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yesno | Should Lubeluzole be used for treatment of ischemic stroke? | ['no'] | [
"no"
]
| ['No. Lubeluzole failed to consistently show an efficacy in the treatment of acute stroke and should not be used.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/29550817",
"http://www.ncbi.nlm.nih.gov/pubmed/28939972",
"http://www.ncbi.nlm.nih.gov/pubmed/8553408",
"http://www.ncbi.nlm.nih.gov/pubmed/11869612",
"http://www.ncbi.nlm.nih.gov/pubmed/11062273",
"http://www.ncbi.nlm.nih.gov/pubmed/12038658",
"http://www.ncbi.nlm.nih.gov/pubmed/9412611",
"http://www.ncbi.nlm.nih.gov/pubmed/9619701"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28939972",
"endSection": "abstract",
"offsetInBeginSection": 729,
"offsetInEndSection": 870,
"text": "Lubeluzole showed promising neuroprotective effects in animal stroke models, but failed to show benefits in acute ischemic stroke in humans. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29550817",
"endSection": "abstract",
"offsetInBeginSection": 142,
"offsetInEndSection": 311,
"text": "However, clinical research on lubeluzole is now at a standstill, since lubeluzole seems to be associated with the acquired long QT syndrome and ventricular arrhythmias. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12038658",
"endSection": "abstract",
"offsetInBeginSection": 302,
"offsetInEndSection": 696,
"text": "Ten classes of neuroprotective agents have reached phase III efficacy trials but have shown mixed results. They included calcium channel antagonists, NMDA receptor antagonists, lubeluzole, CDP-choline, the free radical scavenger tirilazad and ebselen, enlimomab, GABA agonist clomethiazole, the sodium channel antagonist fosphenytoin, magnesium, glycine site antagonist GV150526 and piracetam. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11062273",
"endSection": "abstract",
"offsetInBeginSection": 2385,
"offsetInEndSection": 2484,
"text": "CONCLUSIONS: This study failed to show an efficacy of lubeluzole in the treatment of acute stroke. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11062273",
"endSection": "abstract",
"offsetInBeginSection": 1816,
"offsetInEndSection": 2125,
"text": "Overall, of all treated patients, 401 (22.5%) died: 203 (22.5%) in the lubeluzole group and 198 (22.4%) with placebo. Of all subjects treated, 853 (95%) on lubeluzole and 826 (93%) on placebo reported an adverse event during their treatment period or within the next 2 days after discontinuation of treatment."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9412611",
"endSection": "abstract",
"offsetInBeginSection": 1760,
"offsetInEndSection": 1976,
"text": "CONCLUSIONS: Treatment with lubeluzole within 6 hours of the onset of ischemic stroke had a nonsignificant effect on mortality and resulted in improved clinical outcome compared with placebo, with no safety concerns."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9412611",
"endSection": "abstract",
"offsetInBeginSection": 1088,
"offsetInEndSection": 1700,
"text": "RESULTS: The overall mortality rate at 12 weeks for lubeluzole-treated patients was 20.7% compared to 25.2% for placebo-treated patients (NS). Controlling for relevant covariates, the degree of neurological recovery (NIHSS) at week 12 significantly favored lubeluzole over placebo (P = .033). Lubeluzole treatment similarly resulted in significantly greater improvements in functional status (Barthel Index) (P = .038) and overall disability (Rankin Scale) (P = .034) after 12 weeks. A global test statistic confirmed that lubeluzole-treated patients had a more favorable clinical outcome at 12 weeks (P = .041)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8553408",
"endSection": "abstract",
"offsetInBeginSection": 1922,
"offsetInEndSection": 2121,
"text": "CONCLUSIONS: In patients with acute ischemic stroke, the dosage regimen of 7.5 mg over 1 hour followed by 10 mg/d of intravenous lubeluzole is safe and statistically significantly reduced mortality. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9412611",
"endSection": "abstract",
"offsetInBeginSection": 1766,
"offsetInEndSection": 1982,
"text": "CONCLUSIONS\n\nTreatment with lubeluzole within 6 hours of the onset of ischemic stroke had a nonsignificant effect on mortality and resulted in improved clinical outcome compared with placebo, with no safety concerns."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11869612",
"endSection": "abstract",
"offsetInBeginSection": 2301,
"offsetInEndSection": 2594,
"text": "CONCLUSIONS: Lubeluzole, given in the acute phase of ischaemic stroke, is not associated with a significant reduction of death or dependency at the end of scheduled follow-up period but seems to be associated with a significant increase of heart-conduction disorders (Q-T prolonged >450 msec)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9412611",
"endSection": "abstract",
"offsetInBeginSection": 1721,
"offsetInEndSection": 1924,
"text": "Treatment with lubeluzole within 6 hours of the onset of ischemic stroke had a nonsignificant effect on mortality and resulted in improved clinical outcome compared with placebo, with no safety concerns."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9619701",
"endSection": "abstract",
"offsetInBeginSection": 1963,
"offsetInEndSection": 2123,
"text": "In the overall study population, treatment with intravenous lubeluzole within 6 h of the onset of ischaemic stroke did not affect mortality or clinical outcome."
}
]
| 11 | BioASQ-training11b | null | null | 5e44caaf48dab47f26000024 | 0 |
yesno | Are integrins part of the extracellular matrix? | ['yes'] | [
"yes"
]
| ['Yes, \tintegrins are a central family of extracellular matrix receptors.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/26029690",
"http://www.ncbi.nlm.nih.gov/pubmed/26067407",
"http://www.ncbi.nlm.nih.gov/pubmed/26096733",
"http://www.ncbi.nlm.nih.gov/pubmed/26089687",
"http://www.ncbi.nlm.nih.gov/pubmed/25605337",
"http://www.ncbi.nlm.nih.gov/pubmed/25759527",
"http://www.ncbi.nlm.nih.gov/pubmed/25460334",
"http://www.ncbi.nlm.nih.gov/pubmed/24965068",
"http://www.ncbi.nlm.nih.gov/pubmed/25220424",
"http://www.ncbi.nlm.nih.gov/pubmed/25631868",
"http://www.ncbi.nlm.nih.gov/pubmed/25886986"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26029690",
"endSection": "abstract",
"offsetInBeginSection": 314,
"offsetInEndSection": 451,
"text": "Several constituents of the ECM provide adhesive cues, which serve as binding sites for cell trans-membrane receptors, such as integrins."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26067407",
"endSection": "abstract",
"offsetInBeginSection": 1026,
"offsetInEndSection": 1129,
"text": "We also determined that blocking β1integrins, the major class of receptors for all ECM proteins tested,"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26096733",
"endSection": "abstract",
"offsetInBeginSection": 135,
"offsetInEndSection": 298,
"text": "Here, we elucidate a cross-scale mechanism for tissue assembly and ECM remodeling involving Cadherin 2, the ECM protein Fibronectin, and its receptor Integrin α5. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26089687",
"endSection": "abstract",
"offsetInBeginSection": 410,
"offsetInEndSection": 604,
"text": "due to the diverse functions and variable expression of proteoglycans, matrix proteins, and integrins, it is rather difficult to identify a comprehensive therapeutic target among ECM components."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25605337",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 100,
"text": "Integrin-dependent cell-extracellular matrix (ECM) adhesion is a determinant of spindle orientation."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25759527",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 226,
"text": "The extracellular matrix component periostin is a secreted protein that functions as both a cell attachment protein and an autocrine or paracrine factor that signals through the cell adhesion molecule integrins αvβ3 and αvβ5. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25460334",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 118,
"text": "Integrin receptors connect the extracellular matrix to the cell cytoskeleton to provide essential forces and signals. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24965068",
"endSection": "abstract",
"offsetInBeginSection": 690,
"offsetInEndSection": 839,
"text": " the integrin, talin, and actin filament form a linear complex of which both ends are typically anchored to the extracellular matrices via integrins."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25886986",
"endSection": "abstract",
"offsetInBeginSection": 179,
"offsetInEndSection": 338,
"text": "Integrins, a central family of cellular ECM receptors, have been implicated in these processes but their specific role in ES cell self-renewal remains unclear."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25631868",
"endSection": "abstract",
"offsetInBeginSection": 259,
"offsetInEndSection": 446,
"text": "Attachment to the extracellular matrix is mediated by a complex of adhesion proteins, including integrins, signaling molecules, actin and actin-binding proteins, and scaffolding proteins."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25220424",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 167,
"text": "Beta 1 integrin binding plays a role in the constant traction force generation in response to varying stiffness for cells grown on mature cardiac extracellular matrix."
}
]
| 5 | BioASQ-training5b | []
| []
| 56e83a2342442bac75000001 | 1 |
yesno | Is Baloxavir effective for influenza? | ['yes'] | [
"yes"
]
| ['Yes. Baloxavir is approved for influenza A or B virus infections.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/30395523",
"http://www.ncbi.nlm.nih.gov/pubmed/30316915",
"http://www.ncbi.nlm.nih.gov/pubmed/29623652",
"http://www.ncbi.nlm.nih.gov/pubmed/30184455",
"http://www.ncbi.nlm.nih.gov/pubmed/30476172",
"http://www.ncbi.nlm.nih.gov/pubmed/30396860",
"http://www.ncbi.nlm.nih.gov/pubmed/30203386",
"http://www.ncbi.nlm.nih.gov/pubmed/29941893"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29623652",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 358,
"text": "Baloxavir marboxil (Xofluza™; baloxavir) is an oral cap-dependent endonuclease inhibitor that has been developed by Roche and Shionogi. The drug blocks influenza virus proliferation by inhibiting the initiation of mRNA synthesis. In February 2018, baloxavir received its first global approval in Japan for the treatment of influenza A or B virus infections. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29623652",
"endSection": "abstract",
"offsetInBeginSection": 448,
"offsetInEndSection": 595,
"text": "This article summarized the milestones in the development of baloxavir leading to this first global approval for influenza A or B virus infections."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29941893",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 200,
"text": "Baloxavir acid (BXA), derived from the prodrug baloxavir marboxil (BXM), potently and selectively inhibits the cap-dependent endonuclease within the polymerase PA subunit of influenza A and B viruses."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29941893",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 117,
"text": "Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30184455",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 73,
"text": "Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30184455",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 248,
"text": "BACKGROUND: Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30184455",
"endSection": "abstract",
"offsetInBeginSection": 1917,
"offsetInEndSection": 2209,
"text": "CONCLUSIONS: Single-dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30396860",
"endSection": "abstract",
"offsetInBeginSection": 321,
"offsetInEndSection": 469,
"text": "A single oral dose of baloxavir is usually well tolerated; it hastens alleviation of influenza symptoms and shortens the duration of viral shedding."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30396860",
"endSection": "abstract",
"offsetInBeginSection": 69,
"offsetInEndSection": 156,
"text": "Japan was the first country to approve baloxavir marboxil as a treatment for influenza."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29623652",
"endSection": "abstract",
"offsetInBeginSection": 448,
"offsetInEndSection": 599,
"text": "This article summarized the milestones in the development of baloxavir leading to this first global approval for influenza A or B virus infections.<br>"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29623652",
"endSection": "abstract",
"offsetInBeginSection": 230,
"offsetInEndSection": 357,
"text": "In February 2018, baloxavir received its first global approval in Japan for the treatment of influenza A or B virus infections."
}
]
| 11 | BioASQ-training11b | null | null | 5c58a74e86df2b917400000d | 2 |
yesno | Are there any digital biomarkers for Duchenne Muscular Dystrophy? | ['yes'] | [
"yes"
]
| ['Yes, the KineDMD ethomic biomarker is a digital biomarker for Duchenne Muscular Dystrophy.', 'Yes, wearable full-body motion tracking of activities of daily living is a digital biomarker for Duchenne Muscular Dystrophy that can predict disease trajectory', "Yes, there is a digital biomarker for Duchenne Muscular Dystrophy. It's called the KineDMD ethomic biomarker, which is derived from daily-life behavioral data.", 'Yes, a digital biomarker called the KineDMD ethomic biomarker has been developed for Duchenne Muscular Dystrophy. It is derived from daily-life behavioral data and can predict disease progression.', 'Yes, the KineDMD ethomic biomarker is a digital biomarker for Duchenne Muscular Dystrophy. It is derived from daily-life movement behavior and can predict disease progression in patients with muscular dystrophy and can potentially track the response to therapy', 'Yes, digital biomarkers have been developed for Duchenne Muscular Dystrophy.', 'Yes. Bayesian optimization, machine learning algorithms and movement behavioral fingerprints are used as digital biomarkers for Duchenne Muscular Dystrophy.', 'Yes, there are digital biomarkers for Duchenne Muscular Dystrophy.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/36658421"
]
| [
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36658421",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 124,
"text": "Wearable full-body motion tracking of activities of daily living predicts disease trajectory in Duchenne muscular dystrophy."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36658421",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36658421",
"endSection": "abstract",
"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."
