biopsy for colorectal cancer screening in the US", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971743"}, {"offsetInBeginSection": 133, "offsetInEndSection": 282, "text": " Liquid biopsy tests are in development for cancer early detection, but it is unclear whether they are cost-effective for colorectal cancer screening", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971743"}, {"offsetInBeginSection": 2032, "offsetInEndSection": 2515, "text": "py-liquid biopsy hybrid had a greater gain in life-years if liquid biopsy could detect polyps but remained too costly.Conclusions and Relevance: In this economic evaluation of liquid biopsy for colorectal cancer screening, colonoscopy was a cost-effective strategy for colorectal cancer screening in the general population, and the inclusion of liquid biopsy as a first- or second-line screening strategy was not cost-effective at its current cost and screening performance. Liquid b", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971743"}, {"offsetInBeginSection": 0, "offsetInEndSection": 387, "text": "Importance: Despite recommendations for universal screening, adherence to colorectal cancer screening in the US is approximately 60%. Liquid biopsy tests are in development for cancer early detection, but it is unclear whether they are cost-effective for colorectal cancer screening.Objective: To estimate the cost-effectiveness of liquid biopsy for colorectal cancer screening in the US", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971743"}, {"offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "Importance: Despite recommendations for universal screening, adherence to colorectal cancer screening in the US is approximately 60%. Liquid biopsy tests are in development for cancer early detection, but it is unclear whether they are cost-effective for colorectal cancer screening", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971743"}, {"offsetInBeginSection": 133, "offsetInEndSection": 672, "text": " Liquid biopsy tests are in development for cancer early detection, but it is unclear whether they are cost-effective for colorectal cancer screening.Objective: To estimate the cost-effectiveness of liquid biopsy for colorectal cancer screening in the US.Design, Setting, and Participants: In this economic evaluation, a Markov model was developed to compare no screening and 5 colorectal cancer screening strategies: colonoscopy, liquid biopsy, liquid biopsy following nonadherence to colonoscopy, stool DNA, and fecal immunochemical test", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971743"}, {"offsetInBeginSection": 134, "offsetInEndSection": 673, "text": "Liquid biopsy tests are in development for cancer early detection, but it is unclear whether they are cost-effective for colorectal cancer screening.Objective: To estimate the cost-effectiveness of liquid biopsy for colorectal cancer screening in the US.Design, Setting, and Participants: In this economic evaluation, a Markov model was developed to compare no screening and 5 colorectal cancer screening strategies: colonoscopy, liquid biopsy, liquid biopsy following nonadherence to colonoscopy, stool DNA, and fecal immunochemical test.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971743"}, {"offsetInBeginSection": 1451, "offsetInEndSection": 1730, "text": "A strategy was considered cost-effective if it had an incremental cost-effectiveness ratio less than the US willingness-to-pay threshold of $100\u202f000 per life-year gained.Results: This study used a simulated cohort of patients aged 45 years with average risk of colorectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971743"}, {"offsetInBeginSection": 1886, "offsetInEndSection": 2022, "text": "Colonoscopy-liquid biopsy hybrid had the greatest gain in life-years gained but had an incremental cost-effectiveness ratio of $377\u202f538.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971743"}, {"offsetInBeginSection": 2507, "offsetInEndSection": 2624, "text": "Liquid biopsy tests for colorectal cancer screening may become cost-effective if their cost is substantially lowered.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971743"}, {"offsetInBeginSection": 133, "offsetInEndSection": 293, "text": "east 6 mm. The aim of this analysis is to determine the cost-effectiveness of population-based screening for colorectal cancer (CRC) using CTC with a polyp size", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19574924"}, {"offsetInBeginSection": 96, "offsetInEndSection": 284, "text": "In our study, we estimated the threshold costs for which CTC screening would be a cost-effective alternative to colonoscopy for colorectal cancer (CRC) screening in the general population.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19048626"}, {"offsetInBeginSection": 1122, "offsetInEndSection": 1289, "text": "For this strategy to be as cost-effective as colonoscopy screening, the costs must not exceed $285 or 43% of colonoscopy costs (range in sensitivity analysis: 39-47%).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19048626"}, {"offsetInBeginSection": 853, "offsetInEndSection": 1398, "text": "Based on the detection characteristics and acceptability of CTC screening, it might be a viable screening test. The potential disadvantage of radiation exposure is probably overemphasised, especially with newer technology. At this time-point, it is not entirely clear whether the detection of extracolonic findings at CTC is of net benefit and is cost effective, but with responsible handling, this may be the case. Future efforts will seek to further improve the technique, refine appropriate diagnostic algorithms and study cost-effectiveness.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25468258"}, {"offsetInBeginSection": 207, "offsetInEndSection": 338, "text": " is unclear whether they are cost-effective for colorectal cancer screening.Objective: To estimate the cost-effectiveness of liquid", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971743"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1373, "text": "Colorectal cancer (CRC) is the third most common cancer worldwide, with a global incidence of over 1 million cases. In the era of personalized medicine, tumor sampling is essential for characterizing the molecular profile of individual tumors. This provides pivotal information regarding optimal sequencing of therapy and emergence of drug resistance, allowing for timely therapy adjustment. However, tumor tissue sampling offers static information in a single time point and area of disease at the time of biopsy, which may not entirely represent the heterogeneity of molecular alterations. Moreover, tumor biopsies often involve invasive procedures with potential risks to patients. Less invasive, safer, and real-time methods such as liquid biopsies have generated increasing interest as a surrogate of solid tumor biopsies. Liquid biopsy allows for noninvasive survey with detection of cell-free circulating tumor DNA (ctDNA) or circulating tumor cells. Blood-based assays are the most widely studied. Additionally, the quantity of ctDNA detected has been shown to correlate with tumor burden and enables assessment of tumor heterogeneity. In this article, we discuss the concept of liquid biopsies including ctDNA and circulating tumor cell, and their current application in the diagnosis and management of CRC. We suggest that liquid biopsies can be successfully used", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30268335"}, {"offsetInBeginSection": 1085, "offsetInEndSection": 1212, "text": "d life-years gained in comparison with FIT. (m) SEPT9-based screening was cost-effective in comparison with no screening but wa", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26135268"}, {"offsetInBeginSection": 604, "offsetInEndSection": 813, "text": "benefits and costs.RESULTS: In the base case, (m)SEPT9 decreased colorectal cancer incidence by 35% to 41% and colorectal cancer mortality by 53% to 61% at costs of $8,400 to $11,500/quality-adjusted life year", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23796793"}]}
+{"question_id": "65ef8502dffffb9b6b000003", "question": "What causes Mucormycosis?", "answer": "Mucormycosis is a serious and invasive fungal infection caused by Mucorales fungi.", "relevant_passage_ids": ["36566630", "36571098", "36751448", "23391952", "21482731", "34881204", "35986111", "14748801", "35532252", "35433396", "2782563", "35219907", "35360784", "21891908", "33107473", "37262298", "36005264", "37937225", "35220559", "36159045", "34226483", "15131477", "21761152", "36604110", "36226007", "8848770", "36941816", "32000287", "23510521", "30875744", "37608614", "25386533", "20305117", "19201393", "27284399", "30574450", "21879155", "28560130", "34322352", "35447883", "9475685", "15487636", "38034231", "36227854", "37367595", "29326525", "36224039", "36452533", "33222179", "36625576", "33282040", "35887511", "10756000"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Mucormycosis is a fungal infection which got worsens with time if not diagnosed and treated.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36566630"}, {"offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "Mucormycosis, which is a life threatening condition, is one of the side effects experienced by post-COVID-19 patients. Early identification and timely treatment are essential to stop the dissemination of the disease, since invasive mucormycosis has a very high fatality rate and significant disease dispersion.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36569440"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Mucormycosis is an emerging angioinvasive fungal infection caused by ubiquitous saprophytic filamentous fungus that belongs to the class Zygomycosis. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36571098"}, {"offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Background: Mucormycosis is a life-threatening infection of the paranasal sinuses and nasal cavities that can easily spread to the orbit and the brain. It is caused by fungi of the family Mucoraceae", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36751448"}, {"offsetInBeginSection": 116, "offsetInEndSection": 382, "text": "Mucormycosis, is a severe but rare fungal infection caused by a group of molds called mucormycetes. Diabetes, use of corticosteroids, metabolic/diabetic acidosis and Covid-19 mediated immunosuppression are reported in more than 70% of cases in mucormycosis patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35219907"}, {"offsetInBeginSection": 116, "offsetInEndSection": 483, "text": "Mucormycosis, is a severe but rare fungal infection caused by a group of molds called mucormycetes. Diabetes, use of corticosteroids, metabolic/diabetic acidosis and Covid-19 mediated immunosuppression are reported in more than 70% of cases in mucormycosis patients. Coexisting mucormycosis, Covid-19 along with diabetes mellitus increase the likelihood of mortality.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35219907"}, {"offsetInBeginSection": 0, "offsetInEndSection": 435, "text": "Mucormycosis, caused by saprophytic fungi of the order Mucorales of the class Zygomycetes, is a rare opportunistic fungal infection, which has a rapidly progressive and fulminant course with fatal outcome. These fungi are ubiquitous, found in soil, bread molds, decaying fruits and vegetables. The most common form of mucormycosis is rhinocerebral and is usually seen in uncontrolled diabetes mellitus or in immunocompromised patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21891908"}, {"offsetInBeginSection": 133, "offsetInEndSection": 451, "text": "Mucormycosis is caused by the mucormycetes group of molds. Immunocompromised states such as diabetes, chronic steroid use, and patients receiving immunosuppressant drugs are the risk factors for mucormycosis. The second wave of the COVID-19 pandemic has also invited the notorious mucormycosis in the current scenario.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35360784"}, {"offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Mucormycosis is a rare but life-threatening opportunistic fungal infection caused by a group of molds that belong to Zygomycetes of the order Mucorales. These fungi are found in the environment such as soil, decaying vegetation, and organic matters.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35433396"}, {"offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "INTRODUCTION: Mucormycosis (MCR) is caused by filamentous molds within the Class Zygomycetes and Order Mucorales.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37262298"}, {"offsetInBeginSection": 1076, "offsetInEndSection": 1364, "text": "A literature search of mucormycosis was performed via PubMed (up to November 2022), using the key words: invasivefungal infections; mold; mucormycosis;Mucorales; Zyzomyces; Zygomycosis; Rhizopus, diagnosis.EXPERT OPINION: Mucormycosis occurs primarily in severely immunocompromised hosts.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37262298"}, {"offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Mucormycosis is a rare but serious fungal infection caused by a mold family known as the Mucorales.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36005264"}, {"offsetInBeginSection": 133, "offsetInEndSection": 191, "text": "Mucormycosis is caused by the mucormycetes group of molds.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35360784"}, {"offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Saprophytic molds such as Mucor, Rhizopus, and Absidia cause mucormycosis, a fungal infection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36159045"}, {"offsetInBeginSection": 365, "offsetInEndSection": 601, "text": "Mucormycosis is an invasive fungal disease that primarily affects immunosuppressant patients, mainly caused by mold fungi of the genus mucor, rhizopus, rhizomucor, and absidia, which are in the zygomycetes class and the Mucorales order.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35532252"}, {"offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Mucormycosis (zygomycosis) normally occurs among individuals with predisposing factors such as prematurity, use of broad spectrum antibiotics, metabolic acidosis or advanced stages of immunosuppression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15131477"}, {"offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Mucormycosis (Zygomycosis) is a rare, invasive, opportunistic fungal infection of the paranasal sinuses, caused by a fungus of the order Mucorales.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21761152"}, {"offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Zygomycosis is a fungal infection in humans caused by orders Mucorales and Entomophthorales.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36604110"}, {"offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Mucormycosis is a rare, aggressive angioinvasive deep fungal infection caused by mucorales.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36226007"}, {"offsetInBeginSection": 0, "offsetInEndSection": 371, "text": "Mucormycosis (zygomycosis) is an uncommon mycosis which can be contracted from the environment and which is responsible for rhino-orbital, pulmonary, gastrointestinal, cerebral or disseminated infections. Severe immunodepression, such as that caused by leukemia, lymphomata and organ graft, or treatment by desferrioxamine, may predispose to pulmonary and systemic forms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8848770"}, {"offsetInBeginSection": 343, "offsetInEndSection": 457, "text": "Mucormycosis is a fungal infection that invades the blood vessels and is caused by Mucormycetes, a group of fungi.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36941816"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Mucormycosis is an infection caused by a group of filamentous molds within the order Mucorales.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32000287"}, {"offsetInBeginSection": 142, "offsetInEndSection": 311, "text": "Genera from the order Mucorales (Rhizopus, Mucor, Rhizomucor, Absidia, Apophysomyces, Cunninghamella and Saksenaea) cause an angioinvasive infection called mucormycosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14748801"}, {"offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Mucormycosis is an infection caused by filamentous fungi of the Mucorales order.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23510521"}, {"offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Mucormycosis is an emerging life-threatening fungal infection caused by Mucorales.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30875744"}, {"offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Mucormycosis caused by unusual mucormycetes, non-Rhizopus, -Mucor, and -Lichtheimia species.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21482731"}, {"offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Mucormycosis is a deadly opportunistic disease caused by a group of fungus named mucormycetes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35220559"}, {"offsetInBeginSection": 9, "offsetInEndSection": 185, "text": "mucormycosis is a rare disorder caused by several genera of the family Mucoraceae. The genera Rhizopus, Absidia, and Mucor are the predominant pathogenic groups. Disease caused", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2782563"}, {"offsetInBeginSection": 106, "offsetInEndSection": 214, "text": "The saprophytic fungi of Mucorales species cause the disease, Mucormycosis, only in immunocompromised hosts.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34226483"}, {"offsetInBeginSection": 0, "offsetInEndSection": 434, "text": "Mucormycosis or zygomycosis is a group of infections caused by filamentous fungi of the mucorales order belonging to the zygomycetes family. They generally appear in patients with uncontrolled diabetes or immunodepression, especially neutropenic immunodepression. Incidence has increased with progress in immunosuppressive therapy and chemotherapy and the absence of the use of antifungal prophylactic agents effective against mucors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19201393"}, {"offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "BACKGROUND: The Mucorales are an important opportunistic fungi that can cause mucormycosis in immunocompromis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27284399"}, {"offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "PURPOSE OF REVIEW: Mucormycosis is an emerging opportunistic fungal infection whose causative agents are found within the Mucorales family. A recent increase in immunocompromised cohorts with solid organ transplants, diabetes mellitus, and other medical conditions have resulted in increased fungal infections incl", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30574450"}, {"offsetInBeginSection": 0, "offsetInEndSection": 459, "text": "Mucormycosis or zygomycosis is a rare opportunistic infection caused by aerobic saprophytic fungus that belongs to the class of Zygomycetes Mucorales family. These organisms live in the environment and enter the body by air, gastrointestinal or skin routes, through solutions of continuity of the skin. This microorganism is generally not pathogenic for immunocompetent hosts, being the development of the disease linked with the immune status of the subject.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21879155"}, {"offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Mucormycosis is an opportunistic infection caused by the fungi of the Mucorales order of the class Zygomycetes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28560130"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Mucormycosis is a rare infection caused by fungi of the order Mucorales. The infection frequently involves the rhino-cerebral or respiratory system an", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34322352"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Mucormycosis, caused by saprophytic fungi of the order Mucorales of the class Zygomycetes, is a rare opportunistic fungal infection, which has a rapid", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21891908"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Mucormycosis (also known as black fungus) is caused by fungi of the Zygomycetes class and is the third most common invasive mycosis after candidiasis ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34881204"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Mucormycosis are a group of invasive infections caused by filamentous fungi of the Mucoraceae family. Mucormycosis is essentially limited to immunocom", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25386533"}, {"offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Mucormycoses are rare but serious opportunistic fungal infections caused by filamentous organisms of the order Mucorales.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35447883"}, {"offsetInBeginSection": 901, "offsetInEndSection": 1077, "text": "Mucormycosis is a rare fungal infection induced by exposure to a fungus called mucormycete. The most typically implicated genera are Mucor rhyzuprhizopusdia and Cunninghamella.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35986111"}, {"offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Zygomycosis is a fungal infection in humans caused by orders Mucorales and Entomophthorales. The incidence of Mucorales causing mucormycosis is on a rise and is well documented, whereas Entomophthorales is rare.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36604110"}, {"offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Mucormycosis is an uncommon infection caused by fungi of the order Mucorales, family Mucoraceae, and almost always occurs in individuals with predisposing factors such as diabetes mellitus, metabolic acidosis, or immunodeficiency states.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9475685"}, {"offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Mucormycosis is a form of fulminant invasive fungal infection of the sinonasal tract that often extends to the orbit, brain, palate, and skin. It is caused by members of the order Mucorales,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15487636"}, {"offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Introduction Mucormycosis is a rare opportunistic fungal infection caused by fungi belonging to the Mucorales order and Mucoraceae family", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38034231"}, {"offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Mucormycosis (also known as black fungus) is caused by fungi of the Zygomycetes class and is the third most common invasive mycosis after candidiasis and aspergillosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34881204"}, {"offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Mucormycosis (previously called zygomycosis) is a serious but rare fungal infection caused by a group of fungi belonging to the order Mucorales.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36227854"}, {"offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Mucormycosis is an uncommon, yet deadly invasive fungal infection caused by the Mucorales moulds.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37367595"}, {"offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Mucormycosis, caused by saprophytic fungi of the order Mucorales of the class Zygomycetes, is a rare opportunistic fungal infection, which has a rapidly progressive and fulminant course with fatal outcome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21891908"}, {"offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Mucormycosis are a group of invasive infections caused by filamentous fungi of the Mucoraceae family.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25386533"}, {"offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Mucormycosis is an infection caused by a group of filamentous molds within the order Mucorales. Infections may result", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32000287"}, {"offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Mucormycosis is a serious and invasive fungal infection caused by Mucorales fungi. This review article provides a concise overview of the pathogenesis, epidemiology, microbiology, and diagnosis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37608614"}, {"offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Mucormycosis is a fungal disease caused by fibrous saprophytic fungi called mucorales. The most important", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36224039"}, {"offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Mucormycosis is a devastating fungal infection that is usually seen in immunocompromised hosts. It is caused by fungi of the subphylum Mucoromycotina, order Mucorales, with most cases caused by Mucor, Rhizopus, or Rhizomucor species.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37937225"}, {"offsetInBeginSection": 0, "offsetInEndSection": 433, "text": "Mucormycosis is one of the most rapidly progressing and fulminant forms of fungal infection which usually begins in the nose and paranasal sinuses following inhalation of fungal spores. It is caused by organisms of the subphylum Mucormycotina, including genera as Absidia, Mucor, Rhizomucor, and Rhizopus. The incidence of mucormycosis is approximately 1.7 cases per 1,000,000 inhabitants per year. Mucormycosis affecting the maxilla", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29326525"}, {"offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Mucormycosis is an aggressive, opportunistic infection caused by fungi belonging to the class of Phycomycetes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20305117"}, {"offsetInBeginSection": 0, "offsetInEndSection": 455, "text": "Mucormycosis are a group of invasive infections caused by filamentous fungi of the Mucoraceae family. Mucormycosis is essentially limited to immunocompromised patients with poorly controlled diabetes mellitus, hematologic malignancy, organ transplant, chemotherapy, chronic renal insufficiency, malnutrition, deferoxamine therapy and severe burns. The fungi invade arteries leading to thrombosis that subsequently causes necrosis of hard and soft tissues.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25386533"}, {"offsetInBeginSection": 0, "offsetInEndSection": 347, "text": "Mucormycosis are a group of invasive infections caused by filamentous fungi of the Mucoraceae family. Mucormycosis is essentially limited to immunocompromised patients with poorly controlled diabetes mellitus, hematologic malignancy, organ transplant, chemotherapy, chronic renal insufficiency, malnutrition, deferoxamine therapy and severe burns.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25386533"}, {"offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Mucormycosis is an aggressive, opportunistic infection caused by fungi belonging to the class of Phycomycetes. Rhino-oculo-cerebral mucormycosis is the commonest anatomical presentation of mucormycosis and is a potentially fatal disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20305117"}, {"offsetInBeginSection": 0, "offsetInEndSection": 449, "text": "Mucormycosis, caused by saprophytic fungi of the order Mucorales of the class zygomycetes, is a rare opportunistic fungal infection, which has a rapidly progressive and fulminant course with fatal outcome. Mucormycosis can result in an acute, rapidly advancing and occasionally fatal disease caused by different fungi typically found in the soil in association with decaying organic matter such as leaves, compost piles, or bread molds. Mucormycosis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33107473"}, {"offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "INTRODUCTION: Mucormycosis (MCR) is caused by filamentous molds within the Class Zygomycetes and Order Mucorales. Infections can result from inhalation of spores into the nares, oropharynx, or lungs, ingestion of contaminated food or water, or inoculation into disrupted skin or wounds. In developed countri", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37262298"}, {"offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Mucormycosis is a dreaded clinical entity caused by filamentous fungi of the order Mucorales mainly affecting", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36452533"}, {"offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "BACKGROUND/OBJECTIVES: Cutaneous mucormycosis is an emerging opportunistic mycosis caused by Mucorales. It can be ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33222179"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Mucormycosis is an invasive fungal infection caused by certain members of the fungal order of Mucorales.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36625576"}, {"offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Mucormycosis is a rare and severe invasive fungal infection caused by ubiquitous fungi of the order Mucorales.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33282040"}, {"offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Mucormycosis, also known as phycomycosis or zygomycosis, is caused by common Zygomycete fungi frequently found in soil and decaying vegetation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23391952"}, {"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Mucormycosis is a highly aggressive angio-invasive disease of humans caused by fungi in the zygomycete order, Mucorales.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35887511"}, {"offsetInBeginSection": 864, "offsetInEndSection": 1295, "text": "Human zygomycosis caused by the Mucorales generally occurs in immunocompromised hosts as opportunistic infections. Host risk factors include diabetes mellitus, neutropenia, sustained immunosuppressive therapy, chronic prednisone use, iron chelation therapy, broad-spectrum antibiotic use, severe malnutrition, and primary breakdown in the integrity of the cutaneous barrier such as trauma, surgical wounds, needle sticks, or burns.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10756000"}, {"offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "Mucormycosis, caused by saprophytic fungi of the order Mucorales of the class Zygomycetes, is a rare opportunistic fungal infection, which has a rapidly progressive and fulminant course with fatal outcome. These fungi are ubiquitous, found in soil, bread molds, decaying fruits and vegetables.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21891908"}]}
+{"question_id": "66165f2afdcbea915f000051", "question": "When was the first case of human monkey pox diagnosed?", "answer": "The first case of human monkeypox was diagnosed in September 1970 in the Democratic Republic of the Congo.", "relevant_passage_ids": ["36403582"], "type": "factoid", "snippets": [{"offsetInBeginSection": 150, "offsetInEndSection": 235, "text": "the detection of the first human case in the Democratic Republic of the Congo in 1970", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36403582"}]}
+{"question_id": "661c413f48a2c27714000006", "question": "Does chromatin accessibility affect CRISPR-Cas9 efficiency?", "answer": "While many studies consider DNA sequences of CRISPR target sites as the primary determinant for CRISPR-Cas9 mutagenesis efficiency and mutation profiles, increasing evidence reveals the substantial role of chromatin context. Indeed, results across different organisms have shown that Cas9-mediated editing is more efficient in open chromatin regions (euchromatin) than in closed ones (heterochromatin).", "relevant_passage_ids": ["28580607", "29684067", "31349852", "35689624", "28303677", "28800611", "31799598", "31672284", "26987018", "30189348", "36374245", "30540740", "37985205", "33659408", "30201707", "30413470", "36727449", "27280977", "37162994", "37456665", "31967103"], "type": "yesno", "snippets": [{"offsetInBeginSection": 457, "offsetInEndSection": 621, "text": "Our study indicates that gene editing is more efficient in euchromatin than in heterochromatin, and we validate this finding in HeLa cells and in human fibroblasts.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28580607"}, {"offsetInBeginSection": 1183, "offsetInEndSection": 1280, "text": "We found a correlation between chromatin openness and the efficiency of CRISPR-Cas9 mutagenesis. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29684067"}, {"offsetInBeginSection": 100, "offsetInEndSection": 220, "text": "We show that Cas9-mediated editing is more efficient in open chromatin regions than in closed chromatin regions in rice.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31349852"}, {"offsetInBeginSection": 125, "offsetInEndSection": 343, "text": "While many studies consider DNA sequences of CRISPR target sites as the primary determinant for CRISPR mutagenesis efficiency and mutation profiles, increasing evidence reveals the substantial role of chromatin context", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35689624"}, {"offsetInBeginSection": 1350, "offsetInEndSection": 1550, "text": "Our findings provide strong evidence that specific chromatin features could have substantial and lasting impacts on both CRISPR-Cas9 mutagenesis efficiency and DNA double-strand break repair outcomes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35689624"}, {"offsetInBeginSection": 1469, "offsetInEndSection": 1571, "text": "Furthermore, we demonstrate that DNA target site accessibility influences the activity of CRISPR/Cas9.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28303677"}, {"offsetInBeginSection": 168, "offsetInEndSection": 374, "text": "In this study, we show that chromatin open status is a pivotal determinant of the Cas9 editing activity in mammalian cells, and increasing chromatin accessibility can efficiently improve Cas9 genome editing", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36374245"}, {"offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Chromatin accessibility and guide sequence secondary structure affect CRISPR-Cas9 gene editing efficiency.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28580607"}, {"offsetInBeginSection": 1183, "offsetInEndSection": 1394, "text": "We found a correlation between chromatin openness and the efficiency of CRISPR-Cas9 mutagenesis. These results indicate that CRISPR-Cas9 mutagenesis is influenced by chromatin accessibility in zebrafish embryos.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29684067"}, {"offsetInBeginSection": 1083, "offsetInEndSection": 1294, "text": "Our study demonstrated that chromatin accessibility showed positive correlation with CRISPR/Cas9 efficiency, but we did not observe a clear correlation between nucleosome organization and CRISPR/Cas9 efficiency.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28800611"}, {"offsetInBeginSection": 363, "offsetInEndSection": 497, "text": "Besides the sequence features, local chromatin structures may have effects on CRISPR/Cas9 efficiency, which remain largely unexplored.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28800611"}, {"offsetInBeginSection": 951, "offsetInEndSection": 1394, "text": "In order to further inspect the effect of chromatin on CRISPR-Cas9 mutagenesis, we analysed the relationship of selected chromatin features on CRISPR-Cas9 mutagenesis efficiency using publicly available data from zebrafish embryos. We found a correlation between chromatin openness and the efficiency of CRISPR-Cas9 mutagenesis. These results indicate that CRISPR-Cas9 mutagenesis is influenced by chromatin accessibility in zebrafish embryos.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29684067"}, {"offsetInBeginSection": 951, "offsetInEndSection": 1279, "text": "In order to further inspect the effect of chromatin on CRISPR-Cas9 mutagenesis, we analysed the relationship of selected chromatin features on CRISPR-Cas9 mutagenesis efficiency using publicly available data from zebrafish embryos. We found a correlation between chromatin openness and the efficiency of CRISPR-Cas9 mutagenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29684067"}, {"offsetInBeginSection": 363, "offsetInEndSection": 700, "text": "Besides the sequence features, local chromatin structures may have effects on CRISPR/Cas9 efficiency, which remain largely unexplored. In the only related study in zebrafish, nucleosome organization was not found to have an effect on CRISPR/Cas9 efficiency, which is inconsistent with recent studies in vitro and in mammalian cell lines.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28800611"}, {"offsetInBeginSection": 168, "offsetInEndSection": 375, "text": "In this study, we show that chromatin open status is a pivotal determinant of the Cas9 editing activity in mammalian cells, and increasing chromatin accessibility can efficiently improve Cas9 genome editing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36374245"}, {"offsetInBeginSection": 281, "offsetInEndSection": 377, "text": "Recent studies indicate that heterochromatin can negatively affect Cas9 binding and functioning.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30189348"}, {"offsetInBeginSection": 1171, "offsetInEndSection": 1452, "text": "Combined, our data show that heterochromatin imposes a permeable barrier that influences the kinetics, but not the endpoint, of CRISPR-Cas9 genome editing and suggest that therapeutic applications involving low-level Cas9 exposure will be particularly affected by chromatin status.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30540740"}, {"offsetInBeginSection": 1280, "offsetInEndSection": 1394, "text": "These results indicate that CRISPR-Cas9 mutagenesis is influenced by chromatin accessibility in zebrafish embryos.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29684067"}, {"offsetInBeginSection": 1183, "offsetInEndSection": 1279, "text": "We found a correlation between chromatin openness and the efficiency of CRISPR-Cas9 mutagenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29684067"}, {"offsetInBeginSection": 387, "offsetInEndSection": 717, "text": "We found that both regional constitutive heterochromatin and local nucleosome occlusion of target sites impede editing, while position-specific G/C nucleotides in the primer binding site (PBS) and reverse transcription (RT) template regions of PE guide-RNA (pegRNA) yield high editing efficiency, especially for short PBS designs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37162994"}, {"offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Chromatin structure and context-dependent sequence features control prime editing efficiency.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37456665"}, {"offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "Despite the rapid development of CRISPR/Cas9-mediated gene editing technology, the gene editing potential of CRISPR/Cas9 is hampered by low efficiency, especially for clinical applications. One of the major challenges is that chromatin compaction inevitably limits the Cas9 protein access to the target DNA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31799598"}, {"offsetInBeginSection": 132, "offsetInEndSection": 467, "text": "Different intracellular environments (dependent on cell type or cell cycle state for example) may affect sgRNA efficiency by altering accessibility of genomic DNA through DNA modifications such as epigenetic marks and DNA-binding proteins (e.g., histones) as well as alteration of the chromatin state of genomic DNA within the nucleus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33659408"}, {"offsetInBeginSection": 730, "offsetInEndSection": 877, "text": "Our results indicated that DNA methylation and chromatin features could lead to substantial variations in mutagenesis efficiency by up to 250-fold.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35689624"}, {"offsetInBeginSection": 54, "offsetInEndSection": 1501, "text": "CRISPR/Cas9 has been a major research focus. Whereas sequence complementarity between guide RNA and target DNA substantially dictates cleavage efficiency, DNA accessibility of the targeted\u00a0loci has also been hypothesized to be an important factor.\u00a0In this study, functional data from two genome-wide assays,\u00a0genome-wide, unbiased identification of DSBs enabled by sequencing (GUIDE-seq) and circularization for in\u00a0vitro reporting of cleavage effects by sequencing (CIRCLE-seq), have been computationally analyzed in conjunction with DNA accessibility determined via DNase I-hypersensitive sequencing from the Encyclopedia of DNA Elements (ENCODE) Database and transcriptome from the Sequence Read Archive to determine whether cellular factors influence CRISPR-induced cleavage efficiency. CIRCLE-seq and GUIDE-seq datasets were selected to represent the absence and presence of cellular factors, respectively. Data analysis revealed that correlations between sequence similarity and CRISPR-induced cleavage frequency were altered by the presence of cellular factors that\u00a0modulated the level of DNA accessibility. The above-mentioned correlation was abolished when cleavage sites were located in less accessible regions. Furthermore, CRISPR-mediated edits were permissive even at regions that were insufficient for most endogenous genes to be expressed. These results provide a strong basis to dissect the contribution of local chromatin modulation", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31672284"}, {"offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "The CRISPR/Cas9 system is unable to edit all targetable genomic sites with full efficiency in vivo. We show that Cas9-mediated editing is more efficient in open chromatin regions than in closed chromatin", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31349852"}, {"offsetInBeginSection": 0, "offsetInEndSection": 535, "text": "To investigate whether and how CRISPR-Cas9 on-target and off-target activities are affected by chromatin in eukaryotic cells, we first identified a series of identical endogenous DNA sequences present in both open and closed chromatin regions and then measured mutation frequencies at these sites in human cells using Cas9 complexed with matched or mismatched sgRNAs. Unlike matched sgRNAs, mismatched sgRNAs were highly sensitive to chromatin states, suggesting that off-target but not on-target DNA cleavage is hindered by chromatin.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30413470"}, {"offsetInBeginSection": 809, "offsetInEndSection": 981, "text": "By using these systems, we demonstrate that TALENs and CRISPR/Cas9 nucleases are both significantly affected by the high-order epigenetic context of their target sequences.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27280977"}, {"offsetInBeginSection": 657, "offsetInEndSection": 810, "text": "In vitro experiments demonstrated that nucleosomes in fact directly impede Cas9 binding and cleavage, while chromatin remodeling can restore Cas9 access.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26987018"}, {"offsetInBeginSection": 730, "offsetInEndSection": 967, "text": "We found that heterochromatin can impede mutagenesis, but to a degree that depends on other key experimental parameters. Mutagenesis was impeded by up to 7-fold when Cas9 exposure was brief and when intracellular Cas9 expression was low.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30540740"}, {"offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "The CRISPR/Cas9 system is unable to edit all targetable genomic sites with full efficiency in vivo. We show that Cas9-mediated editing is more efficient in open chromatin regions than in closed chromatin regions in rice.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31349852"}, {"offsetInBeginSection": 530, "offsetInEndSection": 656, "text": "We observed that highly active sgRNAs for Cas9 and dCas9 were found almost exclusively in regions of low nucleosome occupancy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26987018"}]}
+{"question_id": "661d51fdeac11fad3300001d", "question": "What diseases are included in the differential diagnosis of Ehlers-Danlos Syndrome?", "answer": "The differential diagnosis of Ehlers-Danlos Syndrome includes hypermobility spectrum disorders, Marfan syndrome, Loey-Dietz syndrome, Cutis laxa syndromes, autosomal dominant polycystic kidney disease, osteogenesis Imperfecta Type 1,cfibromyalgia, depression, and chronic fatigue syndrome.", "relevant_passage_ids": ["33437956"], "type": "list", "snippets": [{"offsetInBeginSection": 1096, "offsetInEndSection": 1366, "text": "The differential diagnosis of EDS includes hypermobility spectrum disorders, Marfan syndrome, Loey-Dietz syndrome, Cutis laxa syndromes, autosomal dominant polycystic kidney disease, osteogenesis Imperfecta Type 1, fibromyalgia, depression, and chronic fatigue syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33437956"}]}
+{"question_id": "65cfa70f1930410b1300000f", "question": "What is the mechanism of action of Nemolizumab?", "answer": "Nemolizumab is an interleukin-31 receptor alpha antagonist that down-regulates key pathways in the pathogenesis of prurigo nodularis.", "relevant_passage_ids": ["37650357", "37801534", "37556125", "37888917", "28249150", "31449914", "32640132", "32074418", "29753033", "31364023", "27714851", "29433635", "35412530", "35842249", "37121713", "35834124", "35088348", "35766128", "34857395", "36839897", "33711179", "33644103", "33924978", "33644104", "34726262", "37318771"], "type": "summary", "snippets": [{"offsetInBeginSection": 515, "offsetInEndSection": 667, "text": "In 2022, nemolizumab, an anti-IL-31 receptor \u03b1 antibody, was approved for pruritus of AD, and tralokinumab, an anti-IL-13 antibody, was approved for AD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37650357"}, {"offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Nemolizumab is a monoclonal antibody directed against the interleukin-31 receptor A subunit, which is involved in the pathogenesis of pruritus and inflammation in atopic dermatitis (AD).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37801534"}, {"offsetInBeginSection": 133, "offsetInEndSection": 278, "text": "Nemolizumab, a monoclonal antibody targeting interleukin 31 receptor \u03b1, is a promising novel therapy for the treatment of moderate to severe PN. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37556125"}, {"offsetInBeginSection": 111, "offsetInEndSection": 238, "text": "Nemolizumab, an interleukin-31 receptor alpha antagonist, down-regulates key pathways in the pathogenesis of prurigo nodularis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37888917"}, {"offsetInBeginSection": 428, "offsetInEndSection": 601, "text": "We sought to provide a comprehensive view of the transcriptomic changes in PN skin and characterize the mechanism of action of the anti-IL-31 receptor inhibitor nemolizumab.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34857395"}, {"offsetInBeginSection": 751, "offsetInEndSection": 940, "text": "Other drugs with potential include the aryl hydrocarbon receptor modulating agent tapinarof, the IL-4/IL-13 antagonists lebrikizumab and tralokinumab, and the IL-31R\u03b1 antagonist nemolizumab", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31364023"}, {"offsetInBeginSection": 0, "offsetInEndSection": 524, "text": "Nemolizumab (Mitchga\u00ae syringes) is a biologic with a novel mechanism of action that was first approved in Japan in March 2022 for pruritus associated with atopic dermatitis (AD) only when existing treatments were insufficiently effective. Nemolizumab is a humanized antihuman interleukin-31 (IL-31) receptor A (IL-31RA) monoclonal antibody that targets the receptor for IL-31, the major pruritogen in AD. Nemolizumab inhibits IL-31 signaling and suppresses pruritus by competitively preventing IL-31 from binding to IL-31RA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37121713"}, {"offsetInBeginSection": 304, "offsetInEndSection": 656, "text": "Nemolizumab is a humanized monoclonal antibody that blocks the \u03b1 subunit of the IL-31 receptor, modulates the neuroimmune response, and rapidly alleviates itching by directly blocking signaling. It reduces inflammation and lesion severity in atopic dermatitis and prurigo nodularis by restoring epithelial function and promoting skin barrier integrity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35842249"}, {"offsetInBeginSection": 170, "offsetInEndSection": 656, "text": "As the immune and nervous systems are interrelated, IL-31 has a key role in the treatment of atopic dermatitis and prurigo nodularis. Nemolizumab is a humanized monoclonal antibody that blocks the \u03b1 subunit of the IL-31 receptor, modulates the neuroimmune response, and rapidly alleviates itching by directly blocking signaling. It reduces inflammation and lesion severity in atopic dermatitis and prurigo nodularis by restoring epithelial function and promoting skin barrier integrity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35842249"}, {"offsetInBeginSection": 140, "offsetInEndSection": 465, "text": "Interleukin-31 (IL-31) is associated with the pathobiological mechanism of AD, contributing to symptoms such as dermatitis and pruritus. Nemolizumab is an anti-IL-31 receptor \u03b1-chain (IL-31RA) monoclonal antibody agent that is efficacious in improving symptoms of AD in several phase II and phase III studies in recent years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35412530"}, {"offsetInBeginSection": 170, "offsetInEndSection": 498, "text": "As the immune and nervous systems are interrelated, IL-31 has a key role in the treatment of atopic dermatitis and prurigo nodularis. Nemolizumab is a humanized monoclonal antibody that blocks the \u03b1 subunit of the IL-31 receptor, modulates the neuroimmune response, and rapidly alleviates itching by directly blocking signaling.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35842249"}, {"offsetInBeginSection": 140, "offsetInEndSection": 581, "text": "Interleukin-31 (IL-31) is associated with the pathobiological mechanism of AD, contributing to symptoms such as dermatitis and pruritus. Nemolizumab is an anti-IL-31 receptor \u03b1-chain (IL-31RA) monoclonal antibody agent that is efficacious in improving symptoms of AD in several phase II and phase III studies in recent years. Nemolizumab demonstrates great efficacy in reducing pruritus and to a lesser degree, dermatitis associated with AD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35412530"}, {"offsetInBeginSection": 0, "offsetInEndSection": 465, "text": "Atopic dermatitis (AD) is a common inflammatory skin disease that has emerging treatments targeting the underlying immunological mechanism. Interleukin-31 (IL-31) is associated with the pathobiological mechanism of AD, contributing to symptoms such as dermatitis and pruritus. Nemolizumab is an anti-IL-31 receptor \u03b1-chain (IL-31RA) monoclonal antibody agent that is efficacious in improving symptoms of AD in several phase II and phase III studies in recent years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35412530"}, {"offsetInBeginSection": 0, "offsetInEndSection": 404, "text": "Nemolizumab (Mitchga\u00ae syringes) is a biologic with a novel mechanism of action that was first approved in Japan in March 2022 for pruritus associated with atopic dermatitis (AD) only when existing treatments were insufficiently effective. Nemolizumab is a humanized antihuman interleukin-31 (IL-31) receptor A (IL-31RA) monoclonal antibody that targets the receptor for IL-31, the major pruritogen in AD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37121713"}, {"offsetInBeginSection": 96, "offsetInEndSection": 498, "text": "It contributes to skin barrier inflammation, dysfunction, and remodeling. As the immune and nervous systems are interrelated, IL-31 has a key role in the treatment of atopic dermatitis and prurigo nodularis. Nemolizumab is a humanized monoclonal antibody that blocks the \u03b1 subunit of the IL-31 receptor, modulates the neuroimmune response, and rapidly alleviates itching by directly blocking signaling.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35842249"}, {"offsetInBeginSection": 304, "offsetInEndSection": 885, "text": "Nemolizumab is a humanized monoclonal antibody that blocks the \u03b1 subunit of the IL-31 receptor, modulates the neuroimmune response, and rapidly alleviates itching by directly blocking signaling. It reduces inflammation and lesion severity in atopic dermatitis and prurigo nodularis by restoring epithelial function and promoting skin barrier integrity. This review synthesizes the latest information on the functions of IL-31 and presents the current evidence, including clinical trial results, on the use of nemolizumab in the treatment of atopic dermatitis and prurigo nodularis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35842249"}, {"offsetInBeginSection": 239, "offsetInEndSection": 404, "text": "Nemolizumab is a humanized antihuman interleukin-31 (IL-31) receptor A (IL-31RA) monoclonal antibody that targets the receptor for IL-31, the major pruritogen in AD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37121713"}, {"offsetInBeginSection": 0, "offsetInEndSection": 398, "text": "BACKGROUND: Nemolizumab is a humanized anti-IL-31 receptor blocker in phase 3 for atopic dermatitis (AD).OBJECTIVE: Analyse onset of action of nemolizumab 30\u00a0mg and compare efficacy and safety vs placebo (SC q4wk plus loading dose) in moderate-to-severe AD.METHODS: Post hoc analysis of patients with Eczema Area and Severity Index (EASI) scores\u00a0\u2265\u00a016 from a phase 2b trial of moderate-to-severe AD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33711179"}, {"offsetInBeginSection": 405, "offsetInEndSection": 524, "text": "Nemolizumab inhibits IL-31 signaling and suppresses pruritus by competitively preventing IL-31 from binding to IL-31RA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37121713"}, {"offsetInBeginSection": 277, "offsetInEndSection": 465, "text": "Nemolizumab is an anti-IL-31 receptor \u03b1-chain (IL-31RA) monoclonal antibody agent that is efficacious in improving symptoms of AD in several phase II and phase III studies in recent years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35412530"}, {"offsetInBeginSection": 371, "offsetInEndSection": 796, "text": "Nemolizumab is an IL-31A-receptor inhibitor that modulates the neuroimmune response with reported positive efficacy and safety data in a phase 2 study of PN.OBJECTIVES: To evaluate the onset of action of nemolizumab on itch and sleep disturbances.METHODS: Post hoc analysis of a phase 2 trial of nemolizumab 0.5\u2009mg/kg SC vs. placebo in patients (n\u2009=\u200970) with moderate-to-severe PN (\u226520 nodules) and severe pruritus (NRS\u2009\u2265\u20097).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35766128"}, {"offsetInBeginSection": 109, "offsetInEndSection": 680, "text": "We wanted to assess the efficacy and safety of nemolizumab (CIM331), a humanized antibody against interleukin-31 receptor A, in the treatment of atopic dermatitis.METHODS: In this phase 2, randomized, double-blind, placebo-controlled, 12-week trial, we assigned adults with moderate-to-severe atopic dermatitis that was inadequately controlled by topical treatments to receive subcutaneous nemolizumab (at a dose of 0.1 mg, 0.5 mg, or 2.0 mg per kilogram of body weight) or placebo every 4 weeks or an exploratory dose of 2.0 mg of nemolizumab per kilogram every 8 weeks.