}
]
| 13 | BioASQ-training13b | null | null | 66302174187cba990d00002e | 3 |
yesno | Are sleep apnea and snoring associated with cardiac arrhythmias? | ['yes'] | [
"yes"
]
| ['Evidence supports a causal association of sleep apnea with the incidence and morbidity of hypertension, coronary heart disease, arrhythmia, heart failure, and stroke.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/28209226",
"http://www.ncbi.nlm.nih.gov/pubmed/16293956",
"http://www.ncbi.nlm.nih.gov/pubmed/28992834",
"http://www.ncbi.nlm.nih.gov/pubmed/3542725",
"http://www.ncbi.nlm.nih.gov/pubmed/20351955",
"http://www.ncbi.nlm.nih.gov/pubmed/331948",
"http://www.ncbi.nlm.nih.gov/pubmed/7774322",
"http://www.ncbi.nlm.nih.gov/pubmed/28040290",
"http://www.ncbi.nlm.nih.gov/pubmed/22160956",
"http://www.ncbi.nlm.nih.gov/pubmed/10613491",
"http://www.ncbi.nlm.nih.gov/pubmed/22520295",
"http://www.ncbi.nlm.nih.gov/pubmed/25252161",
"http://www.ncbi.nlm.nih.gov/pubmed/17655678",
"http://www.ncbi.nlm.nih.gov/pubmed/27914359",
"http://www.ncbi.nlm.nih.gov/pubmed/28181212",
"http://www.ncbi.nlm.nih.gov/pubmed/22826063",
"http://www.ncbi.nlm.nih.gov/pubmed/18024169",
"http://www.ncbi.nlm.nih.gov/pubmed/8178007",
"http://www.ncbi.nlm.nih.gov/pubmed/16149210",
"http://www.ncbi.nlm.nih.gov/pubmed/3106890",
"http://www.ncbi.nlm.nih.gov/pubmed/2654251"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28040290",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 244,
"text": "Atrial fibrillation (AF) is the commonest arrhythmia in clinical practice and is associated with increased cardiovascular morbidity and mortality. Obstructive sleep apnea (OSA), a common breathing disorder, is an independent risk factor for AF."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27914359",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 280,
"text": "There is a growing consensus in the scientific community that suggests a strong association between obstructive sleep apnea (OSA) and cardiovascular (CVD) conditions and events, including coronary artery disease, hypertension, arrhythmia, heart failure, and sudden cardiac death. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28181212",
"endSection": "abstract",
"offsetInBeginSection": 127,
"offsetInEndSection": 386,
"text": "part from well-established risk factors that increase the odds for the development of AF, e.g. age or arterial hypertension, recent analyses indicate that obstructive sleep apnoea (OSA) may independently, negatively modify the arrhythmia occur-rence profile. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28209226",
"endSection": "abstract",
"offsetInBeginSection": 323,
"offsetInEndSection": 489,
"text": "Evidence supports a causal association of sleep apnea with the incidence and morbidity of hypertension, coronary heart disease, arrhythmia, heart failure, and stroke."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/3106890",
"endSection": "abstract",
"offsetInBeginSection": 263,
"offsetInEndSection": 390,
"text": "Severe snoring may be associated with pulmonary and systemic hypertension, secondary polycythemia, and cardiac arrhythmias.<br>"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/3106890",
"endSection": "abstract",
"offsetInBeginSection": 263,
"offsetInEndSection": 386,
"text": "Severe snoring may be associated with pulmonary and systemic hypertension, secondary polycythemia, and cardiac arrhythmias."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18024169",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 215,
"text": "BACKGROUND AND PURPOSE Nocturnal cardiac arrhythmias occur in patients with obstructive sleep apnea (OSA), reportedly as a consequence of the autonomic effects of recurrent apnea with subsequent oxygen desaturation."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16149210",
"endSection": "abstract",
"offsetInBeginSection": 2295,
"offsetInEndSection": 2500,
"text": "Obstructive apnea is associated with myocardial ischemia (silent or symptomatic), acute coronary events, stroke and transient ischemic attacks, cardiac arrhythmia, pulmonary hypertension and heart failure."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16293956",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 725,
"text": "Obstructive sleep apnea (OSA) is the most common form of sleep-disordered breathing, affecting 5-15% of the population. It is characterized by intermittent episodes of partial or complete obstruction of the upper airway during sleep that disrupts normal ventilation and sleep architecture, and is typically associated with excessive daytime sleepiness, snoring, and witnessed apneas. Patients with obstructive sleep apnea present risk to the general public safety by causing 8-fold increase in vehicle accidents, and they may themselves also suffer from the physiologic consequences of OSA; these include hypertension, coronary artery disease, stroke, congestive heart failure, pulmonary hypertension, and cardiac arrhythmias"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22160956",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 160,
"text": "Obstructive sleep apnea and central sleep apnea with Cheyne-Stokes respiration are associated with an increased risk of cardiac arrhythmia. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17655678",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 269,
"text": "Obstructive sleep apnea (OSA) affects approximately 4% of middle-aged men and 2% of middle-aged women. Cardiac arrhythmias are common problems in patients with OSA, even though the true prevalence and clinical relevance of cardiac arrhythmias remains to be determined. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/331948",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 284,
"text": "Cardiac arrhythmias during wakefulness and sleep in 15 patients with sleep-induced obstructive apnea, and the effect of atropine and tracheostomy on these arrhythmias were studied by continuous overnight Holter electrocardiographic, respiratory and electroencephalographic recordings."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20351955",
"endSection": "abstract",
"offsetInBeginSection": 49,
"offsetInEndSection": 410,
"text": "obstructive sleep apnea (OSA) as its most extreme variant, is characterized by intermittent episodes of partial or complete obstruction of the upper airway, leading to cessation of breathing while asleep. Cardiac arrhythmias are common problems in OSA patients, although the true prevalence and clinical relevance of cardiac arrhythmias remains to be determined"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25252161",
"endSection": "abstract",
"offsetInBeginSection": 12,
"offsetInEndSection": 183,
"text": "The mechanisms associated with the cardiovascular consequences of obstructive sleep apnea include abrupt changes in autonomic tone, which can trigger cardiac arrhythmias. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22520295",
"endSection": "abstract",
"offsetInBeginSection": 161,
"offsetInEndSection": 281,
"text": " Recent studies have shown that cardiac arrhythmias and conduction disorders are common in patients with SA. Sleep apnea"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22826063",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 89,
"text": "Severity of nocturnal cardiac arrhythmias correlates with intensity of sleep apnea in men"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2654251",
"endSection": "abstract",
"offsetInBeginSection": 282,
"offsetInEndSection": 380,
"text": "Patients affected with OSA are frequently hypertensive and can have dangerous cardiac arrhythmias."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8178007",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 99,
"text": "Patients with stable cardiac failure who snore may present sleep hypopnea and cardiac arrhythmias. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28992834",
"endSection": "abstract",
"offsetInBeginSection": 17,
"offsetInEndSection": 170,
"text": " Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality. Cardiac arrhythmias are common in patients with OSA. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/3542725",
"endSection": "abstract",
"offsetInBeginSection": 91,
"offsetInEndSection": 386,
"text": "Nocturnal hypoxia has been associated with serious ventricular tachyarrhythmias as well as life-threatening bradyarrhythmias. Obesity and snoring, both of which increase with age, have been identified as risk factors for sleep-related breathing disorders, as have hypertension and heart disease."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10613491",
"endSection": "abstract",
"offsetInBeginSection": 174,
"offsetInEndSection": 381,
"text": "Obstructive sleep apnea syndrome is associated with excess daytime sleepiness, depression, and an increased incidence of ischemic cardiopathy, cardiac arrhythmias, systemic hypertension and brain infarction."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7774322",
"endSection": "abstract",
"offsetInBeginSection": 486,
"offsetInEndSection": 654,
"text": "We found 58 percent prevalence of arrhythmias in patients with sleep apnea (apnea/hypopnea index = AHI>10), vs 42 percent in nonapneic controls (chi 2 = 16.7, p<0.0001)"
}
]
| 11 | BioASQ-training11b | [
"http://www.disease-ontology.org/api/metadata/DOID:0050847",
"https://meshb.nlm.nih.gov/record/ui?ui=D012891",
"http://www.disease-ontology.org/api/metadata/DOID:9220",
"https://meshb.nlm.nih.gov/record/ui?ui=D012913",
"http://www.disease-ontology.org/api/metadata/DOID:0050848",
"https://meshb.nlm.nih.gov/record/ui?ui=D020181",
"https://meshb.nlm.nih.gov/record/ui?ui=D020182",
"https://meshb.nlm.nih.gov/record/ui?ui=D001049"
]
| null | 5a981dd0fcd1d6a10c00002e | 5 |
yesno | Is Vitamin D deficiency associated with sepsis mortality? | ['yes'] | [
"yes"
]
| ['Yes, Vitamin D deficiency is associated with increased mortality in patients with septic shock.', 'Yes, vitamin D deficiency is associated with mortality in sepsis patients.', 'Yes, vitamin D deficiency is associated with sepsis mortality in patients with severe vitamin D deficiency.', 'Yes, Vitamin D deficiency is prevalent in patients with septic shock and is associated with mortality.', 'Yes, there are studies that show that Vitamin D deficiency is associated with higher mortality in sepsis.', 'Yes, vitamin D deficiency was prevalent in patients with septic shock visiting the emergency department and was associated with mortality.', 'Yes, Vitamin D deficiency has been associated with higher mortality in sepsis patients', 'Yes, Vitamin D deficiency was associated with mortality in patients with septic shock visiting the ED', 'Yes, Vitamin D deficiency is prevalent in patients with septic shock and it has been associated with increased mortality', 'Yes, Vitamin D deficiency is associated with sepsis mortality', 'Yes, Vitamin D deficiency is associated with mortality in patients with septic shock visiting the ED.', 'Yes, Vitamin D deficiency was prevalent in patients with septic shock visiting the ED and was associated with mortality.', 'Yes, vitamin D deficiency is associated with increased mortality in patients with septic shock who visit the emergency department (ED).'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/36265656"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36265656",
"endSection": "abstract",
"offsetInBeginSection": 1504,
"offsetInEndSection": 1619,
"text": "Vitamin D deficiency was prevalent in patients with septic shock visiting the ED and was associated with mortality."
}
]
| 13 | BioASQ-training13b | null | null | 662f401b187cba990d00000e | 6 |
yesno | Is vemurafenib used for thyroid cancer? | ['yes'] | [
"yes"
]
| ['Yes. Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/27460442",
"http://www.ncbi.nlm.nih.gov/pubmed/27554612",
"http://www.ncbi.nlm.nih.gov/pubmed/27754804",
"http://www.ncbi.nlm.nih.gov/pubmed/24987354",
"http://www.ncbi.nlm.nih.gov/pubmed/23489023",
"http://www.ncbi.nlm.nih.gov/pubmed/26751190",
"http://www.ncbi.nlm.nih.gov/pubmed/27127178",
"http://www.ncbi.nlm.nih.gov/pubmed/26735176",
"http://www.ncbi.nlm.nih.gov/pubmed/25353071",
"http://www.ncbi.nlm.nih.gov/pubmed/25467940",
"http://www.ncbi.nlm.nih.gov/pubmed/26284586",
"http://www.ncbi.nlm.nih.gov/pubmed/22649416",
"http://www.ncbi.nlm.nih.gov/pubmed/26176686",
"http://www.ncbi.nlm.nih.gov/pubmed/26636651",
"http://www.ncbi.nlm.nih.gov/pubmed/24262022",
"http://www.ncbi.nlm.nih.gov/pubmed/27432558",
"http://www.ncbi.nlm.nih.gov/pubmed/24756795"
]
| [
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27460442",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 193,
"text": "Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27460442",
"endSection": "abstract",
"offsetInBeginSection": 117,
"offsetInEndSection": 314,
"text": "Vemurafenib, an oncogenic BRAF kinase inhibitor approved for BRAF-positive melanoma, showed clinical benefit in three patients with BRAF(V600E)-positive papillary thyroid cancer in a phase 1 trial."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27460442",
"endSection": "abstract",
"offsetInBeginSection": 2338,
"offsetInEndSection": 2559,
"text": "INTERPRETATION: Vemurafenib showed antitumour activity in patients with progressive, BRAF(V600E)-positive papillary thyroid cancer refractory to radioactive iodine who had never been treated with a multikinase inhibitor. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25353071",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 177,
"text": "CONTEXT: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25353071",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 155,
"text": "Efficacy and tolerability of vemurafenib in patients with BRAF(V600E) -positive papillary thyroid cancer: M.D. Anderson Cancer Center off label experience."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25353071",
"endSection": "abstract",
"offsetInBeginSection": 1685,
"offsetInEndSection": 1840,
"text": "CONCLUSIONS: Vemurafenib is a potentially effective and well-tolerated treatment strategy in patients with advanced PTC harboring the BRAF(V600E) mutation."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25467940",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 459,
"text": "The US Food and Drug Administration-approved BRAF inhibitors, vemurafenib and dabrafenib, have demonstrated superior efficacy in patients with BRAF-mutant melanomas but have limited efficacy in BRAF-mutant colorectal cancer. Little is known at this time regarding BRAF inhibitors in thyroid cancer. Initial reports in patients with progressive, radioactive iodine-refractory BRAF-mutant papillary thyroid cancer suggest response rates of approximately 30-40%."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26176686",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 66,
"text": "Use of vemurafenib in anaplastic thyroid carcinoma: a case report."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27432558",
"endSection": "abstract",
"offsetInBeginSection": 1212,
"offsetInEndSection": 1361,
"text": "Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25353071",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 399,
"text": "CONTEXT: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.OBJECTIVE: To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.DESIGN: A retrospective review at MD Anderson Cancer Center.METHODS: The best responses were evaluated using RECIST v1.1."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25353071",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 361,
"text": "Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.A retrospective review at MD Anderson Cancer Center.The best responses were evaluated using RECIST v1.1"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25353071",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 400,
"text": "CONTEXT: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.OBJECTIVE: To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.DESIGN: A retrospective review at MD Anderson Cancer Center.METHODS: The best responses were evaluated using RECIST v1.1. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27432558",
"endSection": "abstract",
"offsetInBeginSection": 1220,
"offsetInEndSection": 1369,
"text": "Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26284586",
"endSection": "abstract",
"offsetInBeginSection": 1237,
"offsetInEndSection": 1415,
"text": "Metformin or rapamycin adjuvant treatment may provide clinical benefits with minimal side effects to BRAFV600E-positive advanced thyroid cancer patients treated with vemurafenib."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25353071",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 362,
"text": "Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.A retrospective review at MD Anderson Cancer Center.The best responses were evaluated using RECIST v1.1."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27754804",
"endSection": "abstract",
"offsetInBeginSection": 1515,
"offsetInEndSection": 1727,
"text": "Our data demonstrate that vemurafenib induces ER stress response-mediated autophagy in thyroid cancer and autophagy inhibition may be a beneficial strategy to sensitize BRAF-mutant thyroid cancer to vemurafenib.."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26284586",
"endSection": "abstract",
"offsetInBeginSection": 552,
"offsetInEndSection": 729,
"text": "Combination of vemurafenib and metformin decreased cell viability and increased apoptosis in both BCPAP papillary thyroid cancer cells and 8505c anaplastic thyroid cancer cells."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27754804",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 74,
"text": "Targeting autophagy sensitizes BRAF-mutant thyroid cancer to vemurafenib."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27432558",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 80,
"text": "Propranolol sensitizes thyroid cancer cells to cytotoxic effect of vemurafenib."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26284586",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 83,
"text": "mTOR inhibitors sensitize thyroid cancer cells to cytotoxic effect of vemurafenib."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27754804",
"endSection": "abstract",
"offsetInBeginSection": 1010,
"offsetInEndSection": 1092,
"text": "Vemurafenib induced a high level of autophagy in BRAF-mutant thyroid cancer cells."
}
]
| 6 | BioASQ-training6b | [
"http://www.disease-ontology.org/api/metadata/DOID:3963",
"http://www.disease-ontology.org/api/metadata/DOID:1781",
"https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013964"
]
| [
{
"o": "VEMURAFENIB",
"p": "http://www.w3.org/2000/01/rdf-schema#label",
"s": "http://linkedlifedata.com/resource/rxnorm/id/1147220"
},
{
"o": "http://linkedlifedata.com/resource/umls/label/A20020623",
"p": "http://www.w3.org/2008/05/skos-xl#altLabel",
"s": "http://linkedlifedata.com/resource/umls/id/C3192263"
},
{
"o": "VEMURAFENIB",
"p": "http://www.w3.org/2008/05/skos-xl#literalForm",
"s": "http://linkedlifedata.com/resource/umls/label/A20020623"
},
{
"o": "http://linkedlifedata.com/resource/rxnorm/label/4224011",
"p": "http://www.w3.org/2008/05/skos-xl#prefLabel",
"s": "http://linkedlifedata.com/resource/rxnorm/id/1147220"
},
{
"o": "VEMURAFENIB",
"p": "http://www.w3.org/2008/05/skos-xl#literalForm",
"s": "http://linkedlifedata.com/resource/rxnorm/label/4224011"
},
{
"o": "Vemurafenib",
"p": "http://www.w3.org/2000/01/rdf-schema#label",
"s": "http://linkedlifedata.com/resource/chembl/synonym/691867_Vemurafenib_USAN"
},
{
"o": "http://linkedlifedata.com/resource/umls/label/A19613644",
"p": "http://www.w3.org/2008/05/skos-xl#altLabel",
"s": "http://linkedlifedata.com/resource/umls/id/C3192263"
},
{
"o": "Vemurafenib",
"p": "http://www.w3.org/2008/05/skos-xl#literalForm",
"s": "http://linkedlifedata.com/resource/umls/label/A19613644"
},
{
"o": "http://linkedlifedata.com/resource/umls/label/A19649207",
"p": "http://www.w3.org/2008/05/skos-xl#prefLabel",
"s": "http://linkedlifedata.com/resource/umls/id/C3192263"
},
{
"o": "Vemurafenib",
"p": "http://www.w3.org/2008/05/skos-xl#literalForm",
"s": "http://linkedlifedata.com/resource/umls/label/A19649207"
}
]
| 58848ea5e56acf517600000e | 7 |
yesno | Has the proteome of mice hippocampus been analysed? | ['yes'] | [
"yes"
]
| ['Yes, numerous proteomic studies of mice hippcampi has been performed.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/26549202",
"http://www.ncbi.nlm.nih.gov/pubmed/28775826",
"http://www.ncbi.nlm.nih.gov/pubmed/26977433",
"http://www.ncbi.nlm.nih.gov/pubmed/27378549",
"http://www.ncbi.nlm.nih.gov/pubmed/27001617"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26549202",
"endSection": "abstract",
"offsetInBeginSection": 738,
"offsetInEndSection": 972,
"text": "We employed a discovery-based proteomic approach in subcellular fractions of hippocampal tissue from chronic intermittent alcohol (CIE)-exposed C57Bl/6J mice to gain insight into alcohol-induced changes in GluN2B signaling complexes. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27001617",
"endSection": "abstract",
"offsetInBeginSection": 124,
"offsetInEndSection": 359,
"text": " We employed shotgun liquid chromatography-mass spectrometry (LC-MS) proteomic and metabonomic profiling approaches on prefrontal cortex (PFC) and hippocampal (HPC) tissue from Df(16)A+/-mice, a model of the 22q11.2 deletion syndrome. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28775826",
"endSection": "abstract",
"offsetInBeginSection": 743,
"offsetInEndSection": 1033,
"text": " Molecular alterations in the frontal cortex and hippocampus ofTsc1+/-and control mice, with or without rapamycin treatment, were investigated. A quantitative mass spectrometry-based shotgun proteomic approach (LC-MSE) was employed as an unbiased method to detect changes in protein levels."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26977433",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 173,
"text": "This dataset reports on the analysis of mouse hippocampus by LC-MS/MS, from mice fed a diet that was either deficient in n-3 FA (n-3 Def) or sufficient in n-3 FA (n-3 Adq). "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27378549",
"endSection": "abstract",
"offsetInBeginSection": 325,
"offsetInEndSection": 567,
"text": "Using isobaric tags for relative and absolute quantitation (iTRAQ) and proteomic methods, here we identified learning-induced changes in the hippocampal proteome of non-transgenic (NonTg) and 3 × Tg-AD mice, a widely used animal model of AD. "
}
]
| 11 | BioASQ-training11b | null | null | 5a8881118cb19eca6b000006 | 8 |
yesno | Is cytisine superior to nicotine replacement therapy for smoking cessation? | ['yes'] | [
"yes"
]
| ['Yes, one clinical trial that directly compared smoking cessation rates with cytisine versus nicotine replacement therapy reported that cytisine was superior to nicotine-replacement therapy in helping smokers quit smoking, but it was associated with a higher frequency of self-reported adverse events.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/21328282",
"http://www.ncbi.nlm.nih.gov/pubmed/21385905",
"http://www.ncbi.nlm.nih.gov/pubmed/22104038",
"http://www.ncbi.nlm.nih.gov/pubmed/22513936",
"http://www.ncbi.nlm.nih.gov/pubmed/25517706",
"http://www.ncbi.nlm.nih.gov/pubmed/24831822",
"http://www.ncbi.nlm.nih.gov/pubmed/24574554",
"http://www.ncbi.nlm.nih.gov/pubmed/23978314",
"http://www.ncbi.nlm.nih.gov/pubmed/23834141",
"http://www.ncbi.nlm.nih.gov/pubmed/23728690",
"http://www.ncbi.nlm.nih.gov/pubmed/23404838",
"http://www.ncbi.nlm.nih.gov/pubmed/21154363",
"http://www.ncbi.nlm.nih.gov/pubmed/20040957",
"http://www.ncbi.nlm.nih.gov/pubmed/18646137",
"http://www.ncbi.nlm.nih.gov/pubmed/18076335",
"http://www.ncbi.nlm.nih.gov/pubmed/17825502",
"http://www.ncbi.nlm.nih.gov/pubmed/17253581",
"http://www.ncbi.nlm.nih.gov/pubmed/17220536",
"http://www.ncbi.nlm.nih.gov/pubmed/17130378"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25517706",
"endSection": "abstract",
"offsetInBeginSection": 1245,
"offsetInEndSection": 1541,
"text": "The effectiveness of cytisine for continuous abstinence was superior to that of nicotine-replacement therapy at 1 week, 2 months, and 6 months. In a prespecified subgroup analysis of the primary outcome, cytisine was superior to nicotine-replacement therapy among women and noninferior among men."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25517706",
"endSection": "abstract",
"offsetInBeginSection": 1833,
"offsetInEndSection": 2068,
"text": "CONCLUSIONS: When combined with brief behavioral support, cytisine was found to be superior to nicotine-replacement therapy in helping smokers quit smoking, but it was associated with a higher frequency of self-reported adverse events."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25517706",
"endSection": "abstract",
"offsetInBeginSection": 1245,
"offsetInEndSection": 1541,
"text": "The effectiveness of cytisine for continuous abstinence was superior to that of nicotine-replacement therapy at 1 week, 2 months, and 6 months. In a prespecified subgroup analysis of the primary outcome, cytisine was superior to nicotine-replacement therapy among women and noninferior among men."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25517706",
"endSection": "abstract",
"offsetInBeginSection": 1833,
"offsetInEndSection": 2068,
"text": "CONCLUSIONS: When combined with brief behavioral support, cytisine was found to be superior to nicotine-replacement therapy in helping smokers quit smoking, but it was associated with a higher frequency of self-reported adverse events."
}
]
| 5 | BioASQ-training5b | [
"http://www.biosemantics.org/jochem#4251343",
"http://www.biosemantics.org/jochem#4273701"
]
| []
| 54d77f0e3706e8952800001b | 10 |
yesno | Is Stat4 a transcription factor? | ['yes'] | [
"yes"
]
| ['Yes, Stat4 is a transcription factor.\nStat4 is a member of the signal transducer and activator of transcription (STAT) family of molecules that localizes to the cytoplasm. STAT4 regulates various genes expression as a transcription factor after it is phosphorylated, dimerizes and translocates to the nucleus.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/25178516",
"http://www.ncbi.nlm.nih.gov/pubmed/25829541",
"http://www.ncbi.nlm.nih.gov/pubmed/25798064",
"http://www.ncbi.nlm.nih.gov/pubmed/25852285"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25829541",
"endSection": "abstract",
"offsetInBeginSection": 713,
"offsetInEndSection": 750,
"text": "transcription factors T-bet and STAT4"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25798064",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 272,
"text": "STAT4 is a member of the signal transducer and activator of transcription (STAT) family of molecules that localizes to the cytoplasm. STAT4 regulates various genes expression as a transcription factor after it is phosphorylated, dimerizes and translocates to the nucleus. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25178516",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 117,
"text": "STAT4 is a latent cytosolic factor that encodes a transcription factor transmitting signals stimulated by cytokines. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25852285",
"endSection": "abstract",
"offsetInBeginSection": 4,
"offsetInEndSection": 168,
"text": " To investigate the role of signal transduction and activation of transcription 4 (STAT4) in the development and progression of human hepatocellular carcinoma (HCC)"
}
]
| 6 | BioASQ-training6b | null | null | 58bc58c302b8c60953000001 | 11 |
yesno | Can chronological age be predicted by measuring telomere length? | ['no'] | [
"no"
]
| ['No, telomere length measurement by real-time quantitative PCR cannot be used to predict age of a person, due to the presence of large inter-individual variations in telomere lengths.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/23167566",
"http://www.ncbi.nlm.nih.gov/pubmed/18378481"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18378481",
"endSection": "abstract",
"offsetInBeginSection": 356,
"offsetInEndSection": 558,
"text": "Human somatic cells gradually lose telomeric repeats with age. This study investigated if one could use a correlation between telomere length and age, to predict the age of an individual from their DNA."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18378481",
"endSection": "abstract",
"offsetInBeginSection": 1519,
"offsetInEndSection": 1708,
"text": "Therefore, telomere length measurement by real-time quantitative PCR cannot be used to predict age of a person, due to the presence of large inter-individual variations in telomere lengths."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23167566",
"endSection": "abstract",
"offsetInBeginSection": 861,
"offsetInEndSection": 1194,
"text": "ur results provide the first clear and unambiguous evidence of a relationship between telomere length and mortality in the wild, and substantiate the prediction that telomere length and shortening rate can act as an indicator of biological age further to chronological age when exploring life history questions in natural conditions."