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28249150"}, {"offsetInBeginSection": 304, "offsetInEndSection": 497, "text": "Nemolizumab is a humanized monoclonal antibody that blocks the \u03b1 subunit of the IL-31 receptor, modulates the neuroimmune response, and rapidly alleviates itching by directly blocking signaling", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35842249"}, {"offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "BACKGROUND: Nemolizumab targets the IL-31 receptor \u03b1 subunit involved in atopic dermatitis (AD) ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31449914"}, {"offsetInBeginSection": 907, "offsetInEndSection": 1233, "text": "r proinflammatory cytokines.RESULTS: Our results demonstrate that nemolizumab effectively decreases IL-31 responses in PN skin, leading to effective suppression of downstream inflammatory responses including TH2/IL-13 and TH17/IL-17 responses. This is accompanied by decreased keratinocyte proliferation and normalization of e", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34857395"}, {"offsetInBeginSection": 277, "offsetInEndSection": 464, "text": "Nemolizumab is an anti-IL-31 receptor \u03b1-chain (IL-31RA) monoclonal antibody agent that is efficacious in improving symptoms of AD in several phase II and phase III studies in recent years", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35412530"}, {"offsetInBeginSection": 159, "offsetInEndSection": 305, "text": "n pruritus. Nemolizumab, a humanized monoclonal antibody against IL-31 receptor A, reduced pruritus in patients with AD after a 16-week administra", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34726262"}, {"offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Nemolizumab is a monoclonal antibody directed against the interleukin-31 receptor A subunit, which is involved in the pathogenesis of pruritus and inflammation in atopic dermatitis (AD)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37801534"}, {"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "BACKGROUND: Nemolizumab is a humanized anti-IL-31 receptor blocker in phase 3 for atopic dermatitis (AD).OBJECTIVE: Anal", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33711179"}, {"offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "BACKGROUND: Nemolizumab targets the IL-31 receptor \u03b1 subunit involved in atopic dermatitis (AD) pathogenesis.OBJECTIVE: We sought to evaluate", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31449914"}, {"offsetInBeginSection": 277, "offsetInEndSection": 580, "text": "Nemolizumab is an anti-IL-31 receptor \u03b1-chain (IL-31RA) monoclonal antibody agent that is efficacious in improving symptoms of AD in several phase II and phase III studies in recent years. Nemolizumab demonstrates great efficacy in reducing pruritus and to a lesser degree, dermatitis associated with AD", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35412530"}, {"offsetInBeginSection": 121, "offsetInEndSection": 264, "text": "in nodules. Nemolizumab, a monoclonal antibody targeting interleukin 31 receptor \u03b1, is a promising novel therapy for the treatment of moderate ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37556125"}, {"offsetInBeginSection": 106, "offsetInEndSection": 256, "text": "ase. Nemolizumab, an interleukin-31 receptor alpha antagonist, down-regulates key pathways in the pathogenesis of prurigo nodularis.METHODS: In this p", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37888917"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "BACKGROUND: Nemolizumab, an anti-IL-31 receptor A\u00a0mAb, improved pruritus, dermatitis, and sleep in adults with moderate-to-severe atopic dermatitis th", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29753033"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "BACKGROUND: Nemolizumab is a humanized anti-IL-31 receptor blocker in phase 3 for atopic dermatitis (AD)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33711179"}, {"offsetInBeginSection": 50, "offsetInEndSection": 200, "text": "c skin disease with multiple nodular skin lesions. Nemolizumab is a monoclonal antibody targeting the interleukin-31 receptor, which is involved in th", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32074418"}, {"offsetInBeginSection": 0, "offsetInEndSection": 427, "text": "Nemolizumab is a subcutaneously administered humanized anti-interleukin-31 (IL-31) receptor A (IL-31RA) monoclonal antibody that is being developed by Chugai Pharmaceutical Co. Ltd, Maruho Co. Ltd and Galderma Pharma S.A. for the treatment of skin diseases, including atopic dermatitis (AD), AD associated pruritus (ADaP), prurigo nodularis (PN), chronic kidney disease associated pruritus (CKDaP) and systemic sclerosis (SSc).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35834124"}, {"offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "BACKGROUND: Nemolizumab is a subcutaneously administered humanized monoclonal antibody against interleukin-31 receptor A, which is involved in pruritus and inflammation in atopic dermatitis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32640132"}, {"offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "BACKGROUND: Nemolizumab is a subcutaneously administered humanized monoclonal antibody against interleukin-31 receptor A, which is involved in pruritus and inflammation in atopic dermatitis. In phase 2 studies, nemolizumab lessened the severity of atopic dermatitis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32640132"}, {"offsetInBeginSection": 239, "offsetInEndSection": 524, "text": "Nemolizumab is a humanized antihuman interleukin-31 (IL-31) receptor A (IL-31RA) monoclonal antibody that targets the receptor for IL-31, the major pruritogen in AD. Nemolizumab inhibits IL-31 signaling and suppresses pruritus by competitively preventing IL-31 from binding to IL-31RA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37121713"}, {"offsetInBeginSection": 239, "offsetInEndSection": 761, "text": "Nemolizumab is a humanized antihuman interleukin-31 (IL-31) receptor A (IL-31RA) monoclonal antibody that targets the receptor for IL-31, the major pruritogen in AD. Nemolizumab inhibits IL-31 signaling and suppresses pruritus by competitively preventing IL-31 from binding to IL-31RA. In the phase III study, nemolizumab, 60\u2005\u200dmg, was administered subcutaneously once every 4 weeks, in combination with topical therapy, to patients aged 13 years or older who had AD and inadequately controlled moderate-to-severe pruritus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37121713"}, {"offsetInBeginSection": 0, "offsetInEndSection": 587, "text": "BACKGROUND: Nemolizumab is a subcutaneously administered humanized monoclonal antibody against interleukin-31 receptor A, which is involved in pruritus and inflammation in atopic dermatitis. In phase 2 studies, nemolizumab lessened the severity of atopic dermatitis.METHODS: In a 16-week, double-blind, phase 3 trial, we randomly assigned Japanese patients with atopic dermatitis and moderate-to-severe pruritus and an inadequate response to topical agents in a 2:1 ratio to receive subcutaneous nemolizumab (60 mg) or placebo every 4 weeks until week 16, with concomitant topical agents", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32640132"}, {"offsetInBeginSection": 370, "offsetInEndSection": 617, "text": " Nemolizumab is an IL-31A-receptor inhibitor that modulates the neuroimmune response with reported positive efficacy and safety data in a phase 2 study of PN.OBJECTIVES: To evaluate the onset of action of nemolizumab on itch and sleep disturbances", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35766128"}, {"offsetInBeginSection": 370, "offsetInEndSection": 795, "text": " Nemolizumab is an IL-31A-receptor inhibitor that modulates the neuroimmune response with reported positive efficacy and safety data in a phase 2 study of PN.OBJECTIVES: To evaluate the onset of action of nemolizumab on itch and sleep disturbances.METHODS: Post hoc analysis of a phase 2 trial of nemolizumab 0.5\u2009mg/kg SC vs. placebo in patients (n\u2009=\u200970) with moderate-to-severe PN (\u226520 nodules) and severe pruritus (NRS\u2009\u2265\u20097)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35766128"}, {"offsetInBeginSection": 227, "offsetInEndSection": 617, "text": " It is reasonable to expect that rapid relief of itch - and associated improvement of sleep - are highly valued clinical outcomes for patients. Nemolizumab is an IL-31A-receptor inhibitor that modulates the neuroimmune response with reported positive efficacy and safety data in a phase 2 study of PN.OBJECTIVES: To evaluate the onset of action of nemolizumab on itch and sleep disturbances", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35766128"}, {"offsetInBeginSection": 227, "offsetInEndSection": 527, "text": " It is reasonable to expect that rapid relief of itch - and associated improvement of sleep - are highly valued clinical outcomes for patients. Nemolizumab is an IL-31A-receptor inhibitor that modulates the neuroimmune response with reported positive efficacy and safety data in a phase 2 study of PN", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35766128"}, {"offsetInBeginSection": 125, "offsetInEndSection": 527, "text": " Prurigo nodularis patients have a high burden of disease, primarily due to the intensity of the itch. It is reasonable to expect that rapid relief of itch - and associated improvement of sleep - are highly valued clinical outcomes for patients. Nemolizumab is an IL-31A-receptor inhibitor that modulates the neuroimmune response with reported positive efficacy and safety data in a phase 2 study of PN", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35766128"}, {"offsetInBeginSection": 0, "offsetInEndSection": 582, "text": "Nemolizumab is a subcutaneously administered humanized anti-interleukin-31 (IL-31) receptor A (IL-31RA) monoclonal antibody that is being developed by Chugai Pharmaceutical Co. Ltd, Maruho Co. Ltd and Galderma Pharma S.A. for the treatment of skin diseases, including atopic dermatitis (AD), AD associated pruritus (ADaP), prurigo nodularis (PN), chronic kidney disease associated pruritus (CKDaP) and systemic sclerosis (SSc). IL-31 is a neuroimmune cytokine that induces itch, inflammation, keratinocyte differentiation and fibroblast activation in chronic pruritic skin diseases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35834124"}, {"offsetInBeginSection": 370, "offsetInEndSection": 527, "text": " Nemolizumab is an IL-31A-receptor inhibitor that modulates the neuroimmune response with reported positive efficacy and safety data in a phase 2 study of PN", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35766128"}, {"offsetInBeginSection": 0, "offsetInEndSection": 814, "text": "Nemolizumab is a subcutaneously administered humanized anti-interleukin-31 (IL-31) receptor A (IL-31RA) monoclonal antibody that is being developed by Chugai Pharmaceutical Co. Ltd, Maruho Co. Ltd and Galderma Pharma S.A. for the treatment of skin diseases, including atopic dermatitis (AD), AD associated pruritus (ADaP), prurigo nodularis (PN), chronic kidney disease associated pruritus (CKDaP) and systemic sclerosis (SSc). IL-31 is a neuroimmune cytokine that induces itch, inflammation, keratinocyte differentiation and fibroblast activation in chronic pruritic skin diseases. Nemolizumab (Mitchga\u00ae Syringes) was approved in Japan on 28 March 2022 for use in adults and children over the age of 13 years for the treatment of itch associated with AD (only when existing treatment is insufficiently effective).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35834124"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Nemolizumab is a subcutaneously administered humanized anti-interleukin-31 (IL-31) receptor A (IL-31RA) monoclonal antibody", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35834124"}, {"offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "BACKGROUND: Nemolizumab is a subcutaneously administered humanized monoclonal antibody against interleukin-31 receptor A, which is involved in pruritus and inflammation in atopic", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32640132"}, {"offsetInBeginSection": 263, "offsetInEndSection": 548, "text": "Recently, Interleukin (IL)-31 and its receptor complex attracted significant interest, as clinical phase two studies demonstrated therapeutic efficacy of the neutralizing IL-31 receptor A (IL-31RA) antibody nemolizumab in patients suffering from atopic dermatitis or prurigo nodularis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33644104"}, {"offsetInBeginSection": 907, "offsetInEndSection": 1079, "text": "r proinflammatory cytokines.RESULTS: Our results demonstrate that nemolizumab effectively decreases IL-31 responses in PN skin, leading to effective suppression of downstre", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34857395"}, {"offsetInBeginSection": 277, "offsetInEndSection": 654, "text": "Nemolizumab is an anti-IL-31 receptor \u03b1-chain (IL-31RA) monoclonal antibody agent that is efficacious in improving symptoms of AD in several phase II and phase III studies in recent years. Nemolizumab demonstrates great efficacy in reducing pruritus and to a lesser degree, dermatitis associated with AD. Additionally, one advantage of nemolizumab is its quick speed of action.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35412530"}, {"offsetInBeginSection": 419, "offsetInEndSection": 602, "text": "JECTIVE: We sought to provide a comprehensive view of the transcriptomic changes in PN skin and characterize the mechanism of action of the anti-IL-31 receptor inhibitor nemolizumab.M", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34857395"}]}
+{"question_id": "65f774a4c4010b4d78000029", "question": "What type of colorectal cancer screening is the most cost-effective for general population?", "answer": "colonoscopy was the preferred, or cost-effective, strategy with an incremental cost-effectiveness ratio of $28\u202f071 per life-year gained.", "relevant_passage_ids": ["37971743", "26338314", "32294848", "16314648", "20059779", "31939431", "21361717", "19779203", "11033584", "11035892", "33953799", "28561259", "20624866", "28976679", "11297120", "11916165", "12489279", "32001308", "28117881", "32982508", "38088946", "37594967", "37380865", "37050991", "37012077", "36852204", "37099816", "31790657", "33307024", "37968075", "26685321", "32686116", "32167186", "28973514", "34789653", "24672652", "9177140", "15699893", "21444171", "8898453", "29904156", "31891647", "14986736", "10094264", "19575496", "18341782", "28988790", "25285526", "16723013", "24735237", "16434595", "35803353", "33014138", "22901118", "37752872", "12943152", "10998669", "11028135", "11274533", "16514382", "32439083", "19807403", "21633092", "12118964", "35954499", "36276354", "34958279", "35081762", "33840520", "34129408", "33088680", "21623557", "23247579", "29977160", "29702900", "1599742", "35974390", "32761199", "31748260", "35361332", "22898146", "23865368", "30788122", "11863113", "27538046", "11095350"], "type": "factoid", "snippets": [{"offsetInBeginSection": 2255, "offsetInEndSection": 2354, "text": "colonoscopy was a cost-effective strategy for colorectal cancer screening in the general population", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971743"}, {"offsetInBeginSection": 1289, "offsetInEndSection": 1457, "text": "When compared to FIT, colonoscopy is considered cost-effective for screening adenoma, advanced neoplasia, and a composite endpoint of advanced neoplasia or stage I CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26338314"}, {"offsetInBeginSection": 1749, "offsetInEndSection": 1885, "text": "colonoscopy was the preferred, or cost-effective, strategy with an incremental cost-effectiveness ratio of $28\u202f071 per life-year gained.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971743"}, {"offsetInBeginSection": 2177, "offsetInEndSection": 2505, "text": "In this economic evaluation of liquid biopsy for colorectal cancer screening, colonoscopy was a cost-effective strategy for colorectal cancer screening in the general population, and the inclusion of liquid biopsy as a first- or second-line screening strategy was not cost-effective at its current cost and screening performance", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971743"}, {"offsetInBeginSection": 14, "offsetInEndSection": 105, "text": "Screening for colorectal cancer (CRC) is effective in reducing both incidence and mortality", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37594967"}, {"offsetInBeginSection": 197, "offsetInEndSection": 340, "text": "Screening for colorectal cancer is a rational and cost-effective strategy for reducing the incidence of colorectal cancer and related mortality", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37050991"}, {"offsetInBeginSection": 238, "offsetInEndSection": 685, "text": "However, due to the invasiveness, high cost and the need for professional endoscopists of colonoscopy, it is not feasible to directly use this method for mass population screening. Fecal immunochemical test (FIT) is one of the screening techniques recommended by authoritative international guidelines for colorectal cancer screening, and has been widely used in population-based colorectal cancer screening programs in countries around the world.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37968075"}, {"offsetInBeginSection": 238, "offsetInEndSection": 909, "text": "However, due to the invasiveness, high cost and the need for professional endoscopists of colonoscopy, it is not feasible to directly use this method for mass population screening. Fecal immunochemical test (FIT) is one of the screening techniques recommended by authoritative international guidelines for colorectal cancer screening, and has been widely used in population-based colorectal cancer screening programs in countries around the world. This paper elaborates on the value of FIT in colorectal cancer screening from different aspects, such as the technical principles, the screening efficiency, the screening strategies, and the population effects and benefits.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37968075"}, {"offsetInBeginSection": 1781, "offsetInEndSection": 2230, "text": "Other assumptions about the sensitivity and specificity of fecal occult blood testing, screening frequency, efficacy of colonoscopy in preventing cancer, and polyp incidence have a lesser influence on the differences in cost-effectiveness between colonoscopy and fecal occult blood testing.CONCLUSIONS: Colonoscopy represents a cost-effective means of screening for colorectal cancer because it reduces mortality at relatively low incremental costs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11033584"}, {"offsetInBeginSection": 0, "offsetInEndSection": 369, "text": "BACKGROUND: Fecal occult blood testing, flexible sigmoidoscopy, and colonoscopy are used to screen patients for colorectal cancer.OBJECTIVE: To compare the cost-effectiveness of fecal occult blood testing, flexible sigmoidoscopy, and colonoscopy.DESIGN: The cost-effectiveness of the three screening strategies was compared by using computer models of a Markov process.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11033584"}, {"offsetInBeginSection": 736, "offsetInEndSection": 2121, "text": "e authors' consensus. The main outcome measures in this systematic review were the incremental cost-effectiveness ratio (ICER) of screening versus no-screening and then in comparison with other screening techniques. The ICER is defined by the difference in cost between two possible interventions, divided by the difference in their effect.RESULTS: Eight studies were identified and retained for the final analysis. In this study, when screening techniques were compared to no-screening, all CRC screening techniques showed to be cost-effective. The lowest ICER calculated was $PPP -16265/quality-adjusted life-year (QALY) (the negative ICERs were between purchasing power parity in US dollar ($PPP) -16265/QALY to $PPP -1988/QALY, whereas the positive ICERs were between $PPP 1257/QALY to $PPP 55987/QALY). For studies comparing various screening techniques, there was great heterogeneity in terms of the structures of the analyses, leading to diverse conclusions about their incremental cost-effectiveness.CONCLUSION: All CRC screening techniques were cost-effective, compared with the no-screening methods. The cost-effectiveness of the various screening techniques mainly was dependent on the context-specific parameters and highly affected by the framework of the cost-effectiveness analysis. In order to make the studies comparable, it is important to adopt a reference-based met", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32982508"}, {"offsetInBeginSection": 145, "offsetInEndSection": 2010, "text": "g in Europe are available, generating uncertainty over its efficiency. Although immunochemical fecal tests (FIT) and guaiac-based fecal occult blood tests (g-FOBT) have been shown to be cost-effective in France, cost-effectiveness of endoscopic screening has not yet been addressed.METHODS: Cost-effectiveness of screening strategies using colonoscopy, flexible sigmoidoscopy, second-generation colon capsule endoscopy (CCE), FIT and g-FOBT were compared using a Markov model. A 40\u200a% adherence rate was assumed for all strategies. Colonoscopy costs included anesthesiologist assistance. Incremental cost-effectiveness ratios (ICERs) were calculated. Probabilistic and value-of-information analyses were used to estimate the expected benefit of future research. A third-payer perspective was adopted.RESULTS: In the reference case analysis, FIT repeated every year was the most cost-effective strategy, with an ICER of \u20ac48165 per life-year gained vs. FIT every 2 years, which was the next most cost-effective strategy. Although CCE every 5 years was as effective as FIT 1-year, it was not a cost-effective alternative. Colonoscopy repeated every 10 years was substantially more costly, and slightly less effective than FIT 1-year. When projecting the model outputs onto the French population, the least (g-FOBT 2-years) and most (FIT 1-year) effective strategies reduced the absolute number of annual CRC deaths from 16037 to 12916 and 11217, respectively, resulting in an annual additional cost of \u20ac26 million and \u20ac347 million, respectively. Probabilistic sensitivity analysis demonstrated that FIT 1-year was the optimal choice in 20% of the simulated scenarios, whereas sigmoidoscopy 5-years, colonoscopy, and FIT 2-years were the optimal choices in 40%, 26%, and 14%, respectively.CONCLUSIONS: A screening program based on FIT 1-year appeared to be the most cost", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21623557"}, {"offsetInBeginSection": 1470, "offsetInEndSection": 1620, "text": "ch lower than that for repeat screening colonoscopy (474 RMB). Single colonoscopy was a more cost-effective strategy, which was not sensitive to the c", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22901118"}, {"offsetInBeginSection": 200, "offsetInEndSection": 350, "text": "rent screening strategies of faecal occult blood testing (FOBT), flexible sigmoidoscopy combined with FOBT and colonoscopy are all cost effective. In ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11297120"}, {"offsetInBeginSection": 1222, "offsetInEndSection": 1641, "text": "The models discussed in this article suggested that colorectal cancer screening using annual FOBT, flexible sigmoidoscopy at 3 or 5 years, the combination of FOBT and flexible sigmoidoscopy, barium enema, colonoscopy, and even virtual colonoscopy had incremental cost-effectiveness ratios ranging from $6300 to $92,900 per LY saved with most of the cost-effectiveness ratio ranging from $10,000 to $40,000 per LY saved.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11916165"}, {"offsetInBeginSection": 481, "offsetInEndSection": 654, "text": "Colonoscopy-first programs are more expensive initially, but their cost effectiveness may prove to be comparable with the currently recommended programs in certain settings.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10998669"}, {"offsetInBeginSection": 900, "offsetInEndSection": 1028, "text": " published studies.RESULTS: Cost per life-year saved was $12,636 for flexible sigmoidoscopy every 5 years and $14,394 for annual", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11028135"}, {"offsetInBeginSection": 810, "offsetInEndSection": 1150, "text": "Most of these trials were performed by US or UK authors and demonstrate that the incremental cost-effectiveness ratio varies between 5 000 and 15 000 US dollars/one year life gained, with wide variations: these results were highly dependent on the unit costs of the different devices as well as the predictive values of the screening tests.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16514382"}, {"offsetInBeginSection": 608, "offsetInEndSection": 802, "text": "Cost-effectiveness analysis informs decisions in ongoing debates, including preferred age to begin average-risk CRC screening, and implementation of CRC screening tailored to predicted CRC risk.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32439083"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Cost-effectiveness analysis of a community-based colorectal cancer screening program in Shanghai, China.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36276354"}, {"offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Cost-Effectiveness of Outreach Strategies for Stool-Based Colorectal Cancer Screening in a Medicaid Population.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34958279"}, {"offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Cost-Effectiveness of Community-to-Clinic Tailored Navigation for Colorectal Cancer Screening in an Underserved Population: Economic Evaluation Alongside a Group-Randomized Trial.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35081762"}, {"offsetInBeginSection": 1922, "offsetInEndSection": 2825, "text": "Sigmoidoscopy and FIT at lower thresholds (10\u2009\u00b5g/g) and a higher uptake should be given consideration as cost-effective alternatives.PLAIN LANGUAGE SUMMARY: Cost-effectiveness analysis of colorectal cancer screening strategies in high-risk individuals Fecal occult blood testing with an immunochemical test (FIT) is generally considered as the most cost-effective alternative in colorectal cancer screening programs for average risk individuals without family history.Current screening guidelines for high-risk individuals with familial history recommend colonoscopy every 3-5\u2009years.Colonoscopy every 3-5\u2009years for individuals with familial history is the most effective strategy but is associated with a high incremental cost-effectiveness ratio.Compared with colonoscopy, if screening based on FIT is associated with a higher participation rate, it can achieve a similar effectiveness at a lower cost.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33953799"}, {"offsetInBeginSection": 1289, "offsetInEndSection": 1528, "text": "Under varied adherence scenarios, MT-sDNA either dominates or is cost-effective (ICERs, $1740-$75,868 per QALY saved) compared with FIT and colonoscopy.CONCLUSION: Each strategy reduced costs and increased QALYs compared with no screening.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33840520"}, {"offsetInBeginSection": 1625, "offsetInEndSection": 1985, "text": "In the threshold analyses, at equivalent rates to stool-based screening, mt-sDNA was always cost-effective at a willingness-to-pay threshold of $100,000 per QALY versus FIT and FOBT.CONCLUSIONS: Initiating average-risk CRC screening at age 45 instead of age 50 increases the estimated clinical benefit by reducing disease burden while remaining cost-effective.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37752872"}, {"offsetInBeginSection": 2012, "offsetInEndSection": 2308, "text": "Colonoscopy did not become cost saving, but the total net costs of this strategy decreased from $1317 to $296 per individual in the population.CONCLUSIONS: With the increase in chemotherapy costs for advanced colorectal cancer, most colorectal cancer screening strategies have become cost saving.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19779203"}, {"offsetInBeginSection": 1536, "offsetInEndSection": 1921, "text": "With a lower threshold (10\u2009\u00b5g/g) and a higher uptake of 45%, FIT was more effective and less costly than colonoscopy at a 30% uptake and was associated with an incremental cost-effectiveness ratio (ICER) of \u20ac4240/QALY versus no screening.CONCLUSION: At 30% uptake, current screening is the most effective screening strategy for high-risk individuals but is associated with a high ICER.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33953799"}, {"offsetInBeginSection": 1482, "offsetInEndSection": 1632, "text": "procedures than the other strategies.CONCLUSIONS: The total colonoscopy-based strategy could be the most cost-effective for population-based colorecta", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26685321"}, {"offsetInBeginSection": 0, "offsetInEndSection": 445, "text": "INTRODUCTION: Colorectal cancer (CRC) is a significant health problem with an increasing incidence worldwide. Screening is one of the ways, in which cases and deaths of CRC can be prevented. The objective of this systematic review was to evaluate the cost-effectiveness of the different CRC screening techniques and to specify the efficient technique from a cost-effectiveness perspective.METHODS: The economic studies of CRC screening in genera", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32982508"}, {"offsetInBeginSection": 233, "offsetInEndSection": 348, "text": "fectiveness of colorectal cancer screening. We aim to analyze the cost-effectiveness of colorectal cancer screening", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29977160"}, {"offsetInBeginSection": 281, "offsetInEndSection": 1027, "text": "discuss the cost-effectiveness of colorectal cancer screening procedures, in particular, the recent ones through the last eight years. The effectiveness of screening estimated by discounted life years gained (LYGs) compared to no screening, differed considerably between the studies. Despite these differences, all studies consistently emphasized that screening for CRC was cost-effective compared with no screening for each of the recognized screening strategies. Newer technologies for colorectal cancer screening, including computed tomographic colonography (CTC), faecal DNA test, and Pillcam Colon are less invasive and accurate, however, they are not cost-effective, as their cost was higher than all other established screening strategies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28988790"}, {"offsetInBeginSection": 431, "offsetInEndSection": 1469, "text": "as 34%. The objective of this study was to compare the cost effectiveness of screening alternatives taking real-world participation rates into account.METHODS: Eight screening strategies were compared, based either on a screening test (Guaiac or FIT testing, blood-based, stool DNA, computed tomography colonography, colon capsules, and sigmoidoscopy) followed by full colonoscopy if positive or direct colonoscopy. A microsimulation model was used to estimate the cost effectiveness associated with each strategy.RESULTS: Compared with no screening, FIT was associated with a 14.0 quality-adjusted life year (QALY) increase of \u20ac50,520 per 1000 individuals, giving an incremental cost-effectiveness ratio (ICER) of \u20ac3600/QALY. Only stool DNA and blood-based testing were associated with a QALY increase compared with FIT, with stool DNA weakly dominated by blood-based testing, and the latter associated with an ICER of \u20ac154,600/QALY compared with FIT. All other strategies were dominated by FIT.CONCLUSION: FIT every 2\u2009years appears to b", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33014138"}, {"offsetInBeginSection": 134, "offsetInEndSection": 412, "text": " a Markov model to compare the clinical and economic impact in terms of reducing the incidence and mortality from colorectal cancer (CRC). Six screening strategies for adults were compared: fecal occult blood (FOBT) immunochemical and guaiac type, conventional colonoscopy, flex", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29702900"}, {"offsetInBeginSection": 0, "offsetInEndSection": 655, "text": "Colorectal cancer is the second most common cancer killer of Americans. Recently developed and tested methods of screening and surveillance can effectively diagnose and treat the disease in most patients before symptoms develop when the chance of cure is high. It is also possible to prevent colorectal cancer by detecting and resecting premalignant adenomatous polyps. Evidence-based guidelines recommend that the average-risk population greater than age 50 be screened with annual faecal occult blood tests plus periodic flexible sigmoidoscopy. This approach is feasible, efficacious, affordable and cost-effective in a high-risk country such as the US.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28976679"}, {"offsetInBeginSection": 746, "offsetInEndSection": 1183, "text": "Newer technologies for colorectal cancer screening, including computed tomographic colonography (CTC), faecal DNA test, and Pillcam Colon are less invasive and accurate, however, they are not cost-effective, as their cost was higher than all other established screening strategies. When compliance and adherence to such new techniques are increased more than the established strategies they would be more cost-effective particularly CTC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28988790"}, {"offsetInBeginSection": 196, "offsetInEndSection": 512, "text": " Screening for colorectal cancer is a rational and cost-effective strategy for reducing the incidence of colorectal cancer and related mortality. Despite endorsement by academic and healthcare organizations, patient awareness and compliance with screening are low, partly due to patient-related barriers to screening", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37050991"}, {"offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Cost-effective screening strategies for colorectal cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1599742"}, {"offsetInBeginSection": 92, "offsetInEndSection": 512, "text": " Numerous studies have shown the benefit of early screening for colorectal cancer in reducing mortality. Screening for colorectal cancer is a rational and cost-effective strategy for reducing the incidence of colorectal cancer and related mortality. Despite endorsement by academic and healthcare organizations, patient awareness and compliance with screening are low, partly due to patient-related barriers to screening", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37050991"}, {"offsetInBeginSection": 746, "offsetInEndSection": 1027, "text": "Newer technologies for colorectal cancer screening, including computed tomographic colonography (CTC), faecal DNA test, and Pillcam Colon are less invasive and accurate, however, they are not cost-effective, as their cost was higher than all other established screening strategies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28988790"}, {"offsetInBeginSection": 196, "offsetInEndSection": 625, "text": " Screening for colorectal cancer is a rational and cost-effective strategy for reducing the incidence of colorectal cancer and related mortality. Despite endorsement by academic and healthcare organizations, patient awareness and compliance with screening are low, partly due to patient-related barriers to screening.AIM: This study aimed to explore the preferred screening method for colorectal cancer in Saudi Arabia in general", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37050991"}, {"offsetInBeginSection": 2162, "offsetInEndSection": 2517, "text": "and Relevance: In this economic evaluation of liquid biopsy for colorectal cancer screening, colonoscopy was a cost-effective strategy for colorectal cancer screening in the general population, and the inclusion of liquid biopsy as a first- or second-line screening strategy was not cost-effective at its current cost and screening performance. Liquid bio", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971743"}, {"offsetInBeginSection": 2091, "offsetInEndSection": 2249, "text": "copy represents a cost-effective means of screening for colorectal cancer because it reduces mortality at relatively low incremental costs. Low compliance rat", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11033584"}, {"offsetInBeginSection": 2032, "offsetInEndSection": 2515, "text": "py-liquid biopsy hybrid had a greater gain in life-years if liquid biopsy could detect polyps but remained too costly.Conclusions and Relevance: In this economic evaluation of liquid biopsy for colorectal cancer screening, colonoscopy was a cost-effective strategy for colorectal cancer screening in the general population, and the inclusion of liquid biopsy as a first- or second-line screening strategy was not cost-effective at its current cost and screening performance. Liquid b", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971743"}, {"offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Cost-effectiveness of colonoscopy in screening for colorectal cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11033584"}, {"offsetInBeginSection": 1631, "offsetInEndSection": 1894, "text": "his study used a simulated cohort of patients aged 45 years with average risk of colorectal cancer. In the base case, colonoscopy was the preferred, or cost-effective, strategy with an incremental cost-effectiveness ratio of $28\u202f071 per life-year gained. Colonosc", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37971743"}, {"offsetInBeginSection": 0, "offsetInEndSection": 389, "text": "INTRODUCTION: Screening for colorectal cancer (CRC) is effective in reducing both incidence and mortality. Colonoscopy and stool tests are most frequently used for this purpose. Sigmoidoscopy is an alternative screening measure with a strong evidence base. Due to its distinct characteristics, it might be preferred by subgroups. The aim of this systematic review is to analyze the cost-ef", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37594967"}, {"offsetInBeginSection": 0, "offsetInEndSection": 358, "text": "INTRODUCTION: Colorectal cancer (CRC) is the second leading cause of death worldwide and the use of CRC screening tests can reduce the incidence and mortality of the disease by early detection. This study aims to review cost-effectiveness strategies in different ages and countries, systematically.METHODS: We searched ProQuest, Web of Science, Scopus, Cochr", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35974390"}, {"offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "The incidence of colorectal cancer (CRC) is increasing in patients under the age of 50. The purpose of this study was to assess the cost-utility of available screening modalities starting", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32001308"}, {"offsetInBeginSection": 1090, "offsetInEndSection": 2028, "text": "ted States (24,2%) and Asia (24,2%). The main screening modalities considered were fecal immunochemical tests (70%), colonoscopy (67%), guaiac fecal occult blood test (42%) and flexible sigmoidoscopy (30%). In most studies, CRC screening was deemed cost-effective compared to no screening. Sensitivity analyses indicated that cost of CRC screening tests, adherence to screening, screening test sensitivity, and cost of CRC treatment had the greatest impact on cost-effectiveness results across studies. The majority of studies (73%) adequately reported at least 50% of the items included in the CHEERS checklist. Least well reported items included setting, study perspective, discount rate, model choice, and methods to identify effectiveness data or to estimate resource use and costs.CONCLUSIONS: CRC screening is an efficient alternative to no screening. Nevertheless, it is not possible to conclude which strategy should be preferred ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31891647"}, {"offsetInBeginSection": 0, "offsetInEndSection": 493, "text": "Colorectal cancer screening incorporates various testing modalities. Factors including effectiveness, harms, cost, screening interval, patient preferences, and test availability should be considered when determining which test to use. Fecal occult blood testing and endoscopic screening have the most robust evidence, while newer blood- and imaging-based techniques require further evaluation. In this review, we compare the effectiveness, harms, and costs of the various screening strategies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35361332"}, {"offsetInBeginSection": 695, "offsetInEndSection": 1571, "text": "ing and colonoscopy screening every 10\u2009years. Quality-adjusted life-years gained (QALYG), number of colonoscopies, and incremental cost-effectiveness ratios were projected. We assumed a willingness-to-pay threshold of $100\u2009000 per QALYG.RESULTS: Among the alternative tests, computed tomographic colonography every 5\u2009years, annual mSEPT9, and annual multi-target stool DNA screening had incremental cost-effectiveness ratios of $1092, $63\u2009253, and $214\u2009974 per QALYG, respectively. Other screening strategies were more costly and less effective than (a combination of) these 3. Under the assumption of perfect adherence, annual mSEPT9 screening resulted in more QALYG, CRC cases averted, and CRC deaths averted than annual FIT screening but led to a high rate of colonoscopy referral (51% after 3\u2009years, 69% after 5\u2009years). The alternative tests were not cost-effective compar", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32761199"}, {"offsetInBeginSection": 110, "offsetInEndSection": 607, "text": "Alternatives are compared based on an incremental cost-effectiveness ratio reported in terms of cost per quality-adjusted life-year gained. Multiple cost-effectiveness analyses of colorectal cancer (CRC) screening have been performed. Although regional epidemiology of CRC, relevant screening strategies, regional health system, and applicable medical costs in local currencies differ by country and region, several overarching points emerge from literature on cost-effectiveness of CRC screening.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32439083"}, {"offsetInBeginSection": 744, "offsetInEndSection": 987, "text": "All economic evaluations, despite some differences between studies, add further arguments to support the opinion that the immunochemical faecal occult blood test is currently the most cost-effective screening test for average-risk populations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22898146"}, {"offsetInBeginSection": 1883, "offsetInEndSection": 2045, "text": "nal levels of WTP (Willingness to Pay). Annual high-sensitivity fecal occult blood testing, such as a fecal immunochemical test, or colonoscopy every 10 years off", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23865368"}, {"offsetInBeginSection": 1444, "offsetInEndSection": 1653, "text": "mical test programme or 31% for colonoscopy.Conclusion: Biennial faecal immunochemical test screening is better than colonoscopy as it is cost-effective, allows more individuals to get screened, and provides a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30788122"}, {"offsetInBeginSection": 127, "offsetInEndSection": 414, "text": "The best evidence for the effectiveness of screening for colorectal cancer is with annual or biennial fecal occult blood testing. While the benefit of fecal occult blood testing is small in absolute terms, the incremental cost-effectiveness of this screening strategy appears acceptable.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11863113"}, {"offsetInBeginSection": 313, "offsetInEndSection": 842, "text": "Decision models using Markov or microsimulation modelling that compare the cost-effectiveness of different screening strategies are useful in this regard. We have reviewed recent decision models that compare the cost-effectiveness of one-off flexible sigmoidoscopy screening with immunochemical faecal occult blood (FIT) based screening. Models consistently show that any population-based screening is cost-effective compared with no screening, and that FIT-based screening is more effective than one-off sigmoidoscopy screening.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27538046"}, {"offsetInBeginSection": 1386, "offsetInEndSection": 1590, "text": "Regardless of screening modality, CRC screening at 40\u202fyears old is cost-effective with increased QALYs compared to current screening initiation at 50\u202fyears old, with flexible sigmoidoscopy most preferred.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32001308"}, {"offsetInBeginSection": 127, "offsetInEndSection": 256, "text": "The best evidence for the effectiveness of screening for colorectal cancer is with annual or biennial fecal occult blood testing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11863113"}, {"offsetInBeginSection": 1363, "offsetInEndSection": 2127, "text": "wed up until death.RESULTS: Compared with no screening, the treatment savings from preventing advanced colorectal cancer and colorectal cancer deaths by screening more than doubled with the widespread use of new chemotherapies. The lifetime average treatment savings were larger than the lifetime average screening costs for screening with Hemoccult II, immunochemical FOBT, sigmoidoscopy, and the combination of sigmoidoscopy and Hemoccult II (average savings vs costs per individual in the population: Hemoccult II, $1398 vs $859; immunochemical FOBT, $1756 vs $1565; sigmoidoscopy, $1706 vs $1575; sigmoidoscopy and Hemoccult II $1931 vs $1878). Colonoscopy did not become cost saving, but the total net costs of this strategy decreased from $1317 to $296 per i", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19779203"}, {"offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "OBJECTIVES: Fecal occult blood testing has been shown to reduce mortality from colorectal cancer in large randomized, controlled trials conducted in the United States, Denmark, and the United Kingdom, and mathematical simulation modeling found it to be cost-effective relative to other health ca", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11095350"}]}
+{"question_id": "65f37aeac4010b4d7800000c", "question": "Is Cri du Chat syndrome (CdCS) a genetic syndrome caused by deletions in the long arm of chromosome 5", "answer": "Cri du Chat syndrome (CdCS) is a genetic syndrome caused by deletions in the short arm of chromosome 5", "relevant_passage_ids": ["36660031", "37908952", "7713510", "26059676", "23455788", "30711802", "36338241", "25514263", "25236835", "16953888", "32800423", "19239081", "20038906", "36242045", "30587166", "29460462", "31836684", "34434412", "31568707", "15657623", "1978567", "10424821", "18437967", "32739788", "28004033", "22921333", "28523196", "37465584", "11238681", "18484284", "31187941", "27144168", "26601658", "34394178"], "type": "yesno", "snippets": [{"offsetInBeginSection": 14, "offsetInEndSection": 276, "text": "Cri-du-chat syndrome is generally diagnosed when patients present a high-pitched cry at birth, microcephaly, ocular hypertelorism, and prominent nasal bridge. The karyotype is useful to confirm deletions in the short arm of chromosome 5 (5p-) greater than 10 Mb.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36660031"}, {"offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Cri-du-chat syndrome (CdCS) is a rare genetic disorder in which the short arm of chromosome 5 is deleted. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37908952"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Cri-du-chat syndrome (CdCS) is a rare genetic disorder in which the short arm of chromosome 5 is deleted", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37908952"}, {"offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Cri du chat syndrome (CdcS), also known as 5p deletion syndrome is a genetic disorder caused by the partial deletion of chromatin from the short arm of chromosome 5.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25514263"}, {"offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Cri du chat syndrome (CdcS), also known as 5p deletion syndrome is a genetic disorder caused by the partial deletion of chromatin from the short arm of chromosome 5. There is a paucity of literature on the dental manifestations in CdcS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25514263"}, {"offsetInBeginSection": 0, "offsetInEndSection": 423, "text": "Cri du chat syndrome (CdcS), also known as 5p deletion syndrome is a genetic disorder caused by the partial deletion of chromatin from the short arm of chromosome 5. There is a paucity of literature on the dental manifestations in CdcS. The purposes of this report are to present the case of a nine-year-old girl with the syndrome, CdcS and to review its dental and clinical manifestations and their management in children.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25514263"}, {"offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "A new syndrome was identified in 1963, when Lejeune et al. reported a genetic disease resulting from a partial or total deletion on the short arm of chromosome 5 (5p-) and named it the cri du chat syndrome (CdCS).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20038906"}, {"offsetInBeginSection": 59, "offsetInEndSection": 213, "text": "reported a genetic disease resulting from a partial or total deletion on the short arm of chromosome 5 (5p-) and named it the cri du chat syndrome (CdCS).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20038906"}, {"offsetInBeginSection": 59, "offsetInEndSection": 383, "text": "reported a genetic disease resulting from a partial or total deletion on the short arm of chromosome 5 (5p-) and named it the cri du chat syndrome (CdCS). This term makes reference to the main clinical feature of the syndrome, a high-pitched monochromatic cat-like crying, that usually disappears in the first years of life.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20038906"}, {"offsetInBeginSection": 59, "offsetInEndSection": 508, "text": "reported a genetic disease resulting from a partial or total deletion on the short arm of chromosome 5 (5p-) and named it the cri du chat syndrome (CdCS). This term makes reference to the main clinical feature of the syndrome, a high-pitched monochromatic cat-like crying, that usually disappears in the first years of life. CdCS is one of the most common chromosomal deletion syndromes in humans, with an incidence of 1:15.000-1:50.000 live-births.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20038906"}, {"offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "BACKGROUND: Cri du Chat Syndrome (CdCS) is rare and occurs as a result of a partial deletion in the short arm of chromosome 5. There are no reports in the literature from the West African sub-region and indeed very few ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25236835"}, {"offsetInBeginSection": 0, "offsetInEndSection": 383, "text": "A new syndrome was identified in 1963, when Lejeune et al. reported a genetic disease resulting from a partial or total deletion on the short arm of chromosome 5 (5p-) and named it the cri du chat syndrome (CdCS). This term makes reference to the main clinical feature of the syndrome, a high-pitched monochromatic cat-like crying, that usually disappears in the first years of life.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20038906"}, {"offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "The Cri du Chat syndrome (CdCS) is a genetic disease resulting from a deletion of variable size occurring on the short arm of chromosome 5 (5p-).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16953888"}, {"offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "BACKGROUND: Cri du Chat syndrome (CdCS) is a genetic syndrome caused by deletions in the short arm of chromosome 5.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29460462"}, {"offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "The cri du chat syndrome (CdCS) is a chromosomal deletion syndrome associated with a partial deletion of the short (p) arm of chromosome 5.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23455788"}, {"offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "INTRODUCTION: Cri-du-Chat Syndrome (CdCS) is a genetic condition due to deletions showing different breakpoints encompassing a critical region on the short arm of chromosome 5, located between p15.2 and p15.3, first defined by Niebuhr in 1978.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32800423"}, {"offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "The Cri du Chat Syndrome (CdCS) is a genetic disease resulting from variable size deletion occurring on the short arm of chromosome 5.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30711802"}, {"offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Cri du chat syndrome is associated with a deletion on the short arm of chromosome 5.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10424821"}, {"offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "The deletion of the short arm of chromosome 5 is associated with the cri-du-chat syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7713510"}, {"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Cri du chat syndrome (CDCS) is a rare genetic disease that is caused by a deletion in the short arm of chromosome 5 (5p)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31836684"}, {"offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "The Cri du Chat syndrome (CdC) is a rare genetic disorder caused by variable size deletions of the short arm of chromosome 5 (5p-)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28004033"}, {"offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "The cri-du-chat syndrome is a rare genetic disorder caused by deletions in the short arm of chromosome 5.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26059676"}, {"offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "BACKGROUND: Cri du chat syndrome (CCS) is a genetic disorder resulting from the deletion of the short arm of c", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22921333"}, {"offsetInBeginSection": 108, "offsetInEndSection": 225, "text": "The human gene is located on the short arm of chromosome 5, the region deleted in Cri-du-chat syndrome (OMIM #123450)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37465584"}, {"offsetInBeginSection": 12, "offsetInEndSection": 171, "text": "Cri du chat (also called 5p deletion, or monosomy 5p) syndrome is a genetic disease caused by deletions of various lengths in the short (p) arm of chromosome 5", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36242045"}, {"offsetInBeginSection": 4, "offsetInEndSection": 124, "text": "Cri du Chat syndrome (CdC) is a rare genetic disorder caused by variable size deletions of the short arm of chromosome 5", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28004033"}, {"offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "The Cri du Chat Syndrome (CdCS) is one of the most common deletion syndromes, involving the short arm of chromosome 5, with an", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19239081"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Cri du Chat syndrome (CdC) is a chromosomal abnormality (deletion of short arm of chromosome 5)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28523196"}, {"offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Cri du chat syndrome (CdcS), also known as 5p deletion syndrome is a genetic disorder caused by the partial deletion of chromatin from the short arm of chromosome 5. There is a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25514263"}, {"offsetInBeginSection": 59, "offsetInEndSection": 268, "text": "reported a genetic disease resulting from a partial or total deletion on the short arm of chromosome 5 (5p-) and named it the cri du chat syndrome (CdCS). This term makes reference to the main clinical feature", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20038906"}, {"offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "BACKGROUND: Cri du chat syndrome (CdCS), also known as 5p deletion syndrome (5p-) is a syndrome caused by partial deletion of the 5p chromosome in human beings. The incidence accounts for 1/50000 and the cause of CdCS is related to partial deletion of chromosome", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36338241"}, {"offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Cri du chat syndrome is associated with a deletion on the short arm of chromosome 5. The main diagnostic feature", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10424821"}, {"offsetInBeginSection": 937, "offsetInEndSection": 1552, "text": " those found in patients with Cri-du-chat Syndrome (CdCS). CdCS is a genetic disease resulting from a deletion of variable size occurring on the short arm of chromosome 5 (5p-), whose main feature is a high-pitched mewing cry in infancy, accompanied by multiple congenital anomalies, intellectual disability, microcephaly and facial dysmorphism.CONCLUSIONS: The absence of some CdCS features in the current patient could be due to the fact that in her case the critical regions responsible do not lie within the identified deletion. In fact, a literature review revealed a high degree of concordance between the cli", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30587166"}, {"offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "BACKGROUND: Cri du chat (also called 5p deletion, or monosomy 5p) syndrome is a genetic disease caused by deletions of various lengths in the short (p) arm of chromosome 5.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36242045"}, {"offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Cri-du-chat syndrome (CdCS) is a rare genetic disorder in which the short arm of chromosome 5 is deleted.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37908952"}, {"offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "BACKGROUND: Cri-du-chat syndrome is a genetic disorder associated with various sized deletions of the short arm of c", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18437967"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "The Cri du Chat syndrome (CdC) is a rare genetic disorder caused by variable size deletions of the short arm of chromosome 5 (5p-).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28004033"}, {"offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Cri Du Chat (CDC) syndrome is a rare genetic condition caused by the deletion of genetic material on the small arm (the p arm) of chromosome 5.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32739788"}, {"offsetInBeginSection": 106, "offsetInEndSection": 269, "text": "CCS is a rare genetic disorder, with an estimated incidence between 1 in 15,000 and 1 in 50,000 births, resulting from a deletion on the short arm of chromosome 5.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18484284"}, {"offsetInBeginSection": 288, "offsetInEndSection": 407, "text": "Cri du chat (CdC) syndrome, a rare genetic disorder caused by variable size deletions of the short arm of chromosome 5.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31187941"}, {"offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Cri du chat syndrome (CDCS) is a rare genetic disease that is caused by a deletion in the short arm of chromosome 5 (5p) and has a variable clinical spectrum", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31836684"}, {"offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Cri-du-chat syndrome is a chromosomal disorder caused by a deletion of the short arm of chromosome 5", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27144168"}, {"offsetInBeginSection": 14, "offsetInEndSection": 242, "text": "Cri-du-Chat Syndrome (CdCS) is a genetic condition due to deletions showing different breakpoints encompassing a critical region on the short arm of chromosome 5, located between p15.2 and p15.3, first defined by Niebuhr in 1978", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32800423"}, {"offsetInBeginSection": 12, "offsetInEndSection": 138, "text": "Cri du chat syndrome (CdCS) is a rare syndrome caused by a partial or complete deletion of the short arm of chromosome 5 (5p-)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31568707"}, {"offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "Deletion of the short arm of chromosome 5 (5p-) is associated with phenotypic features including a cat-like cry in infancy, dysmorphic facial features, microcephaly, and intellectual disability, and when encompassing a minimal critical region, may be defined as Cri-du-Chat syndrome (CdCS)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26601658"}, {"offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "The Cri du Chat Syndrome (CdCS) is a genetic disease resulting from variable size deletion occurring on the short arm of chromosome 5", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30711802"}, {"offsetInBeginSection": 12, "offsetInEndSection": 114, "text": "Cri du Chat syndrome (CdCS) is a genetic syndrome caused by deletions in the short arm of chromosome 5", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29460462"}, {"offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Cri du Chat syndrome (CdC) is a chromosomal abnormality (deletion of short arm of chromosome 5) associated with intellectual disability and typical anatomical abnormalities", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28523196"}, {"offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The majority of deletions of the short arm of chromosome 5 are associated with cri du chat syndrome (CdCS) and patients show phenotypic and cytogenetic variability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11238681"}, {"offsetInBeginSection": 100, "offsetInEndSection": 392, "text": "Since the cri-du-chat syndrome is correlated with deletions involving the short arm of chromosome 5 (5p), DNA fragments known to detect restriction fragment length polymorphisms (RFLPs) along 5p were used to establish whether the paternal or the maternal chromosome had suffered the deletion.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1978567"}, {"offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Cri du chat syndrome (CdCS) is a chromosomal disorder resulting from a deletion in the short arm of chromosome 5.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34434412"}, {"offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The Cri du Chat Syndrome (CdCS) is one of the most common deletion syndromes, involving the short arm of chromosome 5, with an incidence of 1 in 50.000 live births.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19239081"}, {"offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "BACKGROUND: Cri du Chat syndrome (CdCS) is a genetic syndrome caused by deletions in the short arm of chromosome 5. Altho", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29460462"}, {"offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Cri-du-chat syndrome (CdCS) is a rare genetic disorder in which the short arm of chromosome 5 is deleted. This report aims", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37908952"}, {"offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "BACKGROUND: Cri du Chat Syndrome (CdCS) is rare and occurs as a result of a partial deletion in the short arm of chromosome 5. There are no reports in the literature from the West African sub-region and indeed very few from Africa. A case of Cri du Chat Syndrome is describ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25236835"}, {"offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "The cri-du-chat syndrome is a rare genetic disorder caused by deletions in the short arm of chromosome 5. It presents with a distinctive catlike high-pitched cry, psychomotor delays, microcephaly, craniofacial abnormalities, and, in many cases, ocular findings.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26059676"}, {"offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "BACKGROUND: Cri-du-chat syndrome is a genetic disorder associated with various sized deletions of the short arm of chromosome 5", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18437967"}, {"offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "BACKGROUND: Cri-du-chat syndrome is a genetic disorder associated with various sized deletions of the short arm of chromosome 5. There are typical physical features, but individual phenotypes vary considerably", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18437967"}, {"offsetInBeginSection": 29, "offsetInEndSection": 372, "text": "(5p-Sd, OMIM #123450) formerly known as Cri du Chat syndrome results from the loss of genetic material at the distal region of the short arm of chromosome 5. It is a neurodevelopmental disorder of genetic cause. So far, about 400 patients have been reported worldwide. Individuals affected by this syndrome have large phenotypic heterogeneity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34394178"}, {"offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "BACKGROUND: Cri du chat syndrome (CdCS), also known as 5p deletion syndrome (5p-) is a syndrome caused by partial deletion of the 5p chromosome in h", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36338241"}, {"offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Cri-du-chat syndrome is a chromosomal disorder caused by a deletion of the short arm of chromosome 5.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27144168"}, {"offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Cri-du-chat (CDC, OMIM 123450) is a chromosomal syndrome that results from partial deletions on the short arm of chromosome 5.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15657623"}]}