}
]
| 5 | BioASQ-training5b | []
| []
| 56d34fbcf22319765a000009 | 12 |
yesno | Was ALVAC-HIV effective for HIV prevention in the HVTN 702 trial? | ['no'] | [
"no"
]
| ['No. The ALVAC-gp120 regimen did not prevent HIV-1 infection among participants in South Africa despite previous evidence of immunogenicity'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/33761206",
"http://www.ncbi.nlm.nih.gov/pubmed/34029515",
"http://www.ncbi.nlm.nih.gov/pubmed/32554928"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33761206",
"endSection": "abstract",
"offsetInBeginSection": 1258,
"offsetInEndSection": 1662,
"text": "During the 24-month follow-up, HIV-1 infection was diagnosed in 138 participants in the vaccine group and in 133 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.81 to 1.30; P = 0.84).CONCLUSIONS: The ALVAC-gp120 regimen did not prevent HIV-1 infection among participants in South Africa despite previous evidence of immunogenicity. (HVTN 702 ClinicalTrials.gov number, NCT02968849.)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34029515",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 433,
"text": "The advanced-phase HIV prevention vaccine trials done in South Africa (HVTN 702) and in Thailand (RV144), which both investigated canarypox vectors and adjuvanted gp120 proteins, gave rise to different results. The South African trial did not find vaccine efficacy, whereas the Thai trial had modest, but statistically significant, success with the modified intention-to-treat analysis prespecified in the protocols of both studies. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32554928",
"endSection": "abstract",
"offsetInBeginSection": 280,
"offsetInEndSection": 450,
"text": "However, with the recent failure of the HVTN 702 clinical trial, comprehensive profiling of humoral immune responses may provide insight for these disappointing results. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33761206",
"endSection": "abstract",
"offsetInBeginSection": 112,
"offsetInEndSection": 238,
"text": "A canarypox-protein HIV vaccine regimen (ALVAC-HIV plus AIDSVAX B/E) showed modest efficacy in reducing infection in Thailand."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33761206",
"endSection": "abstract",
"offsetInBeginSection": 1228,
"offsetInEndSection": 1567,
"text": "e vaccine and placebo groups. During the 24-month follow-up, HIV-1 infection was diagnosed in 138 participants in the vaccine group and in 133 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.81 to 1.30; P = 0.84).CONCLUSIONS: The ALVAC-gp120 regimen did not prevent HIV-1 infection among participants in South Africa d"
}
]
| 11 | BioASQ-training11b | null | null | 61faa3bac9dfcb9c0900000b | 13 |
yesno | Can Enlimomab improve stroke outcomes? | ['no'] | [
"no"
]
| ['No. Anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke and, indeed, may significantly worsen stroke outcome.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/19849665",
"http://www.ncbi.nlm.nih.gov/pubmed/12365824",
"http://www.ncbi.nlm.nih.gov/pubmed/9693236",
"http://www.ncbi.nlm.nih.gov/pubmed/12038658",
"http://www.ncbi.nlm.nih.gov/pubmed/9744839",
"http://www.ncbi.nlm.nih.gov/pubmed/11673584",
"http://www.ncbi.nlm.nih.gov/pubmed/11692032"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19849665",
"endSection": "abstract",
"offsetInBeginSection": 1772,
"offsetInEndSection": 2068,
"text": "Treatment with a murine anti-ICAM-1 antibody (enlimomab) has been investigated in patients with acute ischemic stroke in the Enlimomab Acute Stroke Trial (EAST). Unfortunately, the case fatality rate in this trial was significantly higher in the enlimomab patient group than in the placebo group."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12365824",
"endSection": "abstract",
"offsetInBeginSection": 169,
"offsetInEndSection": 351,
"text": "The two clinical trials of therapy aimed at limiting the inflammatory response in acute stroke that have been carried out to date, however, have not shown a benefit to such therapy. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12038658",
"endSection": "abstract",
"offsetInBeginSection": 303,
"offsetInEndSection": 696,
"text": "en classes of neuroprotective agents have reached phase III efficacy trials but have shown mixed results. They included calcium channel antagonists, NMDA receptor antagonists, lubeluzole, CDP-choline, the free radical scavenger tirilazad and ebselen, enlimomab, GABA agonist clomethiazole, the sodium channel antagonist fosphenytoin, magnesium, glycine site antagonist GV150526 and piracetam. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11692032",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 177,
"text": "BACKGROUND AND PURPOSE: Enlimomab, a murine monoclonal anti-human intercellular adhesion molecule (ICAM)-1 antibody, had a negative outcome in a multicenter acute-stroke trial. "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11692032",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 199,
"text": "Examination of several potential mechanisms for the negative outcome in a clinical stroke trial of enlimomab, a murine anti-human intercellular adhesion molecule-1 antibody: a bedside-to-bench study."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584",
"endSection": "abstract",
"offsetInBeginSection": 907,
"offsetInEndSection": 1358,
"text": "ESULTS: At day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004). Fewer patients had symptom-free recovery on enlimomab than placebo (p = 0.004), and more died (22.2 versus 16.2%). The negative effect of enlimomab was apparent on days 5, 30, and 90 of treatment (p = 0.005). There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584",
"endSection": "abstract",
"offsetInBeginSection": 1434,
"offsetInEndSection": 1630,
"text": "CONCLUSIONS: The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584",
"endSection": "abstract",
"offsetInBeginSection": 1440,
"offsetInEndSection": 1636,
"text": "CONCLUSIONS\n\nThe authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584",
"endSection": "abstract",
"offsetInBeginSection": 1247,
"offsetInEndSection": 1362,
"text": "There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584",
"endSection": "abstract",
"offsetInBeginSection": 910,
"offsetInEndSection": 1037,
"text": "RESULTS\n\nAt day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584",
"endSection": "abstract",
"offsetInBeginSection": 1153,
"offsetInEndSection": 1246,
"text": "The negative effect of enlimomab was apparent on days 5, 30, and 90 of treatment (p = 0.005)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9744839",
"endSection": "abstract",
"offsetInBeginSection": 1441,
"offsetInEndSection": 1524,
"text": "However, this treatment failed to show benefit in the Enlimomab Acute Stroke Trial."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584",
"endSection": "abstract",
"offsetInBeginSection": 1242,
"offsetInEndSection": 1357,
"text": "There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11692032",
"endSection": "abstract",
"offsetInBeginSection": 1797,
"offsetInEndSection": 1974,
"text": "These observations provide several possible mechanisms for central nervous system-related clinical deterioration that occurred when Enlimomab was given in acute ischemic stroke."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584",
"endSection": "abstract",
"offsetInBeginSection": 910,
"offsetInEndSection": 1037,
"text": "RESULTS\nAt day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19849665",
"endSection": "abstract",
"offsetInBeginSection": 1934,
"offsetInEndSection": 2069,
"text": "Unfortunately, the case fatality rate in this trial was significantly higher in the enlimomab patient group than in the placebo group."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9693236",
"endSection": "abstract",
"offsetInBeginSection": 1284,
"offsetInEndSection": 1505,
"text": "CONCLUSIONS\nDoses of enlimomab between 140 and 480 mg administered over 5 days did not increase the risk of adverse events in patients with ischaemic or haemorrhagic stroke during an observation period of 30 +/- 10 days."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11692032",
"endSection": "abstract",
"offsetInBeginSection": 15,
"offsetInEndSection": 176,
"text": "PURPOSE: Enlimomab, a murine monoclonal anti-human intercellular adhesion molecule (ICAM)-1 antibody, had a negative outcome in a multicenter acute-stroke trial."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11692032",
"endSection": "abstract",
"offsetInBeginSection": 1791,
"offsetInEndSection": 1968,
"text": "These observations provide several possible mechanisms for central nervous system-related clinical deterioration that occurred when Enlimomab was given in acute ischemic stroke."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11692032",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 152,
"text": "Enlimomab, a murine monoclonal anti-human intercellular adhesion molecule (ICAM)-1 antibody, had a negative outcome in a multicenter acute-stroke trial."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11692032",
"endSection": "abstract",
"offsetInBeginSection": 1739,
"offsetInEndSection": 1916,
"text": "These observations provide several possible mechanisms for central nervous system-related clinical deterioration that occurred when Enlimomab was given in acute ischemic stroke."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584",
"endSection": "abstract",
"offsetInBeginSection": 1407,
"offsetInEndSection": 1590,
"text": "The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome."
}
]
| 11 | BioASQ-training11b | null | null | 5e44c33a48dab47f26000020 | 14 |
yesno | Have microRNAs been implicated in pharmacogenomics? | ['yes'] | [
"yes"
]
| ['Yes. MicroRNAs have been implicated in pharmacogenomics.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/23376192",
"http://www.ncbi.nlm.nih.gov/pubmed/23189953",
"http://www.ncbi.nlm.nih.gov/pubmed/22630332",
"http://www.ncbi.nlm.nih.gov/pubmed/22445829",
"http://www.ncbi.nlm.nih.gov/pubmed/21499217",
"http://www.ncbi.nlm.nih.gov/pubmed/21412770",
"http://www.ncbi.nlm.nih.gov/pubmed/21047203",
"http://www.ncbi.nlm.nih.gov/pubmed/20585341",
"http://www.ncbi.nlm.nih.gov/pubmed/18187804",
"http://www.ncbi.nlm.nih.gov/pubmed/17483436",
"http://www.ncbi.nlm.nih.gov/pubmed/16854228",
"http://www.ncbi.nlm.nih.gov/pubmed/22909203"
]
| [
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23376192",
"endSection": "sections.0",
"offsetInBeginSection": 156,
"offsetInEndSection": 435,
"text": "A major discovery is the ability of miRNAs to determine the efficacy of drugs, which has given rise to the field of 'miRNA pharmacogenomics' through 'Pharmaco-miRs'. miRNAs play a significant role in pharmacogenomics by down-regulating genes that are important for drug function."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23189953",
"endSection": "sections.0",
"offsetInBeginSection": 878,
"offsetInEndSection": 1199,
"text": "The potential modulation of toxicology-related changes in miRNA expression, the role of miRNA in immune-mediated drug-induced liver injuries, the use of circulating miRNAs in body fluids as potential toxicological biomarkers, and the link between miRNA-related pharmacogenomics and adverse drug reactions are highlighted."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22445829",
"endSection": "sections.0",
"offsetInBeginSection": 232,
"offsetInEndSection": 531,
"text": "Single nucleotide polymorphisms (SNPs) in the miRNA target sequences may affect or impair the binding of miRNAs. Studies have shown that SNPs in miRNA target sites (miR-TS-SNPs) have a great influence on diverse biological functions, including pharmacogenomics and disease susceptibilities in human."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21499217",
"endSection": "sections.0",
"offsetInBeginSection": 454,
"offsetInEndSection": 782,
"text": "Pharmacogenomics genes can be divided into drug target genes termed as pharmacodynamics genes (PD) and genes involved in drug transport and metabolism termed as pharmacokinetics genes (PK). To clarify the regulatory potential of miRNAs in pharmacogenomics, we have examined the potential regulation by miRNAs of PK and PD genes."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21499217",
"endSection": "sections.0",
"offsetInBeginSection": 1284,
"offsetInEndSection": 1786,
"text": "Our analysis identify a striking difference in the level of miRNA regulation between PK and PD genes, with the former having less than half predicted conserved miRNA binding sites compared with the latter. Importantly, this finding is reflected in a highly significant difference in the shift in expression levels of PD versus PK genes after depletion of miRNAs. CONCLUSIONS: Our study emphasizes an intrinsic difference between PK and PD genes and helps clarify the role of miRNAs in pharmacogenomics."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21412770",
"endSection": "sections.0",
"offsetInBeginSection": 0,
"offsetInEndSection": 419,
"text": "Pharmacogenomics, toxicogenomics, and small RNA expression analysis are three of the most active research topics in the biological, biomedical, pharmaceutical, and toxicological fields. All of these studies are based on gene expression analysis, which requires reference genes to reduce the variations derived from different amounts of starting materials and different efficiencies of RNA extraction and cDNA synthesis."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21412770",
"endSection": "sections.0",
"offsetInBeginSection": 2269,
"offsetInEndSection": 2426,
"text": "In contrast, hTBCA and small RNAs are more stable during drug treatment, and they are better reference genes for pharmacogenomics and toxicogenomics studies."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21047203",
"endSection": "sections.0",
"offsetInBeginSection": 11,
"offsetInEndSection": 152,
"text": "Polymorphisms of genes involved in the pharmacokinetic and pharmacodynamic processes underlie the divergent drug responses among individuals."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21047203",
"endSection": "sections.0",
"offsetInBeginSection": 1036,
"offsetInEndSection": 1167,
"text": "A panel of drug-response genes was constructed, which contains 923 pharmacokinetic genes, 703 pharmacodynamic genes and 720 miRNAs."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20585341",
"endSection": "sections.0",
"offsetInBeginSection": 123,
"offsetInEndSection": 243,
"text": "miRNA variations can affect drug resistance, efficacy, and metabolism, opening new avenues of pharmacogenomics research."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18187804",
"endSection": "sections.0",
"offsetInBeginSection": 260,
"offsetInEndSection": 467,
"text": "we studied the pharmacologic roles of three microRNAs previously implicated in cancer biology (let-7i, mir-16, and mir-21) and also used in silico methods to test pharmacologic microRNA effects more broadly."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18187804",
"endSection": "sections.0",
"offsetInBeginSection": 1322,
"offsetInEndSection": 1781,
"text": "n silico comparison of drug potencies with microRNA expression profiles across the entire NCI-60 panel revealed that approximately 30 microRNAs, including mir-21, show highly significant correlations with numerous anticancer agents. Ten of those microRNAs have already been implicated in cancer biology. Our results support a substantial role for microRNAs in anticancer drug response, suggesting novel potential approaches to the improvement of chemotherapy."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17483436",
"endSection": "sections.0",
"offsetInBeginSection": 392,
"offsetInEndSection": 603,
"text": "The NCI-60 has also been profiled for mRNA and protein expression, mutational status, chromosomal aberrations, and DNA copy number, generating an unparalleled public resource for integrated chemogenomic studies."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17483436",
"endSection": "sections.0",
"offsetInBeginSection": 738,
"offsetInEndSection": 941,
"text": "To complement the existing NCI-60 data sets, we have measured expression levels of microRNAs in the NCI-60 and incorporated the resulting data into the CellMiner program package for integrative analysis."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17483436",
"endSection": "sections.0",
"offsetInBeginSection": 1375,
"offsetInEndSection": 1765,
"text": ". Comparison of microRNA expression patterns and compound potency patterns showed significant correlations, suggesting that microRNAs may play a role in chemoresistance. Combined with gene expression and other biological data using multivariate analysis, microRNA expression profiles may provide a critical link for understanding mechanisms involved in chemosensitivity and chemoresistance."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22909203",
"endSection": "sections.0",
"offsetInBeginSection": 296,
"offsetInEndSection": 364,
"text": "This study reports on miRNAs implicated in SSRI sensitivity of LCLs."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22909203",
"endSection": "sections.0",
"offsetInBeginSection": 949,
"offsetInEndSection": 1071,
"text": "these miRNAs as tentative SSRI response biomarkers awaits validation with lymphocyte samples of major depression patients."
}
]
| 5 | BioASQ-training5b | [
"http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010597",
"http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035683"
]
| [
{
"o": "http://purl.uniprot.org/pubmed/12052143",
"p": "http://www.w3.org/2004/02/skos/core#exactMatch",
"s": "http://purl.uniprot.org/pubmed/12052143"
},
{
"o": "Pharmacogenomics",
"p": "http://purl.uniprot.org/core/name",
"s": "http://purl.uniprot.org/pubmed/15584875"
},
{
"o": "http://purl.uniprot.org/pubmed/16886893",
"p": "http://www.w3.org/2004/02/skos/core#exactMatch",
"s": "http://purl.uniprot.org/pubmed/16886893"
},
{
"o": "Pharmacogenomics",
"p": "http://purl.uniprot.org/core/name",
"s": "http://purl.uniprot.org/pubmed/16981842"
},
{
"o": "Pharmacogenomics",
"p": "http://purl.uniprot.org/core/name",
"s": "http://purl.uniprot.org/pubmed/17638511"
},
{
"o": "http://purl.uniprot.org/pubmed/17391071",
"p": "http://www.w3.org/2004/02/skos/core#exactMatch",
"s": "http://purl.uniprot.org/pubmed/17391071"
},
{
"o": "http://purl.uniprot.org/pubmed/17716225",
"p": "http://www.w3.org/2004/02/skos/core#exactMatch",
"s": "http://purl.uniprot.org/pubmed/17716225"
},
{
"o": "Pharmacogenomics",
"p": "http://purl.uniprot.org/core/name",
"s": "http://purl.uniprot.org/pubmed/17979512"
}
]
| 5162a089298dcd4e51000043 | 15 |
yesno | Is there an association between Muenke Syndrome and FGFR3 gene mutation? | ['yes'] | [
"yes"
]
| ['Yes, Muenke syndrome is caused by point mutation (C749G) in the Fibroblast Growth Factor Receptor3 (FGFR3) gene. It affects 1 in 30,000 newborns and accounts for 25% to 30% of genetic causes of craniosynostosis.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/17103449",
"http://www.ncbi.nlm.nih.gov/pubmed/11571861",
"http://www.ncbi.nlm.nih.gov/pubmed/21403557",
"http://www.ncbi.nlm.nih.gov/pubmed/22872265",
"http://www.ncbi.nlm.nih.gov/pubmed/21233754",
"http://www.ncbi.nlm.nih.gov/pubmed/10696568",
"http://www.ncbi.nlm.nih.gov/pubmed/14613973",
"http://www.ncbi.nlm.nih.gov/pubmed/18818193",
"http://www.ncbi.nlm.nih.gov/pubmed/19086028",
"http://www.ncbi.nlm.nih.gov/pubmed/24686979",
"http://www.ncbi.nlm.nih.gov/pubmed/26740388",
"http://www.ncbi.nlm.nih.gov/pubmed/15241680",
"http://www.ncbi.nlm.nih.gov/pubmed/26028288",
"http://www.ncbi.nlm.nih.gov/pubmed/19215249",
"http://www.ncbi.nlm.nih.gov/pubmed/19755431",
"http://www.ncbi.nlm.nih.gov/pubmed/24168007",
"http://www.ncbi.nlm.nih.gov/pubmed/20592905",
"http://www.ncbi.nlm.nih.gov/pubmed/18000976",
"http://www.ncbi.nlm.nih.gov/pubmed/23044018",
"http://www.ncbi.nlm.nih.gov/pubmed/24448525",
"http://www.ncbi.nlm.nih.gov/pubmed/16251895",
"http://www.ncbi.nlm.nih.gov/pubmed/24705944",
"http://www.ncbi.nlm.nih.gov/pubmed/19449410",
"http://www.ncbi.nlm.nih.gov/pubmed/14963686",
"http://www.ncbi.nlm.nih.gov/pubmed/17070479",
"http://www.ncbi.nlm.nih.gov/pubmed/22446440",
"http://www.ncbi.nlm.nih.gov/pubmed/23378035",
"http://www.ncbi.nlm.nih.gov/pubmed/22016144",
"http://www.ncbi.nlm.nih.gov/pubmed/22544111"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26028288",
"endSection": "abstract",
"offsetInBeginSection": 579,
"offsetInEndSection": 810,
"text": "RESULTS: Forty-four with a positive FGFR3 mutation, median age 9 years, range 7 months to 52 years were enrolled. In addition, 10 unaffected siblings served as controls (5 males, 5 females; median age, 13 years; range, 3-18 years)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24168007",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 120,
"text": "Muenke is a fibroblast growth factor receptor 3 (FGFR-3)-associated syndrome, which was first described in late 1990 s. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24168007",
"endSection": "abstract",
"offsetInBeginSection": 275,
"offsetInEndSection": 455,
"text": "The syndrome is defined molecularly by a unique point mutation c.749C>G in exon 7 of the FGFR3 gene which results to an amino acid substitution p.Pro250Arg of the protein product. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24448525",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 162,
"text": "Muenke syndrome caused by point mutation (C749G) in the FGFR3 gene affects 1 in 30,000 newborns and accounts for 25% to 30% of genetic causes of craniosynostosis."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24705944",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 78,
"text": "Phenotypic variability in two families of Muenke syndrome with FGFR3 mutation."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24686979",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 282,
"text": "PURPOSE: There are a number of craniosynostosis syndromes with hearing loss-including Muenke, Apert, Pfeiffer, Crouzon, Beare-Stevenson, Crouzon with acanthosis nigricans, and Jackson-Weiss syndromes-that result from mutations in the fibroblast growth factor receptor (FGFR) genes. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23378035",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 163,
"text": "Muenke syndrome is an autosomal dominant craniosynostosis syndrome resulting from a defining point mutation in the Fibroblast Growth Factor Receptor3 (FGFR3) gene."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23378035",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 155,
"text": "Talocalcaneal coalition in Muenke syndrome: report of a patient, review of the literature in FGFR-related craniosynostoses, and consideration of mechanism."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22872265",
"endSection": "abstract",
"offsetInBeginSection": 331,
"offsetInEndSection": 591,
"text": "To better understand the pathophysiology of the Muenke syndrome, we present collective findings from several recent studies that have characterized a genetically equivalent mouse model for Muenke syndrome (FgfR3 (P244R)) and compare them with human phenotypes."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22016144",
"endSection": "abstract",
"offsetInBeginSection": 407,
"offsetInEndSection": 733,
"text": "We show in this study that knock-in mice harboring the mutation responsible for the Muenke syndrome (FgfR3(P244R)) display postnatal shortening of the cranial base along with synchondrosis growth plate dysfunction characterized by loss of resting, proliferating and hypertrophic chondrocyte zones and decreased Ihh expression."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23044018",
"endSection": "abstract",
"offsetInBeginSection": 408,
"offsetInEndSection": 526,
"text": "Muenke syndrome is caused by a single defining point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21403557",
"endSection": "abstract",
"offsetInBeginSection": 265,
"offsetInEndSection": 434,
"text": "The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23044018",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 60,
"text": "Epilepsy in Muenke syndrome: FGFR3-related craniosynostosis."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18000976",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 106,
"text": "Muenke syndrome (FGFR3-related craniosynostosis): expansion of the phenotype and review of the literature."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21403557",
"endSection": "abstract",
"offsetInBeginSection": 267,
"offsetInEndSection": 436,
"text": "The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22872265",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 150,
"text": "PURPOSE: The Muenke syndrome mutation (FGFR3 (P250R)), which was discovered 15 years ago, represents the single most common craniosynostosis mutation."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18818193",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 233,
"text": "The heterozygous Pro250Arg substitution mutation in fibroblast growth factor receptor 3 (FGFR3), which increases ligand-dependent signalling, is the most common genetic cause of craniosynostosis in humans and defines Muenke syndrome."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17103449",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 172,
"text": "P250R mutation in the FGFR3 gene also known as Muenke syndrome is associated with coronal craniosynostosis, sensorineural deafness, craniofacial, and digital abnormalities."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22446440",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 133,
"text": "Muenke syndrome caused by the FGFR3 Pro250Arg mutation is associated with craniosynostosis, hearing loss, and various bony anomalies."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18000976",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 223,
"text": "Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19086028",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 183,
"text": "Muenke syndrome, defined by heterozygosity for a Pro250Arg substitution in fibroblast growth factor receptor 3 (FGFR3), is the most common genetic cause of craniosynostosis in humans."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22872265",
"endSection": "abstract",
"offsetInBeginSection": 1041,
"offsetInEndSection": 1173,
"text": "In addition, sensorineural hearing loss is detected in all FgfR3 (P244R) mutant mice as in the majority of Muenke syndrome patients."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19755431",
"endSection": "abstract",
"offsetInBeginSection": 133,
"offsetInEndSection": 772,
"text": "Genetic testing identifies a pathogenic mutation or chromosomal abnormality in ∼ 21% of cases, but it is likely that further causative mutations remain to be discovered.To identify a shared signature of genetically determined craniosynostosis by comparing the expression patterns in three monogenic syndromes with a control group of patients with non-syndromic sagittal synostosis.Fibroblasts from 10 individuals each with Apert syndrome (FGFR2 substitution S252W), Muenke syndrome (FGFR3 substitution P250R), Saethre-Chotzen syndrome (various mutations in TWIST1) and non-syndromic sagittal synostosis (no mutation detected) were cultured"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11571861",
"endSection": "abstract",
"offsetInBeginSection": 581,
"offsetInEndSection": 819,
"text": "The craniosynostosis syndromes: Apert syndrome, Beare-Stevenson syndrome, Crouzon syndrome, Jackson-Weiss syndrome, Muenke syndrome, Pfeiffer syndrome and Saethre-Chotzen syndrome can be caused by mutation in either FGFR1, FGFR2, or FGFR3"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14613973",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 240,
"text": "Identical proline-->arginine gain-of-function mutations in fibroblast growth factor receptor (FGFR) 1 (Pro252Arg), FGFR2 (Pro253Arg) and FGFR3 (Pro250Arg), result in type I Pfeiffer, Apert and Muenke craniosynostosis syndromes, respectively"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21403557",
"endSection": "abstract",
"offsetInBeginSection": 267,
"offsetInEndSection": 435,
"text": "The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21233754",
"endSection": "abstract",
"offsetInBeginSection": 818,
"offsetInEndSection": 1043,
"text": "Mutation analysis of FGFR-3 revealed a missense mutation in exon 6, c.749 C>G, with a resultant amino acid change from proline to arginine at codon 250 (P250R), in keeping with Muenke syndrome (Am J Hum Genet 1997;60:555-564)"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16251895",
"endSection": "abstract",
"offsetInBeginSection": 219,
"offsetInEndSection": 441,
"text": "In an attempt to delineate functional features separating SCS from Muenkes syndrome, we screened patients presenting with coronal suture synostosis for mutations in the TWIST 1 gene, and for the Pro250Arg mutation in FGFR3"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10696568",
"endSection": "abstract",
"offsetInBeginSection": 942,
"offsetInEndSection": 1237,
"text": "Since the Gly380Arg achondroplasia mutation was recognized, similar observations regarding the conserved nature of FGFR mutations and resulting phenotype have been made regarding other skeletal phenotypes, including hypochondroplasia, thanatophoric dysplasia, and Muenke coronal craniosynostosis"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19215249",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 418,
"text": "Mutations in the gene that encodes Fibroblast Growth Factor Receptor 3 (FGFR3) are associated with Achondroplasia (MIM 100800), Hypochondroplasia (MIM 146000), Muenke Syndrome (MIM 602849), Thanatophoric Dysplasia (MIM 187600, MIM 187601) and Lacrimo-Auriculo-Dento-Digital Syndrome (MIM 149730).Here we report a clinical and molecular study in a large cohort of 125 Portuguese patients with these skeletal disorders. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20592905",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 252,
"text": "The Muenke syndrome (MS) is characterized by unicoronal or bicoronal craniosynostosis, midfacial hypoplasia, ocular hypertelorism, and a variety of minor abnormalities associated with a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17103449",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 173,
"text": "P250R mutation in the FGFR3 gene also known as Muenke syndrome is associated with coronal craniosynostosis, sensorineural deafness, craniofacial, and digital abnormalities. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19755431",
"endSection": "abstract",
"offsetInBeginSection": 539,
"offsetInEndSection": 808,
"text": "METHODS: Fibroblasts from 10 individuals each with Apert syndrome (FGFR2 substitution S252W), Muenke syndrome (FGFR3 substitution P250R), Saethre-Chotzen syndrome (various mutations in TWIST1) and non-syndromic sagittal synostosis (no mutation detected) were cultured. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18000976",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 224,
"text": "Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15241680",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 270,
"text": "Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3). "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14963686",
"endSection": "abstract",
"offsetInBeginSection": 323,
"offsetInEndSection": 487,
"text": "In spite of a variable phenotype, Muenke syndrome has been related to a unique mutation on the FGFR3 gene, Pro 250 to Arg, which is characteristic of this disease. "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19086028",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 102,
"text": "Skeletal analysis of the Fgfr3(P244R) mouse, a genetic model for the Muenke craniosynostosis syndrome."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23044018",
"endSection": "abstract",
"offsetInBeginSection": 410,
"offsetInEndSection": 528,
"text": "Muenke syndrome is caused by a single defining point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23044018",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 61,
"text": "Epilepsy in Muenke syndrome: FGFR3-related craniosynostosis."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15241680",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 269,
"text": "Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22872265",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 141,
"text": "The Muenke syndrome mutation (FGFR3 (P250R)), which was discovered 15 years ago, represents the single most common craniosynostosis mutation."