+{"question_id": "66168d7bfdcbea915f000056", "question": "Mortality in schizophrenia.", "answer": "Mortality rates are significantly higher among individuals with schizophrenia compared to the general population. Studies have shown that people with schizophrenia die 15-20 years prematurely, with a standardized mortality ratio (SMR) of around 2.5. The leading causes of death in schizophrenia include suicide, cardiovascular disease, respiratory infections, and accidents. Comorbidities such as2021), and aggravating or attenuating factors is essential to reduce this gap.", "relevant_passage_ids": ["24313570", "29723811"], "type": "summary", "snippets": [{"offsetInBeginSection": 197, "offsetInEndSection": 249, "text": "excess early mortality in persons with schizophrenia", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24313570"}, {"offsetInBeginSection": 333, "offsetInEndSection": 403, "text": "Persons with schizophrenia have an exceptionally short life expectancy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24313570"}, {"offsetInBeginSection": 463, "offsetInEndSection": 541, "text": "life expectancy of approximately 20 years below that of the general population", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24313570"}, {"offsetInBeginSection": 46, "offsetInEndSection": 79, "text": "excess mortality in schizophrenia", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29723811"}, {"offsetInBeginSection": 1216, "offsetInEndSection": 1377, "text": "The appearance of a static or widening mortality gap over time between people with schizophrenia and psychotic disorders and the general population is of concern", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29723811"}]}
+{"question_id": "661d2428eac11fad33000017", "question": "Is ICD-10 encoding sensitive for capturing paediatric sepsis?", "answer": "No, the current ICD-10 encoding for paediatric sepsis does have high sensitivity.", "relevant_passage_ids": ["37342815", "36382338"], "type": "yesno", "snippets": [{"offsetInBeginSection": 735, "offsetInEndSection": 971, "text": "The sensitivity of ICD-10 coding abstraction was 60% (95%-CI 57-63) for sepsis; 35% (95%-CI 31-39) for sepsis with organ dysfunction, using an explicit abstraction strategy; and 65% (95%-CI 61-69) using an implicit abstraction strategy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37342815"}, {"offsetInBeginSection": 1420, "offsetInEndSection": 1664, "text": "In this population-based study, we found a poor representation of sepsis and sepsis with organ dysfunction by ICD-10 coding abstraction in children with blood culture-proven sepsis when compared against a prospective validated research dataset.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37342815"}, {"offsetInBeginSection": 1665, "offsetInEndSection": 1783, "text": "Sepsis estimates in children based on ICD-10 coding may thus severely underestimate the true prevalence of the disease", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37342815"}, {"offsetInBeginSection": 1415, "offsetInEndSection": 1791, "text": "ons: In this population-based study, we found a poor representation of sepsis and sepsis with organ dysfunction by ICD-10 coding abstraction in children with blood culture-proven sepsis when compared against a prospective validated research dataset. Sepsis estimates in children based on ICD-10 coding may thus severely underestimate the true prevalence of the disease.Supplem", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37342815"}, {"offsetInBeginSection": 1197, "offsetInEndSection": 1664, "text": "The estimated national incidence of sepsis, inferred from ICD-10 coding abstraction, was 12.5 per 100,000 children (95%-CI 11.7-13.5) and 21.0 per 100,000 children (95%-CI 19.8-22.2) using validated study data.Conclusions: In this population-based study, we found a poor representation of sepsis and sepsis with organ dysfunction by ICD-10 coding abstraction in children with blood culture-proven sepsis when compared against a prospective validated research dataset.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37342815"}, {"offsetInBeginSection": 972, "offsetInEndSection": 1058, "text": "For septic shock, the sensitivity of ICD-10 coding abstraction was 43% (95%-CI 37-50).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37342815"}, {"offsetInBeginSection": 1342, "offsetInEndSection": 1588, "text": "Compared with the reference standard of detailed chart review and/or registry databases, the pooled sensitivity for sepsis ICD-10 codes was 35% (95% CI, 22-48, low certainty), whereas the pooled specificity was 98% (95% CI: 98-99, low certainty).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36382338"}, {"offsetInBeginSection": 1665, "offsetInEndSection": 1902, "text": "Sepsis estimates in children based on ICD-10 coding may thus severely underestimate the true prevalence of the disease.Supplementary Information: The online version contains supplementary material available at 10.1007/s44253-023-00006-1.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37342815"}, {"offsetInBeginSection": 29, "offsetInEndSection": 801, "text": "ssification of Diseases 10th edition (ICD-10) is widely used to describe the burden of disease.Aim: To describe how well ICD-10 coding captures sepsis in children admitted to the hospital with blood culture-proven bacterial or fungal infection and systemic inflammatory response syndrome.Methods: Secondary analysis of a population-based, multicenter, prospective cohort study on children with blood culture-proven sepsis of nine tertiary pediatric hospitals in Switzerland. We compared the agreement of validated study data on sepsis criteria with ICD-10 coding abstraction obtained at the participating hospitals.Results: We analyzed 998 hospital admissions of children with blood culture-proven sepsis. The sensitivity of ICD-10 coding abstraction was 60% (95%-CI 57-63", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37342815"}, {"offsetInBeginSection": 693, "offsetInEndSection": 843, "text": "hildren with blood culture-proven sepsis. The sensitivity of ICD-10 coding abstraction was 60% (95%-CI 57-63) for sepsis; 35% (95%-CI 31-39) for sepsi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37342815"}, {"offsetInBeginSection": 650, "offsetInEndSection": 976, "text": "s: We analyzed 998 hospital admissions of children with blood culture-proven sepsis. The sensitivity of ICD-10 coding abstraction was 60% (95%-CI 57-63) for sepsis; 35% (95%-CI 31-39) for sepsis with organ dysfunction, using an explicit abstraction strategy; and 65% (95%-CI 61-69) using an implicit abstraction strategy. For ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37342815"}, {"offsetInBeginSection": 650, "offsetInEndSection": 1063, "text": "s: We analyzed 998 hospital admissions of children with blood culture-proven sepsis. The sensitivity of ICD-10 coding abstraction was 60% (95%-CI 57-63) for sepsis; 35% (95%-CI 31-39) for sepsis with organ dysfunction, using an explicit abstraction strategy; and 65% (95%-CI 61-69) using an implicit abstraction strategy. For septic shock, the sensitivity of ICD-10 coding abstraction was 43% (95%-CI 37-50). Agre", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37342815"}, {"offsetInBeginSection": 507, "offsetInEndSection": 974, "text": "compared the agreement of validated study data on sepsis criteria with ICD-10 coding abstraction obtained at the participating hospitals.Results: We analyzed 998 hospital admissions of children with blood culture-proven sepsis. The sensitivity of ICD-10 coding abstraction was 60% (95%-CI 57-63) for sepsis; 35% (95%-CI 31-39) for sepsis with organ dysfunction, using an explicit abstraction strategy; and 65% (95%-CI 61-69) using an implicit abstraction strategy. Fo", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37342815"}, {"offsetInBeginSection": 1064, "offsetInEndSection": 1669, "text": "ment of ICD-10 coding abstraction with validated study data varied by the underlying infection type and disease severity (p\u2009<\u20090.05). The estimated national incidence of sepsis, inferred from ICD-10 coding abstraction, was 12.5 per 100,000 children (95%-CI 11.7-13.5) and 21.0 per 100,000 children (95%-CI 19.8-22.2) using validated study data.Conclusions: In this population-based study, we found a poor representation of sepsis and sepsis with organ dysfunction by ICD-10 coding abstraction in children with blood culture-proven sepsis when compared against a prospective validated research dataset. Seps", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37342815"}, {"offsetInBeginSection": 1202, "offsetInEndSection": 1669, "text": "stimated national incidence of sepsis, inferred from ICD-10 coding abstraction, was 12.5 per 100,000 children (95%-CI 11.7-13.5) and 21.0 per 100,000 children (95%-CI 19.8-22.2) using validated study data.Conclusions: In this population-based study, we found a poor representation of sepsis and sepsis with organ dysfunction by ICD-10 coding abstraction in children with blood culture-proven sepsis when compared against a prospective validated research dataset. Seps", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37342815"}, {"offsetInBeginSection": 1202, "offsetInEndSection": 1789, "text": "stimated national incidence of sepsis, inferred from ICD-10 coding abstraction, was 12.5 per 100,000 children (95%-CI 11.7-13.5) and 21.0 per 100,000 children (95%-CI 19.8-22.2) using validated study data.Conclusions: In this population-based study, we found a poor representation of sepsis and sepsis with organ dysfunction by ICD-10 coding abstraction in children with blood culture-proven sepsis when compared against a prospective validated research dataset. Sepsis estimates in children based on ICD-10 coding may thus severely underestimate the true prevalence of the disease.Suppl", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37342815"}]}
+{"question_id": "65cf96ce1930410b1300000a", "question": "Is Amivantamab used for non\u2013small-cell lung cancer?", "answer": "Yes. Amivantamab is approved for treatment of patients with Non-Small Cell Lung Cancer with EGFR Exon 20 insertion mutations.", "relevant_passage_ids": ["36756143", "36868177", "35652704", "35616682", "36652175", "37284196", "36979929", "37022784", "32747419", "32414908", "34913823", "34292533", "35983925", "37880647", "35597172", "38012986", "37878779", "34911336", "38001589", "37938161", "37882460", "35785671", "34083225", "36481319", "37870976", "34284994", "37800882", "34880698", "36246734", "34565792", "35899447", "34339292", "36198244", "35963523", "37589131", "35667083", "37776107", "36916182", "35599009", "37879444", "37856922", "35882108"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 775, "text": "Epidermal growth factor receptor (EGFR) mutation is one of the key oncogenic mutations in non-small-cell lung cancer with adenocarcinoma histology. Exon 19 deletions and exon 21 L858R substitutions account for 90%, while EGFR exon 20 insertions constitute 4-10% of EGFR mutations and are the third most prevalent activating EGFR mutations. EGFR exon 20 insertions are associated with decreased sensitivity to EGFR tyrosine kinase inhibitors and, until recently, effective targeted therapy against these tumours remained an unmet clinical need and chemotherapy was the only treatment of choice available. The approval of amivantamab and mobocertinib for patients who have progressed after chemotherapy represents an important step forward in the management of these patients. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36756143"}, {"offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "BACKGROUND: Amivantamab, a fully humanized EGFR-MET bispecific antibody, has antitumor activity in diverse EGFR- and MET-driven non-small cell lung cancer (NSCLC) and a safety profile consistent with associated on-target activities. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36868177"}, {"offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Targeting EGFR Exon 20 Insertion Mutation in Non-small cell Lung Cancer: Amivantamab and Mobocertinib.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35652704"}, {"offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "OBJECTIVE: To evaluate clinical data regarding the use of amivantamab and mobocertinib for epidermal growth factor receptor (EGFR) exon 20 insertion mutation non-small cell lung cancer (NSCLC) and assess their potential impact on the care of patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35652704"}, {"offsetInBeginSection": 1567, "offsetInEndSection": 1773, "text": "CONCLUSION: Amivantamab and mobocertinib target an uncommon NSCLC mutation that has historically marked a poor prognosis because of innate resistance to previously approved EGFR tyrosine kinase inhibitors. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35652704"}, {"offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Amivantamab: A New Hope in Targeting Non-small Cell Lung Cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35616682"}, {"offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "BACKGROUND: Amivantamab was approved on May 21st, 2021, by United States food and drug administration with the brand name Rybervant, used particularly for adult patients with exon20 insertion of epithelial growth factor receptor with locally advanced metastatic non-small cell lung cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35616682"}, {"offsetInBeginSection": 864, "offsetInEndSection": 1089, "text": "CONCLUSION: Amivantamab is a new bispecific antibody that targets non-small cell lung cancer through two different pathways, i.e., by binding to epithelial growth factor receptor and mesenchymal epithelial transition factor. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35616682"}, {"offsetInBeginSection": 290, "offsetInEndSection": 511, "text": " Amivantamab, an EGFR and MET bispecific antibody, demonstrated efficacy and tolerability in patients with advanced EGFR-mutated NSCLC with Exon20ins following platinum-based therapy in CHRYSALIS (NCT02609776; Cohort D+).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36652175"}, {"offsetInBeginSection": 426, "offsetInEndSection": 617, "text": "US Food and Drug Administration has approved mobocertinib and amivantamab for targeting tumors with this aberration, but the number of comprehensive studies on ex20 ins/dup NSCLC is limited. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37284196"}, {"offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Amivantamab-Vmjw: A Novel Treatment for Patients with NSCLC Harboring EGFR Exon 20 Insertion Mutation after Progression on Platinum-Based Chemotherapy.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36979929"}, {"offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "OBJECTIVE: This study is a comprehensive review of the clinical pharmacology, pharmacokinetics, efficacy, safety, and clinical applicability of amivantamab-vmjw for metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion (exon20ins) mutation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36979929"}, {"offsetInBeginSection": 1105, "offsetInEndSection": 1337, "text": "CONCLUSION: The FDA approval of amivantamab-vmjw, the first bispecific antibody to target the exon20ins mutation, represents an important advancement in the treatment of patients with NSCLC with limited effective treatment options. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36979929"}, {"offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "FDA Approval Summary: Amivantamab for the Treatment of Patients with Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37022784"}, {"offsetInBeginSection": 0, "offsetInEndSection": 422, "text": "The FDA granted accelerated approval for amivantamab-vmjw (hereafter referred to as amivantamab), a bispecific antibody directed against EGFR and mesenchymal-epithelial transition receptor, on May 21, 2021, for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37022784"}, {"offsetInBeginSection": 1330, "offsetInEndSection": 1479, "text": "The approval of amivantamab was the first approval of a targeted therapy for patients with advanced NSCLC harboring EGFR exon 20 insertion mutations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37022784"}, {"offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Amivantamab compared with real-world therapies in patients with advanced non-small cell lung cancer ", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37938161"}, {"offsetInBeginSection": 4, "offsetInEndSection": 130, "text": " We assessed relative efficacy and safety of amivantamab versus mobocertinib in patients with non-small-cell lung cancer with ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37882460"}, {"offsetInBeginSection": 0, "offsetInEndSection": 699, "text": "BACKGROUND: Amivantamab was approved on May 21st, 2021, by United States food and drug administration with the brand name Rybervant, used particularly for adult patients with exon20 insertion of epithelial growth factor receptor with locally advanced metastatic non-small cell lung cancer.OBJECTIVE: In this review, we explain the non-small cell lung cancer and molecular distinctions between non-small cell lung cancer and small cell lung cancer. We also conclude numerous components of non-small cell lung cancer, which include signs and symptoms of Amivantamab in inhibiting the cancer cell growth, various clinical trials on Amivantamab, adverse effects, and the contraindications of Amivantamab", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35616682"}, {"offsetInBeginSection": 0, "offsetInEndSection": 446, "text": "BACKGROUND: Amivantamab was approved on May 21st, 2021, by United States food and drug administration with the brand name Rybervant, used particularly for adult patients with exon20 insertion of epithelial growth factor receptor with locally advanced metastatic non-small cell lung cancer.OBJECTIVE: In this review, we explain the non-small cell lung cancer and molecular distinctions between non-small cell lung cancer and small cell lung cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35616682"}, {"offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Amivantamab plus Lazertinib Is Efficacious in Non-Small Cell Lung Cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37800882"}, {"offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Amivantamab plus lazertinib shows clinical efficacy in osimertinib-relapsed non-small cell lung cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37800882"}, {"offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Amivantamab for the treatment of EGFR exon 20 insertion mutant non-small cell lung cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34913823"}, {"offsetInBeginSection": 0, "offsetInEndSection": 447, "text": "BACKGROUND: Amivantamab was approved on May 21st, 2021, by United States food and drug administration with the brand name Rybervant, used particularly for adult patients with exon20 insertion of epithelial growth factor receptor with locally advanced metastatic non-small cell lung cancer.OBJECTIVE: In this review, we explain the non-small cell lung cancer and molecular distinctions between non-small cell lung cancer and small cell lung cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35616682"}, {"offsetInBeginSection": 0, "offsetInEndSection": 348, "text": "The U.S. Food and Drug Administration (FDA) first approved amivantamab, a monoclonal epidermal growth factor receptor (EGFR)-mesenchymal--epithelial transition factor (MET) bispecific antibody, in May 2021, to treat adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with an insertion mutation in exon 20 of EGFR.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35983925"}, {"offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Amivantamab: a monoclonal EGFR-MET bispecific antibody for EGFR exon 20 insertion in non-small cell lung cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35983925"}, {"offsetInBeginSection": 0, "offsetInEndSection": 525, "text": "INTRODUCTION: Amivantamab is a monoclonal bispecific anti-EGFR-MET antibody that is the first targeted therapy to be approved for non-small cell lung cancer (NSCLC) patients harboring EGFR exon 20 insertion mutations following progression on chemotherapy, marking a watershed moment for a class of mutations which is generally associated with poor outcomes.AREAS COVERED: In this article, we outline the drug profile of amivantamab compared with EGFR kinase inhibitors under evaluation in EGFR exon 20 insertion mutant NSCLC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34913823"}, {"offsetInBeginSection": 349, "offsetInEndSection": 442, "text": "The approval of amivantamab represents a targeted therapy for this subtype of advanced NSCLC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35983925"}, {"offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "Amivantamab (amivantamab-vmjw; Rybrevant\u2122), a bispecific monoclonal antibody targeting epidermal growth factor receptor (EGFR) and mesenchymal epithelial transition factor (MET), is being developed by Janssen Biotech for the treatment of non-small cell lung cancer (NSCLC).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34292533"}, {"offsetInBeginSection": 587, "offsetInEndSection": 800, "text": "In this article, we summarize the development of therapeutic drugs for NSCLC, discuss the mechanism of action of amivantamab, review data from clinical trials with amivantamab and suggest future lines of research.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35983925"}, {"offsetInBeginSection": 322, "offsetInEndSection": 607, "text": "Amivantamab, a fully human bispecific antibody targeting EGFR and MET, is approved in the United States and other countries for the treatment of patients with advanced NSCLC with EGFR exon 20 insertion mutations, for whom disease has progressed on or after platinum-based chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36481319"}, {"offsetInBeginSection": 274, "offsetInEndSection": 532, "text": "On 21 May 2021, amivantamab received its first approval in the USA for the treatment of adult patients with locally advanced or metastatic NSCLC harbouring EGFR Exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34292533"}, {"offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "Amivantamab (amivantamab-vmjw; Rybrevant\u2122), a bispecific monoclonal antibody targeting epidermal growth factor receptor (EGFR) and mesenchymal epithelial transition factor (MET), is being developed by Janssen Biotech for the treatment of non-small cell lung cancer (NSCLC). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34292533"}, {"offsetInBeginSection": 129, "offsetInEndSection": 920, "text": "Between 80-85% of all lung cancers are non-small cell lung cancer (NSCLC), and of these, between 2-3% have an EGFR exon 20 insertion, which is associated with increased cell proliferation, metastasis, and a lack of response to chemotherapy and epidermal growth factor receptor (EGFR) inhibitors. Until this year, there were no available targeted therapies for advanced NSCLC with this genetic subtype. However, in May 2021, the US Food and Drug Administration (FDA) granted accelerated approval for amivantamab-vmjw (Rybrevant\u00ae), a bispecific monoclonal antibody, targeting activating and resistant EGFR and MET mutations and amplifications. This FDA approval was for adult patients with locally advanced metastatic NSCLC, with disease progression on or following platinum-based chemotherapy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34565792"}, {"offsetInBeginSection": 430, "offsetInEndSection": 662, "text": "In May 2021, the US Federal Drug Administration (FDA) provided accelerated approval to amivantamab (Rybrevant) in adults with locally advanced or metastatic NSCLC with EGFR exon20ins after treatment with platinum-based chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37880647"}, {"offsetInBeginSection": 0, "offsetInEndSection": 277, "text": "BACKGROUND: Amivantamab was approved on May 21st, 2021, by United States food and drug administration with the brand name Rybervant, used particularly for adult patients with exon20 insertion of epithelial growth factor receptor with locally advanced metastatic non-small cell ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35616682"}, {"offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Amivantamab is the only FDA-approved therapy for non-small cell lung cancer (NSCLC) with EGFR exon 20 insertions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34284994"}, {"offsetInBeginSection": 35, "offsetInEndSection": 188, "text": "ALIS study, amivantamab showed durable responses and manageable safety in patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal g", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35597172"}, {"offsetInBeginSection": 17, "offsetInEndSection": 502, "text": "ntamab-vmjw (amivantamab) is a bispecific EGFR/MET antibody approved for patients with advanced non-small cell lung cancer (NSCLC) with EGFR Exon 20 insertion mutations, after prior therapy. However, the benefits and safety of amivantamab in other EGFR-mutation lung cancer, with or without osimertinib, and with concurrent radiation therapy, are less known.METHODS: We queried the MD Anderson Lung Cancer GEMINI, Fred Hutchinson Cancer Research Center, University of California Davis ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38012986"}, {"offsetInBeginSection": 21, "offsetInEndSection": 698, "text": "e clinical data regarding the use of amivantamab and mobocertinib for epidermal growth factor receptor (EGFR) exon 20 insertion mutation non-small cell lung cancer (NSCLC) and assess their potential impact on the care of patients.DATA SOURCES: A comprehensive literature search of PubMed and Clinicaltrials.gov was conducted using the terms amivantamab, Rybrevant, JNJ-61186372, mobocertinib, Exkivity, TAK-788.STUDY SELECTION AND DATA EXTRACTION: Relevant English-language clinical trials were evaluated.DATA SYNTHESIS: Amivantamab and mobocertinib were Food and Drug Administration (FDA) approved based on phases 1 and 2 studies. Amivantamab demonstrated an overall response ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35652704"}, {"offsetInBeginSection": 27, "offsetInEndSection": 150, "text": "fficacy and safety of amivantamab versus mobocertinib in patients with non-small-cell lung cancer with EGFR exon 20 inserti", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37882460"}, {"offsetInBeginSection": 0, "offsetInEndSection": 380, "text": "BACKGROUND: In the single-arm CHRYSALIS trial, advanced non-small cell lung cancer patients harboring epidermal growth factor receptor (EGFR) exon 20 insertion (Exon 20ins) showed durable responses to amivantamab, an EGFR-MET bispecific antibody targeting tumors with EGFR Exon 20ins. This study compared the effectiveness of amivantamab to real-world systemic anti-cancer therapi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37938161"}, {"offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "BACKGROUND: Amivantamab-vmjw (amivantamab) is a bispecific EGFR/MET antibody approved for patients with advanced non-small cell lung cancer (NSCLC) with EGFR Exon 20 insertion mutations, after prior therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38012986"}, {"offsetInBeginSection": 555, "offsetInEndSection": 802, "text": "In May 2021, the Federal Drug Administration (FDA) provided accelerated approval to amivantamab (Rybrevant) in adults with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations after treatment with platinum-based chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34880698"}, {"offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "BACKGROUND: Amivantamab-vmjw (amivantamab) is a bispecific EGFR/MET antibody approved for patients with advanced non-small cell lung cancer (NSCLC) with EGFR Exon 20 insertion mutations, after pr", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38012986"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "INTRODUCTION: Amivantamab is a monoclonal bispecific anti-EGFR-MET antibody that is the first targeted therapy to be approved for non-small cell lung cancer (NSCLC) patien", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34913823"}, {"offsetInBeginSection": 5, "offsetInEndSection": 155, "text": "ROUND: Amivantamab-vmjw (amivantamab) is a bispecific EGFR/MET antibody approved for patients with advanced non-small cell lung cancer (NSCLC) with EG", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38012986"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "BACKGROUND: Amivantamab has been approved for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37870976"}, {"offsetInBeginSection": 10, "offsetInEndSection": 160, "text": ": Amivantamab, a fully humanized EGFR-MET bispecific antibody, has antitumor activity in diverse EGFR- and MET-driven non-small cell lung cancer (NSCL", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36868177"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "The FDA granted accelerated approval to amivantamab, the first treatment for patients with non-small cell lung cancer whose tumors have EGFR exon 20 i", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34083225"}, {"offsetInBeginSection": 88, "offsetInEndSection": 238, "text": "b, an EGFR-MET bispecific antibody, as a potential contender as a standard treatment for EGFR-mutant non-small cell lung cancer. Amivantamab paired wi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37878779"}, {"offsetInBeginSection": 0, "offsetInEndSection": 368, "text": "Amivantamab is a bispecific antibody that recognizes epidermal growth factor receptor (EGFR) and MET proto-oncogene (MET). In May 2021, the Food and Drug Administration gave an accelerated approval of amivantamab for the treatment of non-small cell lung cancer (NSCLC) patients with EGFR exon 20 insertions (Exon20ins) who progressed after platinum-based chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36246734"}, {"offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "The FDA granted accelerated approval to amivantamab, the first treatment for patients with non-small cell lung cancer whose tumors have EGFR exon 20 insertion mutations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34083225"}, {"offsetInBeginSection": 12, "offsetInEndSection": 160, "text": "Amivantamab has been approved for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37870976"}, {"offsetInBeginSection": 12, "offsetInEndSection": 265, "text": "Amivantamab plus carboplatin-pemetrexed (chemotherapy) with and without lazertinib demonstrated antitumor activity in patients with refractory epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) in phase I studies", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37879444"}, {"offsetInBeginSection": 11, "offsetInEndSection": 295, "text": "This study is a comprehensive review of the clinical pharmacology, pharmacokinetics, efficacy, safety, and clinical applicability of amivantamab-vmjw for metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion (exon20ins) mutation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36979929"}, {"offsetInBeginSection": 12, "offsetInEndSection": 231, "text": "Amivantamab, a fully humanized EGFR-MET bispecific antibody, has antitumor activity in diverse EGFR- and MET-driven non-small cell lung cancer (NSCLC) and a safety profile consistent with associated on-target activities", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36868177"}, {"offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "OBJECTIVE: To evaluate clinical data regarding the use of amivantamab and mobocertinib for epidermal growth factor receptor (EGFR) exon 20 insertion mutation non-small cell lung cancer (NSCLC) and assess their potential impact on the care of patients", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35652704"}, {"offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "BACKGROUND: Amivantamab has been approved for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertions who have had disease progression during or after platinum-based chemotherapy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37870976"}, {"offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "BACKGROUND: In the single-arm CHRYSALIS study, amivantamab showed durable responses and manageable safety in patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations (ex20ins) who progressed on prior platinum-based chemotherapy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35597172"}, {"offsetInBeginSection": 0, "offsetInEndSection": 356, "text": "INTRODUCTION: Amivantamab is a monoclonal bispecific anti-EGFR-MET antibody that is the first targeted therapy to be approved for non-small cell lung cancer (NSCLC) patients harboring EGFR exon 20 insertion mutations following progression on chemotherapy, marking a watershed moment for a class of mutations which is generally associated with poor outcomes", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34913823"}, {"offsetInBeginSection": 162, "offsetInEndSection": 532, "text": "In the ongoing CHRYSALIS study (ClinicalTrials.gov Identifier: NCT02609776), amivantamab demonstrated antitumor activity in patients with non-small cell lung cancer harboring EGFR exon 20 insertion mutations (ex20ins) that progressed on or after platinum-based chemotherapy, a population in which amivantamab use has been approved by the US Food and Drug Administration.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35963523"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1047, "text": "BACKGROUND: Amivantamab was approved on May 21st, 2021, by United States food and drug administration with the brand name Rybervant, used particularly for adult patients with exon20 insertion of epithelial growth factor receptor with locally advanced metastatic non-small cell lung cancer.OBJECTIVE: In this review, we explain the non-small cell lung cancer and molecular distinctions between non-small cell lung cancer and small cell lung cancer. We also conclude numerous components of non-small cell lung cancer, which include signs and symptoms of Amivantamab in inhibiting the cancer cell growth, various clinical trials on Amivantamab, adverse effects, and the contraindications of Amivantamab.METHODS: A comprehensive literature search was conducted in the relevant databases like ScienceDirect, PubMed, ResearchGate, and Google Scholar to identify studies.CONCLUSION: Amivantamab is a new bispecific antibody that targets non-small cell lung cancer through two different pathways, i.e., by binding to epithelial growth factor receptor and ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35616682"}, {"offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "BACKGROUND: Amivantamab was approved on May 21st, 2021, by United States food and drug administration with the brand name Rybervant, used particularly for adult patients with exon20 insertion of epithelial growth factor receptor with locally advanced metastatic non-small cell lung cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35616682"}, {"offsetInBeginSection": 0, "offsetInEndSection": 524, "text": "INTRODUCTION: Amivantamab is a monoclonal bispecific anti-EGFR-MET antibody that is the first targeted therapy to be approved for non-small cell lung cancer (NSCLC) patients harboring EGFR exon 20 insertion mutations following progression on chemotherapy, marking a watershed moment for a class of mutations which is generally associated with poor outcomes.AREAS COVERED: In this article, we outline the drug profile of amivantamab compared with EGFR kinase inhibitors under evaluation in EGFR exon 20 insertion mutant NSCLC", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34913823"}, {"offsetInBeginSection": 0, "offsetInEndSection": 442, "text": "The U.S. Food and Drug Administration (FDA) first approved amivantamab, a monoclonal epidermal growth factor receptor (EGFR)-mesenchymal--epithelial transition factor (MET) bispecific antibody, in May 2021, to treat adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with an insertion mutation in exon 20 of EGFR. The approval of amivantamab represents a targeted therapy for this subtype of advanced NSCLC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35983925"}, {"offsetInBeginSection": 0, "offsetInEndSection": 672, "text": "INTRODUCTION: Amivantamab is a monoclonal bispecific anti-EGFR-MET antibody that is the first targeted therapy to be approved for non-small cell lung cancer (NSCLC) patients harboring EGFR exon 20 insertion mutations following progression on chemotherapy, marking a watershed moment for a class of mutations which is generally associated with poor outcomes.AREAS COVERED: In this article, we outline the drug profile of amivantamab compared with EGFR kinase inhibitors under evaluation in EGFR exon 20 insertion mutant NSCLC. We also review the efficacy and safety data reported from the CHRYSALIS phase I trial, which forms the basis of the recent approval of amivantamab", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34913823"}, {"offsetInBeginSection": 0, "offsetInEndSection": 586, "text": "The U.S. Food and Drug Administration (FDA) first approved amivantamab, a monoclonal epidermal growth factor receptor (EGFR)-mesenchymal--epithelial transition factor (MET) bispecific antibody, in May 2021, to treat adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with an insertion mutation in exon 20 of EGFR. The approval of amivantamab represents a targeted therapy for this subtype of advanced NSCLC. In contrast to other drugs that inhibit the tyrosine kinase activity in the protein, EGFR, amivantamab has efficacy in inhibiting EGFR and MET.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35983925"}, {"offsetInBeginSection": 0, "offsetInEndSection": 431, "text": "OBJECTIVE: To evaluate clinical data regarding the use of amivantamab and mobocertinib for epidermal growth factor receptor (EGFR) exon 20 insertion mutation non-small cell lung cancer (NSCLC) and assess their potential impact on the care of patients.DATA SOURCES: A comprehensive literature search of PubMed and Clinicaltrials.gov was conducted using the terms amivantamab, Rybrevant, JNJ-61186372, mobocertinib, Exkivity, TAK-788", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35652704"}, {"offsetInBeginSection": 40, "offsetInEndSection": 135, "text": "amivantamab, the first treatment for patients with non-small cell lung cancer whose tumors have", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34083225"}, {"offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "BACKGROUND: Amivantamab has been approved for the treatment of patients with advanced non-small-cell lung cancer ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37870976"}, {"offsetInBeginSection": 201, "offsetInEndSection": 368, "text": "amivantamab for the treatment of non-small cell lung cancer (NSCLC) patients with EGFR exon 20 insertions (Exon20ins) who progressed after platinum-based chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36246734"}, {"offsetInBeginSection": 44, "offsetInEndSection": 442, "text": "first approved amivantamab, a monoclonal epidermal growth factor receptor (EGFR)-mesenchymal--epithelial transition factor (MET) bispecific antibody, in May 2021, to treat adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with an insertion mutation in exon 20 of EGFR. The approval of amivantamab represents a targeted therapy for this subtype of advanced NSCLC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35983925"}, {"offsetInBeginSection": 0, "offsetInEndSection": 421, "text": "The FDA granted accelerated approval for amivantamab-vmjw (hereafter referred to as amivantamab), a bispecific antibody directed against EGFR and mesenchymal-epithelial transition receptor, on May 21, 2021, for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37022784"}, {"offsetInBeginSection": 0, "offsetInEndSection": 401, "text": "In 2021, the US Food and Drug Administration (FDA) approved two drugs targeting exon 20 directly: amivantamab and mobocertinib, under the accelerated approval pathway, for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, whose disease has progressed on or after platinum-based chemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35785671"}, {"offsetInBeginSection": 549, "offsetInEndSection": 1010, "text": "Among the different drugs under clinical investigation, both amivantamab and mobocertinib have received regulatory approval in the United States, by the Food and Drugs Administration (FDA), while amivantamab has been recently approved also in Europe, for the clinical treatment of advanced NSCLC patients harboring EGFRex20ins who failed at least one prior line of systemic therapy, representing a major breakthrough in lung cancer treatment over the last year.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35882108"}]}
+{"question_id": "65f7754ec4010b4d7800002b", "question": "Do very elderly stage III colorectal cancer patients present clinical benefit from oxaliplatin-based adjuvant chemotherapy?", "answer": "Yes, adjuvant FOLFOX4 maintains its efficacy and safety ratio in selected elderly patients with colorectal cancer", "relevant_passage_ids": ["37498507", "24071534", "16943526", "28434884", "23204187", "29861156", "25731317", "36252550", "22665536", "34230158", "19563521", "23512326", "23733765", "22915656", "36115817", "35303773", "32823998", "20967408", "37748112", "35146948", "29873684", "21810511", "18621635", "28341242", "37881011", "19111473", "26487941", "26382962", "19729318", "25986478", "19942166", "25954089", "33744715", "29584752", "31906959", "21831168", "36229957", "29698932", "25595934"], "type": "yesno", "snippets": [{"offsetInBeginSection": 807, "offsetInEndSection": 1083, "text": "elderly patients with localized CRC should undergo standard cancer resection, preferably laparoscopically. The indication for adjuvant chemotherapy (CT) should be considered based on the potential benefit, the risk of recurrence, the life expectancy and patient comorbidities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37498507"}, {"offsetInBeginSection": 1476, "offsetInEndSection": 1575, "text": "FOLFOX4 maintains its efficacy and safety ratio in selected elderly patients with colorectal cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16943526"}, {"offsetInBeginSection": 1590, "offsetInEndSection": 1695, "text": "Older patients deemed eligible for chemotherapy did not experience significant changes in living situatio", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24071534"}, {"offsetInBeginSection": 173, "offsetInEndSection": 654, "text": " The incidence and severity of toxicity might be greater among older patients who might also derive less benefit from oxaliplatin. We evaluated the association between adjuvant oxaliplatin-based chemotherapy and neurotoxicity outcomes in an elderly cohort of patients.PATIENTS AND METHODS: A population-based cohort of patients aged > 65 years with stage II and III colorectal cancer treated with adjuvant therapy in Ontario, Canada was identified using the Ontario Cancer Registry", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28434884"}, {"offsetInBeginSection": 303, "offsetInEndSection": 654, "text": " We evaluated the association between adjuvant oxaliplatin-based chemotherapy and neurotoxicity outcomes in an elderly cohort of patients.PATIENTS AND METHODS: A population-based cohort of patients aged > 65 years with stage II and III colorectal cancer treated with adjuvant therapy in Ontario, Canada was identified using the Ontario Cancer Registry", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28434884"}, {"offsetInBeginSection": 0, "offsetInEndSection": 440, "text": "BACKGROUND: The addition of oxaliplatin to adjuvant treatment regimens for colorectal cancer has been shown to improve overall survival at the expense of increased toxicity. The incidence and severity of toxicity might be greater among older patients who might also derive less benefit from oxaliplatin. We evaluated the association between adjuvant oxaliplatin-based chemotherapy and neurotoxicity outcomes in an elderly cohort of patients", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28434884"}, {"offsetInBeginSection": 1383, "offsetInEndSection": 1621, "text": "The Oxa-based adjuvant chemotherapy was tolerated equally well in Stage II and III colorectal cancer patients with or without perforation. Further studies are needed to compare the effect of oxaliplatin with other adjuvant chemotherapies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25731317"}, {"offsetInBeginSection": 170, "offsetInEndSection": 339, "text": " We aimed to clarify the efficacy and complications of adjuvant oxaliplatin and fluoropyrimidine chemotherapy for patients 70 years and older with stage III colon cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29861156"}, {"offsetInBeginSection": 170, "offsetInEndSection": 473, "text": " We aimed to clarify the efficacy and complications of adjuvant oxaliplatin and fluoropyrimidine chemotherapy for patients 70 years and older with stage III colon cancer.PATIENTS AND METHODS: All patients with stage III colon adenocarcinoma were identified from an Australian cancer registry (2006-2013)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29861156"}, {"offsetInBeginSection": 0, "offsetInEndSection": 339, "text": "BACKGROUND: Colon cancer is common in the elderly, but owing to under representation in clinical trials, the benefit of standard therapies is uncertain in this age group. We aimed to clarify the efficacy and complications of adjuvant oxaliplatin and fluoropyrimidine chemotherapy for patients 70 years and older with stage III colon cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29861156"}, {"offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "PURPOSE: While adjuvant therapy with capecitabine and oxaliplatin (CAPOX) has been proven to be effective in stage III colon cancer, capecitabine monotherapy (CapMono) might be equally effective in elderly patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37748112"}, {"offsetInBeginSection": 1199, "offsetInEndSection": 1370, "text": "CSS and RFS were also similar between the \u226570 and <70 years old patients with stage III CRC.CONCLUSIONS: Adjuvant CAPOX therapy was tolerable in elderly Japanese patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36252550"}, {"offsetInBeginSection": 1426, "offsetInEndSection": 1802, "text": "Formal interaction testing confirmed that the effect of oxaliplatin on neuropathy was more pronounced in patients aged\u00a0\u2265 70 years compared with patients aged 66 to 69 years (P\u00a0= .03).CONCLUSION: Colorectal cancer patients aged\u00a0\u2265 70 years at the time of cancer diagnosis who are subsequently treated with oxaliplatin have a significant risk of developing peripheral neuropathy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28434884"}, {"offsetInBeginSection": 1115, "offsetInEndSection": 1375, "text": "No significant difference in the effect of ACT could be observed between age groups (interaction: cancer-specific death HR\u00a0=\u00a01.7948, p\u00a0=\u00a00.1079; death of other cause HR\u00a0=\u00a00.7384, p\u00a0=\u00a00.6705).CONCLUSION: ACT was an independent positive prognostic factor for OS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35146948"}, {"offsetInBeginSection": 1084, "offsetInEndSection": 1590, "text": "uire hospital admission (67.0% vs. 53.5%). The addition of oxaliplatin provided an overall survival benefit for patients\u00a0< 70 years (hazard ratio, 0.44; 95% confidence interval, 0.3-0.6; P\u00a0<\u00a0.0001) and for patients\u00a0\u2265 70 years (hazard ratio, 0.64; 95% confidence interval, 0.5-0.9; P\u00a0= .005).CONCLUSIONS: Despite a modestly increased rate of hospital admission and early chemotherapy cessation, we demonstrate a persistent survival benefit for the addition of oxaliplatin to a fluoropyrimidine as adjuvant t", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29861156"}, {"offsetInBeginSection": 292, "offsetInEndSection": 392, "text": "tal cancer. The use of oxaliplatin as adjuvant treatment in elderly patients with colon cancer is co", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29873684"}, {"offsetInBeginSection": 354, "offsetInEndSection": 466, "text": "A critical issue, which needs to be specifically addressed, is the role of adjuvant therapy in elderly patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21810511"}, {"offsetInBeginSection": 1281, "offsetInEndSection": 1524, "text": ".75 versus 0.80, P = 0.009).CONCLUSIONS: Adjuvant oxaliplatin, fluorouracil and leucovorin chemotherapy resulted in similar efficacy without significant increase in toxicity in older patients aged \u226565 when compared with younger patients with c", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23204187"}, {"offsetInBeginSection": 1127, "offsetInEndSection": 1646, "text": "The addition of oxaliplatin provided an overall survival benefit for patients\u00a0< 70 years (hazard ratio, 0.44; 95% confidence interval, 0.3-0.6; P\u00a0<\u00a0.0001) and for patients\u00a0\u2265 70 years (hazard ratio, 0.64; 95% confidence interval, 0.5-0.9; P\u00a0= .005).CONCLUSIONS: Despite a modestly increased rate of hospital admission and early chemotherapy cessation, we demonstrate a persistent survival benefit for the addition of oxaliplatin to a fluoropyrimidine as adjuvant treatment for stage III colon cancer in elderly patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29861156"}, {"offsetInBeginSection": 1201, "offsetInEndSection": 1637, "text": "No significant interactions by age were detected with oral fluoropyrimidine therapy compared with IV FU; noninferiority was supported in both age populations.CONCLUSION: Patients age \u2265 70 years seemed to experience reduced benefit from adding oxaliplatin to fluoropyrimidines in the adjuvant setting, although statistically, there was not a significant effect modification by age, whereas oral fluoropyrimidines retained their efficacy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23733765"}, {"offsetInBeginSection": 0, "offsetInEndSection": 393, "text": "PURPOSE: Few patients 75 years of age and older participate in clinical trials, thus whether adjuvant chemotherapy for stage III colon cancer (CC) benefits this group is unknown.METHODS: A total of 5,489 patients \u2265 75 years of age with resected stage III CC, diagnosed between 2004 and 2007, were selected from four data sets containing demographic, stage, treatment, and survival information.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22665536"}, {"offsetInBeginSection": 1168, "offsetInEndSection": 1566, "text": "Elderly patients received a lower relative dose intensity of oxaliplatin (0.76 versus 0.79) and 5-fluorouracil (0.75 versus 0.80, P = 0.009).CONCLUSIONS: Adjuvant oxaliplatin, fluorouracil and leucovorin chemotherapy resulted in similar efficacy without significant increase in toxicity in older patients aged \u226565 when compared with younger patients with curatively resected Stage III colon cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23204187"}, {"offsetInBeginSection": 971, "offsetInEndSection": 1166, "text": "Chemotherapy receipt was associated with a survival benefit of comparable magnitude to clinical trials results (SEER-Medicare PS-matched mortality, hazard ratio [HR], 0.60; 95% CI, 0.53 to 0.68).