}
]
| 6 | BioASQ-training6b | [
"http://www.uniprot.org/uniprot/FGFR3_CHICK",
"https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001244",
"http://www.disease-ontology.org/api/metadata/DOID:0060703",
"http://www.uniprot.org/uniprot/FGFR3_PLEWA",
"http://www.uniprot.org/uniprot/FGFR3_HUMAN",
"https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051498"
]
| null | 5895ec5e7d9090f353000015 | 16 |
yesno | Is the apilimod inhibitor effective against SARS-CoV-2? | ['yes'] | [
"yes"
]
| ['To identify therapeutics that can be repurposed as SARS-CoV-2 antivirals, a library of known drugs encompassing approximately 12,000 clinical-stage or FDA-approved small molecules were profiled. In a study the identification of 30 known drugs that inhibit viral replication was reportedd. Of these, six were characterized for cellular dose-activity relationships, and showed effective concentrations likely to be commensurate with therapeutic doses in patients. These include the PIKfyve kinase inhibitor Apilimod, cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825, and ONO 5334, and the CCR1 antagonist MLN-3897. Since many of these molecules have advanced into the clinic, the known pharmacological and human safety profiles of these compounds will accelerate their preclinical and clinical evaluation for COVID-19 treatment.', 'Yes, apilimod inhibition is effective for treatment of SARS-CoV-2.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/32511357"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32511357",
"endSection": "abstract",
"offsetInBeginSection": 656,
"offsetInEndSection": 1482,
"text": "To identify therapeutics that can be repurposed as SARS-CoV-2 antivirals, we profiled a library of known drugs encompassing approximately 12,000 clinical-stage or FDA-approved small molecules. Here, we report the identification of 30 known drugs that inhibit viral replication. Of these, six were characterized for cellular dose-activity relationships, and showed effective concentrations likely to be commensurate with therapeutic doses in patients. These include the PIKfyve kinase inhibitor Apilimod, cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825, and ONO 5334, and the CCR1 antagonist MLN-3897. Since many of these molecules have advanced into the clinic, the known pharmacological and human safety profiles of these compounds will accelerate their preclinical and clinical evaluation for COVID-19 treatment."
}
]
| 11 | BioASQ-training11b | null | null | 60324b771cb411341a000139 | 17 |
yesno | Is Growth factor independence 1b (GFI1B) important for hematopoiesis? | ['yes'] | [
"yes"
]
| ['Yes. Gfi-1B is a transcriptional repressor essential for the regulation of erythropoiesis and megakaryopoiesis. Gfi-1b(-/-) embryonic stem cells fail to contribute to red cells of adult chimeras. Gfi-1b(-/-) embryos exhibit delayed maturation of primitive erythrocytes and subsequently die with failure to produce definitive enucleated erythrocytes.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/22960038",
"http://www.ncbi.nlm.nih.gov/pubmed/22699452",
"http://www.ncbi.nlm.nih.gov/pubmed/22668850",
"http://www.ncbi.nlm.nih.gov/pubmed/22399799",
"http://www.ncbi.nlm.nih.gov/pubmed/21606163",
"http://www.ncbi.nlm.nih.gov/pubmed/21170035",
"http://www.ncbi.nlm.nih.gov/pubmed/20861919",
"http://www.ncbi.nlm.nih.gov/pubmed/20124515",
"http://www.ncbi.nlm.nih.gov/pubmed/19958752",
"http://www.ncbi.nlm.nih.gov/pubmed/19773260",
"http://www.ncbi.nlm.nih.gov/pubmed/18224412",
"http://www.ncbi.nlm.nih.gov/pubmed/17707228",
"http://www.ncbi.nlm.nih.gov/pubmed/17095621",
"http://www.ncbi.nlm.nih.gov/pubmed/16397623",
"http://www.ncbi.nlm.nih.gov/pubmed/14530176",
"http://www.ncbi.nlm.nih.gov/pubmed/12351384",
"http://www.ncbi.nlm.nih.gov/pubmed/11825872",
"http://www.ncbi.nlm.nih.gov/pubmed/24800817",
"http://www.ncbi.nlm.nih.gov/pubmed/23308270",
"http://www.ncbi.nlm.nih.gov/pubmed/20143233",
"http://www.ncbi.nlm.nih.gov/pubmed/20826720",
"http://www.ncbi.nlm.nih.gov/pubmed/21732494",
"http://www.ncbi.nlm.nih.gov/pubmed/22885124",
"http://www.ncbi.nlm.nih.gov/pubmed/16177182",
"http://www.ncbi.nlm.nih.gov/pubmed/15507521"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22960038",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 252,
"text": "Growth Factor Independence (Gfi) transcription factors play essential roles in hematopoiesis, differentially activating and repressing transcriptional programs required for hematopoietic stem/progenitor cell (HSPC) development and lineage specification"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22960038",
"endSection": "abstract",
"offsetInBeginSection": 872,
"offsetInEndSection": 974,
"text": "gfi1aa and gfi1b have distinct roles in regulating primitive and definitive hematopoietic progenitors,"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22960038",
"endSection": "abstract",
"offsetInBeginSection": 1151,
"offsetInEndSection": 1197,
"text": "gfi1b is required for definitive hematopoiesis"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22699452",
"endSection": "abstract",
"offsetInBeginSection": 1052,
"offsetInEndSection": 1140,
"text": "LSD1-kd was associated with the upregulation of key hematopoietic genes, including Gfi1b"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22668850",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 112,
"text": "GFI1 and GFI1B control the loss of endothelial identity of hemogenic endothelium during hematopoietic commitment"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22668850",
"endSection": "abstract",
"offsetInBeginSection": 856,
"offsetInEndSection": 1076,
"text": " Taken together, our findings demonstrate a critical and specific role of the GFI1 transcription factors in the first steps of the process leading to the generation of hematopoietic progenitors from hemogenic endothelium"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22399799",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 57,
"text": "A short Gfi-1B isoform controls erythroid differentiation"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22399799",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 105,
"text": "Gfi-1B is a transcriptional repressor essential for the regulation of erythropoiesis and megakaryopoiesis"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21606163",
"endSection": "abstract",
"offsetInBeginSection": 1070,
"offsetInEndSection": 1162,
"text": "Among the few down-regulated genes was Gfi1b, a known repressor of erythroid differentiation"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21170035",
"endSection": "abstract",
"offsetInBeginSection": 722,
"offsetInEndSection": 922,
"text": "This reversible modulation of endothelial-haematopoietic state is accomplished by targeting key haematopoietic transcription factors for downregulation, including Runx1, Gata1, Gfi1B, Ikaros, and PU.1"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20861919",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 47,
"text": "Gfi1 and Gfi1b: key regulators of hematopoiesis"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20861919",
"endSection": "abstract",
"offsetInBeginSection": 630,
"offsetInEndSection": 851,
"text": "we review how Gfi1 and its paralogue Gfi1b control the development of blood cells, discuss how changes in Gfi1 and Gfi1b function contribute to hematological disease and report on the molecular function of these proteins."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20124515",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 155,
"text": "Gfi-1B controls human erythroid and megakaryocytic differentiation by regulating TGF-beta signaling at the bipotent erythro-megakaryocytic progenitor stage"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20124515",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 119,
"text": "Growth factor independence-1B (Gfi-1B) is a transcriptional repressor essential for erythropoiesis and megakaryopoiesis"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20124515",
"endSection": "abstract",
"offsetInBeginSection": 121,
"offsetInEndSection": 312,
"text": "Targeted gene disruption of GFI1B in mice leads to embryonic lethality resulting from failure to produce definitive erythrocytes, hindering the study of Gfi-1B function in adult hematopoiesis"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20124515",
"endSection": "abstract",
"offsetInBeginSection": 314,
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"text": "We here show that, in humans, Gfi-1B controls the development of erythrocytes and megakaryocytes by regulating the proliferation and differentiation of bipotent erythro-megakaryocytic progenitors"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19958752",
"endSection": "abstract",
"offsetInBeginSection": 1509,
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"text": "To date, we have identified two common integration sites involving genes encoding transcription factors that play a critical role in hematopoiesis (Evi1 and Gfi1b loci)"
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{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19773260",
"endSection": "abstract",
"offsetInBeginSection": 12,
"offsetInEndSection": 304,
"text": "Transcription factors play essential roles in both normal and malignant hematopoiesis. This is the case for the growth factor independent 1b (GFI1B) transcription factor, which is required for erythroid and megakaryocytic differentiation and over-expressed in leukemic patients and cell lines"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19773260",
"endSection": "abstract",
"offsetInBeginSection": 1022,
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"text": "We localized several conserved non-coding elements containing multiple erythroid specific transcription factor binding sites at the GFI1B locus. In GFI1B-expressing cells a subset of these conserved non-coding elements and the promoter adopt a close spatial conformation, localize with open chromatin sites, harbor chromatin modifications associated with gene activation and bind multiple transcription factors and co-repressors"
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{
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/19773260",
"endSection": "abstract",
"offsetInBeginSection": 1464,
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"text": "Our findings indicate that GFI1B regulatory elements behave as activators and repressors"
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{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18224412",
"endSection": "abstract",
"offsetInBeginSection": 0,
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"text": "To investigate the molecular effects of growth factor independence 1B (Gfi-1B), a transcription factor essential for the development of hematopoietic cells and differentiation of erythroid and megakaryocytic lineages"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18224412",
"endSection": "abstract",
"offsetInBeginSection": 1760,
"offsetInEndSection": 1877,
"text": "Our data indicate that Gfi-1B signalling is important for commitment and maturation of hematopoietic cell populations"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17707228",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 142,
"text": "Gfi-1 and Gfi-1b are homologous transcriptional repressors involved in diverse developmental contexts, including hematopoiesis and oncogenesis"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17095621",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 149,
"text": "Gfi1b:green fluorescent protein knock-in mice reveal a dynamic expression pattern of Gfi1b during hematopoiesis that is largely complementary to Gfi1"
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{
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"endSection": "abstract",
"offsetInBeginSection": 546,
"offsetInEndSection": 958,
"text": "We found highly dynamic expression patterns of Gfi1b in erythroid cells, megakaryocytes, and their progenitor cells (MEPS) where Gfi1 is not detected. Vice versa, Gfi1b could not be found in granulocytes, activated macrophages, or their granulomonocytic precursors (GMPs) or in mature naive or activated lymphocytes where Gfi1 is expressed, suggesting a complementary regulation of both loci during hematopoiesis"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16397623",
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"offsetInBeginSection": 0,
"offsetInEndSection": 49,
"text": "Gfi1 and Gfi1b act equivalently in haematopoiesis"
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{
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"endSection": "abstract",
"offsetInBeginSection": 668,
"offsetInEndSection": 814,
"text": "our findings show that an intact SNAG domain is essential for all functions of Gfi1 and that Gfi1b can replace Gfi1 functionally in haematopoiesis"
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{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14530176",
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"text": "Gfi-1 oncoproteins in hematopoiesis"
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"offsetInBeginSection": 101,
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"text": "Recent gene targeting experiments and mutational screening in humans have revealed an essential role for Gfi-1 and Gfi-1B in hematopoiesis"
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"offsetInBeginSection": 608,
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"text": "Gfi-1B disruption is embryonic lethal due to a block of erythropoiesis. Gfi-1B is required for both erythroid and megakaryocyte development"
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"text": "Erythroid expansion mediated by the Gfi-1B zinc finger protein: role in normal hematopoiesis"
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"text": " we identified that the expression of Gfi-1B (growth factor independence-1B) is highly restricted to hematopoietic stem cells, erythroblasts, and megakaryocytes"
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"text": "These findings establish Gfi-1B as a novel erythroid regulator and reveal its specific involvement in the regulation of erythroid cell growth through modulating erythroid-specific gene expression"
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/11825872",
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"text": "The zinc-finger proto-oncogene Gfi-1b is essential for development of the erythroid and megakaryocytic lineages"
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"text": "we establish that Gfi-1b is required for the development of two related blood lineages, erythroid and megakaryocytic, in mice"
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"text": "Gfi-1b(-/-) embryonic stem cells fail to contribute to red cells of adult chimeras. Gfi-1b(-/-) embryos exhibit delayed maturation of primitive erythrocytes and subsequently die with failure to produce definitive enucleated erythrocytes"
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"text": "Growth factor independence 1b (GFI1B) is a DNA binding repressor of transcription with vital functions in hematopoiesis."
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"text": "Conversely, loss of gfi1b silences runx-1, c-myb, ikaros and cd41, indicating that gfi1b is required for definitive hematopoiesis."
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"text": "In fact, we demonstrate that VPA treatment is able to induce the expression of growth factor-independent protein 1B (GFI1B) and of mixed-lineage leukemia translocated to chromosome 3 protein (MLLT3), which are crucial regulators of erythrocyte and megakaryocyte differentiation, and that the up-regulation of these genes is mediated by the histone hyperacetylation at their promoter sites."
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"text": "Gfi-1B (growth factor independence-1B) gene is an erythroid-specific transcription factor, whose expression plays an essential role in erythropoiesis."
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"text": "Evidence that growth factor independence 1b regulates dormancy and peripheral blood mobilization of hematopoietic stem cells."
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"text": "We report here that adult mice conditionally deficient for the transcription Growth factor independence 1b (Gfi1b) show a significant expansion of functional HSCs in the bone marrow and blood."
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"text": "Teleost growth factor independence (gfi) genes differentially regulate successive waves of hematopoiesis."
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"text": "Growth Factor Independence (Gfi) transcription factors play essential roles in hematopoiesis, differentially activating and repressing transcriptional programs required for hematopoietic stem/progenitor cell (HSPC) development and lineage specification"
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"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 252,
"text": "Growth Factor Independence (Gfi) transcription factors play essential roles in hematopoiesis, differentially activating and repressing transcriptional programs required for hematopoietic stem/progenitor cell (HSPC) development and lineage specification"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16177182",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 149,
"text": "Gfi-1B (growth factor independence-1B) gene is an erythroid-specific transcription factor, whose expression plays an essential role in erythropoiesis"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18224412",
"endSection": "abstract",
"offsetInBeginSection": 1760,
"offsetInEndSection": 1878,
"text": "Our data indicate that Gfi-1B signalling is important for commitment and maturation of hematopoietic cell populations."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20124515",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 119,
"text": "Growth factor independence-1B (Gfi-1B) is a transcriptional repressor essential for erythropoiesis and megakaryopoiesis"
}
]
| 5 | BioASQ-training5b | [
"http://www.uniprot.org/uniprot/GFI1B_HUMAN",
"http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030097",
"http://www.uniprot.org/uniprot/GFI1B_MOUSE"
]
| []
| 553bd2f0f321868558000008 | 18 |
yesno | Is rilonacept effective for pericarditis? | ['yes'] | [
"yes"
]
| ['Yes, rilonacept is effective for pericarditis.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/34459270",
"http://www.ncbi.nlm.nih.gov/pubmed/34556390",
"http://www.ncbi.nlm.nih.gov/pubmed/34599390",
"http://www.ncbi.nlm.nih.gov/pubmed/34528670",
"http://www.ncbi.nlm.nih.gov/pubmed/34569270"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34556390",
"endSection": "abstract",
"offsetInBeginSection": 783,
"offsetInEndSection": 1150,
"text": " Concerning acute recurrent pericarditis (RP), an innovative interaction between cardiologists, internists and pediatric rheumatologists led to the intuition of a pivotal role of IL-1 in recurrent pericarditis characterized by an evident inflammatory recurrent phenotype, and recent data have shown the striking efficacy of anakinra and rilonacept in these patients. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34599390",
"endSection": "abstract",
"offsetInBeginSection": 669,
"offsetInEndSection": 1258,
"text": "Pericarditis is regarded as a stereotypical response to an acute damage of the mesothelial cells of the pericardial layers. NLRP3 inflammasome, a macromolecular structure sensing damage and releasing pro-inflammatory cytokines, is centrally involved as it releases interleukin (IL)-1β, whose auto-induction feeds an autoinflammatory disease, mostly responsible for recurrences. Colchicine, an inhibitor of NLRP3 inflammasome formation, and IL-1-targeted therapies, such as anakinra and rilonacept, were found to effectively blunt the acute inflammation and reduce the risk for recurrences."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34569270",
"endSection": "abstract",
"offsetInBeginSection": 810,
"offsetInEndSection": 1069,
"text": "Currently, anakinra and rilonacept, have demonstrated beneficial impact in clinical outcomes with a reasonable safety profile in randomized clinical trials. There is still paucity of data regarding the use of canakinumab in the treatment of patients with RP. "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34459270",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 66,
"text": "Rilonacept: A Newly Approved Treatment for Recurrent Pericarditis."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34459270",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 138,
"text": "OBJECTIVE: To review the pharmacology, efficacy, and safety of rilonacept for the prevention and treatment of recurrent pericarditis (RP)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34459270",
"endSection": "abstract",
"offsetInBeginSection": 1552,
"offsetInEndSection": 1763,
"text": "CONCLUSION: Rilonacept is a safe, once weekly, subcutaneously administered IL-1 \"trap,\" indicated for the treatment of RP, and reduction in risk of recurrent pericarditis in adults and children ≥12 years of age."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34528670",
"endSection": "abstract",
"offsetInBeginSection": 394,
"offsetInEndSection": 835,
"text": "Overproduction of both IL-1α (released by inflamed/damaged pericardial cells) and IL-1β (released by inflammatory cells) is now a well-recognized therapeutic target in patients with recurrent idiopathic pericarditis. Currently, there are three available anti-IL-1 agents: anakinra (recombinant human IL-1Ra), rilonacept (a soluble decoy receptor 'trap', binding both IL-1α and IL-1β), and canakinumab (human monoclonal anti-IL-1β antibody). "
}
]
| 12 | BioASQ-training12b | null | null | 61f7cb37882a024a10000029 | 19 |
yesno | Are Conserved Nonexonic Elements (CNEEs) important in phylogenomics research? | ['yes'] | [
"yes"
]
| ['Yes. Conserved Nonexonic Elements (CNEEs) appear to be promising as phylogenomic markers, yielding phylogenetic resolution as high as for UCEs and introns but with fewer gaps, less ambiguity in alignments and with patterns of nucleotide substitution more consistent with the assumptions of commonly used methods of phylogenetic analysis.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/28417603",
"http://www.ncbi.nlm.nih.gov/pubmed/28637293"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28637293",
"endSection": "abstract",
"offsetInBeginSection": 1555,
"offsetInEndSection": 1865,
"text": "Overall, CNEEs appear to be promising as phylogenomic markers, yielding phylogenetic resolution as high as for UCEs and introns but with fewer gaps, less ambiguity in alignments and with patterns of nucleotide substitution more consistent with the assumptions of commonly used methods of phylogenetic analysis."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28637293",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 72,
"text": "Conserved Nonexonic Elements: A Novel Class of Marker for Phylogenomics."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28417603",
"endSection": "abstract",
"offsetInBeginSection": 316,
"offsetInEndSection": 583,
"text": "Target capture for vertebrate animals is currently dominated by two approaches-anchored hybrid enrichment (AHE) and ultraconserved elements (UCE)-and both approaches have proven useful for addressing questions in phylogenomics, phylogeography and population genomics."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28637293",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 71,
"text": "conserved nonexonic elements a novel class of marker for phylogenomics"
}
]
| 11 | BioASQ-training11b | null | null | 5a6e18d8b750ff4455000038 | 20 |
yesno | Does Rhamnose have any effect on aging? | ['yes'] | [
"yes"
]
| ['Yes, Rhamnose does have an effect on aging.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/28855134",
"http://www.ncbi.nlm.nih.gov/pubmed/22099844"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28855134",
"endSection": "abstract",
"offsetInBeginSection": 740,
"offsetInEndSection": 892,
"text": "The monosaccharide analysis showed that rhamnose (Rha) and glucose (Glu) may play vital roles in maintaining the antioxidant and anti-aging activities. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22099844",
"endSection": "abstract",
"offsetInBeginSection": 629,
"offsetInEndSection": 830,
"text": "Some of these mechanisms will be reviewed as well as the capacity of fucose- and rhamnose-rich oligo- and polysaccharides (FROP and RROP) to counteract several of the mechanisms involved in skin aging."
}
]
| 11 | BioASQ-training11b | null | null | 5c840daf617e120c34000007 | 21 |
yesno | Is telomestatin, a novel statin drug used to treat high cholesterol? | ['no'] | [
"no"
]
| ['Telomestatin is a natural product isolated from Streptomyces anulatus 3533-SV4 and has been shown to be a very potent telomerase inhibitor and is used to treat cancer.', 'Telomestatin is a natural product isolated from Streptomyces anulatus 3533-SV4 and has been shown to be a very potent telomerase inhibitor.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/11878947",
"http://www.ncbi.nlm.nih.gov/pubmed/28611443",
"http://www.ncbi.nlm.nih.gov/pubmed/23909929",
"http://www.ncbi.nlm.nih.gov/pubmed/16652154",
"http://www.ncbi.nlm.nih.gov/pubmed/15283144",
"http://www.ncbi.nlm.nih.gov/pubmed/12917635"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11878947",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 139,
"text": "Telomestatin is a natural product isolated from Streptomyces anulatus 3533-SV4 and has been shown to be a very potent telomerase inhibitor."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11878947",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 131,
"text": "Telomestatin, a potent telomerase inhibitor that interacts quite specifically with the human telomeric intramolecular g-quadruplex."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12917635",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 91,
"text": "Activity of a novel G-quadruplex-interactive telomerase inhibitor, telomestatin (SOT-095), "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12917635",
"endSection": "abstract",
"offsetInBeginSection": 149,
"offsetInEndSection": 220,
"text": " G-quadruplex-interactive telomerase inhibitor, telomestatin (SOT-095),"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12917635",
"endSection": "abstract",
"offsetInBeginSection": 380,
"offsetInEndSection": 509,
"text": " We found that treatment with telomestatin reproducibly inhibited telomerase activity in the BCR-ABL-positive leukemic cell lines"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15283144",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 127,
"text": "A novel telomerase inhibitor, telomestatin, isolated from Streptomyces anulatus is the most potent telomerase inhibitor so far."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15283144",
"endSection": "title",
"offsetInBeginSection": 1,
"offsetInEndSection": 93,
"text": "Telomerase inhibitor, telomestatin, a specific mechanism to interact with telomere structure"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15283144",
"endSection": "abstract",
"offsetInBeginSection": 128,
"offsetInEndSection": 232,
"text": "Telomestatin specifically inhibited telomerase without affecting reverse transcriptases and polymerases."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15283144",
"endSection": "abstract",
"offsetInBeginSection": 233,
"offsetInEndSection": 379,
"text": "In addition, telomestatin induced telomere shortening, but its ratio was extremely faster than that observed in physiological telomere shortening."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15283144",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 128,
"text": "A novel telomerase inhibitor, telomestatin, isolated from Streptomyces anulatus is the most potent telomerase inhibitor so far. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23909929",
"endSection": "abstract",
"offsetInBeginSection": 384,
"offsetInEndSection": 530,
"text": "ructure has been yet resolved for the complex with telomestatin, one of the most promising G-quadruplex-targeting anticancer drug candidates. Here"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28611443",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 138,
"text": "Telomestatin, a strong telomerase inhibitor with G-quadruplex stabilizing activity, is a potential therapeutic agent for treating cancers."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15283144",
"endSection": "abstract",
"offsetInBeginSection": 871,
"offsetInEndSection": 961,
"text": "Thus, telomestatin provide the novel therapeutic molecular target for cancer chemotherapy."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16652154",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 128,
"text": "Telomerase inhibition with a novel G-quadruplex-interactive agent, telomestatin: in vitro and in vivo studies in acute leukemia."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12917635",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 179,
"text": "Activity of a novel G-quadruplex-interactive telomerase inhibitor, telomestatin (SOT-095), against human leukemia cells: involvement of ATM-dependent DNA damage response pathways."