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22665536"}, {"offsetInBeginSection": 1617, "offsetInEndSection": 1898, "text": "The STEPP analysis revealed improved hazard ratios for DFS in patients aged 40-70\u2009years compared with elderly patients treated with oxaliplatin.Conclusion: The addition of oxaliplatin significantly improved DFS and OS in younger patients aged <60\u2009years with advanced rectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29873684"}, {"offsetInBeginSection": 1167, "offsetInEndSection": 1437, "text": "The incremental benefit of oxaliplatin over non-oxaliplatin-containing regimens was also of similar magnitude to clinical trial results (SEER-Medicare, HR, 0.84; 95% CI, 0.69 to 1.04; NYSCR-Medicare, HR, 0.82, 95% CI, 0.51 to 1.33) in two of three examined data sources.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22665536"}, {"offsetInBeginSection": 9, "offsetInEndSection": 214, "text": "While adjuvant therapy with capecitabine and oxaliplatin (CAPOX) has been proven to be effective in stage III colon cancer, capecitabine monotherapy (CapMono) might be equally effective in elderly patients", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37748112"}, {"offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Adjuvant chemotherapy for resected stage III colon cancer is indicated for all patients, including elderly patients >70\u00a0years. In general, adjuvant oxaliplatin-fluoropyrimidine", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20967408"}, {"offsetInBeginSection": 207, "offsetInEndSection": 1084, "text": "is often incurable. Despite the progress achieved with the introduction of new cytotoxic agents, recurrence rates for patients with resected stage II/III disease remain > 20%. Therefore, a great deal of effort and resources have been put into improving early diagnosis and prevention tools as well as the efficacy of adjuvant treatment. Oxaliplatin-based chemotherapy is now considered the standard of care in node-positive colon cancer, but there remains controversy with regard to the indication and type of adjuvant treatment in patients with nodenegative disease. Oral fluoropyrimidines play a growing role in the management of colorectal cancer and can be currently considered an alternative to 5-fluorouracil. Numerous reports have suggested that elderly patients benefit equally from chemotherapy, but the growing numbers of octogenarian and nonagenarian patients in our", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18621635"}, {"offsetInBeginSection": 662, "offsetInEndSection": 812, "text": "otherapy (87 (43.5%) \u226565 years old versus 142 (74.3%) <65 years old). Older patients had similar clinico-pathological characteristics as younger patie", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23204187"}, {"offsetInBeginSection": 345, "offsetInEndSection": 552, "text": "Studies showed that combination of oxaliplatin and capecitabine demonstrated efficacy and safety on par with treatment involving various 5-FU/LV-based regimens in elderly patients as they are in younger ones", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25986478"}, {"offsetInBeginSection": 979, "offsetInEndSection": 1188, "text": "Patients younger than 70 years of age may derive greater disease-free survival and overall survival benefit from adjuvant chemotherapy (in combination with oxaliplatin) compared with those older than 70 years.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28341242"}, {"offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "BACKGROUND: Previous studies on oxaliplatin and fluoropyrimidines as adjuvant therapy in older patients with stage III colon cancer (CC) produced conflicting results.PATIENTS AND METHODS:", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33744715"}, {"offsetInBeginSection": 73, "offsetInEndSection": 393, "text": "resentation in clinical trials, the benefit of standard therapies is uncertain in this age group. We aimed to clarify the efficacy and complications of adjuvant oxaliplatin and fluoropyrimidine chemotherapy for patients 70 years and older with stage III colon cancer.PATIENTS AND METHODS: All patients with stage III col", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29861156"}, {"offsetInBeginSection": 59, "offsetInEndSection": 250, "text": "th the use of adjuvant chemotherapy and the use of oxaliplatin after curative resection in stage III colon cancer patients and assesses the effect of their use in three-year survival.METHODS:", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29584752"}, {"offsetInBeginSection": 0, "offsetInEndSection": 730, "text": "OBJECTIVE: Elderly patients derive similar benefits from 5-fluorouracil-based adjuvant chemotherapy in Stage III colon cancer; however, conflicting data exist regarding additional benefit from oxaliplatin, fluorouracil and leucovorin (FOLFOX) chemotherapy.METHODS: Single-center, retrospective analysis was performed to compare the safety and efficacy of adjuvant oxaliplatin, fluorouracil and leucovorin-4 chemotherapy in older patients (age \u226565 years) with younger patients with Stage III colon cancer after surgical resection.RESULTS: Among 391 patients with Stage III colon cancer, 229 patients received adjuvant oxaliplatin, fluorouracil and leucovorin chemotherapy (87 (43.5%) \u226565 years old versus 142 (74.3%) <65 years old)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23204187"}, {"offsetInBeginSection": 0, "offsetInEndSection": 473, "text": "BACKGROUND: Colon cancer is common in the elderly, but owing to under representation in clinical trials, the benefit of standard therapies is uncertain in this age group. We aimed to clarify the efficacy and complications of adjuvant oxaliplatin and fluoropyrimidine chemotherapy for patients 70 years and older with stage III colon cancer.PATIENTS AND METHODS: All patients with stage III colon adenocarcinoma were identified from an Australian cancer registry (2006-2013)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29861156"}, {"offsetInBeginSection": 0, "offsetInEndSection": 528, "text": "OBJECTIVE: Elderly patients derive similar benefits from 5-fluorouracil-based adjuvant chemotherapy in Stage III colon cancer; however, conflicting data exist regarding additional benefit from oxaliplatin, fluorouracil and leucovorin (FOLFOX) chemotherapy.METHODS: Single-center, retrospective analysis was performed to compare the safety and efficacy of adjuvant oxaliplatin, fluorouracil and leucovorin-4 chemotherapy in older patients (age \u226565 years) with younger patients with Stage III colon cancer after surgical resection", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23204187"}, {"offsetInBeginSection": 1315, "offsetInEndSection": 1571, "text": "SIONS: Adjuvant oxaliplatin, fluorouracil and leucovorin chemotherapy resulted in similar efficacy without significant increase in toxicity in older patients aged \u226565 when compared with younger patients with curatively resected Stage III colon cancer. Ther", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23204187"}, {"offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "OBJECTIVE: Elderly patients derive similar benefits from 5-fluorouracil-based adjuvant chemotherapy in Stage III colon cancer; however, conflicting data exist regarding additional benefit from oxaliplatin, fluorouracil and leucovorin (FOLFOX) chemotherapy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23204187"}, {"offsetInBeginSection": 258, "offsetInEndSection": 732, "text": "THODS: Single-center, retrospective analysis was performed to compare the safety and efficacy of adjuvant oxaliplatin, fluorouracil and leucovorin-4 chemotherapy in older patients (age \u226565 years) with younger patients with Stage III colon cancer after surgical resection.RESULTS: Among 391 patients with Stage III colon cancer, 229 patients received adjuvant oxaliplatin, fluorouracil and leucovorin chemotherapy (87 (43.5%) \u226565 years old versus 142 (74.3%) <65 years old). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23204187"}, {"offsetInBeginSection": 1537, "offsetInEndSection": 1683, "text": " 1.07 (0.66-1.74, P\u2009=\u20090.78) in older patients.CONCLUSIONS: The clinical effectiveness of adjuvant chemotherapy in older patients with stage III co", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31906959"}, {"offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "INTRODUCTION: Adjuvant chemotherapy improves the prognosis of patients with colorectal cancer (CRC) following radical resection. However, the safety and efficacy of oxaliplatin-based chemotherapeutic regimens for elderly patients remains to be elucidated. The aim of the present study ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36252550"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1328, "text": "The value of adjuvant chemotherapy in elderly patients has been the subject of many overviews, with opinions varying from \"not effective\", since randomized trials have not been performed, to \"as effective as in young individuals\", based upon many retrospective analyses of randomized trials that have included patients of all ages. In the absence of randomized trials performed specifically with elderly patients, retrospective analyses demonstrate that the influence on the time to tumour recurrence (TTR) may be the same as in young individuals, but that endpoints that include death for any reason, such as recurrence-free survival (RFS), disease-free survival (DFS), and overall survival (OS), are poorer in the elderly. This is particularly true if oxaliplatin has been part of the treatment. The need for adjuvant chemotherapy after colorectal cancer surgery in elderly patients is basically the same as that in younger patients. The reduction in recurrence risks may be similar, provided the chosen treatment is tolerated but survival gains are less. Adding oxaliplatin to a fluoropyrimidine is probably not beneficial in individuals above a biological age of approximately 70 years. If an oxaliplatin combination is administered to elderly patients, three months of therapy is in all probability the most realistic goal.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32823998"}, {"offsetInBeginSection": 0, "offsetInEndSection": 787, "text": "Adjuvant chemotherapy improves the prognosis of patients with colorectal cancer (CRC) following radical resection. The aim of the present study is to review appropriate chemotherapeutic regimens for elderly patients. We examined 1138 Japanese patients who were operated for high-risk stage II or stage III CRC between July 2010 and June 2021 at our hospital. Patients were divided according to an age of 70\u2009years. The efficacy of adjuvant therapy was analyzed in association with age and adjuvant chemotherapeutic regimens. A total of 507 patients (45%) were \u226570\u2009years old. They were less likely to receive adjuvant chemotherapy (p\u2009<\u20090.001) or palliative chemotherapy after recurrence (p\u2009<\u20090.001) than patients aged <70\u2009years. Cancer-specific survival (CSS) in stage III CRC patients was", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37881011"}, {"offsetInBeginSection": 2284, "offsetInEndSection": 2461, "text": "ortant role for stage III colon cancer. Our findings suggested that benefit of oxaliplatin-contained therapy is limited to patients aged under 70 and oral fluoropyrimidines may ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26382962"}, {"offsetInBeginSection": 1850, "offsetInEndSection": 2072, "text": "h statistical significance. In contrast to the survival benefits of above therapeutic settings for the patients aged under 70, there was less advantage in the old patients when they received intensive therapies or even oxa", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26382962"}, {"offsetInBeginSection": 1567, "offsetInEndSection": 1776, "text": "ributable to confounding.CONCLUSION: The noninvestigational experience suggests patients with stage III CC \u2265 75 years of age may anticipate a survival benefit from adjuvant chemotherapy. Oxaliplatin offers no ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22665536"}, {"offsetInBeginSection": 0, "offsetInEndSection": 731, "text": "OBJECTIVE: Elderly patients derive similar benefits from 5-fluorouracil-based adjuvant chemotherapy in Stage III colon cancer; however, conflicting data exist regarding additional benefit from oxaliplatin, fluorouracil and leucovorin (FOLFOX) chemotherapy.METHODS: Single-center, retrospective analysis was performed to compare the safety and efficacy of adjuvant oxaliplatin, fluorouracil and leucovorin-4 chemotherapy in older patients (age \u226565 years) with younger patients with Stage III colon cancer after surgical resection.RESULTS: Among 391 patients with Stage III colon cancer, 229 patients received adjuvant oxaliplatin, fluorouracil and leucovorin chemotherapy (87 (43.5%) \u226565 years old versus 142 (74.3%) <65 years old).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23204187"}, {"offsetInBeginSection": 66, "offsetInEndSection": 555, "text": "Oxaliplatin-based adjuvant chemotherapy improved disease-free survival after stage III colon cancer resection, but this improvement was not demonstrated in older patients.METHODS: The purpose of ADAGE-PRODIGE 34, randomized open phase III trial is to compare in patients over 70 years oxaliplatin plus fluoropyrimidine with fluoropyrimidine alone in fit patients (Group 1) and fluoropyrimidine with observation in frail patients (Group 2) after resection of stage III colon adenocarcinoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36115817"}, {"offsetInBeginSection": 1464, "offsetInEndSection": 1776, "text": "ficance was inconsistent. The beneficial effect of chemotherapy and oxaliplatin did not seem solely attributable to confounding.CONCLUSION: The noninvestigational experience suggests patients with stage III CC \u2265 75 years of age may anticipate a survival benefit from adjuvant chemotherapy. Oxaliplatin offers no ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22665536"}, {"offsetInBeginSection": 1238, "offsetInEndSection": 1455, "text": "I 0.78-0.83), respectively. The only subpopulations that did not benefit from doublet chemotherapy were low-risk patients older than 72 years (HR\u00a0=\u00a00.95, 95% CI 0.90-1.01) and high-risk patients older than 85 years (H", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29698932"}, {"offsetInBeginSection": 483, "offsetInEndSection": 766, "text": "Patients with completely resected stage III colon cancer have an overall survival benefit from adjuvant chemotherapy. Combination chemotherapy (5-fluorouracil/leucovorin/oxaliplatin or capecitabine/oxaliplatin) provides a larger benefit than monotherapy but with additional toxicity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28341242"}]}
+{"question_id": "660982eefdcbea915f000012", "question": "Where would Odocoileus virginianus be found?", "answer": "The White tailed deer, Odocoileus virginianus is found in North America", "relevant_passage_ids": ["37429851", "36710856", "37494882", "25973622", "19069784", "33308731", "1255915", "35637865", "35057829", "12678047", "27379074", "526903", "27777720", "448613", "35511871", "34295372", "8437050", "31098728", "2541261", "8028099", "25588013", "12910761", "2067060", "10073357", "10073356", "7241711", "21283515", "21080319", "7563421", "33767835", "14567218", "9359075", "2915397", "3373647", "1602587", "37651350", "37439882", "36314676", "34205799", "29889005", "8445781", "29792761", "30339101", "14629342", "30279590"], "type": "factoid", "snippets": [{"offsetInBeginSection": 28, "offsetInEndSection": 81, "text": "n free-ranging white-tailed deer in the United States", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37429851"}, {"offsetInBeginSection": 103, "offsetInEndSection": 456, "text": "Transmission of SARS-CoV-2 from humans to free-ranging white-tailed deer (Odocoileus virginianus) poses a unique public health risk due to the potential for reservoir establishment where variants may persist and evolve. We collected 8,830 respiratory samples from free-ranging white-tailed deer across Washington, D.C. and 26 states in the United States", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37429851"}, {"offsetInBeginSection": 134, "offsetInEndSection": 207, "text": "free-ranging white-tailed deer (Odocoileus virginianus) in North America ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36710856"}, {"offsetInBeginSection": 1126, "offsetInEndSection": 1319, "text": "white-tailed deer (Odocoileus virginianus), the primary reproductive host for I. scapularis adults, during the 1800s presumably led to the tick disappearing from large areas of the eastern US w", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37494882"}, {"offsetInBeginSection": 803, "offsetInEndSection": 988, "text": "Over 50 years ago, serologic surveys first suggested the susceptibility of white-tailed deer (Odocoileus virginianus), the most abundant free-ranging ruminant in North America, to BVDV.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27379074"}, {"offsetInBeginSection": 96, "offsetInEndSection": 491, "text": "Clinical diseases due to Theileria cervi have been reported in white-tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus) in the USA, however, information about this parasite has not been documented in Mexico. Here, blood samples from three white-tailed deer (Odocoileus virginianus) from a region in northeastern Mexico were analyzed by blood smear, PCR, and DNA sequencing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33308731"}, {"offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "First molecular evidence of Theileria cervi infection in white-tailed deer (Odocoileus virginianus) in Mexico.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33308731"}, {"offsetInBeginSection": 326, "offsetInEndSection": 589, "text": "Here, blood samples from three white-tailed deer (Odocoileus virginianus) from a region in northeastern Mexico were analyzed by blood smear, PCR, and DNA sequencing. The results confirmed the presence of T. cervi for the first time in white-tailed deer in Mexico.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33308731"}, {"offsetInBeginSection": 96, "offsetInEndSection": 589, "text": "Clinical diseases due to Theileria cervi have been reported in white-tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus) in the USA, however, information about this parasite has not been documented in Mexico. Here, blood samples from three white-tailed deer (Odocoileus virginianus) from a region in northeastern Mexico were analyzed by blood smear, PCR, and DNA sequencing. The results confirmed the presence of T. cervi for the first time in white-tailed deer in Mexico.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33308731"}, {"offsetInBeginSection": 803, "offsetInEndSection": 1113, "text": "Over 50 years ago, serologic surveys first suggested the susceptibility of white-tailed deer (Odocoileus virginianus), the most abundant free-ranging ruminant in North America, to BVDV. However, susceptibility of white-tailed deer to BVDV infection does not alone imply a role in the epidemiology of the virus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27379074"}, {"offsetInBeginSection": 96, "offsetInEndSection": 325, "text": "Clinical diseases due to Theileria cervi have been reported in white-tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus) in the USA, however, information about this parasite has not been documented in Mexico.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33308731"}, {"offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "BACKGROUND: White-tailed deer (Odocoileus virginianus) host numerous ectoparasitic species in the eastern USA, most notably various species of ticks and two species of deer keds.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35057829"}, {"offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Two species of Apteragia were found in white-tailed deer (Odocoileus virginianus) from 152 counties in 13 southeastern states.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/448613"}, {"offsetInBeginSection": 737, "offsetInEndSection": 903, "text": "Both A. odocoilei and A. pursglovei were found in Alabama, Arkansas, Florida, Georgia, Kentucky, Louisiana, Mississippi, North Carolina, South Carolina, and Virginia.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/448613"}, {"offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Hybridization of mule deer (Odocoileus hemionus) and white-tailed deer (O.\u00a0virginianus) appears to be a semi-regular occurrence in western North America.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34295372"}, {"offsetInBeginSection": 208, "offsetInEndSection": 395, "text": "White-tailed deer (Odocoileus virginianus) are commonly infested with H. longicornis in the eastern U.S. and are also infected with several genotypes of piroplasms such as a Theileria sp.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35637865"}, {"offsetInBeginSection": 91, "offsetInEndSection": 274, "text": "White-tailed deer (Odocoileus virginianus) are widely distributed in North America and deer densities are frequently high in unhunted areas, including most major metropolitan regions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31098728"}, {"offsetInBeginSection": 257, "offsetInEndSection": 413, "text": "Widely distributed in North America, the white-tailed deer (Odocoileus virginianus) has recreational, commercial, and food source value for many households.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35511871"}, {"offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "High white-tailed deer (Odocoileus virginianus) population densities and the occurrence of harsh environmental conditions are present on Anticosti Island, located in the Gulf of Saint-Lawrence (Quebec, Canada). This island is the northernmost region of white-tailed deer distribution in northeastern North America.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2541261"}, {"offsetInBeginSection": 0, "offsetInEndSection": 377, "text": "We determined the antibody prevalence to Ehrlichia spp., in white-tailed deer (Odocoileus virginianus) and the geographic distribution of seropositive animals in 84 counties in Alabama, Arkansas, Florida, Georgia, Illinois, Kentucky, Louisiana, Maryland, Massachusetts, Mississippi, Missouri, North Carolina, South Carolina, Tennessee, Texas, Virginia, and West Virginia (USA).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8028099"}, {"offsetInBeginSection": 0, "offsetInEndSection": 337, "text": "The meningeal worm (Parelaphostrongylus tenuis) is a nematode parasite that commonly infects white-tailed deer (Odocoileus virginianus; WTD) throughout the deciduous forest biome and deciduous-coniferous ecotone of eastern and central North America; the species is not known to occur west of the grassland biome of central North America.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25588013"}, {"offsetInBeginSection": 0, "offsetInEndSection": 854, "text": "Meningeal worm (Parelaphostrongylus tenuis), a common nematode parasite in white-tailed deer (Odocoileus virginianus) and pathogenic for several species of ungulates in eastern North America, is not known to occur in the west. Heads of 1,902 white-tailed deer were examined for adult meningeal worm to determine geographic distribution of the parasite in Saskatchewan and Manitoba (Canada) and North Dakota (USA). Finding the parasite in a deer in eastern Saskatchewan near the Manitoba border established the current northern and western limits in Canada. Prevalence of infection was < 1, 18.6, and 8.2% in Saskatchewan, Manitoba, and North Dakota, respectively. Infected deer occurred throughout southern Manitoba and eastern North Dakota. Distribution appears to have changed little since the last published survey for P. tenuis in the region in 1972.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12910761"}, {"offsetInBeginSection": 0, "offsetInEndSection": 586, "text": "The meningeal worm (Parelaphostrongylus tenuis) is a parasite of white-tailed deer (Odocoileus virginianus) and is also a significant pathogen of moose (Alces alces) and other ungulates. Changes in climate or habitat may facilitate range expansion or increase the prevalence of meningeal worm infection in white-tailed deer, resulting in increased exposure to susceptible ungulates. We examined 3,730 white-tailed deer during 2002-05 to determine the prevalence and range of meningeal worm infection in North Dakota, US, and investigated whether these had changed since earlier surveys.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25973622"}, {"offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Meningeal worm (Parelaphostrongylus tenuis), a common nematode parasite in white-tailed deer (Odocoileus virginianus) and pathogenic for several species of ungulates in eastern North America, is not known to occur in the west.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12910761"}, {"offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "An update is presented on the distribution of the meningeal worm (Parelaphostrongylus tenuis) of white-tailed deer (Odocoileus virginianus) in the southeastern United States.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2067060"}, {"offsetInBeginSection": 1025, "offsetInEndSection": 1191, "text": "(Odocoileus virginianus) in a typical north-eastern United States urban-suburban landscape, where livestock are rare but where these potentially susceptible, ungulate", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21080319"}, {"offsetInBeginSection": 249, "offsetInEndSection": 635, "text": "(Odocoileus virginianus) have been expanding their range into the North American boreal forest over the last half of the 20th century. This has already altered predator-prey dynamics in Alberta, Canada, where the distribution likely reaches the northern extent of its continuous range. Although current white-tailed deer distribution is explained by both climate and human land use, the", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27777720"}, {"offsetInBeginSection": 46, "offsetInEndSection": 203, "text": "(Odocoileus virginianus) from July through October 1988 in Missouri (USA). From late July through September, nine necropsied deer had lesions of the peracute", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7563421"}, {"offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Parelaphostrongylus tenuis (Nematoda) in white-tailed deer (Odocoileus virginianus) in central Iowa.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8437050"}, {"offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "An isolated white-tailed deer (Odocoileus virginianus) population on St. John, US Virgin Islands shows low inbreeding and comparable heterozygosity to other larger populations.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33767835"}, {"offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Chronic wasting disease (CWD) was first identified in Wisconsin (USA) in whitetailed deer (Odocoileus virginianus) in February 2002.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14567218"}, {"offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "The meningeal worm (Parelaphostrongylus tenuis) was found in 22 (7%) of 300 white-tailed deer (Odocoileus virginianus) (257 adults, 43 fawns) examined from Nebraska (USA) during November 1996.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10073356"}, {"offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Meningeal worms (Parelaphostrongylus tenuis) were found in each of five white-tailed deer (Odocoileus virginianus) examined from Wassaw Island, Chatham County, Georgia,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9359075"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "An adult, female white-tailed deer (Odocoileus virginianus) died due to acute arsenic intoxication in an intensively managed northern hardwood forest in northern New York.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2915397"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "A 6-week-old white-tailed deer fawn (Odocoileus virginianus), found in Vermont, was presented with carpal contraction, 90 degrees medial deviation of ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7241711"}, {"offsetInBeginSection": 16, "offsetInEndSection": 166, "text": "nation of 21 neonatal white-tailed deer ( Odocoileus virginianus) from Delaware, US identified six fawns with Theileria spp. organisms or suspected in", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29792761"}, {"offsetInBeginSection": 17, "offsetInEndSection": 167, "text": " from white-tailed deer (Odocoileus virginianus) collected in southeastern North Carolina in 1991 for neutralizing antibodies to six mosquito-borne bu", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12678047"}, {"offsetInBeginSection": 19, "offsetInEndSection": 169, "text": "ia similar to that in domestic ruminants was diagnosed in two wild white-tailed deer (Odocoileus virginianus) with abnormal behaviour in Saskatchewan.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/526903"}, {"offsetInBeginSection": 9, "offsetInEndSection": 159, "text": " to 1986 110 white-tailed deer (Odocoileus virginianus) from Big Cypress National Preserve in southern Florida were examined for intestinal coccidial ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3373647"}, {"offsetInBeginSection": 85, "offsetInEndSection": 235, "text": "led deer (Odocoileus virginianus) (257 adults, 43 fawns) examined from Nebraska (USA) during November 1996. None of 53 mule deer (Odocoileus hemionus)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10073356"}, {"offsetInBeginSection": 9, "offsetInEndSection": 159, "text": "us dorsi muscles from 42 white-tailed deer (Odocoileus virginianus) from Maine (USA) were examined for the Parelaphostrongylus andersoni. No adult nem", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1602587"}, {"offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "White-tailed deer (Odocoileus virginianus) fawn survival and the influence of landscape characteristics on fawn predation risk in the Southern Appalachian Mountains, USA.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37651350"}, {"offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Characterization of two novel reassortant bluetongue virus serotype 1 strains isolated from farmed white-tailed deer (Odocoileus virginianus) in Florida, USA.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37439882"}, {"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Statewide survey of medically important ticks on white-tailed deer, Odocoileus virginianus Zimmerman, in Alabama, U.S.A.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36314676"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Wide Genetic Diversity of Blastocystis in White-Tailed Deer (Odocoileus virginianus) from Maryland, USA.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34205799"}, {"offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Identification of White-tailed Deer ( Odocoileus virginianus) as a Novel Reservoir Species for Trypanosoma cruzi in Texas, USA.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29889005"}, {"offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "A 6-week-old white-tailed deer fawn (Odocoileus virginianus), found in Vermont, was presented with carpal contraction, 90 degrees medial deviation of the rear legs from the hock distally, and an abnormal coat color.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7241711"}, {"offsetInBeginSection": 1147, "offsetInEndSection": 1297, "text": "coileus species before the migration of O. virginianus from North America to South America. Moreover, the maximum parsimony analysis showed an intense", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19069784"}, {"offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "From 1984 to 1986 110 white-tailed deer (Odocoileus virginianus) from Big Cypress National Preserve in southern Florida were examined for intestinal coccidial infections.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3373647"}, {"offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Postmortem examination of 21 neonatal white-tailed deer ( Odocoileus virginianus) from Delaware, US identified six fawns with Theileria spp.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29792761"}, {"offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Longissimus dorsi muscles from 42 white-tailed deer (Odocoileus virginianus) from Maine (USA) were examined for the Parelaphostrongylus andersoni.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1602587"}, {"offsetInBeginSection": 88, "offsetInEndSection": 238, "text": " deer (Odocoileus virginianus) (257 adults, 43 fawns) examined from Nebraska (USA) during November 1996. None of 53 mule deer (Odocoileus hemionus) (4", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10073356"}, {"offsetInBeginSection": 93, "offsetInEndSection": 243, "text": "(O. hemionus) killed between 28 November to 14 December 1991 from Wainwright, Alberta were examined for Thelazia spp. One immature male and two immatu", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8445781"}, {"offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Lymph nodes from 271 white-tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus) in Nebraska (USA) were examined microscopically for tuberculoid lesions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10073357"}, {"offsetInBeginSection": 76, "offsetInEndSection": 674, "text": "( Odocoileus virginianus), is being increasingly recognized as a cause of disease in captive cervids in North America. Historically endemic in white-tailed deer, the natural wildlife reservoir in the southeastern US, B. odocoilei has been recently associated with hemolytic anemia in captive Eurasian tundra reindeer ( Rangifer tarandus tarandus), wapiti ( Cervus canadensis), and woodland caribou ( Rangifer tarandus caribou) in the northcentral and northeastern US and several Canadian provinces. The emergence of B. odocoilei is likely related to the northward expansion of the range of the tick", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30339101"}, {"offsetInBeginSection": 375, "offsetInEndSection": 578, "text": "(Odocoileus virginianus) from a region in northeastern Mexico were analyzed by blood smear, PCR, and DNA sequencing. The results confirmed the presence of T. cervi for the first time in white-tailed deer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33308731"}, {"offsetInBeginSection": 194, "offsetInEndSection": 312, "text": "this species. White-tailed deer (Odocoileus virginianus) are commonly infested with H. longicornis in the eastern U.S.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35637865"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Theileriosis in Multiple Neonatal White-tailed Deer ( Odocoileus virginianus) in Delaware, USA.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29792761"}, {"offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Postmortem examination of 21 neonatal white-tailed deer ( Odocoileus virginianus) from Delaware, US identified six fawns with Theileria spp. organisms or suspected infection.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29792761"}, {"offsetInBeginSection": 0, "offsetInEndSection": 610, "text": "BACKGROUND: White-tailed deer (Odocoileus virginianus) host numerous ectoparasitic species in the eastern USA, most notably various species of ticks and two species of deer keds. Several pathogens transmitted by ticks to humans and other animal hosts have also been found in deer keds. Little is known about the acquisition and potential for transmission of these pathogens by deer keds; however, tick-deer ked co-feeding transmission is one possible scenario. On-host localization of ticks and deer keds on white-tailed deer was evaluated across several geographical regions of the eastern US to define tick-d", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35057829"}, {"offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "The white-tailed deer (Odocoileus virginianus) represents one of the most successful and widely distributed large mammal species within North America, yet very little nucleotide sequence information is available.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21283515"}, {"offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "White-tailed deer (Odocoileus virginianus) were nearly extirpated from the southeastern USA during the late 19th and early 20th centuries.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14629342"}, {"offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Ixodes scapularis Say was the only species of tick found on white-tailed deer, Odocoileus virginianus, collected at Long Point, Ontario from October 1972 to August 1973.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1255915"}, {"offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "In the northeastern United States, chronic wasting disease has recently been detected in white-tailed deer (Odocoileus virginianus) populations", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30279590"}]}
+{"question_id": "65f868eac4010b4d78000056", "question": "What is the rationale behind treating melanoma with immunotherapy?", "answer": "The rationale behind treating melanoma with immunotherapy is that melanoma is a highly immunogenic cancer, meaning the immune system can recognize and attack it. Key points:\n\n1. Melanoma cells express tumor-specific antigens that immune cells can target.\n\n2. Melanomas often have lymphocytic infiltrates, showing the immune system does react to the cancer. \n\n3. Melanoma patients can respond to immunotherapies like immune checkpoint inhibitors (anti-CTLA-4, anti-PD-1), which take the brakes off the immune response.\n\n4. Adoptive cell transfer using a patient's own anti-tumor T cells extracted from the tumor can lead to responses.\n\n5. Melanoma has multiple mechanisms of immune evasion that immunotherapies can counteract.\n\nIn summary, melanoma's immunogenicity and evidence that boosting anti-tumor immunity with immunotherapies can lead to clinical responses provides a strong rationale for this treatment approach. Harnessing the immune system allows specific targeting of melanoma cells.", "relevant_passage_ids": ["32671117", "35247927", "33256089", "33202676", "33002195", "25746916", "37989956", "22697295", "30040090", "27345592", "35339277", "27454404", "16895565", "30245770", "28238077", "32235439", "34161002", "30914573", "32640053", "31824260", "27430520"], "type": "summary", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 354, "text": "Melanoma is one of the most immunologic malignancies based on its higher prevalence in immune-compromised patients, the evidence of brisk lymphocytic infiltrates in both primary tumors and metastases, the documented recognition of melanoma antigens by tumor-infiltrating T lymphocytes and, most important, evidence that melanoma responds to immunotherapy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32671117"}, {"offsetInBeginSection": 868, "offsetInEndSection": 1012, "text": "A comparison between primary and metastatic acral melanoma identified gene signatures associated with changes in immune responses and metabolism", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35247927"}, {"offsetInBeginSection": 1014, "offsetInEndSection": 1210, "text": "Acral melanoma was characterized by a lower overall immune infiltrate, fewer effector CD8 T cells and NK cells, and a near-complete absence of \u03b3\u03b4 T cells compared with nonacral cutaneous melanomas", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35247927"}, {"offsetInBeginSection": 1212, "offsetInEndSection": 1441, "text": "Immune cells associated with acral melanoma exhibited expression of multiple checkpoints including PD-1, LAG-3, CTLA-4, V-domain immunoglobin suppressor of T cell activation (VISTA), TIGIT, and the Adenosine A2A receptor (ADORA2)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35247927"}, {"offsetInBeginSection": 1549, "offsetInEndSection": 1743, "text": "Acral melanoma has a suppressed immune environment compared with that of cutaneous melanoma from nonacral skin. Expression of multiple, therapeutically tractable immune checkpoints were observed", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35247927"}, {"offsetInBeginSection": 658, "offsetInEndSection": 705, "text": "immune evasion strategies utilized by melanomas", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33256089"}, {"offsetInBeginSection": 784, "offsetInEndSection": 948, "text": "roles of immunotherapeutic agents, ipilimumab, nivolumab, pembrolizumab, and atezolizumab, adoptive T- cell therapy plus T-VEC in the treatment of advanced melanoma", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33256089"}, {"offsetInBeginSection": 581, "offsetInEndSection": 988, "text": "As there is lot of evidence that melanoma is immunogenic, a concept of immunotherapy has risen. Immunotherapy uses molecules of the body's own immune system and disrupts the growth of cancer cells has gained a lot of attention in the past two decades. Adoptive cell therapies (ACT), vaccines, viruses, and cytokine administration in immunotherapy stimulate T cells to recognize and destroy the cancer cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22697295"}, {"offsetInBeginSection": 581, "offsetInEndSection": 832, "text": "As there is lot of evidence that melanoma is immunogenic, a concept of immunotherapy has risen. Immunotherapy uses molecules of the body's own immune system and disrupts the growth of cancer cells has gained a lot of attention in the past two decades.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22697295"}, {"offsetInBeginSection": 833, "offsetInEndSection": 1124, "text": "Adoptive cell therapies (ACT), vaccines, viruses, and cytokine administration in immunotherapy stimulate T cells to recognize and destroy the cancer cells. This article is a brief review of various molecules and strategies that are currently used in immunotherapy against malignant melanoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22697295"}, {"offsetInBeginSection": 677, "offsetInEndSection": 1124, "text": "Immunotherapy uses molecules of the body's own immune system and disrupts the growth of cancer cells has gained a lot of attention in the past two decades. Adoptive cell therapies (ACT), vaccines, viruses, and cytokine administration in immunotherapy stimulate T cells to recognize and destroy the cancer cells. This article is a brief review of various molecules and strategies that are currently used in immunotherapy against malignant melanoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22697295"}, {"offsetInBeginSection": 392, "offsetInEndSection": 832, "text": "Although chemotherapy is one of the treatment options, it also interferes with all rapidly dividing cells including the non-cancerous cells; therefore one should consider the side effects. As there is lot of evidence that melanoma is immunogenic, a concept of immunotherapy has risen. Immunotherapy uses molecules of the body's own immune system and disrupts the growth of cancer cells has gained a lot of attention in the past two decades.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22697295"}, {"offsetInBeginSection": 0, "offsetInEndSection": 312, "text": "Immunotherapy for the treatment of advanced melanoma has become a primary treatment in the clinic. Current therapies include systemic cytokines, immune checkpoint inhibitors, and localized intratumoral therapies. Checkpoint inhibitors block natural pathways that dampen or inhibit an immune response to stimulus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30040090"}, {"offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Immunotherapy for the treatment of advanced melanoma has become a primary treatment in the clinic. Current therapies include systemic cytokines, immune checkpoint inhibitors, and localized intratumoral therapies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30040090"}, {"offsetInBeginSection": 273, "offsetInEndSection": 676, "text": "Therefore, tremendous effort has been made in the past decades to treat metastatic melanoma patients more efficiently. Although chemotherapy is one of the treatment options, it also interferes with all rapidly dividing cells including the non-cancerous cells; therefore one should consider the side effects. As there is lot of evidence that melanoma is immunogenic, a concept of immunotherapy has risen.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22697295"}, {"offsetInBeginSection": 166, "offsetInEndSection": 393, "text": "The emergence of immune checkpoint blockade as a crucial element in current immunotherapy and combination strategies has significantly transformed the treatments of resectable and advanced (unresectable or metastatic) melanoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37989956"}, {"offsetInBeginSection": 1237, "offsetInEndSection": 1454, "text": "Our data emphasize the importance of robust MHC-I expression for anti-PD-1 monotherapy response and provide a rationale for the selection of combination immunotherapy as the first-line treatment in MHC-I low melanoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33202676"}, {"offsetInBeginSection": 62, "offsetInEndSection": 423, "text": "Evidence that melanoma tumor cells are highly immunogenic and a better understanding of T-cell immune checkpoints have changed the therapeutic approach to advanced melanoma. Instead of targeting the tumor directly, immunotherapy targets and activates the immune response using checkpoint inhibitors, monoclonal antibodies, vaccines, and adoptive T cell therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27454404"}, {"offsetInBeginSection": 0, "offsetInEndSection": 358, "text": "Immunotherapy has assumed increasing importance in the therapy of malignant melanoma. The main reason is the high immunogenicity of the tumor itself, so that an immune response against the tumor often exists even without immune stimulation. The goal of modern immunotherapeutic approaches is to augment these anti-tumoral immune reactions to fight the tumor.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16895565"}, {"offsetInBeginSection": 0, "offsetInEndSection": 369, "text": "Immunotherapy is a treatment strategy that has demonstrated survival benefit for metastatic melanoma. Ipilimumab and nivolumab are examples of immunotherapy, in which monoclonal antibodies antagonize cytotoxic T-lymphocyte-associated protein 4 and programmed death-ligand 1 receptors, respectively, resulting in upregulation of the host immune response to cancer cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30245770"}, {"offsetInBeginSection": 78, "offsetInEndSection": 362, "text": "The rationale comes from the knowledge that many patients with melanoma have endogenous immune responses against their tumor cells and clinically meaningful tumor regression can be achieved in a minority of patients using cytokines such as interleukin-2 and adoptive cellular therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25746916"}, {"offsetInBeginSection": 363, "offsetInEndSection": 704, "text": "In the last 5 years there has been a revolution in the clinical management of melanoma in large measure based on the development of antibodies that influence T cell regulatory pathways by overcoming checkpoint inhibition and providing co-stimulation, either of which results in significantly more effective immune-mediated tumor destruction.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25746916"}, {"offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Clinical trials have demonstrated the efficacy of immunotherapy, especially checkpoint blockade inhibitors, in the treatment of patients with metastatic melanoma. More recently, improvements in survival have", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33002195"}, {"offsetInBeginSection": 225, "offsetInEndSection": 560, "text": " Inhibition of MAPK pathway signaling with BRAF (BRAFi) and MEK inhibitors (MEKi) attenuates immune escape and increases the melanoma immunogenicity through multiple mechanisms, including elevation of melanoma antigen expression and improved T cell infiltration and function. These changes sustain the TME for response to immunotherapy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28238077"}, {"offsetInBeginSection": 0, "offsetInEndSection": 524, "text": "Although melanoma is one of the most immunogenic tumors, it has an ability to evade anti-tumor immune responses by exploiting tolerance mechanisms, including negative immune checkpoint molecules. The most extensively studied checkpoints represent cytotoxic T lymphocyte-associated protein-4 (CTLA-4) and programmed cell death protein 1 (PD-1). Immune checkpoint inhibitors (ICI), which were broadly applied for melanoma treatment in the past decade, can unleash anti-tumor immune responses and result in melanoma regression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32235439"}, {"offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Clinical trials have demonstrated the efficacy of immunotherapy, especially checkpoint blockade inhibitors, in the treatment of patients with metastatic melanoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33002195"}, {"offsetInBeginSection": 0, "offsetInEndSection": 413, "text": "INTRODUCTION: The therapeutic landscape of metastatic melanoma drastically changed after the introduction of targeted therapies and immunotherapy, in particular immune checkpoints inhibitors (ICI). In recent years, positive effects on the immune system associated to radiotherapy (RT) were discovered, and radiation has been tested in combination with ICI in both pre-clinical and clinical studies (many of them s", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27345592"}, {"offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Treatment of melanoma with immune checkpoints inhibitors .Immunotherapy with checkpoints inhibitors stimulates the anti-tumor response. It has", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34161002"}, {"offsetInBeginSection": 0, "offsetInEndSection": 890, "text": "Melanomas are malignant tumors that can partly and very rarely completely regress in response to immune responses. Analyzing the mechanisms underlying this immune-mediated rejection, melanomas became leading in developing general cancer immunotherapy. This resulted in the discovery of tumor-specific neoantigens and mutations autoantigens, now called tumor-associated antigens, and their specific recognition by cytotoxic T lymphocytes. Melanomas were of key importance for the development of adoptive T-cell therapy and active tumor vaccines, namely dendritic cell vaccines. Melanoma therapy with antibodies against CTLA-4 provided the proof of concept that solid cancers can be susceptible to cancer immunotherapy, and melanoma therapy with antibodies against PD-1 resulted in the clinical breakthrough of cancer immunotherapy. Still, about half of patients die from metastatic melanoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35339277"}, {"offsetInBeginSection": 0, "offsetInEndSection": 457, "text": "Cancer immunotherapy has become a new entity of cancer treatment with successes in various clinical trials. Immune checkpoint inhibitors, particularly targeting PD-1 and CTLA-4 show an efficient antitumor effect via reinvigorating antitumor immune responses which are generally suppressed in the tumor microenvironment, resulting in the approval for the treatment of multiple cancer types including malignant melanoma, lung cancer, gastric cancer and so on.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30914573"}, {"offsetInBeginSection": 214, "offsetInEndSection": 327, "text": "Melanoma has a high mutational burden making it more capable of evoking immune responses than many other tumours.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32640053"}, {"offsetInBeginSection": 0, "offsetInEndSection": 362, "text": "Immune checkpoints restrain the immune system following its activation and their inhibition unleashes anti-tumor immune responses. Immune checkpoint inhibitors revolutionized the treatment of several cancer types, including melanoma, and immune checkpoint blockade with anti-PD-1 and anti-CTLA-4 antibodies is becoming a frontline therapy in metastatic melanoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31824260"}, {"offsetInBeginSection": 600, "offsetInEndSection": 703, "text": "Since melanoma has a high mutational burden, it is considered more immunogenic than many other tumours.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32640053"}, {"offsetInBeginSection": 391, "offsetInEndSection": 535, "text": "The most significant and impactful immunotherapies for melanoma utilize immune checkpoint inhibition to stimulate T cell mediated tumor killing.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27430520"}]}
+{"question_id": "661d56c0eac11fad3300001f", "question": "Is there a specific cure for Ehlers-Danlos Syndrome?", "answer": "No, there is no specific cure for Ehlers-Danlos Syndrome.", "relevant_passage_ids": ["34560710", "30512708", "20847697", "12208159", "11218502", "29032848", "24267684"], "type": "yesno", "snippets": [{"offsetInBeginSection": 385, "offsetInEndSection": 470, "text": "The management of this disease is possible; however, there is no cure as of present. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34560710"}, {"offsetInBeginSection": 9, "offsetInEndSection": 561, "text": "Ehlers-Danlos syndrome (vEDS) is a rare autosomal dominant genetic disorder. It is the most fatal among all types of EDS. In addition to typical EDS characteristics, vEDS patients are at risk of blood vessel rupture due to possession of pathogenic variants of the COL3A1 gene, which encodes type III collagen. Type III collagen is a major component of humans' vascular walls. The management of this disease is possible; however, there is no cure as of present. Recently, discoveries with potential impact on the management of vEDS have been elucidated.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34560710"}, {"offsetInBeginSection": 695, "offsetInEndSection": 845, "text": "d the diagnosis of Ehlers-Danlos syndrome type VIII. As there is no specific treatment for the disorder, management is limited to the symptomatic trea", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11218502"}, {"offsetInBeginSection": 1557, "offsetInEndSection": 1707, "text": "e-phenotype correlations have been observed. No treatment for the underlying defect is presently available for Ehlers-Danlos syndrome. However, a seri", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20847697"}, {"offsetInBeginSection": 1162, "offsetInEndSection": 1312, "text": "e and/or variable phenotypic expression. Ehlers-Danlos syndrome do not have any specific etiological treatment. The management is poorly systematized ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30512708"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1519, "text": "Ehlers-Danlos syndromes (EDS) are a heterogeneous group of inheritable connective tissue disorders characterized by skin hyperextensibility, joint hypermobility and cutaneous fragility with delayed wound healing. Over and above these common features, they differ in the presence or absence of various organ and tissue abnormalities, and differences in genetic causal mechanisms and degree of severity. They are complex and multisystem diseases, with the majority being highly disabling because of major joint problems and neurosensory deficiencies, and in some cases, they may be life-threatening due to associated complications, especially vascular disorders. In 1997, the Villefranche classification defined 6\u00a0subtypes of EDS. However, many other new variants have been described over the last years. The \"historical\" EDS were characterized by abnormalities in fibrillar collagen protein synthesis. More recently, disorders of synthesis and organization of the extracellular matrix have been shown to be responsible for other types of EDS. Thus, many EDS are in fact metabolic diseases related to enzymatic defects. While there is no curative treatment for any type of EDS, early diagnosis is of utmost importance in order to optimize the symptomatic management of patients and to prevent avoidable complications. Patients must be treated and monitored by multidisciplinary teams in highly specialized reference centers. In this article, we present the current state of knowledge on these diseases that continue to be", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29032848"}, {"offsetInBeginSection": 1203, "offsetInEndSection": 1273, "text": "Ehlers-Danlos syndrome do not have any specific etiological treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30512708"}, {"offsetInBeginSection": 1118, "offsetInEndSection": 1315, "text": "While there is no curative treatment for any type of EDS, early diagnosis is of utmost importance in order to optimize the symptomatic management of patients and to prevent avoidable complications.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29032848"}]}
+{"question_id": "65cfa8f81930410b13000010", "question": "What mutation is associated with the VEXAS syndrome?", "answer": "Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a recently recognized multisystem disorder caused by somatic mutations in the UBA1 gene.", "relevant_passage_ids": ["37418279", "36948992", "37062498", "37062784", "36537591", "33779074", "34046042", "34480172", "35201420", "34864445", "37662628", "36549759", "35885496", "34489099", "34817788", "33741056", "35986821", "35793467", "38091008", "37586319", "34651299", "37084382", "35941354", "34802545", "36692560", "35795842", "37673972", "36722042", "36168114", "34427584", "37223371", "36879894", "37953404", "36762418", "36607374", "36252945", "37501758", "34802543", "34802546", "34999727", "36115693", "35172893", "36735069", "35179640", "36544501", "37595794", "36045928", "35239266", "37868330", "37078566", "36082915", "35419965", "36251488", "35385616", "33971000", "33987129", "34714914", "37532466", "37666646", "37839908", "36662445", "37652853", "34632574", "36641501", "36272567", "34802541", "36823397", "34802544", "36038944", "34048852", "37404435"], "type": "factoid", "snippets": [{"offsetInBeginSection": 550, "offsetInEndSection": 642, "text": "Bone marrow aspiration revealed an UBA1 mutation, which is pathognomonic for VEXAS syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37418279"}, {"offsetInBeginSection": 137, "offsetInEndSection": 239, "text": "Somatic mutations of the UBA1 gene in hematopoietic stem cells constitute the genetic basis of VEXAS. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36948992"}, {"offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "BACKGROUND: Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a recently recognized multisystem disorder caused by somatic mutations in the UBA1 gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37062498"}, {"offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a new disease entity with autoinflammatory disorders (AID) driven by somatic variants in UBA1 that frequently co-exists with myelodysplastic syndromes (MDS). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37062784"}, {"offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "INTRODUCTION: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently described, late-onset, acquired autoinflammatory disorder caused by mutations in the UBA1 gene. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36537591"}, {"offsetInBeginSection": 238, "offsetInEndSection": 456, "text": "The majority of UBA1 mutations in VEXAS syndrome comprise hemizygous mutations affecting methionine-41 (M41), leading to the expression of UBA1M41T, UBA1M41V, or UBA1M41L and globally reduced protein polyubiquitination", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38091008"}, {"offsetInBeginSection": 165, "offsetInEndSection": 400, "text": "VEXAS syndrome results from a somatic mutation affecting UBA1, a gene that codes for the E1 ubiquitin activating protein. Loss of UBA1 leads to a broad range of inflammatory conditions and a clinical course often refractive to therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35201420"}, {"offsetInBeginSection": 726, "offsetInEndSection": 844, "text": "Following blood analysis, both patients were diagnosed with VEXAS syndrome resulting from a mutation in the UBA1 gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35201420"}, {"offsetInBeginSection": 1281, "offsetInEndSection": 1643, "text": "Finally, we report a patient, clinically diagnosed with VEXAS syndrome, with 2 novel mutations in UBA1 occurring in cis on the same allele. One mutation (c.121 A>T; p.Met41Leu) caused severely reduced translation of UBA1b in a reporter assay, but coexpression with the second mutation (c.119 G>C; p.Gly40Ala) rescued UBA1b levels to those of canonical mutations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35793467"}, {"offsetInBeginSection": 583, "offsetInEndSection": 735, "text": "Here we describe a unique case of VEXAS syndrome in a patient harbouring DNMT3A gene mutation with coexisting UBA1 mutation with a review of literature.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34480172"}, {"offsetInBeginSection": 0, "offsetInEndSection": 400, "text": "Vacuoles, E1 enzyme, x-linked, autoinflammatory, and somatic mutation (VEXAS) syndrome is a recently described disease associated with high morbidity and mortality. VEXAS syndrome results from a somatic mutation affecting UBA1, a gene that codes for the E1 ubiquitin activating protein. Loss of UBA1 leads to a broad range of inflammatory conditions and a clinical course often refractive to therapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35201420"}, {"offsetInBeginSection": 238, "offsetInEndSection": 457, "text": "The majority of UBA1 mutations in VEXAS syndrome comprise hemizygous mutations affecting methionine-41 (M41), leading to the expression of UBA1M41T, UBA1M41V, or UBA1M41L and globally reduced protein polyubiquitination.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38091008"}, {"offsetInBeginSection": 726, "offsetInEndSection": 955, "text": "Following blood analysis, both patients were diagnosed with VEXAS syndrome resulting from a mutation in the UBA1 gene. Our report highlights the pivotal role dermatologists have in early diagnosis of patients with VEXAS syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35201420"}, {"offsetInBeginSection": 1281, "offsetInEndSection": 1420, "text": "Finally, we report a patient, clinically diagnosed with VEXAS syndrome, with 2 novel mutations in UBA1 occurring in cis on the same allele.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35793467"}, {"offsetInBeginSection": 197, "offsetInEndSection": 295, "text": "VEXAS syndrome is caused by a somatic mutation of the UBA1 gene in hematopoietic progenitor cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37223371"}, {"offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "OBJECTIVE: Somatic mutations in UBA1 have recently been causally linked to a severe adult-onset inflammatory condition referred to as VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36762418"}, {"offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Vacuoles, E1 enzyme, X linked, autoinflammatory, somatic (VEXAS) syndrome is a recently described X-linked autoinflammatory condition associated with somatic mutation of the ubiquitin-like modifier activating enzyme 1 (UBA1) gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34480172"}, {"offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly-described adult-onset inflammatory syndrome characterized by vacuoles in myeloid and erythroid precursor cells and somatic mutations affecting methionine-41 (p.Met41) in UBA1.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33741056"}, {"offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "VEXAS syndrome is a recently identified autoinflammatory systemic disease caused by an acquired somatic mutation of the X-linked UBA1 gene, the key enzyme of the first step of ubiquitylation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37953404"}, {"offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "INTRODUCTION: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently described, late-onset, acquired autoinflammatory disorder caused by mutations in the UBA1 gene. The various clinical manifestations of VEXAS broadly divided into inflammatory or", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36537591"}, {"offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "ABSTRACT: VEXAS (vacuoles, E1 enzyme, X-LINKED, autoinflammatory, somatic) syndrome is a complex inflammatory disease associated with somatic mutations of the ubiquitin-like modifier activating enzyme 1 (U", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36607374"}, {"offsetInBeginSection": 0, "offsetInEndSection": 325, "text": "VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly defined refractory adult-onset autoinflammatory syndrome caused by somatic mutations in the ubiquitin-like modifier-activating enzyme 1 (UBA1) gene in hematopoietic stem and progenitor cells, resulting in a shift in UBA1 isoform expression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37501758"}, {"offsetInBeginSection": 150, "offsetInEndSection": 219, "text": "Patients with VEXAS syndrome have a somatic mutation in the UBA1 gene", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36549759"}, {"offsetInBeginSection": 0, "offsetInEndSection": 415, "text": "VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently described autoinflammatory syndrome characterized by diffuse inflammatory manifestations, predisposition to hematological malignancy, and an association with a high rate of thrombosis. VEXAS is attributed to somatic mutations in the UBA1 gene in hematopoietic stem and progenitor cells with myeloid restriction in mature forms.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34802545"}, {"offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "The identification of the VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome as a myeloid-driven inflammatory disease resulting from somatic mutations in the UBA1 gene", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34802543"}, {"offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is caused by UBA1 somatic mutations and is characterized by late-onset", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36641501"}, {"offsetInBeginSection": 26, "offsetInEndSection": 103, "text": "ns in UBA1 cause a newly defined syndrome known as VEXAS (vacuoles, E1 enzyme", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33779074"}, {"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "OBJECTIVES: VEXAS syndrome is a newly described autoinflammatory disease associated with UBA1 somatic mutations and vacu", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36722042"}, {"offsetInBeginSection": 61, "offsetInEndSection": 170, "text": "ry, somatic (VEXAS) syndrome is a newly identified autoinflammatory disorder related to somatic UBA1 mutation", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36272567"}, {"offsetInBeginSection": 180, "offsetInEndSection": 469, "text": "(VEXAS) is a new monogenic autoinflammatory syndrome caused by somatic ubiquitin-like modifier-activating enzyme 1 (UBA1) mutation, often associated with MDS, whose treatment is difficult and not yet codified. Based on a French nationwide registry of 116 patients with VEXAS, we report the", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34651299"}, {"offsetInBeginSection": 150, "offsetInEndSection": 283, "text": "Patients with VEXAS syndrome have a somatic mutation in the UBA1 gene, inflammatory conditions and usually haematological conditions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36549759"}, {"offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly described autoinflammatory entity caused by a UBA-1 gene mutation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37595794"}, {"offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "BACKGROUND: VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic syndrome) first described in 2020, is caused by a limited repertoire of somatic mutations in UBA1, a gene involved in the initiation of ubi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35239266"}, {"offsetInBeginSection": 149, "offsetInEndSection": 299, "text": " and mortality. VEXAS syndrome results from a somatic mutation affecting UBA1, a gene that codes for the E1 ubiquitin activating protein. Loss of UBA1", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35201420"}, {"offsetInBeginSection": 585, "offsetInEndSection": 735, "text": "ays and systemic inflammation occur. The specific mechanism by which the UBA1 mutation leads to the clinical features of VEXAS syndrome is not yet ful", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37662628"}, {"offsetInBeginSection": 559, "offsetInEndSection": 709, "text": "od smears of three groups: participants with VEXAS syndrome (identified UBA1 mutation) (VEXAS); participants with features strongly suggestive of VEXA", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36722042"}, {"offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "VEXAS is a newly recognised adult-onset autoinflammatory syndrome resulting from a somatic mutation in the UBA1 gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35419965"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a newly discovered syndrome caused by a somatic mutation in the UBA1 gene, located in the X chromosome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36082915"}, {"offsetInBeginSection": 0, "offsetInEndSection": 395, "text": "VEXAS syndrome was recently discovered in patients who developed late in adulthood an inflammatory syndrome with fever, cytopenias, dysplastic bone marrow, cutaneous and pulmonary neutrophilic inflammation, arthritis, chondritis, or vasculitis. It is the result of an inactivating somatic mutation affecting methionine codon 41 of the UBA1 gene which encodes an ubiquitin activating enzyme (E1).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35385616"}, {"offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a monogenic disease of adulthood caused by somatic mutations in UBA1 in hematopoietic progenitor cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33971000"}, {"offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "The VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently described X-linked autoinflammatory condition caused by a somatic mutation of the UBA1 gene", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33987129"}, {"offsetInBeginSection": 217, "offsetInEndSection": 359, "text": "VEXAS syndrome is a rare condition that primarily affects adult males and is caused by a mutation in the UBA1 gene located on the X chromosome", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37662628"}, {"offsetInBeginSection": 641, "offsetInEndSection": 751, "text": "The underlying diagnosis of VEXAS syndrome was confirmed by genetic testing, which revealed the UBA1 mutation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37673972"}, {"offsetInBeginSection": 648, "offsetInEndSection": 882, "text": "More recently the discovery of a new disease, called (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) VEXAS syndrome, due to mutations in UBA1 gene, identified the cause of 8\u00a0% of the patients with a clinical diagnosis of RP", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37839908"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly described autoinflammatory entity caused by a UBA-1 gene mutation", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37595794"}, {"offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "BACKGROUND: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome')", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34632574"}, {"offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "TO THE EDITOR: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly described entity linked to somatic mutation of UBA1, encompassing inflammatory disorders and hematologica", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34999727"}, {"offsetInBeginSection": 1318, "offsetInEndSection": 1481, "text": "Key Points \u2022 VEXAS syndrome is a recently described genetic (somatic mutations in UBA1 gene) disorder that gathers autoinflammatory and hematologic manifestations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35986821"}, {"offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "VEXAS syndrome, an autoinflammatory syndrome due to a Ubiquitin Like Modifier Activating Enzyme 1 (UBA1) somatic mutation, has a high thrombotic burden.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34817788"}, {"offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a newly discovered syndrome caused by a somatic mutation in the UBA1 gene, located in the X chromosome. The syndrome mainly affects older", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36082915"}, {"offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "The VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is an adult-onset systemic autoinflammatory condition that is caused by an acquired deficiency of the UBA1 gene in", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37532466"}, {"offsetInBeginSection": 165, "offsetInEndSection": 599, "text": "VEXAS syndrome results from a somatic mutation affecting UBA1, a gene that codes for the E1 ubiquitin activating protein. Loss of UBA1 leads to a broad range of inflammatory conditions and a clinical course often refractive to therapy. We present the cases of two patients who demonstrated a rapid decline in overall health, decreased energy, arthralgias, anemia, fever, increased inflammatory markers, and characteristic bone marrow.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35201420"}, {"offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "VEXAS syndrome, an autoinflammatory syndrome due to a Ubiquitin Like Modifier Activating Enzyme 1 (UBA1) somatic mutation, has a high thrombotic burden. We report a case of a 69-year-old male that was diagnosed with VEXAS syndrome who developed venous thromboembolism (VTE).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34817788"}, {"offsetInBeginSection": 114, "offsetInEndSection": 389, "text": "Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome (VEXAS) is a new monogenic autoinflammatory syndrome caused by somatic ubiquitin-like modifier-activating enzyme 1 (UBA1) mutation, often associated with MDS, whose treatment is difficult and not yet codified.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34651299"}, {"offsetInBeginSection": 57, "offsetInEndSection": 248, "text": "(VEXAS) syndrome is a recently described X-linked autoinflammatory condition associated with somatic mutation of the ubiquitin-like modifier activating enzyme 1 (UBA1) gene. It often coexists", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34480172"}, {"offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "OBJECTIVE: Somatic mutations in UBA1 have recently been causally linked to a severe adult-onset inflammatory condition referred to as VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36762418"}, {"offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is caused by UBA1 somatic mutations", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36641501"}]}
+{"question_id": "65f774dec4010b4d7800002a", "question": "Should routine PET-CT scan be indicated in the initial evaluation of locally advanced rectal cancer patients?", "answer": "Yes, the cutoff value of 1.5 for lymph node SUVmax in PET is a reasonable measure to predict the risk of preoperative LLN metastases in rectal cancer patients", "relevant_passage_ids": ["33962569", "30899056", "14751524", "25181962", "23420438", "23445625", "21571386", "35201442", "36117452", "16485158", "24764662", "34435447", "37132268", "37062021", "36620536", "36593016", "36569918", "36154291", "35523224", "36437550", "31337428", "23196674", "37092877", "22426260", "28972796", "26338180", "33402312", "24348839", "19486092", "26490751", "32712447", "33054291", "25348731", "36468505", "25731264", "30508883", "30854604"], "type": "yesno", "snippets": [{"offsetInBeginSection": 1429, "offsetInEndSection": 1582, "text": "The cutoff value of 1.5 for lymph node SUVmax in PET is a reasonable measure to predict the risk of preoperative LLN metastases in rectal cancer patients", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33962569"}, {"offsetInBeginSection": 1357, "offsetInEndSection": 1517, "text": " the combination model showed improved performance for risk prediction; thus, [18F]FDG PET/CT might have a role in rectal cancer staging and treatment planning.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30899056"}, {"offsetInBeginSection": 11, "offsetInEndSection": 393, "text": "In this pilot study, we investigated the feasibility of response prediction using digital [ 18 F]FDG PET/computed tomography (CT) and multiparametric MRI before, during, and after neoadjuvant chemoradiation therapy in locally advanced rectal cancer (LARC) patients and aimed to select the most promising imaging modalities and timepoints for further investigation in a larger trial.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37132268"}, {"offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Positron emission tomography (PET) in the era of personalized medicine has a unique role in the management of oncological patients and offers several advantages over standard anatomical imaging", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37062021"}, {"offsetInBeginSection": 132, "offsetInEndSection": 344, "text": "ET-CT) imaging parameters for the response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC).Methods: From January 2016 to March 2020, 52 LARC patients who underwent 18F-FDG PET-CT ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36620536"}, {"offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "DWI-MR and PET-CT Functional Imaging for Boost Tumor Volume Delineation in Neoadjuvant Rectal Cancer Treatment.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36593016"}, {"offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Neoadjuvant chemoradiotherapy combined with immunotherapy for locally advanced rectal cancer: A new era for anal preservation.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36569918"}, {"offsetInBeginSection": 2078, "offsetInEndSection": 2295, "text": "A successor trial in locally advanced rectal cancer has been initiated to further evaluate this agent's ability to define tumor extent before and assess disease response after neoadjuvant chemotherapy and radiotherapy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36154291"}, {"offsetInBeginSection": 0, "offsetInEndSection": 3210, "text": "ESGE recommends that the evaluation of superficial gastrointestinal (GI) lesions should be made by an experienced endoscopist, using high definition white-light and chromoendoscopy (virtual or dye-based).ESGE does not recommend routine performance of endoscopic ultrasonography (EUS), computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET)-CT prior to endoscopic resection.ESGE recommends endoscopic submucosal dissection (ESD) as the treatment of choice for most superficial esophageal squamous cell and superficial gastric lesions.For Barrett's esophagus (BE)-associated lesions, ESGE suggests the use of ESD for lesions suspicious of submucosal invasion (Paris type 0-Is, 0-IIc), for malignant lesions >\u200a20\u200amm, and for lesions in scarred/fibrotic areas.ESGE does not recommend routine use of ESD for duodenal or small-bowel lesions.ESGE suggests that ESD should be considered for en bloc resection of colorectal (but particularly rectal) lesions with suspicion of limited submucosal invasion (demarcated depressed area with irregular surface pattern or a large protruding or bulky component, particularly if the lesions are larger than 20\u200amm) or for lesions that otherwise cannot be completely removed by snare-based techniques.ESGE recommends that an en bloc R0 resection of a superficial GI lesion with histology no more advanced than intramucosal cancer (no more than m2 in esophageal squamous cell carcinoma), well to moderately differentiated, with no lymphovascular invasion or ulceration, should be considered a very low risk (curative) resection, and no further staging procedure or treatment is generally recommended.ESGE recommends that the following should be considered to be a low risk (curative) resection and no further treatment is generally recommended: an en bloc R0 resection of a superficial GI lesion with superficial submucosal invasion (sm1), that is well to moderately differentiated, with no lymphovascular invasion, of size \u2264\u200a20\u200amm for an esophageal squamous cell carcinoma or \u2264\u200a30\u200amm for a stomach lesion or of any size for a BE-related or colorectal lesion, and with no lymphovascular invasion, and no budding grade 2 or 3 for colorectal lesions.ESGE recommends that, after an endoscopically complete resection, if there is a positive horizontal margin or if resection is piecemeal, but there is no submucosal invasion and no other high risk criteria are met, this should be considered a local-risk resection and endoscopic surveillance or re-treatment is recommended rather than surgery or other additional treatment.ESGE recommends that when there is a diagnosis of lymphovascular invasion, or deeper infiltration than sm1, or positive vertical margins, or undifferentiated tumor, or, for colorectal lesions, budding grade 2 or 3, this should be considered a high risk (noncurative) resection, and complete staging and strong consideration for additional treatments should be considered on an individual basis in a multidisciplinary discussion.ESGE recommends scheduled endoscopic surveillance with high definition white-light and chromoendoscopy (virtual or dye-based) with biopsies of only the suspicious areas after a curative ESD.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35523224"}, {"offsetInBeginSection": 0, "offsetInEndSection": 311, "text": "OBJECTIVE: The aim of this study was to investigate the feasibility of F-fluoroazomycinarabinofuranoside (F-FAZA) positron emission tomography (PET)/computed tomography (CT) in patients with locally advanced rectal cancer.MATERIALS AND METHODS: The study included 14 patients with locally advanced rectal cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23196674"}, {"offsetInBeginSection": 224, "offsetInEndSection": 558, "text": "TERIALS AND METHODS: The study included 14 patients with locally advanced rectal cancer. Before chemoradiotherapy, PET/CT with F-FAZA was performed with static 15 min images 2 h after injection of F-FAZA. Attenuation correction was obtained with a low-dose CT, and a contrast-enhanced CT was performed immediately after the PET scan.R", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23196674"}, {"offsetInBeginSection": 175, "offsetInEndSection": 634, "text": " Positron emission tomography(PET) is used in detection of recurrence or metastasis, but its value in routine preoperative rectal cancer staging remains unclear. Studies report that preoperative PET altered the stage in 39% and changed the management in 17-27% of patients. Our study aims to look at the utility of PET in routine preoperative staging of rectal cancer within 2 two colorectal units, and to determine if PET did result in a change in management", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36117452"}, {"offsetInBeginSection": 1038, "offsetInEndSection": 1298, "text": "3% of the patients had Stage 3 rectal cancer. 71.7% received neoadjuvant therapy. PET scan provided additional information in 55.5% of patients when compared with CT and MRI alone; 18.2% of the PET findings resulted in an altered management for the patient.CON", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36117452"}, {"offsetInBeginSection": 175, "offsetInEndSection": 447, "text": " Positron emission tomography(PET) is used in detection of recurrence or metastasis, but its value in routine preoperative rectal cancer staging remains unclear. Studies report that preoperative PET altered the stage in 39% and changed the management in 17-27% of patients", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36117452"}, {"offsetInBeginSection": 0, "offsetInEndSection": 427, "text": "OBJECTIVE: The aim of this study was to investigate the feasibility of F-fluoroazomycinarabinofuranoside (F-FAZA) positron emission tomography (PET)/computed tomography (CT) in patients with locally advanced rectal cancer.MATERIALS AND METHODS: The study included 14 patients with locally advanced rectal cancer. Before chemoradiotherapy, PET/CT with F-FAZA was performed with static 15 min images 2 h after injection of F-FAZA", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23196674"}, {"offsetInBeginSection": 448, "offsetInEndSection": 634, "text": " Our study aims to look at the utility of PET in routine preoperative staging of rectal cancer within 2 two colorectal units, and to determine if PET did result in a change in management", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36117452"}, {"offsetInBeginSection": 0, "offsetInEndSection": 447, "text": "BACKGROUND: Accurate staging for rectal cancer is pertinent with recent introduction of rectum-sparing approaches for patients showing complete clinical response on restaging. Positron emission tomography(PET) is used in detection of recurrence or metastasis, but its value in routine preoperative rectal cancer staging remains unclear. Studies report that preoperative PET altered the stage in 39% and changed the management in 17-27% of patients", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36117452"}, {"offsetInBeginSection": 1621, "offsetInEndSection": 2097, "text": "The degree of rectal cancer response to chemoradiation, established as mic vs. mac categories, was not associated with SUVmax differences (mean values of 2.0 vs. 2.7).CONCLUSION: Preliminary results observed suggest the potential utility of FDG-PET as a complementary diagnostic procedure in the initial clinical evaluation (8% of unsuspected liver metastases) as well as in the assessment of chemoradiation response (any T downstaged event) of locally advanced rectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14751524"}, {"offsetInBeginSection": 0, "offsetInEndSection": 376, "text": "PURPOSE: To assess the information supplied by FDG-PET in patients with locally advanced rectal cancer both in the initial staging and in the evaluation of tumor changes induced by preoperative chemoradiation (restaging).METHODS AND MATERIALS: Twenty-five consecutive patients with rectal cancer were included, with tumor stages (c)T(2-4)N(x)M(0), during the period 1997-1999.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14751524"}, {"offsetInBeginSection": 1270, "offsetInEndSection": 1549, "text": "Independent predictors for 5-year distant recurrence-free survival were pathological and PET metabolic response, nodal staging and lymphovascular invasion (LVI).CONCLUSION: In conclusion, a PET/CT has the potential to better stratify patients of their risk of distant metastasis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34435447"}, {"offsetInBeginSection": 1120, "offsetInEndSection": 1542, "text": "PET scan provided additional information in 55.5% of patients when compared with CT and MRI alone; 18.2% of the PET findings resulted in an altered management for the patient.CONCLUSION: PET scan can be a valuable tool in accurate staging, especially for ambiguous or equivocal lesions on CT. Our study demonstrated that additional information from PET scan resulted in an altered management plan in 18.2% of the patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36117452"}, {"offsetInBeginSection": 1247, "offsetInEndSection": 1583, "text": "There was a significant association between the SUVmax and tumor size (odds ratio [OR] 4.254,\u00a0p\u2009=\u20090.003) and the depth of tumor invasion (OR 1.696,\u00a0p\u2009=\u20090.026).CONCLUSIONS: Based on its ability to aid in preoperative evaluation and definitively alter surgical treatment planning, 18 FDG-PET/CT should be further evaluated in primary CRC.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37092877"}, {"offsetInBeginSection": 0, "offsetInEndSection": 960, "text": "BACKGROUND: At present there is no defined role for routine FDG-PET in the preoperative evaluation of nonmetastatic rectal cancer.OBJECTIVE: The primary objective of this study was to evaluate the ability of FDG-PET to predict long-term prognosis based on the response to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer.DESIGN: This was a prospective study.SETTINGS: This study was performed at an academic, tertiary care, comprehensive cancer center.PATIENTS: One hundred twenty-seven patients with locally advanced rectal cancer were enrolled between September 1999 and December 2005.INTERVENTIONS: All patients underwent FDG-PET scans before and after neoadjuvant chemoradiotherapy.MAIN OUTCOME MEASURES: FDG-PET parameters were evaluated by at least 2 study board-certified nuclear medicine physicians, and included mean standard uptake value, maximum standard uptake value, total lesion glycolysis, and visual response score.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22426260"}, {"offsetInBeginSection": 1781, "offsetInEndSection": 1977, "text": "No FDG-PET parameter was associated with disease-specific survival.CONCLUSIONS: Assessment of rectal cancer response to neoadjuvant chemoradiotherapy by FDG-PET provides no prognostic information.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22426260"}, {"offsetInBeginSection": 991, "offsetInEndSection": 1399, "text": "In a multivariate analysis including the clinicopathologic parameters, the TLG of the primary tumor was associated with a worse disease-free survival after neoadjuvant CCRT (HR 20.035, 95 % CI 1.726-232.559; P = 00.017).CONCLUSIONS: The TLG of the primary tumor in the initial FDG-PET/CT can be considered as a prognostic factor for patients with locally advanced rectal cancer treated with neoadjuvant CCRT.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23420438"}, {"offsetInBeginSection": 0, "offsetInEndSection": 423, "text": "PURPOSE: The present study evaluated the predictive and prognostic impact of initial fluorine-18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in patients with locally advanced rectal cancer treated with neoadjuvant concurrent chemoradiotherapy (CCRT).METHODS: Eighty-one consecutive patients with locally advanced rectal cancer (cT3-T4 N-/N+) treated with neoadjuvant CCRT were enrolled.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23420438"}, {"offsetInBeginSection": 987, "offsetInEndSection": 1271, "text": "Complete response on PET or PET/CT is a good prognostic factor for overall and progression-free survival.CONCLUSIONS: PET/CT seems to add value to conventional imaging in the initial staging of patients with T2-4 disease but further high-quality research is required to validate this.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28972796"}, {"offsetInBeginSection": 1978, "offsetInEndSection": 2092, "text": "Therefore, serial FDG-PET before and after neoadjuvant chemoradiotherapy should not be performed for this purpose.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22426260"}, {"offsetInBeginSection": 1277, "offsetInEndSection": 1382, "text": "Nine patients had unresectable metastatic disease and were excluded from the time-to-recurrence analysis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22426260"}, {"offsetInBeginSection": 4, "offsetInEndSection": 162, "text": "OSE: The aim of this study was to prospectively investigate the predictive value of (18)F-FDG PET/CT semiquantitative parameters for locally advanced low rect", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25348731"}, {"offsetInBeginSection": 104, "offsetInEndSection": 262, "text": "18)F]FDG PET/CT scans for the prediction of neoadjuvant radiation chemotherapy response and 3-year disease-free survival (DFS) in patients with locally advanc", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26338180"}, {"offsetInBeginSection": 306, "offsetInEndSection": 481, "text": "ight patients, diagnosed with locally advanced rectal cancer and referred for pre-operative treatment with CRT were included in this study. All patients underwent FDG-PET-CT i", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21571386"}, {"offsetInBeginSection": 203, "offsetInEndSection": 407, "text": "The current case report presents a unique case of a mass that was identified in the tonsil by positron emission tomography-computed tomography (PET-CT), indicating a metastasis from rectal adenocarcinoma.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24348839"}, {"offsetInBeginSection": 9, "offsetInEndSection": 215, "text": "Our primary objective was to determine if [(18)F]FPRGD2 PET/CT performed at baseline and/or after chemoradiotherapy (CRT) could predict tumour regression grade (TRG) in locally advanced rectal cancer (LARC)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26490751"}, {"offsetInBeginSection": 12, "offsetInEndSection": 192, "text": "Although many patients with locally advanced rectal cancer undergo restaging imaging after neoadjuvant chemoradiotherapy and before surgery, the benefit of this practice is unclear", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32712447"}, {"offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "PURPOSE: There appears to be no gold standard concerning preoperative imaging studies in patients with locally advanced lower rectal cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25731264"}, {"offsetInBeginSection": 742, "offsetInEndSection": 883, "text": "Positron emission tomography (PET)-CT may be useful in detecting occult synchronous tumors or metastases at the time of initial presentation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24764662"}, {"offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "BACKGROUND: At present there is no defined role for routine FDG-PET in the preoperative evaluation of nonmetastatic rectal cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22426260"}, {"offsetInBeginSection": 91, "offsetInEndSection": 1373, "text": "tum-sparing approaches for patients showing complete clinical response on restaging. Positron emission tomography(PET) is used in detection of recurrence or metastasis, but its value in routine preoperative rectal cancer staging remains unclear. Studies report that preoperative PET altered the stage in 39% and changed the management in 17-27% of patients. Our study aims to look at the utility of PET in routine preoperative staging of rectal cancer within 2 two colorectal units, and to determine if PET did result in a change in management.METHODS: Patients in Nepean Hospital (NSW) and Peter MacCallum Cancer Centre (VIC) who were diagnosed with rectal cancer between 1 January 2017 and 31 December 2021 were included in this retrospective study. All patients who did not have a PET scan were excluded. PET scan results were then compared with MRI and CT results.RESULTS: Three hundred and fifty-seven patients were included in the study. 30.3% of the patients had Stage 3 rectal cancer. 71.7% received neoadjuvant therapy. PET scan provided additional information in 55.5% of patients when compared with CT and MRI alone; 18.2% of the PET findings resulted in an altered management for the patient.CONCLUSION: PET scan can be a valuable tool in accurate staging, especially fo", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36117452"}, {"offsetInBeginSection": 0, "offsetInEndSection": 963, "text": "BACKGROUND: The risk of local recurrence (LR) continues to threat patients with rectal cancer after surgery or chemoradiotherapy. The main reason is that there is frequently extensive scarring and reactive changes after radiotherapy and resection. Thus, the diagnosis of LR can be challenging. There are different imaging modalities that have been used in the follow-up of rectal cancer, including computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and positron emission tomography-computed tomography (PET-CT) in clinical practice.METHODS: We will systematically search PubMed, EMBASE, the Cochrane Library, and Chinese Biomedical Literature Database for diagnostic trials using CT, MRI, PET, and PET-CT to detect LR of rectal cancer in April, 2018. Two review authors will independently screen titles and abstracts for relevance, assess full texts for inclusion, and carry out data extraction and methodological qual", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30508883"}, {"offsetInBeginSection": 1327, "offsetInEndSection": 1695, "text": "s found to have 92% PPV and perirectal lymphadenopathy 96% PPV for predicting a locally advanced stage. A combination of those two parameters results in a predictive PPV of 98%.LIMITATIONS: This was a single center retrospective study, with a relatively small cohort.CONCLUSIONS: CT is a valuable tool in the assessment and management of rectal carcinoma as it can ide", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30854604"}, {"offsetInBeginSection": 175, "offsetInEndSection": 335, "text": " Positron emission tomography(PET) is used in detection of recurrence or metastasis, but its value in routine preoperative rectal cancer staging remains unclear", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36117452"}, {"offsetInBeginSection": 1123, "offsetInEndSection": 1545, "text": " scan provided additional information in 55.5% of patients when compared with CT and MRI alone; 18.2% of the PET findings resulted in an altered management for the patient.CONCLUSION: PET scan can be a valuable tool in accurate staging, especially for ambiguous or equivocal lesions on CT. Our study demonstrated that additional information from PET scan resulted in an altered management plan in 18.2% of the patients. PE", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36117452"}, {"offsetInBeginSection": 67, "offsetInEndSection": 211, "text": "oxyglucose PET/computed tomography (18F-FDG PET/CT) parameters in the prediction of treatment response and the prognosis in locally advanced rec", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36437550"}, {"offsetInBeginSection": 1668, "offsetInEndSection": 1877, "text": "n 27% of patients (n = 10).CONCLUSIONS: FDG-PET/CT frequently yields additional staging information in patients with low rectal cancer. Improved accuracy of pretreatment imaging with FDG-PET/CT will allow for ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16485158"}, {"offsetInBeginSection": 788, "offsetInEndSection": 1011, "text": "umour in all 20 patients. Comparing PET/CT with conventional staging modalities, there were 11 discordant or incidental findings in nine patients (45%). This resulted in a potential change in stage in 30% (four patients dow", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19486092"}, {"offsetInBeginSection": 1759, "offsetInEndSection": 1898, "text": " did not effect surgical management. PET/CT may be most appropriately used selectively in more advanced stages and where indeterminate find", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19486092"}, {"offsetInBeginSection": 1863, "offsetInEndSection": 2104, "text": "se management for 96.8% of our patients. The results of our study conclude that PET/CT should not be routinely used for primary staging of colorectal cancer. More studies are required for identifying the subgroup of patients who might benefi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23445625"}, {"offsetInBeginSection": 2533, "offsetInEndSection": 2776, "text": "b&gt; Given the fact that PET/CT can detect all primary rectal cancer in preoperative staging, it can be effectively used in selected cases, particularly in those suspected of local and advanced disease and with metastases (T3N0, T3N1, and/or ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36468505"}]}
+{"question_id": "65f03163dffffb9b6b000005", "question": "Please list the selective endothelin A receptor antagonists", "answer": "The class of elective endothelin A receptor antagonist drugs include sitaxsentan , zibotentan, atrasentan, clozosentan, ambrisentan and darusentan", "relevant_passage_ids": ["32197449", "31593221", "32249614", "32985601", "32942043", "32726116", "15838362", "9761426", "14555186", "11922964", "15500395", "34175819", "26064237", "37820676", "37716952", "32472357", "8854203", "24498134", "15194180", "16292989", "21184655", "18238950", "17163810", "12193067", "16507220", "26196225", "15838329", "16544441", "19198697", "30579233", "22890981", "7982465", "7509976", "26192308", "31004470", "16219361", "12437501", "15363992", "22205719", "7891325", "7473559", "7813549", "8282010", "20660536", "7930556", "22332138", "12617928", "12193066", "23674888", "35084435", "9464847"], "type": "list", "snippets": [{"offsetInBeginSection": 801, "offsetInEndSection": 959, "text": ". The selective ERA clazosentan has been shown to be effective in preventing cerebral vasospasm and delaying ischemic neurological deficits and new infarcts. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32197449"}, {"offsetInBeginSection": 761, "offsetInEndSection": 828, "text": "sitaxentan (selective ETA receptor antagonist; 30 or 100\u2009mg/kg/day)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31593221"}, {"offsetInBeginSection": 357, "offsetInEndSection": 617, "text": "Selective antagonism of the endothelin-1 type A receptor (ETAR) by atrasentan treatment in combination with renin-angiotensin-aldosterone system inhibition with losartan has been shown to have the therapeutic benefit of lowering proteinuria in patients with DN", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32249614"}, {"offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Ambrisentan, an endothelin receptor type A-selective antagonist, inhibits cancer cell migration, invasion, and metastasis.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32985601"}, {"offsetInBeginSection": 404, "offsetInEndSection": 579, "text": "Zibotentan is a potent, selective inhibitor of the ETA receptor. We have identified zibotentan as a potential disease-modifying therapy for patients with microvascular angina.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32942043"}, {"offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Comparison of the protective effects of selective endothelin-a receptor antagonist, ambrisentan, a", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32726116"}, {"offsetInBeginSection": 58, "offsetInEndSection": 119, "text": "ambrisentan, a selective endothelin typeA receptor antagonist", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32726116"}, {"offsetInBeginSection": 225, "offsetInEndSection": 350, "text": "Atrasentan is a selective endothelin receptor type A (ETA) antagonist initially studied for the potential treatment of cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37820676"}, {"offsetInBeginSection": 1641, "offsetInEndSection": 1698, "text": "The endothelin receptor antagonist atrasentan reduced IR.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37716952"}, {"offsetInBeginSection": 883, "offsetInEndSection": 998, "text": "The selective endothelin receptor-A antagonists sitaxsentan and ambrisentan are currently undergoing investigation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15194180"}, {"offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Evaluation of the endothelin receptor antagonists ambrisentan, bosentan, macitentan, and sitaxsentan as hepatobiliary transporter inhibitors and substrates in sandwich-cultured human hepatocytes.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24498134"}, {"offsetInBeginSection": 743, "offsetInEndSection": 998, "text": "In addition to its efficacy as sole therapy, bosentan may have a role as part of a combination of drugs such as a prostanoid or sildenafil. The selective endothelin receptor-A antagonists sitaxsentan and ambrisentan are currently undergoing investigation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15194180"}, {"offsetInBeginSection": 581, "offsetInEndSection": 998, "text": "Bosentan, a dual-receptor antagonist, is approved by the U.S. Food and Drug Administration for class III and IV patients with PAH, based on two phase III trials. In addition to its efficacy as sole therapy, bosentan may have a role as part of a combination of drugs such as a prostanoid or sildenafil. The selective endothelin receptor-A antagonists sitaxsentan and ambrisentan are currently undergoing investigation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15194180"}, {"offsetInBeginSection": 378, "offsetInEndSection": 882, "text": "Oral endothelin receptor antagonists (ERAs) have been shown to improve pulmonary hemodynamics, exercise capacity, functional status, and clinical outcome in several randomized placebo-controlled trials. Bosentan, a dual-receptor antagonist, is approved by the U.S. Food and Drug Administration for class III and IV patients with PAH, based on two phase III trials. In addition to its efficacy as sole therapy, bosentan may have a role as part of a combination of drugs such as a prostanoid or sildenafil.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15194180"}, {"offsetInBeginSection": 378, "offsetInEndSection": 742, "text": "Oral endothelin receptor antagonists (ERAs) have been shown to improve pulmonary hemodynamics, exercise capacity, functional status, and clinical outcome in several randomized placebo-controlled trials. Bosentan, a dual-receptor antagonist, is approved by the U.S. Food and Drug Administration for class III and IV patients with PAH, based on two phase III trials.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15194180"}, {"offsetInBeginSection": 122, "offsetInEndSection": 742, "text": "Laboratory and clinical investigations have clearly shown that endothelin (ET)-1 is overexpressed in several forms of pulmonary vascular disease and likely plays a significant pathogenetic role in the development and progression of pulmonary vasculopathy. Oral endothelin receptor antagonists (ERAs) have been shown to improve pulmonary hemodynamics, exercise capacity, functional status, and clinical outcome in several randomized placebo-controlled trials. Bosentan, a dual-receptor antagonist, is approved by the U.S. Food and Drug Administration for class III and IV patients with PAH, based on two phase III trials.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15194180"}, {"offsetInBeginSection": 0, "offsetInEndSection": 353, "text": "OBJECTIVE: To provide an overview of the drug profile of the orally active, selective endothelin A receptor antagonist ambrisentan, and its efficacy and safety in the treatment of patients with pulmonary arterial hypertension (PAH).RESEARCH DESIGN AND METHODS: Medical literature on the use of ambrisentan in PAH was identified using MEDLINE and EMBASE.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26196225"}, {"offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Pharmacology of endothelin receptor antagonists ABT-627, ABT-546, A-182086 and A-192621: ex vivo and in vivo studies.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12193067"}, {"offsetInBeginSection": 369, "offsetInEndSection": 555, "text": "One of these substances, bosentan, blocks both ET(A) and ET(B) receptors, whereas the two other compounds, sitaxsentan and ambrisentan, are more selective blockers of the ET(A) receptor.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18238950"}, {"offsetInBeginSection": 186, "offsetInEndSection": 249, "text": "Atrasentan is a novel and selective inhibitor of ET-1 and ET-A.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16507220"}, {"offsetInBeginSection": 4, "offsetInEndSection": 128, "text": "Atrasentan (Xinlay(R)) is an anti-cancer drug from a new class of agents called selective endothelin-A receptor antagonists.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16544441"}, {"offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Ambrisentan is the second selective endothelin-A receptor antagonist to be licensed in Europe, and the first in the United States, for the management of pulmonary arterial hypertension (PAH).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19198697"}, {"offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Ambrisentan is a highly selective endothelin-A receptor antagonist for the treatment of pulmonary arterial hypertension (PAH).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30579233"}, {"offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Sitaxentan sodium (Thelin) is a once daily, orally bioavailable, highly selective endothelin A receptor antagonist.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22890981"}, {"offsetInBeginSection": 46, "offsetInEndSection": 153, "text": "BQ-123 (cyclo(D-Trp-D-Asp-L-Pro-D-Val-L-Leu-), sodium salt), a selective endothelin ETA receptor antagonist", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7982465"}, {"offsetInBeginSection": 360, "offsetInEndSection": 426, "text": "Atrasentan (a selective endothelin-A receptor antagonist; 6 mg/kg)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15838362"}, {"offsetInBeginSection": 689, "offsetInEndSection": 753, "text": "Zibotentan or Atrasentan, two selective ETA receptor antagonists", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26064237"}, {"offsetInBeginSection": 0, "offsetInEndSection": 555, "text": "Until recently, a role for endothelin-1 (ET-1) in the development and/or maintenance of hypertension has been based solely on indirect findings, e.g., elevated circulating levels of peptide. However, with the development of specific ET-1 receptor antagonists it is now possible to examine this relationship directly. The present study describes the hemodynamic effects of systemic infusions of BQ-123, a selective endothelin (ETA)-receptor antagonist, in conscious, freely moving spontaneously hypertensive (SHRs) and normotensive Wistar-Kyoto (WKY) rats.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7509976"}, {"offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "BACKGROUND: Endothelin A (ET-A) receptor antagonists including zibotentan and atrasentan, have been suggested as a treatment for castration-resistant prostate ca", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26192308"}, {"offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Clazosentan is a selective endothelin A receptor antagonist in development for the prevention and treatment of vasospasm postsubarachnoid hemorrhage.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31004470"}, {"offsetInBeginSection": 1209, "offsetInEndSection": 1307, "text": "In conclusion, YM598 is a potent and orally active selective endothelin ET(A) receptor antagonist.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14555186"}, {"offsetInBeginSection": 490, "offsetInEndSection": 777, "text": "endothelin receptor antagonists has been introduced for treatment of patients with pulmonary arterial hypertension (PAH). Bosentan, a dual endothelin receptor antagonist as well as Sitaxsentan and Ambrisentan, selective blockers of the ETA receptor have proven effective in SSc-PAH. This", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21184655"}, {"offsetInBeginSection": 26, "offsetInEndSection": 79, "text": "YM598, a novel endothelin-A (ETA) receptor antagonist", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15838329"}, {"offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "BMS-182874 is a selective, nonpeptide endothelin ETA receptor antagonist.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7891325"}, {"offsetInBeginSection": 1717, "offsetInEndSection": 1803, "text": "compound 8 (BQ-123) is a highly soluble, potent, and selective ETA receptor antagonist", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7473559"}, {"offsetInBeginSection": 450, "offsetInEndSection": 507, "text": "the selective endothelin ETA receptor antagonist FR139317", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7813549"}, {"offsetInBeginSection": 70, "offsetInEndSection": 128, "text": "FR139317 as a selective endothelin ETA-receptor antagonist", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8854203"}, {"offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "27-O-Caffeoyl myricerone (50-235) is a nonpeptide endothelin receptor antagonist which is highly selective for the endothelin ETA receptor subtype.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8282010"}, {"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Sitaxsentan, a highly selective endothelin-A (ET(A)) receptor antagonist (6500-fold more selective for ET(A) receptors than endothelin-B (ET(B)) receptors)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15500395"}, {"offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Darusentan, a selective endothelin A receptor antagonist, for the oral treatment of resistant hypertension.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20660536"}, {"offsetInBeginSection": 0, "offsetInEndSection": 426, "text": "The binding affinities of (E)-N-[6-methoxy-5-(2-methoxyphenoxy)[2,2'-bipyrimidin]-4-yl]-2-phenylethenesulfonamide monopotassium salt (YM598) for native human endothelin ETA and ETB receptors expressed in human coronary artery smooth muscle cells (CASMC) and a human melanoma cell line, SK-Mel-28, respectively, were examined, and the results compared with those for the endothelin receptor antagonists atrasentan and bosentan.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15363992"}, {"offsetInBeginSection": 1044, "offsetInEndSection": 1168, "text": "These responses were improved by Compound-E, but not by BQ-123 nor by bosentan, an ETAR and endothelin B receptor antagonist", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34175819"}, {"offsetInBeginSection": 0, "offsetInEndSection": 631, "text": "OBJECTIVE: To investigate the role of endothelin-1 in the pathogenesis of hypertension directly by using the selective endothelin subtype A-receptor antagonist BQ-123.METHODS: The antihypertensive and hemodynamic effects of sustained BQ-123 administration were examined in conscious, unrestrained spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto (WKY) rats and renin hypertensive rats.RESULTS: Sustained infusions of BQ-123 (0.16-164 nmol/kg per min, intravenously, for 6 h) produced dose-dependent reductions in mean arterial pressure in SHR, the maximal reduction being obtained with a dose of 16 nmol/kg per min.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7930556"}, {"offsetInBeginSection": 491, "offsetInEndSection": 759, "text": "Preliminary data suggests that selective endothelin type A (ET(A)) receptor antagonists (BQ-123, sitaxsentan) may be more beneficial than the non-selective ET receptor antagonists in heart failure, especially when the failure is associated with pulmonary hypertension.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12437501"}, {"offsetInBeginSection": 290, "offsetInEndSection": 440, "text": "eptor antagonists on endothelin-1-induced increase in blood pressure. Atrasentan (a selective endothelin-A receptor antagonist; 6 mg/kg) and A-192621 ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15838362"}, {"offsetInBeginSection": 516, "offsetInEndSection": 724, "text": "The ET(A) plus ET(B) receptor antagonist, PD145065 (1 microM), and the selective ET(A) receptor antagonist, BQ610 (3 microM), completely relaxed the hypocapnic constriction, as determined in a cranial window.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11922964"}, {"offsetInBeginSection": 606, "offsetInEndSection": 1091, "text": "Stimulation by endothelin-1 ranging from 10(-11) to 10(-9) M time and dose dependently increased the production of prostaglandin E2 and the expression of cyclooxygenase 2 protein without changing that of cyclooxygenase 1 protein, an effect which was inhibited by dexamethasone, nonsteroidal anti-inflammatory drugs and the selective endothelin ET(B) receptor antagonist, BQ788 (N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methyl-leucyl-D-L-me thoxycarbonyl-tryptophanyl-D-norleucine).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9761426"}, {"offsetInBeginSection": 24, "offsetInEndSection": 174, "text": "gonists are commonly used in the treatment of pulmonary hypertension. Sitaxsentan, a selective endothelin A receptor blocker, induces a mild transamin", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22332138"}, {"offsetInBeginSection": 0, "offsetInEndSection": 411, "text": "Modification of the structure of bosentan 1, the first marketed endothelin receptor antagonist (Tracleer), by introduction of a second sulfonamide function at the alkoxy side chain, led to bis-sulfonamides 2. This allowed to prepare dual ET(A)/ET(B) as well as ET(B) receptor selective antagonists, which could serve as tools to investigate the pharmacological consequences of selective ET(B) receptor blockade.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12617928"}, {"offsetInBeginSection": 617, "offsetInEndSection": 1042, "text": "The first dual ETA/ETB receptor blocker, bosentan, has already been approved by the Food and Drug Administration for the treatment of pulmonary arterial hypertension (PAH). Trials of endothelin receptor antagonists in heart failure have been completed with mixed results so far. Studies are ongoing on the effects of selective ETA antagonists or dual ETA/ETB antagonists in lung fibrosis, cancer, and subarachnoid hemorrhage.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16219361"}, {"offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "Sitaxsentan is an orally active, selective endothelin-A receptor antagonist that may benefit patients with pulmonary arterial hypertension by blocking the vasoconstrictive effects of endothelin-A receptors, while maintaining the vasodilator and endothelin-1 clearance functions of the endothelin-B receptors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16292989"}, {"offsetInBeginSection": 84, "offsetInEndSection": 258, "text": "Sitaxsentan, a selective endothelin-A receptor antagonist, is an effective, safe and well-tolerated endothelin receptor antagonist for the treatment of PAH in adult patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17163810"}, {"offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Pharmacology of endothelin receptor antagonists ABT-627, ABT-546, A-182086 and A-192621: in vitro studies.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12193066"}, {"offsetInBeginSection": 121, "offsetInEndSection": 293, "text": "resistance. Ambrisentan is an oral, propanoic acid based-endothelin receptor antagonist (ERA), selective for the endothelin type-A receptor, which is approved for the treat", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32472357"}, {"offsetInBeginSection": 167, "offsetInEndSection": 314, "text": "Ambrisentan is a selective endothelin type A receptor antagonist approved for the treatment of patients with PAH World Health Organization group 1.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23674888"}, {"offsetInBeginSection": 402, "offsetInEndSection": 603, "text": "Ambrisentan, a selective ET(A) receptor antagonist, is metabolized primarily by uridine 5'diphosphate glucuronosyltransferases (UGTs) 1A9S, 2B7S, and 1A3S and, to a lesser extent, by CYP3A and CYP2C19.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22205719"}, {"offsetInBeginSection": 880, "offsetInEndSection": 925, "text": "BQ-123, the selective ETA receptor antagonist", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35084435"}, {"offsetInBeginSection": 647, "offsetInEndSection": 691, "text": "BQ 123 (a selective ETA receptor antagonist)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9464847"}]}
+{"question_id": "65f846bfc4010b4d78000045", "question": "What is the transmission mechanism of the Hendra virus in humans?", "answer": "Transmission of Hendra virus to humans occurs with exposure to body fluids and tissues or excretions of infected horses. \nNo human-to-human transmission has been documented.", "relevant_passage_ids": ["33363250", "22752412"], "type": "summary", "snippets": [{"offsetInBeginSection": 105, "offsetInEndSection": 291, "text": "Recognized human infections have all resulted from a HeV infected horse that was unusually efficient in transmitting the virus and a person with a high exposure to infectious secretions.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22752412"}]}
+{"question_id": "661d5c97eac11fad33000021", "question": "What is the cause of Prader-Willi Syndrome?", "answer": "Prader-Willi syndrome is a complex epigenetic disorder caused by the deficiency of paternally expressed genes in chromosome 15q11-q13.", "relevant_passage_ids": ["37491450", "9401540", "22903639", "17522286", "9391886", "20837313", "36515769", "12699864", "16038620", "32961075", "28266014", "37987848", "37958807", "32922110", "10626556", "22237428", "18781185", "24737477", "17159828", "23700380", "32555988", "14749005", "19066619", "18554170", "30365815", "10910667", "24704109", "37511333", "36873672", "36582000", "37405372", "37223137", "28933395", "31333129", "27330749", "21503198", "24859787", "16357227", "16075369"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Prader-Willi syndrome (PWS), which is a complex epigenetic disorder caused by the deficiency of paternally expressed genes in chromosome 15q11-q13, ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37491450"}, {"offsetInBeginSection": 206, "offsetInEndSection": 461, "text": "The 15q11-q13 locus is a hotspot of recurrent copy number variation associated with Prader-Willi/Angelman syndromes, developmental delay, autism, and epilepsy and is mediated by complex segmental duplications, many of which arose recently during evolution", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37958807"}, {"offsetInBeginSection": 126, "offsetInEndSection": 338, "text": "Prader-Willi syndrome is caused by the absence of certain paternally inherited genes on the long arm of chromosome 15, resulting in a complete absence of the active copy of the genetic information in this region.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17522286"}, {"offsetInBeginSection": 126, "offsetInEndSection": 464, "text": "Prader-Willi syndrome is caused by the absence of certain paternally inherited genes on the long arm of chromosome 15, resulting in a complete absence of the active copy of the genetic information in this region. It is most commonly known for its food-related characteristics of hyperphagia, food-seeking behavior, and consequent obesity.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17522286"}, {"offsetInBeginSection": 0, "offsetInEndSection": 397, "text": "The genetic basis of Prader-Willi syndrome involves imprinted genes on the proximal long arm of chromosome 15. The basic defect appears to be the absence of function of genes that are normally expressed in a monoallelic fashion only from the paternal chromosome. In 60-70% of patients with Prader-Willi syndrome, the genetic defect is a deletion in the area of 15q11-13 on the paternal chromosome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9401540"}, {"offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "The genetic basis of Prader-Willi syndrome involves imprinted genes on the proximal long arm of chromosome 15. The basic defect appears to be the absence of function of genes that are normally expressed in a monoallelic fashion only from the paternal chromosome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9401540"}, {"offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Prader-Willi syndrome is a multigenic disorder with developmental and neurobehavioural abnormalities. There are multiple genetic causes, although all ultimately involve the loss of paternally derived gene expression of chromosome region 15q11-q13.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10626556"}, {"offsetInBeginSection": 590, "offsetInEndSection": 928, "text": "Consensus clinical diagnostic criteria exist, but diagnosis should be confirmed through genetic testing. Prader-Willi syndrome is due to absence of paternally expressed imprinted genes at 15q11.2-q13 through paternal deletion of this region (65-75% of individuals), maternal uniparental disomy 15 (20-30%), or an imprinting defect (1-3%).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22237428"}, {"offsetInBeginSection": 546, "offsetInEndSection": 928, "text": "Management is otherwise largely supportive. Consensus clinical diagnostic criteria exist, but diagnosis should be confirmed through genetic testing. Prader-Willi syndrome is due to absence of paternally expressed imprinted genes at 15q11.2-q13 through paternal deletion of this region (65-75% of individuals), maternal uniparental disomy 15 (20-30%), or an imprinting defect (1-3%).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22237428"}, {"offsetInBeginSection": 695, "offsetInEndSection": 928, "text": "Prader-Willi syndrome is due to absence of paternally expressed imprinted genes at 15q11.2-q13 through paternal deletion of this region (65-75% of individuals), maternal uniparental disomy 15 (20-30%), or an imprinting defect (1-3%).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22237428"}, {"offsetInBeginSection": 263, "offsetInEndSection": 397, "text": "In 60-70% of patients with Prader-Willi syndrome, the genetic defect is a deletion in the area of 15q11-13 on the paternal chromosome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9401540"}, {"offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Prader-Willi syndrome (PWS) is caused by the loss of function of the paternally inherited 15q11-q13 locus.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32961075"}, {"offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Prader-Willi syndrome (PWS) is caused by the lack of expression of genes located on paternal chromosome 15q11-q13.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24737477"}, {"offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "The genetic basis of Prader-Willi syndrome involves imprinted genes on the proximal long arm of chromosome 15.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9401540"}, {"offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "Prader-Willi syndrome is caused by the lack of paternal contribution for the imprinted 15q11-q13 region that originates through a number of mechanisms such as paternal deletion of 15q11-q13, maternal uniparental disomy, or by an imprinting defect due to epimutations in the paternal imprinting center.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22903639"}, {"offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Prader-Willi syndrome (PWS) is a rare genetic disorder caused by the loss of imprinted gene expression on the paternal chromosome 15q11-q13.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37987848"}, {"offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "INTRODUCTION: Prader-Willi syndrome is a complex neurodevelopmental genetic disorder due to lack of paternal expression of critical imprinted genes in the 15q11.2-q13.1 chromosomal region, generally from a pate", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36515769"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1243, "text": "The genetic basis of Prader-Willi syndrome involves imprinted genes on the proximal long arm of chromosome 15. The basic defect appears to be the absence of function of genes that are normally expressed in a monoallelic fashion only from the paternal chromosome. In 60-70% of patients with Prader-Willi syndrome, the genetic defect is a deletion in the area of 15q11-13 on the paternal chromosome. A further 25-30% of patients with Prader-Willi syndrome do not have paternal deletions, the defect being due to uniparental disomy (UPD) for maternal chromosome 15. Paternal deletions and maternal UPD are functionally equivalent, as they both result in the absence of a paternal contribution to the genome in the 15q11-13 region. The SNRPN (small nuclear ribonucleoprotein-associated polypeptide N) gene has a critical role in the 15q11-13 region, as it is probably part of the putative imprinting centre that regulates the expression of several genes in the Prader-Willi syndrome transcriptional domain. Two further rare causes of Prader-Willi syndrome are imprinting mutations, which are microdeletions or point mutations in the putative imprinting control region, and translocations with their breakpoints in the Prader-Willi syndrome region.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9401540"}, {"offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Prader-Willi syndrome (PWS) is caused by the loss of RNA expression from an imprinted region on chromosome 15 that includes SNRPN, SNORD115, and SNORD116.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23700380"}, {"offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Prader-Willi syndrome (PWS) is a genetic disorder caused by the absence of gene expression in the 15q11.2-q13 paternal chromosome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32555988"}, {"offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "Prader-Willi syndrome (PWS) is caused by the lack of expression of genes located on paternal chromosome 15q11-q13. This lack of gene expression may be due to a deletion in this chromosomal segment, to maternal uniparental disomy of chromosome 15, or to a defect in the imprinting center on 15q11-q13.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24737477"}, {"offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "OBJECTIVE: Prader-Willi syndrome (PWS) is an example of a human genetic disorder that involves imprinting genes on the proximal long arm of chromosome 15 and SNRPN gene as a candidate gene for thi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14749005"}, {"offsetInBeginSection": 406, "offsetInEndSection": 573, "text": "Prader-Willi syndrome is caused by abnormalities of the imprinted region of proximal 15q and results from absence of the normally active paternal genes in this region.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9391886"}, {"offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "The Prader-Willi syndrome (PWS) is caused by a 5-6 Mbp de novo deletion on the paternal chromosome 15, maternal uniparental disomy 15 or an imprinting defect.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19066619"}, {"offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Prader-Willi syndrome (PWS) is a contiguous gene syndrome caused by the loss of function of genes situated within the 15q11-q13 region.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18554170"}, {"offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Prader-Willi syndrome is a rare neurogenetic disorder, which is evidence of genomic imprinting in undercentromeric region of chromosome 15. Defects of the SNRPN gene are the main cause of the syndrome. PWS", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10910667"}, {"offsetInBeginSection": 346, "offsetInEndSection": 856, "text": "cles in such databases.DATA SYNTHESIS: The Prader-Willi Syndrome (PWS) is a rare genetic disorder resulting from the loss of imprinted gene expression within the paternal chromosome 15q11-q13. PWS is characterized by endocrine abnormalities, such as growth hormone (GH) deficiency, obesity, central adrenal insufficiency, hypothyroidism, hypogonadism and complex behavioral and intellectual difficulties. PWS individuals also may present other comorbidities, such as sleep disorders, scoliosis, constipation, d", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30365815"}, {"offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Prader-Willi syndrome (PWS) is a neurodevelopmental disorder that arises from lack of expression of paternally inherited genes known to be imprinted and located in the chromosome 15q11-q13 region.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16038620"}, {"offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Prader-Willi syndrome is a chromosomal disorder caused by absence of expression of the paternal active genes in the 15q11\u223cq13 chromosome region; it is associated with an increased incidence of epilepsy and narcolepsy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20837313"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "The genetic basis of Prader-Willi syndrome involves imprinted genes on the proximal long arm of chromosome 15. The basic defect appears to be the abse", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9401540"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Prader-Willi syndrome is caused by the lack of paternal contribution for the imprinted 15q11-q13 region that originates through a number of mechanisms", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22903639"}, {"offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Prader-Willi syndrome (PWS) is a neuroendocrine genetic disorder resulting from the loss of paternally expressed imprinted genes in chromosome 15q11-q13 [...].", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37511333"}, {"offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Prader-Willi syndrome (PWS) is a rare genetic disorder due to lack of genes expression inherited from the paternal chromosome 15q11-q13 region usually from paternal deletions, maternal uniparental disomy 15 or imprinting defect", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36873672"}, {"offsetInBeginSection": 12, "offsetInEndSection": 175, "text": "Prader-Willi syndrome (PWS) is a multisystemic complex genetic disorder caused by the loss of paternally expressed genes in the human chromosome region 15q11.2-q13", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36582000"}, {"offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "The genetic disorder Prader-Willi syndrome (PWS) is mainly caused by the loss of multiple paternally expressed genes in chromosome 15q11-q13 (the PWS region)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37405372"}, {"offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Prader-Willi syndrome (PWS) is a congenital neurodevelopmental disorder caused by loss of function of paternally expressed genes on chromosome 15 due to paternal deletion of 15q11-q13, maternal uniparental disomy for chromosome 15, or an imprinting mutation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28933395"}, {"offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Prader-Willi syndrome is a chromosomal disorder caused by absence of expression of the paternal active genes in the 15q11\u223cq13 chromosome region; it is associated with an increased incidence of epilepsy and narcolepsy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20837313"}, {"offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "Prader-Willi syndrome (PWS) is a complex, multisystem neurodevelopmental disorder affecting approximately 1 in 25,000 live births. PWS is caused by absence of expression of paternally inherited imprinted genes on chromosome 15q11-q13. The syndrome typically occurs due to one of three genetic mechanisms:", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32922110"}, {"offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Prader-Willi syndrome (PWS) is a congenital neurodevelopmental disorder caused by loss of function of paternally expressed genes on chromosome 15 due to paternal deletion of 15q11-q13, maternal uniparental disomy for chromosome 15, or an imprinting mutation. We previously", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28933395"}, {"offsetInBeginSection": 0, "offsetInEndSection": 904, "text": "BACKGROUND: Prader-Willi Syndrome (PWS) is a neurodevelopmental genomic imprinting disorder with lack of expression of genes inherited from the paternal chromosome 15q11-q13 region usually from paternal 15q11-q13 deletions (about 60%) or maternal uniparental disomy 15 or both 15s from the mother (about 35%). An imprinting center controls the expression of imprinted genes in the chromosome 15q11-q13 region. Key findings include infantile hypotonia, a poor suck, failure to thrive and hypogonadism/hypogenitalism. Short stature and small hands/feet due to growth and other hormone deficiencies, hyperphagia and marked obesity occur in early childhood, if uncontrolled. Cognitive and behavioral problems (tantrums, compulsions, compulsive skin picking) are common.OBJECTIVE: Hyperphagia and obesity with related complications are major causes of morbidity and mortality in PWS. This report will describe", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31333129"}, {"offsetInBeginSection": 0, "offsetInEndSection": 386, "text": "Prader-Willi syndrome is a neurologic disorder caused by a mutation on chromosome 15. It is characterized by short stature, obesity, mild-to-moderate mental retardation, and multiple behavior problems including mood, self-abusive behavior, and compulsive-eating disorder. These behaviors have detrimental effects on the mental and physical health of patients with Prader-Willi syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12699864"}, {"offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Prader-Willi syndrome is a neurologic disorder caused by a mutation on chromosome 15. It is characterized by short stature, obesity, mild-to-moderate mental retardation, and multiple behavior problems including mood, self-abusive behavior, and compulsive-eating disorder.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12699864"}, {"offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Prader-Willi syndrome is a neurologic disorder caused by a mutation on chromosome 15.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12699864"}, {"offsetInBeginSection": 406, "offsetInEndSection": 870, "text": "Prader-Willi syndrome is caused by abnormalities of the imprinted region of proximal 15q and results from absence of the normally active paternal genes in this region. Such absence results from paternal interstitial deletion, maternal uniparental disomy, or a mutation or other abnormality in the imprinting process. Diagnostic identification of all causes has become available in recent years, permitting early detection and institution of appropriate management.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9391886"}, {"offsetInBeginSection": 406, "offsetInEndSection": 722, "text": "Prader-Willi syndrome is caused by abnormalities of the imprinted region of proximal 15q and results from absence of the normally active paternal genes in this region. Such absence results from paternal interstitial deletion, maternal uniparental disomy, or a mutation or other abnormality in the imprinting process.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9391886"}, {"offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "Background Prader-Willi syndrome (PWS) is a complex genetic disorder caused by a deficit in gene\u00a0expression on the paternal inherited chromosome 15q11.2-q13. It affects various aspects of growth and development, including feeding, cognitive function, and behavior. Early diagnosis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37223137"}, {"offsetInBeginSection": 530, "offsetInEndSection": 808, "text": "PWS is an example of a genetic condition involving genomic imprinting. It can occur by three main mechanisms, which lead to absence of expression of paternally inherited genes in the 15q11.2-q13 region: paternal microdeletion, maternal uniparental disomy, and imprinting defect.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18781185"}, {"offsetInBeginSection": 0, "offsetInEndSection": 339, "text": "Prader-Willi syndrome (PWS) is a neurobehavioral imprinting disorder, which arises due to an absence of paternally expressed genes within the 15q11.2-q13 region. This occurs via one of the three main genetic mechanisms, as follows: Deletion of the paternally inherited 15q11.2-q13 region, maternal uniparental disomy and imprinting defect.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27330749"}, {"offsetInBeginSection": 413, "offsetInEndSection": 693, "text": "PWS is an example of a genetic condition caused by genomic imprinting. It can occur via 3 main mechanisms that lead to the absence of expression of paternally inherited genes in the 15q11.2-q13 region: paternal microdeletion, maternal uniparental disomy, and an imprinting defect.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21503198"}, {"offsetInBeginSection": 258, "offsetInEndSection": 509, "text": "Prader-Willi syndrome is due to the absence of paternally expressed imprinted genes at 15q11.2-13, and 3 main mechanisms are known to be involved in its pathogenesis: paternal microdeletions, maternal uniparental disomy events, and imprinting defects.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24859787"}, {"offsetInBeginSection": 0, "offsetInEndSection": 323, "text": "Prader-Willi syndrome (PWS) is caused by the lack of paternal expression of imprinted genes in the human chromosomal region 15q11.2-q13.2, which can be due to an interstitial deletion at 15q11.2-q13 of paternal origin (65-75%), maternal uniparental disomy (matUPD) of chromosome 15 (20-30%), or an imprinting defect (1-3%).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24704109"}, {"offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "The Prader-Willi syndrome is a congenital disease that is caused by the loss of paternal gene expression from a maternally imprinted region on chromosome 15.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16357227"}, {"offsetInBeginSection": 157, "offsetInEndSection": 390, "text": "the allele. Prader-Willi syndrome is a neurobehavioral disorder in which the expression of active paternal alleles of imprinted genes from chromosomal region 15q11-q13 is abolished by deletions, maternal uniparental disomy or imprint", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17159828"}, {"offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Prader-Willi syndrome (PWS) is a neurobehavioral disorder caused by the lack of paternal expression of imprinted genes in the human chromosome region 15q11-13.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16075369"}, {"offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Prader-Willi syndrome is a complex condition caused by lack of expression of imprinted genes in the paternally derived region of chromosome 15 (15q11q13).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28266014"}]}
+{"question_id": "65cfe1d21930410b1300002a", "question": "Can capivasertib be used for breast cancer?", "answer": "Yes. Capivasertib is effective and be used for treatment of breast cancer", "relevant_passage_ids": ["36508589", "37046675", "37256976", "35398754", "35671774", "36901954"], "type": "yesno", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Capivasertib Doubles PFS in Some Breast Cancers.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36508589"}, {"offsetInBeginSection": 0, "offsetInEndSection": 311, "text": "In the phase III CAPItello-291 study, the combination of fulvestrant and capivasertib more than doubled progression-free survival compared with fulvestrant alone in patients with hormone receptor-positive, HER2-negative breast cancer who have developed resistance to aromatase inhibitors and CDK4/6 inhibitors. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36508589"}, {"offsetInBeginSection": 633, "offsetInEndSection": 1189, "text": "In this setting of high unmet need, several clinical trials of novel drugs have recently reported encouraging results: the addition of the AKT-inhibitor capivasertib to fulvestrant demonstrated a significant improvement in progression-free survival (PFS); the oral selective estrogen receptor degrader (SERD) elacestrant prolonged PFS compared to traditional ET in a phase 3 trial, particularly among patients with detectable ESR1 mutations; finally, PARP inhibitors are available treatment options for patients with pathogenic BRCA1/2 germline mutations. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37046675"}, {"offsetInBeginSection": 2088, "offsetInEndSection": 2418, "text": "CONCLUSIONS: Capivasertib-fulvestrant therapy resulted in significantly longer progression-free survival than treatment with fulvestrant alone among patients with hormone receptor-positive advanced breast cancer whose disease had progressed during or after previous aromatase inhibitor therapy with or without a CDK4/6 inhibitor. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37256976"}, {"offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37256976"}, {"offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "\"The emerging role of capivasertib in breast cancer\".", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35398754"}, {"offsetInBeginSection": 2094, "offsetInEndSection": 2422, "text": "SIONS: Capivasertib-fulvestrant therapy resulted in significantly longer progression-free survival than treatment with fulvestrant alone among patients with hormone receptor-positive advanced breast cancer whose disease had progressed during or after previous aromatase inhibitor therapy with or without a CDK4/6 inhibitor. (Fun", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37256976"}, {"offsetInBeginSection": 255, "offsetInEndSection": 1646, "text": "re limited.METHODS: In a phase 3, randomized, double-blind trial, we enrolled eligible pre-, peri-, and postmenopausal women and men with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer who had had a relapse or disease progression during or after treatment with an aromatase inhibitor, with or without previous cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor therapy. Patients were randomly assigned in a 1:1 ratio to receive capivasertib plus fulvestrant or placebo plus fulvestrant. The dual primary end point was investigator-assessed progression-free survival assessed both in the overall population and among patients with AKT pathway-altered (PIK3CA, AKT1, or PTEN) tumors. Safety was assessed.RESULTS: Overall, 708 patients underwent randomization; 289 patients (40.8%) had AKT pathway alterations, and 489 (69.1%) had received a CDK4/6 inhibitor previously for advanced breast cancer. In the overall population, the median progression-free survival was 7.2 months in the capivasertib-fulvestrant group, as compared with 3.6 months in the placebo-fulvestrant group (hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.51 to 0.71; P<0.001). In the AKT pathway-altered population, the median progression-free survival was 7.3 months in the capivasertib-fulvestrant group, as compared with 3.1 months in the", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37256976"}, {"offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "BACKGROUND: Capivasertib, an AKT inhibitor, added to fulvestrant, was previously reported to improve progression-free survival in women with aromatase inhibitor-resistant oestrogen receptor (ER)-positive, HER2-negative advanced breast cancer. The benefit ap", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35671774"}, {"offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "BACKGROUND: Capivasertib, an AKT inhibitor, added to fulvestrant, was previously reported to improve progression-free survival in women with aromatase inhibitor-resistant oestrogen receptor (ER)-positive, HER2-negative advanced breast cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35671774"}, {"offsetInBeginSection": 12, "offsetInEndSection": 241, "text": "Capivasertib, an AKT inhibitor, added to fulvestrant, was previously reported to improve progression-free survival in women with aromatase inhibitor-resistant oestrogen receptor (ER)-positive, HER2-negative advanced breast cancer", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35671774"}, {"offsetInBeginSection": 357, "offsetInEndSection": 635, "text": "Among these, the PIK3CA isoform-specific inhibitor alpelisib and the pan-AKT inhibitor capivasertib were recently approved in combination with the estrogen receptor degrader fulvestrant for the treatment of ER+ advanced breast cancer after progression on an aromatase inhibitor.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36901954"}, {"offsetInBeginSection": 4246, "offsetInEndSection": 4453, "text": "RETATION: Updated FAKTION data showed that capivasertib addition to fulvestrant extends the survival of participants with aromatase inhibitor-resistant ER-positive, HER2-negative advanced breast cancer. The ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35671774"}, {"offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "In the phase III CAPItello-291 study, the combination of fulvestrant and capivasertib more than doubled progression-free survival compared with fulvestrant alone in patients with hormone receptor-positive, HER2-negative breast cancer who have developed resistance to aromatase inhibitors and CDK4/6 inhibitors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36508589"}]}
+{"question_id": "65f777d7c4010b4d78000032", "question": "What is the optimal timing of surgical resection after a neoadjuvant chemoradiotherapy for locally advanced rectal cancer patients?", "answer": "Depending the clinical response, 8 weeks (for poor responders) or 10 weeks after completing neoadjuvant Chemoradiotherapy (CRT) are the recommended interval to surgical resection", "relevant_passage_ids": ["34586340", "32966845", "26897480", "29178095", "23741691", "27797248", "29594111", "23739201", "32884221", "19153567", "26514119", "37227524", "30155949", "36042105", "26589718", "31392039", "36169163", "37312044", "18650634", "37261511", "34633256", "35279746", "30963399", "26206642", "31579713", "32232742", "26144023", "32848330", "34661871", "36271070", "23328971", "29153429", "22202303", "19879716", "25538402", "21494121", "35660797", "37757518", "27251135"], "type": "factoid", "snippets": [{"offsetInBeginSection": 581, "offsetInEndSection": 755, "text": " Patients were classified into Early (<\u200925\u00a0days) and Delayed (\u2265\u200925\u00a0days) cohorts after an adjusted analysis of the relationship between time to surgery and 10-year survival. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38012438"}, {"offsetInBeginSection": 1720, "offsetInEndSection": 1914, "text": " Patients with CC who underwent resection\u2009\u2265\u200925\u00a0days following diagnosis demonstrated similar 1-year, but inferior 5- and 10-year survival, compared to those who underwent surgery within 25\u00a0days.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38012438"}, {"offsetInBeginSection": 1435, "offsetInEndSection": 1577, "text": "A total of 579 patients (54.4%) had a shorter wait time (8 weeks or less) 485 patients (45.6%) had a longer wait time (greater than 8 weeks). ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34586340"}, {"offsetInBeginSection": 2338, "offsetInEndSection": 2676, "text": "a longer interval before surgery after completing neoadjuvant CRT was associated with worse overall and disease-free survival in tumors with a poor pathological response to preoperative CRT. Based on these findings, patients who do not respond well to CRT should be identified early after the end of CRT and undergo surgery without delay.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34586340"}, {"offsetInBeginSection": 1538, "offsetInEndSection": 1712, "text": "This pooled analysis suggests that the best time to achieve pCR in LARC is at 10\u00a0weeks, considering that the lengthening of SI is not detrimental concerning survival outcomes", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32966845"}, {"offsetInBeginSection": 1611, "offsetInEndSection": 1851, "text": " This study objectively determined the optimal time for surgery after completion of nCRT for rectal cancer based on completeness of resection and tumor downstaging. Eight weeks appears to be the critical threshold for optimal tumor response", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26897480"}, {"offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Appropriate Timing of Surgery after Neoadjuvant ChemoRadiation Therapy for Locally Advanced Rectal Cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27797248"}, {"offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Optimal Timing to Surgery after Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26897480"}, {"offsetInBeginSection": 793, "offsetInEndSection": 1173, "text": "CoCStom is a randomised multicentre trial comparing completeness of adjuvant chemotherapy as primary endpoint after early (8-10 days after resection, before starting adjuvant therapy) versus late (~26 weeks after resection and completion of adjuvant therapy) stoma closure in patients with locally advanced rectal cancer undergoing low anterior resection after neoadjuvant therapy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26589718"}, {"offsetInBeginSection": 241, "offsetInEndSection": 753, "text": " However, the optimal timing of surgical resection after neoadjuvant CRT remains debatable.OBJECTIVE AND METHODS: We conducted a retrospective review of 65 consecutive patients with locally advanced rectal cancer who underwent preoperative CRT followed by surgical resection in order to evaluate the optimal time for surgical treatment. We used two alternative groups for analysis: patients who underwent surgery up to 6 weeks after CRT (n = 28) and those who underwent surgery 6 weeks or more after CRT (n = 27)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29594111"}, {"offsetInBeginSection": 0, "offsetInEndSection": 576, "text": "BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) is considered the standard approach before any surgical intervention for locally advanced rectal tumors and has been proven to significantly improve the local recurrence rates of rectal cancer. However, the optimal timing of surgical resection after neoadjuvant CRT remains debatable.OBJECTIVE AND METHODS: We conducted a retrospective review of 65 consecutive patients with locally advanced rectal cancer who underwent preoperative CRT followed by surgical resection in order to evaluate the optimal time for surgical treatment", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29594111"}, {"offsetInBeginSection": 241, "offsetInEndSection": 576, "text": " However, the optimal timing of surgical resection after neoadjuvant CRT remains debatable.OBJECTIVE AND METHODS: We conducted a retrospective review of 65 consecutive patients with locally advanced rectal cancer who underwent preoperative CRT followed by surgical resection in order to evaluate the optimal time for surgical treatment", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29594111"}, {"offsetInBeginSection": 0, "offsetInEndSection": 331, "text": "BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) is considered the standard approach before any surgical intervention for locally advanced rectal tumors and has been proven to significantly improve the local recurrence rates of rectal cancer. However, the optimal timing of surgical resection after neoadjuvant CRT remains debatable", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29594111"}, {"offsetInBeginSection": 1432, "offsetInEndSection": 1652, "text": "Time to surgery was statistically significant on both the univariate and multivariate analyses.CONCLUSIONS: Our findings suggest that surgery should not be delayed more than 8\u00a0weeks (56\u00a0days) after neoadjuvant treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37261511"}, {"offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "INTRODUCTION: In locally advanced rectal cancer, the optimal interval between completion of neoadjuvant radiochemotherapy (RT-ChT) and surgical resection remains unclear due to contradictory data on the benefits of extending this interval.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37261511"}, {"offsetInBeginSection": 1953, "offsetInEndSection": 2256, "text": "There was no significant difference between the groups in terms of both local recurrence and distant metastasis (p = 0.98, p = 0.43, respectively).CONCLUSION: The optimal time for postoperative complications and sphincter-preserving surgery in patients with locally advanced rectal cancer is 8-10 weeks.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37227524"}, {"offsetInBeginSection": 1285, "offsetInEndSection": 1677, "text": "Time interval to surgery was not an independent prognostic factor for overall (HR = 1.04 CI = .4-2.65, P = .9) and disease-free survival (HR = 1.2 CI = .5-2.9, P = .6).CONCLUSION: The time interval between neoadjuvant radiotherapy completion and surgical resection does not affect anastomotic leak rate, achievement of pCR, or overall and disease-free survival in patients with rectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34633256"}, {"offsetInBeginSection": 932, "offsetInEndSection": 1457, "text": "There was no significant difference in the R0 resection rate (P\u2009=\u20090.85), anal preservation rate (P\u2009=\u20090.89), morbidity rate (P\u2009=\u20090.60), anastomotic leakage rate (P\u2009=\u20090.06), operation time (P\u2009=\u20090.58), local recurrence rate (P\u2009=\u20090.56), distant metastasis rate (P\u2009=\u20090.32), or overall survival (OS) rate (P\u2009=\u20090.17) between the two groups.CONCLUSION: A longer interval between neoadjuvant chemoradiotherapy and surgery can improve the PCR rate; however, it has no significant impact on the clinical efficacy or long-term prognosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35279746"}, {"offsetInBeginSection": 1745, "offsetInEndSection": 1918, "text": "e response (pCR) rate was 27.2% (n = 25) in the longer time interval group (> 9 wk) and 10.8% (n = 15) in the shorter time interval group (\u2264 9 wk, P = 0.001). The postoperat", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32884221"}, {"offsetInBeginSection": 1566, "offsetInEndSection": 1806, "text": ", 95% CI 1.02 to 1.23, p\u00a0= 0.01).CONCLUSIONS: This study objectively determined the optimal time for surgery after completion of nCRT for rectal cancer based on completeness of resection and tumor downstaging. Eight weeks appears to be the ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26897480"}, {"offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "BACKGROUND: Increasing the interval from completion of neoadjuvant therapy to surgery beyond 8\u00a0weeks is associated with increased response of rectal cancer to neoadjuv", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30963399"}, {"offsetInBeginSection": 296, "offsetInEndSection": 509, "text": " morbidity.METHODS: Patients who presented with a tumor within 15\u00a0cm of the anal verge in 2009-2015 were grouped according to the interval between completion of neoadjuvant therapy and surgery: <\u20098\u00a0weeks, 8-12\u00a0wee", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30963399"}, {"offsetInBeginSection": 1074, "offsetInEndSection": 1735, "text": "ents met the inclusion criteria. An nCRT-surgery interval time >8 weeks was associated with higher odds of pCR (odds ratio [OR] 1.12, 95% CI 1.01 to 1.25) and tumor downstaging (OR 1.11, 95% CI 1.02 to 1.25). The longer time delay was also associated with lower odds of 30-day readmission (OR 0.82, 95% CI 0.70 to 0.92).CONCLUSIONS: An nCRT-surgery interval time >8 weeks results in increased odds of pCR, with no evidence of associated increased surgical complications compared with an interval of 6 to 8 weeks. These data support implementation of a lengthened interval after nCRT to optimize the chances of pCR and perhaps add to the possibility of ultimate ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26206642"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1171, "text": "BACKGROUND: Neoadjuvant long-course chemoradiotherapy is commonly used to improve the local control and resectability of locally advanced rectal cancer, with surgery performed after an interval of a number of weeks.OBJECTIVE: We report an evidence-based systematic review of published data supporting the optimal time to perform surgical resection after long-course neoadjuvant therapy.DATA SOURCES: A systematic literature search was undertaken of the MEDLINE and Embase electronic databases from 1995 to 2012.STUDY SELECTION: English language articles were included that compared outcomes following rectal cancer surgery performed at different times after a long course of neoadjuvant radiation-based therapy.INTERVENTIONS: : Patients received a long course of neoadjuvant therapy followed by radical surgical resection after an interval period.MAIN OUTCOME MEASURES: The rates of tumor response, R0 resection, sphincter preservation, surgical complications, and disease recurrence were the primary outcomes measured.RESULTS: Fifteen studies were identified: 1 randomized controlled trial, 1 prospective nonrandomized interventional study, and 13 observational studies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23739201"}, {"offsetInBeginSection": 1606, "offsetInEndSection": 2094, "text": "No significant differences have been consistently demonstrated in rates of surgical complications, sphincter preservation, or long-term recurrence and survival.LIMITATIONS: Neoadjuvant regimes, indications for neoadjuvant therapy, and time intervals after chemoradiotherapy were heterogeneous between studies; consequently, meta-analysis could not be performed.CONCLUSIONS: There is limited evidence to support decisions regarding when to resect rectal cancer following chemoradiotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23739201"}, {"offsetInBeginSection": 1172, "offsetInEndSection": 1338, "text": "Studies compared time intervals that varied between <5 days and >12 weeks, with a large degree of variation in what the standard interval length was considered to be.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23739201"}, {"offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "BACKGROUND: In most institutions, locally advanced rectal cancer is treated with neoadjuvant chemoradiotherapy followed by surgery 6-8 weeks later, allowing time for tumor response and recovery from chemoradiotherapy-related toxicities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26144023"}, {"offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) is considered the standard approach before any surgical intervention for locally advanced rectal tumors and has been proven to significantly improve the local recurrence rates of rectal cancer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29594111"}, {"offsetInBeginSection": 0, "offsetInEndSection": 652, "text": "BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) is considered the standard approach before any surgical intervention for locally advanced rectal tumors and has been proven to significantly improve the local recurrence rates of rectal cancer. However, the optimal timing of surgical resection after neoadjuvant CRT remains debatable.OBJECTIVE AND METHODS: We conducted a retrospective review of 65 consecutive patients with locally advanced rectal cancer who underwent preoperative CRT followed by surgical resection in order to evaluate the optimal time for surgical treatment. We used two alternative groups for analysis: patients who underwent surger", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29594111"}, {"offsetInBeginSection": 24, "offsetInEndSection": 436, "text": "long-course chemoradiotherapy is commonly used to improve the local control and resectability of locally advanced rectal cancer, with surgery performed after an interval of a number of weeks.OBJECTIVE: We report an evidence-based systematic review of published data supporting the optimal time to perform surgical resection after long-course neoadjuvant therapy.DATA SOURCES: A systematic literature search was u", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23739201"}, {"offsetInBeginSection": 0, "offsetInEndSection": 498, "text": "PURPOSE: The optimal time between neoadjuvant chemoradiotherapy (CRT) and surgery for rectal cancer has been debated. This study evaluated the influence of this interval on oncological outcomes.METHODS: We compared postoperative complications, pathological downstaging, disease recurrence, and survival in patients with locally advanced rectal cancer who underwent surgical resection <8 weeks (group A, n = 105) to those who had surgery \u22658 weeks (group B, n = 48) after neoadjuvant CRT.RESULTS: Of ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23741691"}, {"offsetInBeginSection": 84, "offsetInEndSection": 702, "text": "y extended resection for locally advanced rectal cancer after neoadjuvant chemoradiotherapy.METHODS: From colorectal cancer database in The Sixth Affiliated Hospital of Sun Yat-sen University, a cohort of patients who underwent neoadjuvant chemoradiotherapy(1.8-2.0 Gy per day, 25-28 fractions, concurrent fluorouracil-based chemotherapy) followed by curative sphincter-preserving surgery for locally advanced rectal cancer between May 2016 and June 2017 were retrospectively identified. Exclusion criteria were synchronous colon cancer, intraoperatively confirmed distal metastasis, multiple visceral resection, and e", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29178095"}, {"offsetInBeginSection": 0, "offsetInEndSection": 988, "text": "BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) has demonstrated proven benefit in tumor regression and improved long-term local control for patients with locally advanced rectal cancer. However, precise analysis of the optimal waiting time that maximizes oncologic benefits of nCRT has not been established.STUDY DESIGN: The 2006-2012 National Cancer Data Base was queried for patients with stage II and III rectal adenocarcinoma who underwent nCRT followed by surgical resection. Time to surgery was defined as the difference between last date of radiotherapy and date of surgery. Primary study endpoints included resection margin positivity and pathologic downstaging. Multivariable regression modeling with restricted cubic splines was used to evaluate the adjusted association between time to surgery and our study endpoints, and to establish an optimal time threshold for surgery.RESULTS: A total of 11,760 patients were included. Median time to surgery was 53 days (interquartile ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26897480"}, {"offsetInBeginSection": 65, "offsetInEndSection": 1412, "text": "ter failure of neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC) has never been explored. We conducted a single-center, retrospective analysis to address this question.PATIENTS AND METHODS: Patients with newly diagnosed LARC who were inoperable or candidates for extensive (i.e., beyond total mesorectal excision [TME]) surgery after long-course chemoradiotherapy and who received salvage chemotherapy were included. The primary objective was to estimate the proportion of patients who became suitable for TME after chemotherapy.RESULTS: Forty-five patients were eligible (39 candidates for extensive surgery and 6 unresectable). Previous radiotherapy was given concurrently with chemotherapy in 43 cases (median dose: 54.0 Gy). Oxaliplatin- and irinotecan-based salvage chemotherapy was administered in 40 (88.9%) and 5 (11.1%) cases, respectively. Eight patients (17.8%) became suitable for TME after chemotherapy, 10 (22.2%) ultimately underwent TME with clear margins, and 2 (4.4%) were managed with a watch and wait approach. Additionally, 13 patients had extensive surgery with curative intent. Three-year progression-free survival and 5-year overall survival in the entire population were 30.0% (95% confidence interval [CI]: 15.0-46.0) and 44.0% (95% CI: 26.0-61.0), respectively. For the curatively resected and \"wat", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28476941"}, {"offsetInBeginSection": 0, "offsetInEndSection": 903, "text": "BACKGROUND: Many rectal cancer patients experience tumor downstaging and some are found to achieve a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT). Previous data suggest that there is an association between the time interval from nCRT completion to surgery and tumor response rates, including pCR. However, these studies have been primarily from single institutions with small sample sizes. The aim of this study was to examine the relationship between a longer interval after nCRT and pCR in a nationally representative cohort of rectal cancer patients.STUDY DESIGN: Clinical stage II to III rectal cancer patients undergoing nCRT with a documented surgical resection were selected from the 2006 to 2011 National Cancer Data Base. Multivariable logistic regression analysis was used to assess the association between the nCRT-surgery interval time (<6 weeks, 6 to 8 week", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26206642"}, {"offsetInBeginSection": 197, "offsetInEndSection": 941, "text": "long-course neoadjuvant chemoradiotherapy (nCRT) is not well defined.METHODS: Review of a single institution's prospectively maintained database from 1998 to 2007 identified 563 patients with locally advanced rectal cancer (T3/T4 and/or N1) receiving nCRT, followed after 6\u00a0weeks by total mesorectal excision (TME). Kaplan-Meier, Cox regression, and competing risk analysis were performed.RESULTS: The authors noted that 75\u00a0% of all patients had stage III disease as determined by endorectal ultrasound (ERUS) and/or magnetic resonance imaging (MRI). With median follow-up of 39\u00a0months after resection, local and distant relapse were noted in 12 (2.1\u00a0%) and 98 (17.4\u00a0%) patients, respectively. On competing risk analysis, the optimal cutoff poi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328971"}, {"offsetInBeginSection": 673, "offsetInEndSection": 1976, "text": "for complete resection with clear surgical margins, which is a prerequisite for cure. Studies suggest that local tumor control is increased in some visceral tumor types, especially with neoadjuvant chemoradiotherapy. In some other studies, a better control of systemic disease has contributed to significantly improved survival rates. Additionally, delaying surgery offers the chance to bring the patient into a better general condition for major surgery, but it also confers the risk of progression. Although it is a relatively rare event, cancers may progress locally during neoadjuvant treatment or distant metastases may occur, jeopardizing a curative surgical treatment approach. Although this is seen as risk of neoadjuvant treatment, it can also be seen as a chance to select only those patients for surgery who have a better control of systemic disease. Some studies showed increased perioperative morbidity in patients who underwent neoadjuvant treatment, which is another potential disadvantage. Optimal multidisciplinary teamwork is key to controlling that risk. Meanwhile, the neoadjuvant treatment period is also used as a \"window of opportunity\" for studying the activity of novel drugs and for investigating predictive and prognostic biomarkers of chemoradiotherapy and radiochemotherapy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31579713"}, {"offsetInBeginSection": 666, "offsetInEndSection": 1245, "text": " rectal cancer.METHODS: A total of 231 patients who were classified as having clinical stage II or III advanced rectal cancer and underwent neoadjuvant chemoradiation followed by surgery at the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from November 2014 to August 2017 were involved in this retrospective cohort study. The patients were divided into two groups based on the different time intervals between neoadjuvant therapy and surgery: 139 (60.2%) patients were in group A (\u2264 9 wk), and 92 (39.2%) patients ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32884221"}, {"offsetInBeginSection": 369, "offsetInEndSection": 519, "text": "derwent a curative resection with lateral lymph node resection at 6-8 weeks intervals after neoadjuvant CRT. The response rate on pathological study w", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22202303"}, {"offsetInBeginSection": 646, "offsetInEndSection": 771, "text": "surgery up to 6 weeks after CRT (n = 28) and those who underwent surgery 6 weeks or more after CRT (n = 27). Also, we compare", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29594111"}, {"offsetInBeginSection": 1029, "offsetInEndSection": 1245, "text": "ospective cohort study. The patients were divided into two groups based on the different time intervals between neoadjuvant therapy and surgery: 139 (60.2%) patients were in group A (\u2264 9 wk), and 92 (39.2%) patients ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32884221"}, {"offsetInBeginSection": 355, "offsetInEndSection": 904, "text": "Surgical resection is associated with significant morbidity and decreased quality of life (QoL), which is especially relevant given the favourable prognosis in this patient subset. Accordingly, there has been a growing interest in alternative approaches with less morbidity, including the organ-preserving watch and wait strategy, in which surgery is omitted in patients who have achieved a cCR. These patients are managed with a specific follow-up protocol to ensure adequate cancer control, including the early identification of recurrent disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32848330"}, {"offsetInBeginSection": 1037, "offsetInEndSection": 1139, "text": "ned regimen and dose. The surgery was performed laparoscopicaly within 4-8 weeks following the concomi", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19879716"}, {"offsetInBeginSection": 358, "offsetInEndSection": 477, "text": "Patients underwent a curative resection with lateral lymph node resection at 6-8 weeks intervals after neoadjuvant CRT.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22202303"}, {"offsetInBeginSection": 56, "offsetInEndSection": 422, "text": "interval of\u00a0\u2265 8 weeks between the end of preoperative neoadjuvant chemoradiotherapy (nCRT) and surgery on the outcomes of patients with locally advanced rectal cancer. We conducted a comprehensive literature review of retrospective and prospective studies from PubMed, Embase, and Cochrane Library databases to investigate the length of the preoperative nCRT-surgery", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29153429"}, {"offsetInBeginSection": 0, "offsetInEndSection": 425, "text": "BACKGROUND AND OBJECTIVES: Despite the standard interval of 6-8 weeks between neoadjuvant chemoradiotherapy (nCRT) and surgery, it is debated whether an interval of >8 weeks increases the pathologic complete response (pCR) rate. We investigated the interval between nCRT and surgery, and its impact on oncological outcomes and postoperative complications in patients with locally advanced rectal cancer.METHODS: We retrospect", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36169163"}, {"offsetInBeginSection": 337, "offsetInEndSection": 507, "text": "hat compared two intervals between neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer: after 8\u00a0weeks (long interval, LI) and within 8\u00a0weeks (sho", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35279746"}, {"offsetInBeginSection": 271, "offsetInEndSection": 841, "text": "valuate the effect and safety of the current trend of increasing time interval between the end of chemoradiotherapy and surgery (<\u200910\u00a0weeks vs.\u2009\u2265\u200910\u00a0weeks) on postoperative morbidity and pathological outcomes. This study analyzed 232 consecutive patients with locally advanced rectal cancer treated with long-course neoadjuvant chemoradiotherapy from January 2012 to August 2018. 125 patients underwent surgery before 10\u00a0weeks from the end of chemoradiotherapy (Group 1) and 107 patients underwent surgery after 10 or more weeks after the end of chemoradiotherapy (Group", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32232742"}, {"offsetInBeginSection": 218, "offsetInEndSection": 992, "text": "ent radical resection.METHODS: This was a propensity-score matched cohort analysis study that included patients of all ages diagnosed with locally advanced rectal cancer (LARC) who had received neoadjuvant chemoradiotherapy (nCRT) at the Fujian Medical University Union Hospital and Fujian Medical University Affiliated Zhangzhou Hospital, China, between Jan 10, 2011, to Dec 28, 2021. Partial patients with a significant downstage of the tumor were offered management with the local resection approach, and most of the rest were offered radical resection if eligible.FINDINGS: One thousand six hundred ninety-three patients underwent radical resection after nCRT, and another 60 patients performed local resection. The median follow-up times were 44.0\u00a0months (interquartile", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37312044"}, {"offsetInBeginSection": 1002, "offsetInEndSection": 1232, "text": "ding to treatment interval. Compared with a treatment interval of 7-8\u00a0weeks, pCR rates in LARC patients were higher after 9-10\u00a0weeks (18.4\u00a0%; odds ratio [OR] 1.56, 95\u00a0% CI 1.03-2.37) and 11-12\u00a0weeks of treatment interval (20.8\u00a0%; ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27251135"}, {"offsetInBeginSection": 1297, "offsetInEndSection": 1432, "text": " OS in ET or LARC patients.CONCLUSIONS: Treatment intervals of 9-12\u00a0weeks between surgery and CRT seem to improve the chances of pCR in", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27251135"}, {"offsetInBeginSection": 1418, "offsetInEndSection": 1553, "text": " Our study suggests that a prolonged time interval between the end of CRT and surgery (\u2265\u200910\u00a0weeks) increases pathological response rate", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34661871"}, {"offsetInBeginSection": 1455, "offsetInEndSection": 1607, "text": " significantly different.CONCLUSION: It is worth delaying surgical resection for 8 weeks or more after completion of CRT as it is safe and is associated", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23741691"}, {"offsetInBeginSection": 1362, "offsetInEndSection": 1541, "text": " (OR 0.82, 95% CI 0.70 to 0.92).CONCLUSIONS: An nCRT-surgery interval time >8 weeks results in increased odds of pCR, with no evidence of associated increased surgical complicatio", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26206642"}, {"offsetInBeginSection": 118, "offsetInEndSection": 561, "text": "This study evaluated the influence of this interval on oncological outcomes.METHODS: We compared postoperative complications, pathological downstaging, disease recurrence, and survival in patients with locally advanced rectal cancer who underwent surgical resection <8 weeks (group A, n = 105) to those who had surgery \u22658 weeks (group B, n = 48) after neoadjuvant CRT.RESULTS: Of 153 patients, 117 (76.5%) were male and 36 (23.5%) were female.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23741691"}, {"offsetInBeginSection": 611, "offsetInEndSection": 749, "text": "There was no difference in the rate of sphincter preserving surgery between the two groups (group A, 82.7% vs. group B, 77.6%; P = 0.509).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23741691"}]}
+{"question_id": "660812b4fdcbea915f000006", "question": "Is Kagami-Ogata associated with a deletion in chromosome 14", "answer": "Kagami-Ogata syndrome is a rare genetic imprinting disorder involving the 14q32.2 genomic location of chromosome 14.", "relevant_passage_ids": ["35864517", "34055463", "33179779", "34746047", "31853915", "32878913", "31753000", "33067531", "30232357", "27406249", "28635951", "30693591", "31994200", "33579810", "37222159", "26377239", "32592473", "32211354", "25820903", "35953028"], "type": "yesno", "snippets": [{"offsetInBeginSection": 12, "offsetInEndSection": 128, "text": "Kagami-Ogata syndrome is a rare genetic imprinting disorder involving the 14q32.2 genomic location of chromosome 14.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35864517"}, {"offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Kagami-Ogata syndrome (KOS) (OMIM #608149) is a genetic imprinting disorder affecting chromosome 14 that results in a characteristic phenotype consisting of typical facial features, skeletal abnormalities including rib abnormalities described as \"coat hanger ribs,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34055463"}, {"offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Kagami-Ogata syndrome (KOS14) is a rare congenital disorder associated with defective genomic imprinting of the chromosome 14q32 domain. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33179779"}, {"offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "The Kagami-Ogata syndrome (KOS) is a rare imprinting disorder with a distinct clinical phenotype. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34746047"}, {"offsetInBeginSection": 1157, "offsetInEndSection": 1253, "text": "The maternally inherited 14q32 deletion was responsible for Kagami-Ogata syndrome in our patient", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37222159"}, {"offsetInBeginSection": 14, "offsetInEndSection": 164, "text": "Kagami-Ogata syndrome (KOS14) and Temple syndrome (TS14) are two disorders associated with reciprocal alterations within the chr14q32 imprinted domain", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33579810"}, {"offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Kagami-Ogata syndrome (KOS14) is a rare imprinting disorder characterized by a unique constellation of phenotypes including bell-shaped small thorax with coat-hanger appearance of the ribs", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33067531"}, {"offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Temple and Kagami-Ogata syndromes are genomic imprinting diseases caused by maternal and paternal duplication of human chromosome 14, respectively", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32878913"}, {"offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Temple syndrome (TS) and Kagami-Ogata syndrome (KOS) are imprinting disorders caused by absence or overexpression of genes within a single imprinted cluster on human chromosome 14q32", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32592473"}, {"offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Maternally inherited 133kb deletion of 14q32 causing Kagami-Ogata syndrome.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30232357"}, {"offsetInBeginSection": 456, "offsetInEndSection": 614, "text": "Disruption of imprinting in the 14q32 region results in two clinically distinct imprinting disorders, Temple syndrome (TS14) and Kagami-Ogata syndrome (KOS14)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28635951"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Kagami-Ogata syndrome: a clinically recognizable upd(14)pat and related disorder affecting the chromosome 14q32.2 imprinted region.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26377239"}, {"offsetInBeginSection": 1157, "offsetInEndSection": 1254, "text": "The maternally inherited 14q32 deletion was responsible for Kagami-Ogata syndrome in our patient.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37222159"}, {"offsetInBeginSection": 1157, "offsetInEndSection": 1372, "text": "The maternally inherited 14q32 deletion was responsible for Kagami-Ogata syndrome in our patient. It was not sufficient, however, to produce Temple syndrome or any other pathogenic phenotype in the patient's mother.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37222159"}, {"offsetInBeginSection": 1031, "offsetInEndSection": 1254, "text": "The mother's chromosomal microarray also confirmed the identical 14q32.2 deletion, although she presented a normal phenotype. The maternally inherited 14q32 deletion was responsible for Kagami-Ogata syndrome in our patient.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37222159"}, {"offsetInBeginSection": 1031, "offsetInEndSection": 1372, "text": "The mother's chromosomal microarray also confirmed the identical 14q32.2 deletion, although she presented a normal phenotype. The maternally inherited 14q32 deletion was responsible for Kagami-Ogata syndrome in our patient. It was not sufficient, however, to produce Temple syndrome or any other pathogenic phenotype in the patient's mother.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37222159"}, {"offsetInBeginSection": 888, "offsetInEndSection": 1254, "text": "Deletions of the 14q32 region without involving DMRs, and encompassing only the RTL1as and MEG8 genes, are poorly described in the literature. The mother's chromosomal microarray also confirmed the identical 14q32.2 deletion, although she presented a normal phenotype. The maternally inherited 14q32 deletion was responsible for Kagami-Ogata syndrome in our patient.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37222159"}, {"offsetInBeginSection": 0, "offsetInEndSection": 651, "text": "Kagami-Ogata syndrome and Temple syndrome are imprinting disorders caused by the abnormal expression of genes in an imprinted cluster on chromosome 14q32. Here, we report a female with mild features of the Kagami-Ogata syndrome phenotype with polyhydramnios, neonatal hypotonia, feeding difficulties, abnormal foot morphology, patent foramen ovale, distal arthrogryposis, normal facial profile, and a bell-shaped thorax without coat hanger ribs. The single nucleotide polymorphism array revealed the interstitial deletion of chromosome 14q32.2-q32.31 (117\u2009kb in size), involving the RTL1as and MEG8 genes, and other small nucleolar RNAs and microRNAs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37222159"}, {"offsetInBeginSection": 0, "offsetInEndSection": 348, "text": "In approximately 20% of individuals with Kagami-Ogata syndrome (KOS14, MIM 608149), characterized by a bell-shaped thorax with coat-hanger configuration of the ribs, joint contractures, abdominal wall defects and polyhydramnios during the pregnancy, the syndrome is caused by a maternal deletion of the imprinted gene cluster in chromosome 14q32.2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27406249"}, {"offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "BACKGROUND: Kagami-Ogata syndrome is also known as paternal uniparental disomy 14 and related disorders and is caused by abnormal genomic imprinting in the long arm of the chromosome 14q32.2 region.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31753000"}, {"offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Kagami-Ogata syndrome (KOS14) is a rare congenital disorder associated with defective genomic imprinting of the chromosome 14q32 domain.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33179779"}, {"offsetInBeginSection": 295, "offsetInEndSection": 586, "text": "After excluding upd(14)pat and an epimutation (hypermethylation) and a deletion affecting the maternally derived 14q32.2 imprinted region, we performed whole-genome sequencing, revealing that the translocation was generated between noncoding region at 2q11.2 and intron 6 of MEG3 at 14q32.2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33067531"}, {"offsetInBeginSection": 789, "offsetInEndSection": 908, "text": "KOS in our patient was caused by a large deletion in the MEG3-region on chromosome 14q32 affecting the maternal allele.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31994200"}, {"offsetInBeginSection": 1041, "offsetInEndSection": 1283, "text": "In the second case, CMA was performed due to severely abnormal maternal serum analytes and revealed a deletion in 14q32.2q32.31 on the maternally inherited copy, leading to a diagnosis of Kagami-Ogata syndrome, which is an imprinting disorder", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30693591"}, {"offsetInBeginSection": 137, "offsetInEndSection": 555, "text": "chromosome 14q32. Here, we report a female with mild features of the Kagami-Ogata syndrome phenotype with polyhydramnios, neonatal hypotonia, feeding difficulties, abnormal foot morphology, patent foramen ovale, distal arthrogryposis, normal facial profile, and a bell-shaped thorax without coat hanger ribs. The single nucleotide polymorphism array revealed the interstitial deletion of chromosome 14q32.2-q32.31 (117", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37222159"}, {"offsetInBeginSection": 0, "offsetInEndSection": 540, "text": "Kagami-Ogata syndrome (KOS) is a rare imprinting disorder characterized by skeletal abnormalities, dysmorphic facial features, growth retardation and developmental delay. The genetic etiology of KOS includes paternal uniparental disomy 14 [upd(14)pat], epimutations and microdeletions affecting the maternally derived imprinted region of chromosome 14q32.2. More than seventy KOS cases have been reported thus far; however, only 10, including two familial, are associated with upd(14)pat harboring Robertsonian translocation (ROB). Here, we", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32211354"}, {"offsetInBeginSection": 25, "offsetInEndSection": 586, "text": "Kagami-Ogata syndrome (KOS) are imprinting disorders caused by absence or overexpression of genes within a single imprinted cluster on human chromosome 14q32. TS most frequently arises from maternal UPD14 or epimutations/deletions on the paternal chromosome, whereas KOS most frequently arises from paternal UPD14 or epimutations/deletions on the maternal chromosome. In this review, we describe the clinical symptoms and genetic/epigenetic features of this imprinted region. The locus encompasses paternally expressed protein-coding genes (DLK1, RTL1 and DIO3)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32592473"}, {"offsetInBeginSection": 0, "offsetInEndSection": 506, "text": "The Kagami-Ogata syndrome (KOS) is a rare imprinting disorder with a distinct clinical phenotype. In KOS, polyhydramnios is associated with a small bell-shaped thorax and coat-hanger ribs. The genetic etiology of KOS includes paternal uniparental disomy 14 [upd(14)pat], epimutations, and microdeletions affecting the maternally derived imprinted region of chromosome 14q32.2. More than 77 cases of KOS have been reported; however, only one mosaic upd(14)pat case has been reported. Here we report a second", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34746047"}, {"offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "INTRODUCTION: Kagami-Ogata syndrome (KOS14) and Temple syndrome (TS14) are two disorders associated with reciprocal alterations within the chr14q32 imprinted domain.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33579810"}, {"offsetInBeginSection": 292, "offsetInEndSection": 546, "text": "Abnormal expression of the imprinted genes on chromosome 14q32.2 causes KOS. Epimutation with aberrant hypermethylation of the MEG3/DLK1: intergenic differentially methylated region (MEG3/DLK1:IG-DMR) and the MEG3:TSS-DMR is one of the etiologies of KOS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35953028"}, {"offsetInBeginSection": 209, "offsetInEndSection": 463, "text": "Two syndromes associated with chromosome 14q32 abnormalities have been described, Kagami-Ogata and Temple syndromes. Both of these syndromes are characterised by specific impairments of intrauterine development, placentation and early postnatal survival.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25820903"}, {"offsetInBeginSection": 12, "offsetInEndSection": 127, "text": "Kagami-Ogata syndrome is a rare genetic imprinting disorder involving the 14q32.2 genomic location of chromosome 14", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35864517"}, {"offsetInBeginSection": 448, "offsetInEndSection": 1083, "text": "suggestive of the entity. Kagami-Ogata syndrome is caused by an aberrant gene expression of chromosome 14 and was first described in 1991. Possible causes are paternal uniparental disomy of chromosome 14, epimutations and microdeletions. Approximately 70 cases have been reported in the literature, with 34 comprising the original cohort of M. Kagami and T. Ogata. The incidence of the disease is unknown. Patients often manifest a developmental delay and an intellectual disability, although in the meantime cases with milder clinical courses have been described. In the cohort of Kagami and Ogata 3 patients developed hepatoblastoma,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31853915"}, {"offsetInBeginSection": 0, "offsetInEndSection": 360, "text": "Kagami-Ogata syndrome (KOS14) is a rare congenital disorder associated with defective genomic imprinting of the chromosome 14q32 domain. Typical features include polyhydramnios, small and bell-shaped thorax, coat-hanger ribs, dysmorphic facial features, abdominal wall defects, placentomegaly, severe postnatal respiratory distress and intellectual disability.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33179779"}]}
+{"question_id": "6614f672fdcbea915f000042", "question": "Are children affected by multiple sclerosis?", "answer": "Yes, children can be affected by multiple sclerosis (MS). While MS is more common in adults, it can also occur in children and adolescents before the age of 18. This is known as pediatric MS (PMS) and accounts for 3-5% of the general population of patients with MS. The incidence of pediatric MS is relatively rare, affecting 0.2 to 0.64/100,000 subjects, and cases with MS onset before age 10-12 years account for less than 1% of all MS cases. However, 2.7 to 10.5% of all MS cases worldwide are seen in children <18 years of age, with a strong female preponderance. The first episode of central nervous system (CNS) symptoms with a presumed inflammatory demyelinating cause is defined as clinically isolated syndrome (CIS) in children, and 34% of patients with CIS develop childhood onset multiple sclerosis (MS).", "relevant_passage_ids": ["34940954", "32940341"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Pediatric-onset multiple sclerosis (POMS) is a rare neuroinflammatory and neurodegenerative disease that has a significant impact on long-term physical and cognitive patient outcomes. A small percentage of multiple sclerosis (MS) diagnoses occur before the age of 18\u00a0years", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34940954"}, {"offsetInBeginSection": 151, "offsetInEndSection": 267, "text": "the first symptoms of MS can appear in children and adolescents before the age of 18, and we call this paediatric MS", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32940341"}, {"offsetInBeginSection": 275, "offsetInEndSection": 373, "text": "It is estimated that paediatric MS accounts for 3-5% of the general population of patients with MS", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32940341"}]}
+{"question_id": "661d4aa3eac11fad33000019", "question": "What are the current approaches for gene therapy for Phenylketonuria (PKU)?", "answer": "The current approaches for gene therapy for Phenylketonuria (PKU) include recombinant viral (AdV, AAV, and LV) and non-viral (naked DNA or LNP-mRNA) vector delivery methods, combined with gene addition, genome, gene or base editing, and gene insertion or replacement", "relevant_passage_ids": ["37401651", "22348550", "16319947", "10203136", "16150627", "31970201", "20151201", "7766948", "8828602", "26835324", "7584088", "16319949", "33335942", "15057263", "25787029"], "type": "list", "snippets": [{"offsetInBeginSection": 809, "offsetInEndSection": 1057, "text": "The list of experiments for proof of principle includes recombinant viral (AdV, AAV, and LV) and non-viral (naked DNA or LNP-mRNA) vector delivery methods, combined with gene addition, genome, gene or base editing, and gene insertion or replacement", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37401651"}, {"offsetInBeginSection": 513, "offsetInEndSection": 837, "text": "Gene therapy for PKU is a promising novel approach to promote lifelong neurological protection while allowing unrestricted dietary phenylalanine intake. In this study, liver-tropic recombinant AAV2/8 vectors were used to deliver CRISPR/Cas9 machinery and facilitate correction of the Pah enu2 allele by homologous recombinat", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31970201"}, {"offsetInBeginSection": 513, "offsetInEndSection": 1029, "text": "Gene therapy for PKU is a promising novel approach to promote lifelong neurological protection while allowing unrestricted dietary phenylalanine intake. In this study, liver-tropic recombinant AAV2/8 vectors were used to deliver CRISPR/Cas9 machinery and facilitate correction of the Pah enu2 allele by homologous recombination. Additionally, a non-homologous end joining (NHEJ) inhibitor, vanillin, was co-administered with the viral drug to promote homology-directed repair (HDR) with the AAV-provided repair templ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31970201"}, {"offsetInBeginSection": 174, "offsetInEndSection": 837, "text": "Restriction of dietary phenylalanine intake remains the standard of PKU care and prevents the major neurologic manifestations of the disease, yet shortcomings of dietary therapy remain, including poor adherence to a difficult and unpalatable diet, an increased incidence of neuropsychiatric illness, and imperfect neurocognitive outcomes. Gene therapy for PKU is a promising novel approach to promote lifelong neurological protection while allowing unrestricted dietary phenylalanine intake. In this study, liver-tropic recombinant AAV2/8 vectors were used to deliver CRISPR/Cas9 machinery and facilitate correction of the Pah enu2 allele by homologous recombinat", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31970201"}, {"offsetInBeginSection": 838, "offsetInEndSection": 1438, "text": "on. Additionally, a non-homologous end joining (NHEJ) inhibitor, vanillin, was co-administered with the viral drug to promote homology-directed repair (HDR) with the AAV-provided repair template. This combinatorial drug administration allowed for lifelong, permanent correction of the Pah enu2 allele in a portion of treated hepatocytes of mice with PKU, yielding partial restoration of liver PAH activity, substantial reduction of blood phenylalanine, and prevention of maternal PKU effects during breeding. This work reveals that CRISPR/Cas9 gene editing is a promising tool for permanent PKU gene ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31970201"}, {"offsetInBeginSection": 1030, "offsetInEndSection": 1438, "text": "te. This combinatorial drug administration allowed for lifelong, permanent correction of the Pah enu2 allele in a portion of treated hepatocytes of mice with PKU, yielding partial restoration of liver PAH activity, substantial reduction of blood phenylalanine, and prevention of maternal PKU effects during breeding. This work reveals that CRISPR/Cas9 gene editing is a promising tool for permanent PKU gene ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31970201"}, {"offsetInBeginSection": 0, "offsetInEndSection": 665, "text": "Phenylketonuria (PKU) due to recessively inherited phenylalanine hydroxylase (PAH) deficiency results in hyperphenylalaninemia, which is toxic to the central nervous system. Restriction of dietary phenylalanine intake remains the standard of PKU care and prevents the major neurologic manifestations of the disease, yet shortcomings of dietary therapy remain, including poor adherence to a difficult and unpalatable diet, an increased incidence of neuropsychiatric illness, and imperfect neurocognitive outcomes. Gene therapy for PKU is a promising novel approach to promote lifelong neurological protection while allowing unrestricted dietary phenylalanine intake.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31970201"}, {"offsetInBeginSection": 996, "offsetInEndSection": 1478, "text": "Research into novel therapies for PKU has taken many different approaches to address the lack of PAH activity at the core of this disorder: enzyme replacement via virus-mediated gene transfer, transplantation of donor liver and recombinant PAH protein, enzyme substitution using phenylalanine ammonia lyase (PAL) to provide an alternative pathway for the metabolism of phenylalanine, and restoration of native PAH activity using chemical chaperones and nonsense read-through agents.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26835324"}, {"offsetInBeginSection": 274, "offsetInEndSection": 1322, "text": "Here, we show that a liver-directed PAH gene transfer brought about long-term correction of hyperphenylalaninemia and behavioral improvement in a mouse model of PKU. A recombinant adeno-associated virus (AAV) vector carrying the murine PAH cDNA was constructed and administered to PAH-deficient mice (strain PAH(enu2)) via the portal vein. Within 2 weeks of treatment, the hyperphenylalaninemic phenotype improved and completely normalized in the animals treated with higher vector doses. The therapeutic effect persisted for 40 weeks in male mice, while serum phenylalanine concentrations in female animals gradually returned to pretreatment levels. Notably, this long-term correction of hyperphenylalaninemia was associated with a reversal of hypoactivity observed in PAH(enu2) mice. While locomotory activity over 24 h and exploratory behavior were significantly decreased in untreated PAH(enu2) mice compared with the age-matched controls, these indices were completely normalized in 12-month-old male PKU mice with lowered serum phenylalanine.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15057263"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1396, "text": "Current therapy for phenylketonuria (PKU) consists of life-long dietary restriction of phenylalanine (Phe), which presents problems of adherence for patients. Alternative therapies under investigation include, among others, the use of gene therapy to provide copies of wild-type, non-mutant, phenylalanine hydroxylase (PAH) enzyme. Expression of PAH in both liver (the usual metabolic source of this enzyme) and skeletal muscle is under investigation. Liver gene therapy, using a viral vector based on the adeno-associated viruses (AAVs), provided effective clearance of serum Phe that was sustained for 1 year in some mice. In order for PAH expression to be effective in skeletal muscle, the essential metabolic cofactor, tetrahydrobiopterin (BH(4)), must also be provided, either by supplementation or gene therapy. Both these approaches were effective. When transgenic PKU mice that constitutively expressed PAH in muscle were given intraperitoneal supplementation with BH(4), this produced (transient) effective clearance of Phe to normal levels. In addition, use of an AAV vector containing the genes for PAH, and for two key synthetic enzymes for BH(4), provided substantial and long-lasting correction (more than 1 year) of blood Phe levels when injected into skeletal muscle of PKU mice. These two strategies provide promising treatment alternatives for the management of PKU in patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20151201"}, {"offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Gene therapy for phenylketonuria: phenotypic correction in a genetically deficient mouse model by adenovirus-mediated hepatic gene transfer.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7584088"}, {"offsetInBeginSection": 172, "offsetInEndSection": 881, "text": "A recombinant adenoviral vector containing the human PAH cDNA was constructed and administered to PAH-deficient mice (strain PAHenu2). The hyperphenylalaninemic phenotype of these animals was completely normalized within 1 week of treatment. Although this therapeutic effect did not persist, analysis of the relationship between hepatic PAH activity and serum phenylalanine levels indicated that only 10-20% of normal enzymatic activity in the mouse liver is sufficient to restore normal serum phenylalanine levels. These results demonstrate that PKU and other metabolic disorders secondary to hepatic deficiencies can be completely corrected by gene therapy when more persistent vector systems are developed.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7584088"}, {"offsetInBeginSection": 590, "offsetInEndSection": 1437, "text": "We explored a gene therapy approach aimed at long-term correction of the pathologic phenotype of BTBR-PahEnu2 mice, a mouse model of PKU. To this aim, we developed a helper-dependent adenoviral (HD-Ad) vector expressing phenylalanine hydroxylase and administered it to 3-week-old PKU mice. This resulted in complete normalization of Phe and Tyr levels and reversal of coat hypopigmentation that lasted throughout the observation period of six months. The spatial learning deficits observed in PKU mice were also reversed and hippocampus levels of the N-methyl-D-Aspartate and 2-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl) propanoic acid receptor subunits returned to normal. Long-term potentiation, which is impaired in PKU mice, was also restored by treatment. Therefore, HD-Ad vector-mediated gene therapy is a promising approach to PKU treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22348550"}, {"offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "Classical phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH). Limitations of the current dietary treatment for PKU have led to the development of potential treatments based on somatic gene transfer. Three different vector systems have been examined.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8828602"}, {"offsetInBeginSection": 134, "offsetInEndSection": 465, "text": "Three different vector systems have been developed to examine the potential of somatic gene therapy for the treatment of PKU. Recombinant retroviral vectors and DNA/protein complexes can efficiently transduce PAH-deficient hepatocytes in vitro, but their present application is limited by their low transduction efficiency in vivo.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7766948"}, {"offsetInBeginSection": 134, "offsetInEndSection": 703, "text": "Three different vector systems have been developed to examine the potential of somatic gene therapy for the treatment of PKU. Recombinant retroviral vectors and DNA/protein complexes can efficiently transduce PAH-deficient hepatocytes in vitro, but their present application is limited by their low transduction efficiency in vivo. In contrast, infusion of a recombinant adenoviral vector expressing the human PAH cDNA into the portal circulation of PAH-deficient mice restores 10-80% of normal hepatic PAH activity and completely normalizes serum phenylalanine levels.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7766948"}, {"offsetInBeginSection": 134, "offsetInEndSection": 583, "text": "Limitations of the current dietary treatment for PKU have led to the development of potential treatments based on somatic gene transfer. Three different vector systems have been examined. Vectors derived from a recombinant retrovirus or a DNA/protein complex can efficiently transduce the PAH cDNA into PAH-deficient hepatocytes in vitro, but the application of these vector systems is presently limited by their low transduction efficiency in vivo.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8828602"}, {"offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "Classical phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH). Limitations of the current dietary treatment for PKU have led to the development of potential treatments based on somatic gene transfer.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8828602"}, {"offsetInBeginSection": 0, "offsetInEndSection": 538, "text": "Phenylketonuria (PKU) is an inherited metabolic disorder caused by mutation within phenylalanine hydroxylase (PAH) gene. Loss-of-function of PAH leads to accumulation of phenylalanine in the blood/body of an untreated patient, which damages the developing brain, causing severe mental retardation. Current gene therapy strategies based on adeno-associated vector (AAV) delivery of PAH gene were effective in male animals but had little long-term effects on blood hyperphenylalaninemia in females. Here, we designed a gene therapy strategy", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33335942"}]}
+{"question_id": "65d134bd1930410b13000037", "question": "What disease can be treated with Trofinetide?", "answer": "Trofinetide is approved for Rett syndrome.", "relevant_passage_ids": ["37291210", "37191913", "37635789", "37568516", "28964591", "30918097", "35622206", "35149233", "38035006", "38017349", "37714122"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37291210"}, {"offsetInBeginSection": 1209, "offsetInEndSection": 1414, "text": "Significant improvement for trofinetide compared with placebo was observed for the coprimary efficacy endpoints, suggesting that trofinetide provides benefit in treating the core symptoms of Rett syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37291210"}, {"offsetInBeginSection": 317, "offsetInEndSection": 459, "text": "Trofinetide was approved in March 2023 in the USA for the treatment of Rett syndrome in adult and pediatric patients 2\u00a0years of age and older.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37191913"}, {"offsetInBeginSection": 964, "offsetInEndSection": 1188, "text": "In LAVENDER, the FDA-approved drug trofinetide significantly improved the RSBQ total score over placebo in girls and women with RTT and change from baseline for all RSBQ subscores were directionally in favor of trofinetide. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37635789"}, {"offsetInBeginSection": 276, "offsetInEndSection": 369, "text": " Recently, Trofinetide was approved by the USFDA on 10 March 2023 as the first RTT treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37568516"}, {"offsetInBeginSection": 1678, "offsetInEndSection": 1873, "text": "Trofinetide is one of the important milestones for RTT therapy and is the beginning of a new era for the therapy of RTT, FXS, autism spectrum disorder (ASD), brain injury, stroke, and other NDDs.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37568516"}, {"offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Trofinetide-a new chapter in rett syndrome's treatment.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38035006"}, {"offsetInBeginSection": 0, "offsetInEndSection": 480, "text": "Trofinetide is the first drug approved by the FDA to treat Rett Syndrome in children aged 2\u00a0years or above. The drug significantly improved Rett syndrome behavioral scores Rett syndrome behavioral questionnaire in clinical studies. Although further research is needed to assess potential adverse events, Trofinetide's notable efficacy signifies a significant advancement in Rett syndrome treatment, offering a new therapeutic avenue with the potential to ameliorate the condition.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38035006"}, {"offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Trofinetide is the first drug approved by the FDA to treat Rett Syndrome in children aged 2\u00a0years or above. The drug significantly improved Rett syndrome behavioral scores Rett syndrome behavioral questionnaire in clinical studies.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38035006"}, {"offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Trofinetide is the first drug approved by the FDA to treat Rett Syndrome in children aged 2\u00a0years or above.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38035006"}, {"offsetInBeginSection": 108, "offsetInEndSection": 480, "text": "The drug significantly improved Rett syndrome behavioral scores Rett syndrome behavioral questionnaire in clinical studies. Although further research is needed to assess potential adverse events, Trofinetide's notable efficacy signifies a significant advancement in Rett syndrome treatment, offering a new therapeutic avenue with the potential to ameliorate the condition.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38035006"}, {"offsetInBeginSection": 232, "offsetInEndSection": 480, "text": "Although further research is needed to assess potential adverse events, Trofinetide's notable efficacy signifies a significant advancement in Rett syndrome treatment, offering a new therapeutic avenue with the potential to ameliorate the condition.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38035006"}, {"offsetInBeginSection": 1237, "offsetInEndSection": 1586, "text": "SION: Trofinetide was well tolerated in adolescent and adult females with Rett syndrome. Although this study had a relatively short duration in a small number of subjects with an advanced stage of disease, consistent efficacy trends at the higher dose were observed in several outcome measures that assess important dimensions of Rett syndrome. Thes", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28964591"}, {"offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "BACKGROUND AND OBJECTIVE: Trofinetide, a synthetic analog of tripeptide glycine-proline-glutamate, is an investigational agent for the treatment of Rett syndrome, a neurodevelopmental disorder with affected individuals requiring lifelong support.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35622206"}, {"offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "BACKGROUND AND OBJECTIVE: Trofinetide is the first drug to be approved for the treatment of Rett syndrome, a ne", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38017349"}, {"offsetInBeginSection": 0, "offsetInEndSection": 369, "text": "Rett syndrome (RTT) is a rare disability causing female-oriented pediatric neurodevelopmental unmet medical need. RTT was recognized in 1966. However, over the past 56 years, the United States Food and Drug Administration (USFDA) has authorized no effective treatment for RTT. Recently, Trofinetide was approved by the USFDA on 10 March 2023 as the first RTT treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37568516"}, {"offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "BACKGROUND AND OBJECTIVE: Trofinetide, a synthetic analog of tripeptide glycine-proline-glutamate, is an investigational agent for the treatment of Rett syndrome, a neurodevelopmental disorder with affected individuals r", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35622206"}, {"offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "OBJECTIVE: To determine safety, tolerability, and pharmacokinetics of trofinetide and evaluate its efficacy in female children/adolescents with Rett syndrome (RTT), a debilitating neurodevelopmental condition for which no pharmacotherapies directed at core features are", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30918097"}, {"offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "BACKGROUND: This study aimed to determine the safety and tolerability of trofinetide and to evaluate efficacy measures in adolescent and adult females with Rett syndrome, a serious and debilitating neurodevelopmental condition for which no therapies are available for its co", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28964591"}, {"offsetInBeginSection": 997, "offsetInEndSection": 1230, "text": "There are drugs in the research phase such as oxytocin, vasopressin and even some developed for specific entities related to autism such as arbaclofen in Fragile X and Trofinetide that has just been approved for use in Rett syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37714122"}, {"offsetInBeginSection": 0, "offsetInEndSection": 460, "text": "Trofinetide (DAYBUE\u2122), an oral, small molecule, synthetic analog of glycine-proline-glutamate [GPE; the N-terminal tripeptide derivative of insulin like growth factor-1 (IGF-1)], is being developed by Neuren Pharmaceuticals and Acadia Pharmaceuticals for the treatment of rare childhood neurodevelopmental disorders. Trofinetide was approved in March 2023 in the USA for the treatment of Rett syndrome in adult and pediatric patients 2\u00a0years of age and older. ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37191913"}, {"offsetInBeginSection": 0, "offsetInEndSection": 844, "text": "INTRODUCTION: Rett syndrome (RTT) is a debilitating neurodevelopmental disorder with no approved treatments. Trofinetide is a synthetic analog of glycine-proline-glutamate, the N-terminal tripeptide of insulin-like growth factor 1. In a phase 2, placebo-controlled trial in 82 females with RTT aged 5-15\u00a0years, a significant (p\u00a0\u2264\u00a00.042) improvement over placebo was observed with the highest trofinetide dose (200\u00a0mg/kg twice daily [BID]) on three measures: Rett Syndrome Behaviour Questionnaire (RSBQ), Clinical Global Impression-Improvement (CGI-I), and RTT-Clinician Domain Specific Concerns-Visual Analog Scale (RTT-DSC-VAS). Trofinetide was well tolerated at all doses (50, 100, and 200\u00a0mg/kg BID). A phase 3 trial utilizing disease-specific and novel scales was designed to investigate the efficacy and safety of trofinetide in girls and ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35149233"}, {"offsetInBeginSection": 22, "offsetInEndSection": 172, "text": "VE: Trofinetide is the first drug to be approved for the treatment of Rett syndrome, a neurodevelopmental disorder. The purpose of the study is to ful", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38017349"}, {"offsetInBeginSection": 1165, "offsetInEndSection": 1230, "text": "Trofinetide that has just been approved for use in Rett syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37714122"}, {"offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "BACKGROUND AND OBJECTIVE: Trofinetide, a synthetic analog of tripeptide glycine-proline-glutamate, is an investigational agent for the treatment of Rett syndrome, a neurodevelopmental disorder with affected individuals requiring lifelong support", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35622206"}, {"offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "BACKGROUND AND OBJECTIVE: Trofinetide is the first drug to be approved for the treatment of Rett syndrome, a neurodevelopmental disorder", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38017349"}, {"offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "OBJECTIVE: To determine safety, tolerability, and pharmacokinetics of trofinetide and evaluate its efficacy in female children/adolescents with Rett syndrome (RTT), a debilitating neurodevelopmental condition for which no pharmacotherapies directed at core features are available", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30918097"}, {"offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "BACKGROUND: This study aimed to determine the safety and tolerability of trofinetide and to evaluate efficacy measures in adolescent and adult females with Rett syndrome, a serious and debilitating neurodevelopmental condition for which no therapies are available for its core features", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28964591"}, {"offsetInBeginSection": 0, "offsetInEndSection": 582, "text": "Trofinetide (DAYBUE\u2122), an oral, small molecule, synthetic analog of glycine-proline-glutamate [GPE; the N-terminal tripeptide derivative of insulin like growth factor-1 (IGF-1)], is being developed by Neuren Pharmaceuticals and Acadia Pharmaceuticals for the treatment of rare childhood neurodevelopmental disorders. Trofinetide was approved in March 2023 in the USA for the treatment of Rett syndrome in adult and pediatric patients 2\u00a0years of age and older. This article summarizes the milestones in the development of trofinetide leading to this first approval for Rett syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37191913"}, {"offsetInBeginSection": 0, "offsetInEndSection": 459, "text": "Trofinetide (DAYBUE\u2122), an oral, small molecule, synthetic analog of glycine-proline-glutamate [GPE; the N-terminal tripeptide derivative of insulin like growth factor-1 (IGF-1)], is being developed by Neuren Pharmaceuticals and Acadia Pharmaceuticals for the treatment of rare childhood neurodevelopmental disorders. Trofinetide was approved in March 2023 in the USA for the treatment of Rett syndrome in adult and pediatric patients 2\u00a0years of age and older.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37191913"}, {"offsetInBeginSection": 317, "offsetInEndSection": 582, "text": "Trofinetide was approved in March 2023 in the USA for the treatment of Rett syndrome in adult and pediatric patients 2\u00a0years of age and older. This article summarizes the milestones in the development of trofinetide leading to this first approval for Rett syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37191913"}, {"offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "BACKGROUND AND OBJECTIVE: Trofinetide is the first drug to be approved for the treatment of Rett syndrome, a neurodevelopmental disorder. The purpose of the study is to fully characterize the metabolic and excretion profiles of trofinetide in humans", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38017349"}, {"offsetInBeginSection": 62, "offsetInEndSection": 271, "text": "Trofinetide is a synthetic analog of glycine-proline-glutamate, the N-terminal tripeptide of the insulin-like growth factor 1 protein, and has demonstrated clinical benefit in phase 2 studies in Rett syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37291210"}, {"offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Rett Syndrome.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28964591"}, {"offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Rett syndrome is a rare, genetic neurodevelopmental disorder. Trofinetide is a synthetic analog of glycine-proline-glutamate, the N-terminal tripeptide of the insulin-like growth factor 1 protein, and has demonstrated clinical benefit in phase 2 studies in Rett syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37291210"}, {"offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Double-blind, randomized, placebo-controlled study of trofinetide in pediatric Rett syndrome.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30918097"}, {"offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "INTRODUCTION: Rett syndrome (RTT) is a debilitating neurodevelopmental disorder with no approved treatments. Trofinetide is a synthetic analog of glycine-proline-glutamate, the N-terminal tripeptide of insulin-like gr", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35149233"}]}
+{"question_id": "65f7789dc4010b4d78000034", "question": "Which is the most reliable liquid biopsy technique after complete resection of  colorectal cancer metastases?", "answer": "Among all liquid biopsy methods (cell-free DNA, exosomes and circulating tumor cells), circulating tumor cells showed the best diagnostic performance", "relevant_passage_ids": ["32628360", "33667566", "31060647", "35337361", "37273078", "30554222", "34150757", "32184665", "36077774", "32566042", "31142037", "37541105", "34587798", "33301640", "32545981", "31930130", "33738696", "25959553", "31269959", "25332962", "27516729", "34572727", "34327297", "35962648", "36382087", "29589077", "36992914", "29627453", "34066481", "37910091", "34298740", "34408162", "28344745", "30053724", "35857852", "35284120", "30626171"], "type": "factoid", "snippets": [{"offsetInBeginSection": 1397, "offsetInEndSection": 1473, "text": "Among all liquid biopsy methods, CTCs showed the best diagnostic performance", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32628360"}, {"offsetInBeginSection": 11, "offsetInEndSection": 183, "text": "We aimed to evaluate the prognostic value of circulating tumor cells (CTCs) and the impact of intraoperative tumor manipulation on CTCs in colorectal cancer (CRC) patients.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34587798"}, {"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Circulating tumor cell (CTC) analysis holds great potential to be a noninvasive solution for clinical cancer management", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33301640"}, {"offsetInBeginSection": 311, "offsetInEndSection": 420, "text": "In patients with detectable circulating tumor DNA (ctDNA), liquid biopsy can be an effective monitoring tool.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32545981"}, {"offsetInBeginSection": 772, "offsetInEndSection": 1095, "text": "Liquid biopsy is noninvasive and allows repeated analyses to monitor tumor recurrence, metastasis or treatment responses in real time. With the advanced development of new molecular techniques, HCC circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) detection have achieved interesting and encouraging results.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31269959"}, {"offsetInBeginSection": 661, "offsetInEndSection": 1095, "text": "Over the past years, a new diagnostic concept known as \"liquid biopsy\" has emerged with substantial attention. Liquid biopsy is noninvasive and allows repeated analyses to monitor tumor recurrence, metastasis or treatment responses in real time. With the advanced development of new molecular techniques, HCC circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) detection have achieved interesting and encouraging results.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31269959"}, {"offsetInBeginSection": 0, "offsetInEndSection": 625, "text": "Capturing circulating tumor cells (CTCs) and/or circulating tumor DNA from blood, which represents a precious source of biological material derived from both primary and metastatic tumors, has been named a 'liquid biopsy'. While the circulating tumor DNA might be more representative of the bulk of the metastatic tumor, CTCs are thought to reflect more of the metastases-initiating cells. Consequently, a liquid biopsy made of tumor cells and tumor DNA that is able to track cancer evolution, as a fingerprint of the patient's individual tumor, and is easy to perform at every stage of the disease course, sounds attractive.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25959553"}, {"offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are emerging noninvasive multifunctional biomarkers in liquid biopsy allowing for early diagnosis, accurate prognosis, therapeutic target selection, spatiotemporal monitoring of metastasis, as well as monitoring response and resistance to treatment.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27516729"}, {"offsetInBeginSection": 0, "offsetInEndSection": 453, "text": "Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are emerging noninvasive multifunctional biomarkers in liquid biopsy allowing for early diagnosis, accurate prognosis, therapeutic target selection, spatiotemporal monitoring of metastasis, as well as monitoring response and resistance to treatment. CTCs and ctDNA are released from different tumor types at different stages and contribute complementary information for clinical decision.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27516729"}, {"offsetInBeginSection": 0, "offsetInEndSection": 894, "text": "Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are emerging noninvasive multifunctional biomarkers in liquid biopsy allowing for early diagnosis, accurate prognosis, therapeutic target selection, spatiotemporal monitoring of metastasis, as well as monitoring response and resistance to treatment. CTCs and ctDNA are released from different tumor types at different stages and contribute complementary information for clinical decision. Although big strides have been taken in technology development for detection, isolation and characterization of CTCs and sensitive and specific detection of ctDNA, CTC-, and ctDNA-based liquid biopsies may not be widely adopted for routine cancer patient care until the suitability, accuracy, and reliability of these tests are validated and more standardized protocols are corroborated in large, independent, prospectively designed trials.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27516729"}, {"offsetInBeginSection": 541, "offsetInEndSection": 1148, "text": "Liquid biopsies provide direct non-invasive access to tumor material, which is shed into the circulation; this enables the analysis of circulating tumor cells (CTC) and genomic components such as circulating free DNA (cfDNA), which could provide the key for personalized therapy. Liquid biopsy (LB) allows for the identification of patients with a high risk for disease progression after curative surgery, as well as longitudinal monitoring for disease progression and therapy response. Here, we will review the most recent studies on CRC, demonstrating the clinical potential and utility of CTCs and ctDNA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34572727"}, {"offsetInBeginSection": 223, "offsetInEndSection": 761, "text": "While the circulating tumor DNA might be more representative of the bulk of the metastatic tumor, CTCs are thought to reflect more of the metastases-initiating cells. Consequently, a liquid biopsy made of tumor cells and tumor DNA that is able to track cancer evolution, as a fingerprint of the patient's individual tumor, and is easy to perform at every stage of the disease course, sounds attractive. This article mainly focuses on the applications of CTCs to track tumor dynamics in real time using colorectal cancer as a model system.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25959553"}, {"offsetInBeginSection": 390, "offsetInEndSection": 935, "text": "Consequently, a liquid biopsy made of tumor cells and tumor DNA that is able to track cancer evolution, as a fingerprint of the patient's individual tumor, and is easy to perform at every stage of the disease course, sounds attractive. This article mainly focuses on the applications of CTCs to track tumor dynamics in real time using colorectal cancer as a model system. The analysis of viable CTCs at DNA, RNA and protein levels, as well as their expansion in vitro, may allow deep investigation of the features of metastases-initiating cells.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25959553"}, {"offsetInBeginSection": 1508, "offsetInEndSection": 1826, "text": "In the multivariate analysis, ctDNA-based MRD status was the most significant prognostic factor associated with disease-free survival (HR: 5.78; 95% CI, 3.34 to 10.0; P < .001).CONCLUSION: This study confirms that in mCRC undergoing resection of metastases, postoperative MRD analysis is a strong prognostic biomarker.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34327297"}, {"offsetInBeginSection": 353, "offsetInEndSection": 933, "text": "biomarkers.CONTENT: Following curative-intent surgery for cancer, the presence of ctDNA is highly predictive of early disease recurrence, while in metastatic cancer an early decline in ctDNA following the initiation of treatment is predictive of good outcome. Compared with protein biomarkers, ctDNA provides greater cancer specificity and sensitivity for detecting early recurrent/metastatic disease. Thus, in patients with surgically resected colorectal cancer, multiple studies have shown that ctDNA is superior to carcinoembryonic antigen (CEA) in detecting residual disease a", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35962648"}, {"offsetInBeginSection": 1467, "offsetInEndSection": 1695, "text": " volumes (9 cm vs 2 cm, p=0.05).Conclusions: Treatment with BA in patients with ctDNA-detected, liver-limited mCRC did not clear ctDNA and was associated with large-volume recurrence, highlighting the potential context-specific ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36382087"}, {"offsetInBeginSection": 97, "offsetInEndSection": 602, "text": "liver disease develops in 50% of cases and drives patient outcomes. Although the ideal treatment for colorectal cancer liver metastases (CRLM) is resection, only a third of patients are suitable for this approach. Reports of liver transplantation in selected patients with unresectable CRLM have shown encouraging results compared to conventional forms of therapy. No study to date has examined the utility of liquid biopsy circulating tumor DNA (ctDNA) for evaluation of residual disease in this cohort o", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37273078"}, {"offsetInBeginSection": 162, "offsetInEndSection": 1210, "text": "metastases of colorectal cancer. For good oncological results complete macroscopic cytoreduction is crucial; furthermore, a\u00a0linear correlation between peritoneal tumor load, as determined by the peritoneal cancer index (PCI) and overall survival has been demonstrated; therefore, surgical treatment should be initiated as early as possible. Synchronous resection of up to three liver metastases may be performed safely and with good results and no influence on the morbidity. With respect to intraperitoneal chemotherapy, mitomycin\u00a0C and oxaliplatin are most commonly used and may be regarded as equal; however, for perioperative chemotherapy study results are so far inconclusive with some trials hinting at decreased overall survival following neoadjuvant chemotherapy. Adjuvant therapy is likely to improve overall survival if at least 6\u00a0cycles are applied. Early detection of peritoneal metastases is difficult at present but might be facilitated in the future by the use of liquid biopsies, which may detect circulating free tumor-specific DNA", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29589077"}, {"offsetInBeginSection": 10, "offsetInEndSection": 894, "text": "is the most common site of metastasis in colorectal cancer. Multimodal treatment, including liver resection, is potentially curative and prolongs survival for selected patients with colorectal liver metastases (CRLM). However, the treatment of CRLM remains challenging because recurrence is common, and prognosis varies widely between patients despite curative-intent treatment. Clinicopathological features and tissue-based molecular biomarkers, either alone or in combination, are insufficient for accurate prognostication. As most of the functional information in cells resides in the proteome, circulating proteomic biomarkers may be useful for rationalising the molecular complexities of CRLM and identifying potentially prognostic molecular subtypes. High-throughput proteomics has accelerated a range of applications including protein profiling of liquid biopsies for biomarker", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36992914"}, {"offsetInBeginSection": 904, "offsetInEndSection": 1585, "text": "staged hepatectomy techniques to expand indications for liver resection. Added to this complexity is the increasing number of molecular markers, which appear to hold important prognostic and predictive information, for which some will be discussed here. Beyond characteristics of tissue-based genomic profiles will be liquid biopsies derived from circulating tumor cells and cell-free circulating tumor DNA in the blood. These markers are present in the peripheral circulation in the majority of patients with metastatic cancer disease. Circulating biomarkers may represent more readily available methods to monitor, characterize and predict cancer biology with future implications", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28344745"}, {"offsetInBeginSection": 438, "offsetInEndSection": 1142, "text": "A levels are prognostic. Although their levels correlate with treatment response, CTC-guided systemic regimen switches for nonresponders have not been shown to improve clinical outcomes. ctDNA genomic profiling has succeeded, and there are now multiple plasma-based assays approved by the US Food and Drug Administration that can detect actionable mutations to guide systemic therapy. Technological advancements in assay sensitivity have expanded the use of ctDNA to early-stage and resectable disease, allowing for detection of minimal residual disease. Postoperative ctDNA levels are a strong predictor of disease recurrence, and ctDNA detection often precedes serum carcinoembryonic antigen elevation ", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37910091"}, {"offsetInBeginSection": 1094, "offsetInEndSection": 1388, "text": "Ongoing trials, focusing on circulating tumor cells (CTCs) and, even more, circulating tumor DNA (ctDNA), seem to pave the way to a promising, minimally invasive but accurate and life-saving monitoring, not only supporting personalized treatment but favoring patients' quality of life, as well.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34298740"}, {"offsetInBeginSection": 454, "offsetInEndSection": 698, "text": "Here, we analyzed cfDNA originating from nucleus and mitochondria and investigated their characteristics and mutation status in a cohort of 18 CRC patients and 10 healthy controls using targeted next-generation sequencing (NGS) and digital PCR.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34408162"}, {"offsetInBeginSection": 182, "offsetInEndSection": 1418, "text": "\"Liquid biopsy\" is one of the most recent domains of interest in oncology, as it may provide important details regarding the characteristics of the main tumor and its metastases. Malignant cells are in a continuous dynamic, which makes the initial diagnostic biopsy and the pathological specimen evaluation insufficient in the late evolution of the disease, when relapse or metastases may appear. The fact that the healthcare provider is able to find out additional information about the tumor at a given time, by evaluating a blood sample to obtain a \"liquid biopsy\" is of utmost importance and gives multiple potentially usable data. There are three means of obtaining biological material that may be used as \"liquid biopsy\": evaluation of circulating tumor cells, circulating tumor DNA and exosomes. The most intensely studied entity is that of circulating tumor cells, with different applications, amongst which the most important, at present time, is the prognostic value that has important demonstrated implications, not only in breast and prostate cancer, but also in colorectal cancer. Although surgery will, most certainly, not be replaced by other treatments when aiming for a curative approach to rectal cancer, it is importa", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31060647"}, {"offsetInBeginSection": 1623, "offsetInEndSection": 1868, "text": "by the heterogeneity of the cohort and the small number of postoperative plasma samples.CONCLUSIONS: These data indicate that tumor-informed circulating tumor DNA detection in the plasma of patients undergoing surgery for metastatic colorectal c", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35857852"}, {"offsetInBeginSection": 813, "offsetInEndSection": 1206, "text": "This means that, in this sample, the preoperative sensitivity and specificity of the test were 88.9% and 100%, respectively, and there is 100% correlation between the positive results of the SEPT9 test and a recurrence/persistence of the disease in patients after surgical resection.CONCLUSIONS: Our study shows that circulating hypermethylated SEPT9 is a specific colorectal cancer biomarker.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32566042"}, {"offsetInBeginSection": 996, "offsetInEndSection": 1388, "text": "Under this perspective, early detection of post-operative CRC recurrence is of utmost importance. Ongoing trials, focusing on circulating tumor cells (CTCs) and, even more, circulating tumor DNA (ctDNA), seem to pave the way to a promising, minimally invasive but accurate and life-saving monitoring, not only supporting personalized treatment but favoring patients' quality of life, as well.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34298740"}, {"offsetInBeginSection": 91, "offsetInEndSection": 280, "text": "Detecting and enumerating circulating tumor cells (CTCs) in patients with colorectal cancer emerged as an important prognostic tool which provides a direct estimate of metastatic potential.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30626171"}]}
+{"question_id": "65f59e46c4010b4d78000015", "question": "Where is the tumor of follicular infundibulum usually found?", "answer": "Tumor of follicular infundibulum is usually found in the skin", "relevant_passage_ids": ["28550716", "26143173", "25761672", "26170707", "11401679", "30809409", "21747619", "23531053", "7490369", "20137756", "36788082", "19377761", "25051108", "19633534", "29440859", "2069339"], "type": "factoid", "snippets": [{"offsetInBeginSection": 23, "offsetInEndSection": 52, "text": "scalp follicular infundibulum", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28550716"}, {"offsetInBeginSection": 12, "offsetInEndSection": 311, "text": "Tumor of the follicular infundibulum (TFI) is considered as a rare benign neoplasm providing two distinctive clinical patterns: the solitary and the eruptive form. The clinical presentations resemble many other dermatologic conditions and require histopathological study to make a definite diagnosis", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26143173"}, {"offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "Herein, we describe a 63-year-old male with multiple tumors arising within a nevus sebaceus on the posterior scalp. On histopathologic examination, four distinct tumors were identified: trichoblastoma, syringocystadenoma papilliferum, desmoplastic trichilemmoma and tumor of the follicular infundibulum (TFI)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25761672"}, {"offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Microneedling dilates the follicular infundibulum and increases transfollicular absorption of liposomal sepia melanin.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26170707"}, {"offsetInBeginSection": 159, "offsetInEndSection": 360, "text": "GATA6 transcription factor has been identified as a new marker of the upper folliculosebaceous compartment (lower infundibulum, junctional zone and isthmus, and upper sebaceous gland) in the human skin", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36788082"}, {"offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Tumor of the follicular infundibulum or infundibuloma is a relatively rare benign adnexal tumor usually solitary and located in the head, neck, and trunk.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30809409"}, {"offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Tumor of the follicular infundibulum or infundibuloma is a relatively rare benign adnexal tumor usually solitary and located in the head, neck, and trunk. Here we present a 70-year-old woman with a tender vulvar lesion.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30809409"}, {"offsetInBeginSection": 0, "offsetInEndSection": 292, "text": "BACKGROUND: Tumor of the follicular infundibulum (TFI) is a relatively rare tumor which clinically presents as a solitary keratotic papule usually on the head and neck which on microscopic examination typically reveals a plate-like fenestrated epithelial tumor composed of pale staining cells", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11401679"}, {"offsetInBeginSection": 0, "offsetInEndSection": 335, "text": "BACKGROUND: Tumor of the follicular infundibulum (TFI) is a relatively rare tumor which clinically presents as a solitary keratotic papule usually on the head and neck which on microscopic examination typically reveals a plate-like fenestrated epithelial tumor composed of pale staining cells.METHODS: We describe a new variant of TFI.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11401679"}, {"offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "BACKGROUND: Tumor of the follicular infundibulum (TFI) is an uncommon benign adnexal tumor that usually presents as a solitary keratotic papule in the head and neck area.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23531053"}, {"offsetInBeginSection": 0, "offsetInEndSection": 379, "text": "BACKGROUND: Tumor of the follicular infundibulum (TFI) is a rare benign adnexal tumor that has characteristic histopathologic features.OBJECTIVE: Our purpose was to describe the clinical and pathologic features of 12 patients with TFI.METHODS: Of 121,500 cutaneous biopsy specimens recorded between 1981 and 1993, all TFIs were identified and examined by conventional microscopy.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7490369"}, {"offsetInBeginSection": 9, "offsetInEndSection": 402, "text": "D: Tumor of the follicular infundibulum (TFI) is an uncommon benign adnexal tumor that usually presents as a solitary keratotic papule in the head and neck area. Infrequently, it may present as multiple lesions or in association with other conditions. Although it was initially described in 1961, the pathogenesis of this lesion is still controversial.METHODS: The clinical and histologic feat", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23531053"}, {"offsetInBeginSection": 65, "offsetInEndSection": 600, "text": "tumor of the follicular infundibulum (TFI) is not, as previously believed, entirely uncommon. To clarify the defining clinical and microscopic features of TFI with special relevance to the histologic variants, we retrospectively reviewed cases with a histologic diagnosis of TFI between 1999 and 2008. Of the 74 cases retrieved, 53 TFI cases in 50 patients were identified with an incidence approximating 17 per 100,000. Clinically, TFI seems to be slightly more common in men (52% vs. 48%) and more common on the head and neck (around", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19633534"}, {"offsetInBeginSection": 0, "offsetInEndSection": 335, "text": "Tumor of the follicular infundibulum (TFI) is an uncommon benign adnexal tumor that usually presents as a solitary keratotic papule on the face or scalp of elderly patients. Histopathologically, it typically manifests as a plate-like fenestrated proliferation of monomorphic pale-staining cells. A 76-year-old male presented with about", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21747619"}, {"offsetInBeginSection": 0, "offsetInEndSection": 361, "text": "Tumor of the follicular infundibulum was first described in 1961 by Mehregan and Butler in a patient presenting with multiple papules. It is more frequent, however, as an isolated lesion affecting mainly the face, neck, and upper trunk. Clinical presentation is variable, requiring histology for the diagnosis, which reveals typically a plate-like proliferation", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20137756"}, {"offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Tumor of the follicular infundibulum was first described in 1961 by Mehregan and Butler in a patient presenting with multiple papules. It is more frequent, however, as an isolated lesion affecting mainly the face, neck, and upper trunk.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20137756"}, {"offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "Tumor of follicular infundibulum (TFI) is currently believed to be a benign epithelial neoplasm with follicular differentiation. It has been suggested that TFI is associated with dermal scarring, but further investigation is needed to confirm this correlation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25051108"}, {"offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "BACKGROUND: Tumor of the follicular infundibulum (TFI) is an uncommon benign adnexal tumor that usually presents as a solitary keratotic papule in the head an", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23531053"}, {"offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Nevus comedonicus (NC) is a rare developmental anomaly of follicular infundibulum plugged with keratinous material that resembles comedo-like lesions. Frequently affected sites are face, neck, trunk, and upper arm.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29440859"}, {"offsetInBeginSection": 0, "offsetInEndSection": 522, "text": "Tumor of the follicular infundibulum was first described in 1961 by Mehregan and Butler in a patient presenting with multiple papules. It is more frequent, however, as an isolated lesion affecting mainly the face, neck, and upper trunk. Clinical presentation is variable, requiring histology for the diagnosis, which reveals typically a plate-like proliferation of keratinocytes in continuity with the epidermis and hair follicles; some morphological features are reminiscent of the outer root sheath of the hair follicle.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20137756"}, {"offsetInBeginSection": 659, "offsetInEndSection": 984, "text": "Four distinctive presentations of this tumor can be observed, in spite of its rarity: multiple macules of the upper chest or face (4 cases have previously been described), tumors of follicular infundibulum occurring in Cowden's disease or in the natural course of organoid nevi, and the most common solitary form of the face.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2069339"}, {"offsetInBeginSection": 0, "offsetInEndSection": 478, "text": "Tumor of the follicular infundibulum or infundibuloma is a relatively rare benign adnexal tumor usually solitary and located in the head, neck, and trunk. Here we present a 70-year-old woman with a tender vulvar lesion. Histopathologic exam shows a well-circumscribed lesion with a subepidermal horizontally oriented, plate-like proliferation of pale appearing squamous epithelial cells with numerous points of connections with the overlying epidermis and peripheral palisading.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30809409"}, {"offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "Tumor of the follicular infundibulum is an uncommon cutaneous lesion with different forms of clinical presentation, namely solitary and multiple/eruptive variants. The former shows predilection for head and neck and presents as a papulonodular scaly tumor.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19377761"}]}
+{"question_id": "6616576afdcbea915f000050", "question": "Mechanisms that explain irritable bowel syndrome.", "answer": "Underlying mechanisms that could lead to irritable bowel syndrome include genetic factors (most notably an identified mutation of SCN5A); post-infectious changes, chronic infections and disturbances in the intestinal microbiota; low-grade mucosal inflammation, immune activation, and altered intestinal permeability; disordered bile salt metabolism (in 10-20% of cases with diarrhoea); abnormalities in serotonin metabolism; and alterations in brain function, which could be primary or secondary factors.", "relevant_passage_ids": ["28404070", "27159638", "25083061", "36250361", "37048642", "37049488", "26528001", "21860817", "37160449", "35431513", "34631603", "22363132", "34709996", "27713358", "19682813", "34741163", "24944466", "16440408"], "type": "summary", "snippets": [{"offsetInBeginSection": 626, "offsetInEndSection": 1129, "text": "Underlying mechanisms that could lead to irritable bowel syndrome include genetic factors (most notably an identified mutation of SCN5A); post-infectious changes, chronic infections and disturbances in the intestinal microbiota; low-grade mucosal inflammation, immune activation, and altered intestinal permeability; disordered bile salt metabolism (in 10-20% of cases with diarrhoea); abnormalities in serotonin metabolism; and alterations in brain function, which could be primary or secondary factors", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28404070"}, {"offsetInBeginSection": 0, "offsetInEndSection": 435, "text": "Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder, affecting about 10 to 20% of the population in developed countries. The mechanisms underlying the symptoms of this condition are poorly understood. Considered initially as the consequence of abnormal gut motility, visceral hypersensitivity, psychosocial factors and brain-gut axis dysfunction, IBS is now acknowledged as a multifactorial disorder.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26528001"}, {"offsetInBeginSection": 0, "offsetInEndSection": 640, "text": "Irritable bowel syndrome (IBS) is a complex disorder characterized by abdominal symptoms including chronic abdominal pain or discomfort and altered bowel habits. The etiology of IBS is multifactorial, as abnormal gut motility, visceral hypersensitivity, disturbed neural function of the brain-gut axis and an abnormal autonomic nervous system are all implicated in disease progression. Based on recent experimental and clinical studies, it has been suggested that additional etiological factors including low-grade inflammation, altered gut microbiota and alteration in the gut immune system play important roles in the pathogenesis of IBS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21860817"}, {"offsetInBeginSection": 0, "offsetInEndSection": 494, "text": "Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by abdominal pain associated with defecation or a change in bowel habits. The pathogenesis of IBS is not completely clear, but it is known to be multifactorial and complex. Endogenous and exogenous factors such as abnormal GI motility, low-grade inflammation, increased epithelial permeability and visceral hypersensitivity, but diet and psychosocial aspects are also recognized as important actors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37049488"}, {"offsetInBeginSection": 0, "offsetInEndSection": 385, "text": "Irritable bowel syndrome (IBS) is a complex disorder characterized by abdominal symptoms including chronic abdominal pain or discomfort and altered bowel habits. The etiology of IBS is multifactorial, as abnormal gut motility, visceral hypersensitivity, disturbed neural function of the brain-gut axis and an abnormal autonomic nervous system are all implicated in disease progression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21860817"}, {"offsetInBeginSection": 142, "offsetInEndSection": 301, "text": "The etiology of IBS is multifactorial, including abnormal gut-brain interactions, visceral hypersensitivity, altered colon motility, and psychological factors.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36250361"}, {"offsetInBeginSection": 156, "offsetInEndSection": 624, "text": "The mechanisms underlying the symptoms of this condition are poorly understood. Considered initially as the consequence of abnormal gut motility, visceral hypersensitivity, psychosocial factors and brain-gut axis dysfunction, IBS is now acknowledged as a multifactorial disorder. Specific peripheral mechanisms are involved, including mucosal immune activation, increased intestinal permeability, entero-endocrine cell products, an excess of bile acids, gut dysbiosis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26528001"}, {"offsetInBeginSection": 753, "offsetInEndSection": 979, "text": "Recently, accumulating evidence has highlighted the important role of the gut microbiota in the development of IBS. Microbial dysbiosis within the gut is thought to contribute to all aspects of its multifactorial pathogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35431513"}, {"offsetInBeginSection": 621, "offsetInEndSection": 825, "text": "Metabolites-focused research has identified multiple microbial targets relevant to IBS patients, important roles of microbiota-derived metabolites in the development of IBS symptoms have been established.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34631603"}, {"offsetInBeginSection": 0, "offsetInEndSection": 408, "text": "From a pure motor disorder of the bowel, in the past few years, irritable bowel syndrome (IBS) has become a multifactorial disease that implies visceral hypersensitivity, alterations at the level of nervous and humoral communications between the enteric nervous system and the central nervous system, alteration of the gut microflora, an increased intestinal permeability and minimum intestinal inflammation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22363132"}, {"offsetInBeginSection": 64, "offsetInEndSection": 394, "text": "irritable bowel syndrome (IBS) has become a multifactorial disease that implies visceral hypersensitivity, alterations at the level of nervous and humoral communications between the enteric nervous system and the central nervous system, alteration of the gut microflora, an increased intestinal permeability and minimum intestinal", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22363132"}, {"offsetInBeginSection": 666, "offsetInEndSection": 1399, "text": "Additionally, immune activation, and particularly chronic mast cell activation, have been shown to underlie the development of abdominal pain in IBS.RESULTS: By releasing increased levels of mediators, including histamine, mast cells sensitize enteric nociceptors and lead to VHS development.\u00c2\u00a0The mechanisms underlying aberrant mast cell activation in IBS are still under investigation, but we recently showed that a local break in oral tolerance to food antigens led to IgE-mediated mast cell activation and food-induced abdominal pain in preclinical models and in IBS patients.CONCLUSION: The concept of food-mediated VHS highlights the potential of therapies targeting upstream mechanisms of mast cell sensitization to treat IBS.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34709996"}, {"offsetInBeginSection": 0, "offsetInEndSection": 501, "text": "Irritable bowel syndrome (IBS) is a functional bowel disorder without any structural or metabolic abnormalities that sufficiently explain the symptoms, which include abdominal pain and discomfort, and bowel habit changes such as diarrhea and constipation. Its pathogenesis is multifactorial: visceral hypersensitivity, dysmotility, psychosocial factors, genetic or environmental factors, dysregulation of the brain-gut axis, and altered intestinal microbiota have all been proposed as possible causes.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25083061"}, {"offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "Irritable bowel syndrome (IBS) is the most common functional bowel disorder worldwide and is associated with visceral hypersensitivity, gut motility, immunomodulation, gut microbiota alterations, and dysfunction of the brain-gut axis; however, its pathophysiology remains poorly understood.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34631603"}, {"offsetInBeginSection": 0, "offsetInEndSection": 296, "text": "Functional gastrointestinal symptoms such us bloating, fullness, flatulence, diarrhea, and constipation due to irritable bowel syndrome (IBS) were recently attributed to small bowel bacterial overgrowth, a condition depending on the presence of an increased number of bacteria in the small bowel.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27713358"}, {"offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Irritable bowel syndrome (IBS) is a complex multifactorial condition including alterations of the gut-brain axis, intestinal permeability, mucosal neuro-immune interactions, and microbiota imbalance.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37160449"}, {"offsetInBeginSection": 604, "offsetInEndSection": 868, "text": "Neurological abnormalities may be triggered by inflammation, mast cell dysfunction or increased intestinal permeability while the neuro-immune consequences of stress (mainly chronic) play a major role in the genesis and the maintenance of irritable bowel syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19682813"}, {"offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Irritable bowel syndrome (IBS) results from disordered brain-gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34741163"}, {"offsetInBeginSection": 0, "offsetInEndSection": 551, "text": "Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that is characterized by abdominal pain and disordered bowel habits. The etiology of IBS is multifactorial, including abnormal gut-brain interactions, visceral hypersensitivity, altered colon motility, and psychological factors. Recent studies have shown that the intestinal microbiota and its metabolites short chain fatty acids (SCFAs) may be involved in the pathogenesis of IBS. SCFAs play an important role in the pathophysiology of IBS. We discuss the underlying mechanisms", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36250361"}, {"offsetInBeginSection": 470, "offsetInEndSection": 759, "text": "Although the pathophysiology of IBS has not been fully elucidated, it involves dysregulation of communication between the brain and gut (brain-gut axis) which is associated with alterations in intestinal motility, gut permeability, visceral hypersensitivity and gut microbiota composition.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37048642"}, {"offsetInBeginSection": 0, "offsetInEndSection": 376, "text": "Irritable bowel syndrome (IBS) is considered a biopsychosocial disorder, whose onset and precipitation are a consequence of interaction among multiple factors which include motility disturbances, abnormalities of gastrointestinal sensation, gut inflammation and infection, altered processing of afferent sensory information, psychological distress, and affective disturbances.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24944466"}, {"offsetInBeginSection": 269, "offsetInEndSection": 572, "text": "Advances in our understanding of gut flora-mucosal interactions, the enteric nervous system and the brain-gut axis have led to substantial progress in the pathogenesis of symptoms in IBS and have provided some hints towards the basic etiology of this disorder, in some subpopulations, at the very least.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16440408"}]}
+{"question_id": "661d4c2eeac11fad3300001a", "question": "What is the cause of Rett Syndrome?", "answer": "Rett Syndrome is caused by mutations of the X-linked gene encoding methyl-CpG-binding protein 2 (MECP2).", "relevant_passage_ids": ["37408271", "28007990", "12503649", "20682201", "24423488", "17874730", "16225827", "12615169", "24291980", "15070486", "26755454", "15367913", "38057990", "33552148", "30447288", "11262731", "15866439", "12966522", "17986102", "11738862", "12112735", "36778467", "22106023", "20236870", "31333401", "20473347", "27491552", "25982834", "27934853", "20970936", "16225828", "31542590", "30502397", "36056801", "16690727", "24615633", "35785421", "24059803", "29694339", "15809268", "37906876", "37914350", "37885019", "34308425", "37461668", "27328325", "31409060", "30430747", "30905360", "34209228", "31387202", "31450191", "22586411", "20139413", "31796123", "12750821", "25960047", "20951500", "16932552", "31629059", "15757975", "36253345"], "type": "factoid", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Mutations of the X-linked gene encoding methyl-CpG-binding protein 2 (MECP2) cause classical forms of Rett syndrome (RTT) in girls", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37408271"}, {"offsetInBeginSection": 0, "offsetInEndSection": 325, "text": "Rett syndrome is caused by mutation in MECP2, a gene located on Xq28 and subject to X-inactivation. MECP2 encodes methyl CpG-binding protein 2, a widely expressed transcriptional repressor of methylated DNA. Mutations in MECP2 are primarily de novo events in the male germ line and thus lead to an excess of affected females.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12966522"}, {"offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Rett syndrome is caused by mutation in MECP2, a gene located on Xq28 and subject to X-inactivation. MECP2 encodes methyl CpG-binding protein 2, a widely expressed transcriptional repressor of methylated DNA.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12966522"}, {"offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Rett syndrome is caused by mutation in MECP2, a gene located on Xq28 and subject to X-inactivation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12966522"}, {"offsetInBeginSection": 1032, "offsetInEndSection": 1153, "text": " MECP2 rearrangements cause Rett syndrome in a significant number of girls without 'classic' mutations in this gene. Ther", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17986102"}, {"offsetInBeginSection": 120, "offsetInEndSection": 566, "text": "Rett syndrome is frequently caused by a mutation in methyl-CpG-binding protein (MECP2) gene, localized on chromosome Xq28, whereas Angelman syndrome is frequently caused by different genetic anomalies at chromosome 15q11-q13 (deletions, uniparental disomy, imprinting center mutations, ubiquitin E3 ligase [UBE3A] gene mutations). Recently, some patients with a clinical diagnosis of Angelman syndrome were found to have a mutation in MECP2 gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15866439"}, {"offsetInBeginSection": 120, "offsetInEndSection": 450, "text": "Rett syndrome is frequently caused by a mutation in methyl-CpG-binding protein (MECP2) gene, localized on chromosome Xq28, whereas Angelman syndrome is frequently caused by different genetic anomalies at chromosome 15q11-q13 (deletions, uniparental disomy, imprinting center mutations, ubiquitin E3 ligase [UBE3A] gene mutations).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15866439"}, {"offsetInBeginSection": 120, "offsetInEndSection": 664, "text": "Rett syndrome is frequently caused by a mutation in methyl-CpG-binding protein (MECP2) gene, localized on chromosome Xq28, whereas Angelman syndrome is frequently caused by different genetic anomalies at chromosome 15q11-q13 (deletions, uniparental disomy, imprinting center mutations, ubiquitin E3 ligase [UBE3A] gene mutations). Recently, some patients with a clinical diagnosis of Angelman syndrome were found to have a mutation in MECP2 gene. This report describes another patient with an Angelman-like phenotype and with an MECP2 mutation.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15866439"}, {"offsetInBeginSection": 1032, "offsetInEndSection": 1293, "text": " MECP2 rearrangements cause Rett syndrome in a significant number of girls without 'classic' mutations in this gene. Therefore, we developed a specific quantitative PCR method, covering MECP2 exons 3 and 4, which previously has not been used for screening. No d", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17986102"}, {"offsetInBeginSection": 0, "offsetInEndSection": 566, "text": "Rett syndrome and Angelman syndrome are two neurodevelopmental disorders characterized by partial overlapping features. Rett syndrome is frequently caused by a mutation in methyl-CpG-binding protein (MECP2) gene, localized on chromosome Xq28, whereas Angelman syndrome is frequently caused by different genetic anomalies at chromosome 15q11-q13 (deletions, uniparental disomy, imprinting center mutations, ubiquitin E3 ligase [UBE3A] gene mutations). Recently, some patients with a clinical diagnosis of Angelman syndrome were found to have a mutation in MECP2 gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15866439"}, {"offsetInBeginSection": 1032, "offsetInEndSection": 1387, "text": " MECP2 rearrangements cause Rett syndrome in a significant number of girls without 'classic' mutations in this gene. Therefore, we developed a specific quantitative PCR method, covering MECP2 exons 3 and 4, which previously has not been used for screening. No dosage alterations of the two exons were found in the four tested mutation-negative girls.CONCL", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17986102"}, {"offsetInBeginSection": 176, "offsetInEndSection": 306, "text": "The majority of cases of sporadic Rett syndrome are caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15070486"}, {"offsetInBeginSection": 396, "offsetInEndSection": 633, "text": "Genotype/phenotype analysis revealed that the phenotypic spectrum of MECP2 mutations in humans is broader than initially suspected: Mutations have been discovered in Rett syndrome variants, mentally retarded males, and autistic children.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15070486"}, {"offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Rett syndrome, a neurodevelopmental disorder that is a leading cause of mental retardation in females, is caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11262731"}, {"offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Mutations in methyl CpG binding protein 2 (MeCP2) are the major cause of Rett syndrome (RTT), a rare neurodevelopmental disorder with a notable period of developmental regression following apparently normal initial development.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33552148"}, {"offsetInBeginSection": 73, "offsetInEndSection": 169, "text": "Mutations in the MECP2 gene on chromosome Xq28 have been shown to be the cause of Rett syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26755454"}, {"offsetInBeginSection": 285, "offsetInEndSection": 582, "text": "Rett syndrome is the first pervasive developmental disorder with a known genetic cause. The majority of cases are caused by de novo mutations in an X-linked MECP2 gene. Its product, methyl-CpG-binding protein 2, plays an important role in the regulation of gene expression and chromatin structure.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17874730"}, {"offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Rett syndrome is a rare neurological disorder affecting girls and usually caused by a mutation on the MECP2 gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22106023"}, {"offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Rett syndrome, a neurodevelopmental disorder affecting mainly females, is caused by a mutation of the MeCP2 gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20236870"}, {"offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Rett syndrome is an X-linked autism-spectrum disorder caused by mutations in MECP2, encoding methyl CpG-binding protein 2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20473347"}, {"offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Rett syndrome is a\u00a0rare neurodevelopmental disorder caused by a\u00a0mutation in the MECP2 gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27491552"}, {"offsetInBeginSection": 308, "offsetInEndSection": 449, "text": "Recent studies have shown that mutations in the X-linked methyl CpG binding protein 2 gene (MeCP2) cause most typical cases of Rett syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12112735"}, {"offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "BACKGROUND: Rett syndrome is caused by mutations in the X-linked MECP2 gene, encoding MeCP2 protein.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24423488"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Somatic mosaicism for Y120X mutation in the MECP2 gene causes atypical Rett syndrome in a male.", "beginSection": "title", "endSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20970936"}, {"offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "Rett syndrome is a devastating neurodevelopmental disorder, primarily caused by mutations of methyl CpG-binding protein 2 (MeCP2). Although the genetic cause of disease was identified over a decade ago, a significant gap still remains in both our clinical and scientific understanding of its pathogenesis.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25982834"}, {"offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Rett Syndrome (RTT) is a genetic disorder that is caused by mutations in the x-linked gene coding for methyl-CpG-biding-protein 2 (MECP2)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30502397"}, {"offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Rett syndrome (RTT) is an X-linked neurogenetic disorder caused by mutations of the MECP2 (methyl-CpG-binding protein 2) gene. Over two decades of work", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36056801"}, {"offsetInBeginSection": 30, "offsetInEndSection": 578, "text": "Rett first described the syndrome that came to bear his name, and is now known to be caused by a mutation in the methyl-CpG-binding protein 2 (MECP2) gene, a compelling blend of astute clinical observations and clinical and laboratory research has substantially enhanced our understanding of this rare disorder. Here, we document the contributions of the early pioneers in Rett syndrome (RTT) research, and describe the evolution of knowledge in terms of diagnostic criteria, clinical variation, and the interplay with other Rett-related disorders.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27934853"}, {"offsetInBeginSection": 129, "offsetInEndSection": 579, "text": "cause various neuro-developmental diseases. We recently reported that neurological symptoms of Rett syndrome, which is an autistic disorder caused by mutations in methyl-CpG binding protein 2 (MeCP2), was associated with failure of epigenomic gene regulation in neuronal cells, and that clinical differences in the identical twins with Rett syndrome in the differences in DNA methylation in neuronal genes, but not caused by DNA sequence differences.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291980"}, {"offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Mutations in MECP2 give rise to Rett syndrome (RTT), an X-linked neurodevelopmental disorder that results in broad cognitive impairments in females. While the exact etiology of RTT symptoms remains unknown, one possible explanation", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37461668"}, {"offsetInBeginSection": 221, "offsetInEndSection": 481, "text": "Rett syndrome (RTT), a postnatal neurological disorder caused by loss-of-function mutations in MECP2, display impaired excitatory neurotransmission, the RTT phenotype can be largely reproduced in mice simply by removing MeCP2 from inhibitory GABAergic neurons.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27328325"}, {"offsetInBeginSection": 93, "offsetInEndSection": 210, "text": "About 80% of classic Rett syndrome is caused by mutations in the gene for methyl-CpG-binding protein (MeCP2) in Xq28.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11738862"}, {"offsetInBeginSection": 107, "offsetInEndSection": 218, "text": "Mutations of the methyl-CpG binding protein 2 (MECP2) gene are the most prevalent cause of classical RTT cases.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24615633"}, {"offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Mutations in the methyl-CpG binding protein 2 (MECP2) gene cause Rett syndrome (RTT), a progressive X-linked neurological disorder characterized by loss of developmental milestones, intellectual disability and breathing abnormality.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30447288"}, {"offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Rett syndrome (RTT) is an X-linked neurodevelopmental disease caused by MECP2 mutations.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24059803"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Mutations in MECP2 are a cause of Rett syndrome. Recently, a new isoform of MeCP2 was described, which has an alternative N-terminus, transcribed from", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15367913"}, {"offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Rett syndrome is a neurodevelopmental disorder caused by mutations in the methyl CpG binding protein 2 gene (MECP2). The MECP2 protein is expressed pr", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20682201"}, {"offsetInBeginSection": 15, "offsetInEndSection": 165, "text": "mon in Rett syndrome, an X-linked dominant disorder caused by mutations in the MECP2 gene, and in Rett-related disorders, such as MECP2 duplication. H", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28007990"}, {"offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Rett syndrome is a neurodevelopmental disorder caused by mutations in the methyl CpG binding protein 2 gene (MECP2).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20682201"}, {"offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Mutations in MECP2 are a cause of Rett syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15367913"}, {"offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "In 1999, mutations in the MECP2 gene were identified as the primary cause of Rett syndrome. MECP2 mutations can be found in 70% to 80% of all clinically defined Rett syndrome cases; in classic Rett syndrome, this frequency is even higher.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16225827"}, {"offsetInBeginSection": 133, "offsetInEndSection": 273, "text": " MeCP2 mutations have been linked to Rett syndrome, a neurodevelopmental disorder characterized by severe intellectual disability in females", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29694339"}, {"offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "The discovery in 1999 that Rett syndrome (RTT) is caused by mutations in a gene encoding the methyl-CpG-binding repressor protein MECP2 provided a significant breakthrough in the understanding of this devastating disease.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15809268"}, {"offsetInBeginSection": 109, "offsetInEndSection": 247, "text": "Recently, mutations in the gene encoding X-linked methyl-CpG binding protein 2 (MECP2) have been identified as the cause of Rett syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12503649"}, {"offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Mutations in the methyl-DNA binding domain of MECP2 cause Rett syndrome; however, distinct mutations are associated with different severity of the disease", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37914350"}, {"offsetInBeginSection": 12, "offsetInEndSection": 113, "text": "Rett syndrome (RS) is a rare neurodevelopmental disorder characterized by mutations in the MECP2 gene", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37885019"}, {"offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Mutations in MECP2 cause the neurodevelopmental disorder Rett syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36778467"}, {"offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "Rett syndrome is a neurodevelopmental disorder caused by loss-of-function mutations in the methyl-CpG binding protein-2 (MeCP2) gene that is characterized by epilepsy, intellectual disability, autistic features, speech deficits, and sleep and breathing abnormalities.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38057990"}, {"offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Mutations in the MECP2 (methyl-CpG-binding protein 2) gene are known to cause Rett syndrome, a well-known and clinically defined neurodevelopmental disorder.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12615169"}, {"offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the Methyl CpG binding protein 2 (MeCP2) gene. This Science & Society article focuses on", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30905360"}, {"offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Rett syndrome is a neurodevelopmental disorder caused by loss-of-function mutations in the methyl-CpG binding protein-2 (MeCP2)", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/38057990"}, {"offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Rett syndrome (RTT) is a monogenic neurodevelopmental disorder caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene. Patients with RTT develop symptoms after 6-18 months of age,", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30430747"}, {"offsetInBeginSection": 0, "offsetInEndSection": 655, "text": "Rett syndrome (RTT) is an early-onset neurodevelopmental disorder that primarily affects females, resulting in severe cognitive and physical disabilities, and is one of the most prevalent causes of intellectual disability in females. More than fifty years after the first publication on Rett syndrome, and almost two decades since the first report linking RTT to the MECP2 gene, the research community's effort is focused on obtaining a better understanding of the genetics and the complex biology of RTT and Rett-like phenotypes without MECP2 mutations. Herein, we review the current molecular genetic studies, which investigate the genetic causes of RTT", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31409060"}, {"offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder characterized by neurodevelopmental regression between 6 and 18 months of life and associated with multi-system comorbidities. Caused mainly by pathogenic variants in the MECP2 (methyl CpG", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34308425"}, {"offsetInBeginSection": 0, "offsetInEndSection": 538, "text": "Rett syndrome (RS) is a rare neurodevelopmental disorder first described in 1966. It is characterized by the arrest and regression of intellectual, motor, and communicative developmental milestones, followed by the appearance of hand stereotypies after an apparently normal development period. Pathogenic variants in the MECP2 gene have been identified as a cause in most cases. The following review focuses on analyzing updated information regarding the medical and social aspects of RS globally, with a special emphasis of the situation", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/37906876"}, {"offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "In 1999, mutations in the MECP2 gene were identified as the primary cause of Rett syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16225827"}, {"offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "Rett syndrome, one of the leading causes of mental retardation and developmental regression in girls, is the first pervasive developmental disorder with a known genetic cause. The majority of cases of sporadic Rett syndrome are caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15070486"}, {"offsetInBeginSection": 0, "offsetInEndSection": 340, "text": "In 1999, mutations in the MECP2 gene were identified as the primary cause of Rett syndrome. MECP2 mutations can be found in 70% to 80% of all clinically defined Rett syndrome cases; in classic Rett syndrome, this frequency is even higher. In most cases, missense and nonsense mutations affecting functionally important domains can be found.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16225827"}, {"offsetInBeginSection": 109, "offsetInEndSection": 357, "text": "Recently, mutations in the gene encoding X-linked methyl-CpG binding protein 2 (MECP2) have been identified as the cause of Rett syndrome. Along with the classic form, variant forms of Rett syndrome and Rett syndrome phenotypes are also recognized.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12503649"}, {"offsetInBeginSection": 176, "offsetInEndSection": 395, "text": "The majority of cases of sporadic Rett syndrome are caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). MeCP2 binds methylated DNA and likely regulates gene expression and chromatin structure.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15070486"}, {"offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Rett syndrome is a progressive neurodevelopmental disorder with a well-defined clinical spectrum and course. Recently, mutations in the gene encoding X-linked methyl-CpG binding protein 2 (MECP2) have been identified as the cause of Rett syndrome.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12503649"}, {"offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Rett syndrome (RTT) is one of the most common causes of intellectual and developmental disabilities in girls, and is caused by mutations in the gene encoding methyl-CpG binding protein 2 (MECP2). Here we will review our current understanding", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31542590"}, {"offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Rett syndrome (RTT) is a childhood neurodevelopmental disorder caused by mutations in MECP2. To study the molecular mechanisms underlying RTT, four", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31450191"}, {"offsetInBeginSection": 0, "offsetInEndSection": 366, "text": "Rett syndrome (RTT) is an extremely invalidating, cureless, developmental disorder, and it is considered one of the leading causes of intellectual disability in female individuals. The vast majority of RTT cases are caused by de novo mutations in the X-linked Methyl-CpG binding protein 2 (MECP2) gene, which encodes a multifunctional reader of methylated DNA. MeCP2", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34209228"}, {"offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "Rett syndrome (RTT) is a rare, X-linked neurodevelopmental disorder typically affecting females, resulting in a range of symptoms including autistic features, intellectual impairment, motor deterioration, and autonomic abnormalities. RTT is primarily caused by the genetic mutation of the Mecp2 gene. Initially", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31387202"}, {"offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Rett syndrome (RTT) is a progressive neurodevelopmental disorder that occurs mainly in girls with a range of typical symptoms of autism spectrum disorders. MeCP2 protein loss-of-function in neural lineage cells is the main cause", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/35785421"}, {"offsetInBeginSection": 77, "offsetInEndSection": 171, "text": "Rett syndrome is caused by mutations in MECP2, the gene encoding methyl-CpG binding protein 2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16225828"}, {"offsetInBeginSection": 172, "offsetInEndSection": 273, "text": "In up to 96% of all classic cases, Rett syndrome cases are caused by mutations or deletions in MECP2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16225828"}, {"offsetInBeginSection": 422, "offsetInEndSection": 566, "text": "Rett syndrome (RTT) is a neurological disorder of genetic origin, caused by mutations in the X-linked gene methyl-CpG binding protein 2 (MeCP2).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22586411"}, {"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Rett syndrome is a neurodevelopmental disorder mainly caused by de novo mutations in the MECP2 (methyl-CpG-binding protein 2) gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20139413"}, {"offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Rett Syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the Methyl CpG binding protein\u00a02 (MECP2) gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31796123"}, {"offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Rett syndrome is an X-linked dominant neurodevelopmental disorder primarily affecting girls. About 80% of classic Rett syndrome is caused by mutations in the gene for methyl-CpG-binding protein (MeCP2) in Xq28.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11738862"}, {"offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting almost exclusively girls. It is currently considered a monogenic X-linked dominant disorder due to mutations in MECP2 gene, encoding the methyl-CpG binding protein 2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12750821"}, {"offsetInBeginSection": 394, "offsetInEndSection": 643, "text": "RTT is known to be caused in 95% of the cases by sporadic de novo loss-of-function mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene encoding methyl-CpG binding protein 2 (MeCP2), a nuclear protein able to regulate gene expression.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25960047"}, {"offsetInBeginSection": 0, "offsetInEndSection": 345, "text": "Rett syndrome (RTT) is an X-linked dominant postnatal severe and disabling neurodevelopmental disorder which is the second most common cause for genetic mental retardation in girls and the first pervasive disorder with a known genetic basis. The syndrome is primarily caused by mutations in the Methyl CpG binding protein 2 (MECP2) gene on Xq28.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20951500"}, {"offsetInBeginSection": 240, "offsetInEndSection": 357, "text": "RTT is caused by heterozygosity for mutations in the X-linked gene MECP2, which encodes methyl-CpG binding protein 2.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16932552"}, {"offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Rett syndrome (RTT) is a leading cause of severe intellectual disability in females, caused by de novo loss-of function mutations in the X-linked methyl-CpG binding protein 2 (MECP2).", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31629059"}, {"offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Rett syndrome (RS) is a severe and progressive neurodevelopmental disorder caused by heterozygous mutations in the X-linked methyl CpG binding protein 2 (MeCP2) gene.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15757975"}, {"offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily caused by heterozygous loss-of-function mutations in the X-linked gene MECP2 that is a global transcriptional regulator.", "beginSection": "abstract", "endSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/36253345"}]}