}
]
| 11 | BioASQ-training11b | null | null | 623a24d6f0baec9a1b000002 | 22 |
yesno | Was modafinil tested for schizophrenia treatment? | ['yes'] | [
"yes"
]
| ['Yes. Modafinil has been shown to improve attention, memory, executive function and antipsychotic-induced parkinsonism in patients with schizophrenia. However, some authors have failed to demonstrate beneficial action of modafinil for schizophrenia.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/23938173",
"http://www.ncbi.nlm.nih.gov/pubmed/22820555",
"http://www.ncbi.nlm.nih.gov/pubmed/22820554",
"http://www.ncbi.nlm.nih.gov/pubmed/23983964",
"http://www.ncbi.nlm.nih.gov/pubmed/21947320",
"http://www.ncbi.nlm.nih.gov/pubmed/21909634",
"http://www.ncbi.nlm.nih.gov/pubmed/21565464",
"http://www.ncbi.nlm.nih.gov/pubmed/21412225",
"http://www.ncbi.nlm.nih.gov/pubmed/21109234",
"http://www.ncbi.nlm.nih.gov/pubmed/20810469",
"http://www.ncbi.nlm.nih.gov/pubmed/20653641",
"http://www.ncbi.nlm.nih.gov/pubmed/19914296",
"http://www.ncbi.nlm.nih.gov/pubmed/19689921",
"http://www.ncbi.nlm.nih.gov/pubmed/19572020",
"http://www.ncbi.nlm.nih.gov/pubmed/19026265",
"http://www.ncbi.nlm.nih.gov/pubmed/18729534",
"http://www.ncbi.nlm.nih.gov/pubmed/18516718",
"http://www.ncbi.nlm.nih.gov/pubmed/18392753",
"http://www.ncbi.nlm.nih.gov/pubmed/17712350",
"http://www.ncbi.nlm.nih.gov/pubmed/17634412",
"http://www.ncbi.nlm.nih.gov/pubmed/17503979",
"http://www.ncbi.nlm.nih.gov/pubmed/17151173",
"http://www.ncbi.nlm.nih.gov/pubmed/17077439",
"http://www.ncbi.nlm.nih.gov/pubmed/16965205",
"http://www.ncbi.nlm.nih.gov/pubmed/16634707",
"http://www.ncbi.nlm.nih.gov/pubmed/16013898",
"http://www.ncbi.nlm.nih.gov/pubmed/15994572",
"http://www.ncbi.nlm.nih.gov/pubmed/15090936",
"http://www.ncbi.nlm.nih.gov/pubmed/15085092",
"http://www.ncbi.nlm.nih.gov/pubmed/24964814",
"http://www.ncbi.nlm.nih.gov/pubmed/25306261"
]
| [
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23938173",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 226,
"text": "Modafinil improves antipsychotic-induced parkinsonism but not excessive daytime sleepiness, psychiatric symptoms or cognition in schizophrenia and schizoaffective disorder: a randomized, double-blind, placebo-controlled study."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23938173",
"endSection": "abstract",
"offsetInBeginSection": 1382,
"offsetInEndSection": 1565,
"text": "CONCLUSION: The data suggest that modafinil was a safe adjunctive treatment which improved parkinsonian symptoms and signs in patients with schizophrenia or schizoaffective disorder. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22820555",
"endSection": "abstract",
"offsetInBeginSection": 747,
"offsetInEndSection": 1027,
"text": "A review of its effects in schizophrenia suggests that modafinil facilitates cognitive functions, with pro-mnemonic effects and problem solving improvements. Emotional processing also appears to be enhanced by the drug, although to date there are only a limited number of studies."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22820554",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 242,
"text": "BACKGROUND: Modafinil, a putative cognitive enhancing drug, has previously been shown to improve performance of healthy volunteers as well as patients with attention deficit disorder and schizophrenia, mainly in tests of executive functions. "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23983964",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 109,
"text": "A review of modafinil and armodafinil as add-on therapy in antipsychotic-treated patients with schizophrenia."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23983964",
"endSection": "abstract",
"offsetInBeginSection": 224,
"offsetInEndSection": 487,
"text": "It has been suggested that modafinil and its isomer armodafinil as an add-on strategy to antipsychotic treatment in patients with schizophrenia may improve cognitive functioning, attenuate fatigue, inactiveness and other negative functions as well as weight gain."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23983964",
"endSection": "abstract",
"offsetInBeginSection": 794,
"offsetInEndSection": 1235,
"text": "Evidence for the use of modafinil or armodafinil as add-on therapy to antipsychotic drugs to alleviate fatigue, sleepiness and inactivity is inconclusive. One cohort study and one out of two single-dose crossover RCTs in which modafinil addition was studied could demonstrate a positive effect. All five RCTs of modafinil (three RCTs) and armodafinil (two RCTs) addition with a longer study duration could not demonstrate a positive effect. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23983964",
"endSection": "abstract",
"offsetInBeginSection": 1351,
"offsetInEndSection": 2139,
"text": "In RCTs with a treatment duration of 4 weeks or more, however, no positive effect could be demonstrated on cognitive functioning with modafinil and armodafinil addition. Yet, four single-dose crossover RCTs of modafinil addition show significant positive effects on executive functioning, verbal memory span, visual memory, working memory, spatial planning, slowing in latency, impulse control and recognition of faces expressing sadness and sadness misattribution in the context of disgust recognition. The addition of modafinil or armodafinil to an antipsychotic regime, despite theoretical and preclinical considerations, has not been proved to enhance cognitive function, attenuate fatigue, enhance activity, improve negative symptoms and reduce weight in patients with schizophrenia."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21947320",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 172,
"text": "RATIONAL: In recent years, evidence suggests that modafinil may be useful for certain symptom domains of schizophrenia, especially for the negative and cognitive symptoms. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21947320",
"endSection": "abstract",
"offsetInBeginSection": 1243,
"offsetInEndSection": 1405,
"text": "CONCLUSION: The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21909634",
"endSection": "abstract",
"offsetInBeginSection": 156,
"offsetInEndSection": 324,
"text": "Modafinil is a wake-promoting drug that has been shown to improve attention, memory and executive function in the healthy population and in patients with schizophrenia."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21565464",
"endSection": "abstract",
"offsetInBeginSection": 1097,
"offsetInEndSection": 1261,
"text": "CONCLUSIONS: Results of this pilot trial do not support routine use of modafinil to counteract increased weight and metabolic diseases in patients taking clozapine."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21412225",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 196,
"text": "Modafinil (2-((diphenylmethyl)sulfinyl)acetamide) is described as an atypical stimulant and is a putative cognition enhancer for schizophrenia, but the precise mechanisms of action remain unclear."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21109234",
"endSection": "abstract",
"offsetInBeginSection": 152,
"offsetInEndSection": 319,
"text": "Modafinil is a wake-promoting drug that has been shown to improve emotion discrimination in healthy individuals and attention and executive function in schizophrenia. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20810469",
"endSection": "abstract",
"offsetInBeginSection": 1613,
"offsetInEndSection": 1900,
"text": "CONCLUSIONS: These data support clinical evidence that modafinil may alleviate cognitive deficits in schizophrenia and also demonstrate the benefit of applying PLSR modeling to characterize functional brain networks in translational models relevant to central nervous system dysfunction."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20653641",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 257,
"text": "Modafinil improves working memory in healthy subjects and individuals diagnosed with schizophrenia and Attention Deficit/Hyperactivity Disorder, though the effects of modafinil have not been evaluated on working memory in methamphetamine-dependent subjects."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19914296",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 221,
"text": "Modafinil is a psychostimulant approved for treating excessive sleepiness in adults; off-label uses (e.g., treatment of cognitive impairment in schizophrenia, ADHD and age-related dementias) are currently being explored. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19689921",
"endSection": "abstract",
"offsetInBeginSection": 1064,
"offsetInEndSection": 1241,
"text": "CONCLUSIONS: Results of this pilot trial do not support routine use of modafinil to treat negative symptoms, cognitive deficits, or wakefulness/fatigue in patients on clozapine."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19572020",
"endSection": "abstract",
"offsetInBeginSection": 81,
"offsetInEndSection": 316,
"text": "We have previously shown that the amount of movement exhibited by patients with schizophrenia is positively correlated with the volume of left anterior cingulate cortex and that this quantity of movement can be increased by modafinil. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 456,
"text": "OBJECTIVE: Given recent reports about the off-label use of modafinil as an adjuvant for the treatment of antipsychotic-associated sedation in schizophrenia patients and the recent interest in its putative cognitive-enhancing effects in this population, we present a systematic review of available data on trials of modafinil as an adjuvant in the treatment of cognitive deficits, negative symptoms, and antipsychotic-induced fatigue, and its tolerability. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265",
"endSection": "abstract",
"offsetInBeginSection": 1281,
"offsetInEndSection": 1648,
"text": "RESULTS: One of 4 reviewed studies found a significant effect of modafinil as an alerting agent for antipsychotic-induced fatigue and sedation. Neither of 2 reviewed studies found modafinil to improve negative symptoms of schizophrenia. Three of 6 reviewed studies showed that modafinil may improve short-term memory, attention, and the ability to shift mental sets. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265",
"endSection": "abstract",
"offsetInBeginSection": 1972,
"offsetInEndSection": 2439,
"text": "CONCLUSIONS: While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265",
"endSection": "abstract",
"offsetInBeginSection": 2743,
"offsetInEndSection": 2883,
"text": "Hence, before prescribing modafinil to a schizophrenia patient, the possible risks and benefits of each particular case should be evaluated."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18729534",
"endSection": "abstract",
"offsetInBeginSection": 2211,
"offsetInEndSection": 2506,
"text": "Modafinil had a substantial placebo effect on outcomes such as fatigue, excessive sleepiness and depression in patients with traumatic brain injury, major depressive disorder, schizophrenia, post-polio fatigue and multiple sclerosis; however, it did not provide any benefit greater than placebo."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18516718",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 211,
"text": "RATIONALE: The wake-promoting agent modafinil selectively improves neuropsychological task performance in healthy volunteers, in adults with attention deficit hyperactivity disorder (ADHD) and in schizophrenia. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18392753",
"endSection": "abstract",
"offsetInBeginSection": 271,
"offsetInEndSection": 394,
"text": "Recently, however, modafinil has been shown to improve attentional set-shifting performance in patients with schizophrenia."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17712350",
"endSection": "abstract",
"offsetInBeginSection": 261,
"offsetInEndSection": 462,
"text": "In addition, modafinil shows initial promise for a variety of off-label indications in psychiatry, including treatment-resistant depression, attention-deficit/hyperactivity disorder, and schizophrenia."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17634412",
"endSection": "abstract",
"offsetInBeginSection": 226,
"offsetInEndSection": 396,
"text": "There is increasing interest in the use of modafinil to improve cognition in schizophrenia as well as in other disorders such as attention-deficit/hyperactivity disorder."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17634412",
"endSection": "abstract",
"offsetInBeginSection": 560,
"offsetInEndSection": 702,
"text": "Initial findings indicate that modafinil may lead to better executive functioning and attentional performance in patients with schizophrenia. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17503979",
"endSection": "abstract",
"offsetInBeginSection": 1501,
"offsetInEndSection": 1701,
"text": "CONCLUSIONS: Although no effect on negative symptoms was found, adjunctive therapy with modafinil may result in global improvements in patients with schizophrenia who have prominent negative symptoms."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17151173",
"endSection": "abstract",
"offsetInBeginSection": 972,
"offsetInEndSection": 1059,
"text": "CONCLUSIONS: Modafinil did not improve cognitive control in all schizophrenia patients."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17077439",
"endSection": "abstract",
"offsetInBeginSection": 364,
"offsetInEndSection": 492,
"text": ". These data suggest that modafinil increases quantifiable motor behaviour in schizophrenia and may have an impact on avolition."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16965205",
"endSection": "abstract",
"offsetInBeginSection": 1537,
"offsetInEndSection": 1784,
"text": "One patient was on treatment with both modafinil and trazodone and reported no change after tapering each in separate discontinuation trials, while another 3 patients were taking sleeping medications and also noted no change after discontinuation."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16634707",
"endSection": "abstract",
"offsetInBeginSection": 551,
"offsetInEndSection": 743,
"text": " Neuroprotective agents as add-on therapies (e.g., modafinil, erythropoietin, glycine, D-serine, memantine and celecoxib) are currently being evaluated in schizophrenia and related disorders. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16013898",
"endSection": "abstract",
"offsetInBeginSection": 666,
"offsetInEndSection": 887,
"text": "In the modafinil (N = 10) and placebo (N = 10) groups, fatigue improved significantly over time (p < .01), but there were no differences between groups on changes in fatigue, positive and negative symptoms, or cognition. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15994572",
"endSection": "abstract",
"offsetInBeginSection": 929,
"offsetInEndSection": 1136,
"text": "CONCLUSIONS: Modafinil modulates anterior cingulate cortex function in chronic schizophrenia but its beneficial cognitive effects may be restricted to a subset of patients requiring further characterisation."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15090936",
"endSection": "abstract",
"offsetInBeginSection": 687,
"offsetInEndSection": 873,
"text": "Modafinil significantly improved overall clinical condition, with 64% and 82% of patients rated as clinically improved at week 4 by a blinded clinician and the investigator respectively."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15090936",
"endSection": "abstract",
"offsetInBeginSection": 955,
"offsetInEndSection": 1068,
"text": "Modafinil significantly improved fatigue (P = 0.025, week 3) and tended to improve cognitive functioning scores. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15090936",
"endSection": "abstract",
"offsetInBeginSection": 1349,
"offsetInEndSection": 1597,
"text": "Although preliminary, these results suggest modafinil may be an effective and well-tolerated adjunct treatment that improves global functioning and clinical condition, and reduces fatigue in patients with schizophrenia or schizoaffective disorder. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15085092",
"endSection": "abstract",
"offsetInBeginSection": 666,
"offsetInEndSection": 807,
"text": "Modafinil had some cognitive enhancing properties in schizophrenia similar to those observed in healthy adults and adult patients with ADHD. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15085092",
"endSection": "abstract",
"offsetInBeginSection": 1222,
"offsetInEndSection": 1407,
"text": "Modafinil may have potential as an important therapy for cognitive impairment in patients with schizophrenia, particularly because of its beneficial effects on attentional set shifting."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265",
"endSection": "abstract",
"offsetInBeginSection": 1887,
"offsetInEndSection": 2340,
"text": "While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 444,
"text": "Given recent reports about the off-label use of modafinil as an adjuvant for the treatment of antipsychotic-associated sedation in schizophrenia patients and the recent interest in its putative cognitive-enhancing effects in this population, we present a systematic review of available data on trials of modafinil as an adjuvant in the treatment of cognitive deficits, negative symptoms, and antipsychotic-induced fatigue, and its tolerability."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21947320",
"endSection": "abstract",
"offsetInBeginSection": 1190,
"offsetInEndSection": 1339,
"text": "The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23983964",
"endSection": "abstract",
"offsetInBeginSection": 221,
"offsetInEndSection": 485,
"text": " It has been suggested that modafinil and its isomer armodafinil as an add-on strategy to antipsychotic treatment in patients with schizophrenia may improve cognitive functioning, attenuate fatigue, inactiveness and other negative functions as well as weight gain."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23983964",
"endSection": "abstract",
"offsetInBeginSection": 224,
"offsetInEndSection": 487,
"text": "It has been suggested that modafinil and its isomer armodafinil as an add-on strategy to antipsychotic treatment in patients with schizophrenia may improve cognitive functioning, attenuate fatigue, inactiveness and other negative functions as well as weight gain."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21947320",
"endSection": "abstract",
"offsetInBeginSection": 1243,
"offsetInEndSection": 1404,
"text": "CONCLUSION: The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 455,
"text": "OBJECTIVE: Given recent reports about the off-label use of modafinil as an adjuvant for the treatment of antipsychotic-associated sedation in schizophrenia patients and the recent interest in its putative cognitive-enhancing effects in this population, we present a systematic review of available data on trials of modafinil as an adjuvant in the treatment of cognitive deficits, negative symptoms, and antipsychotic-induced fatigue, and its tolerability."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265",
"endSection": "abstract",
"offsetInBeginSection": 1971,
"offsetInEndSection": 2437,
"text": "CONCLUSIONS: While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23938173",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 226,
"text": "Modafinil improves antipsychotic-induced parkinsonism but not excessive daytime sleepiness, psychiatric symptoms or cognition in schizophrenia and schizoaffective disorder: a randomized, double-blind, placebo-controlled study."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23938173",
"endSection": "abstract",
"offsetInBeginSection": 1382,
"offsetInEndSection": 1565,
"text": "CONCLUSION: The data suggest that modafinil was a safe adjunctive treatment which improved parkinsonian symptoms and signs in patients with schizophrenia or schizoaffective disorder. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21947320",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 149,
"text": "The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15090936",
"endSection": "abstract",
"offsetInBeginSection": 1349,
"offsetInEndSection": 1596,
"text": "Although preliminary, these results suggest modafinil may be an effective and well-tolerated adjunct treatment that improves global functioning and clinical condition, and reduces fatigue in patients with schizophrenia or schizoaffective disorder."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23983964",
"endSection": "abstract",
"offsetInBeginSection": 224,
"offsetInEndSection": 487,
"text": "It has been suggested that modafinil and its isomer armodafinil as an add-on strategy to antipsychotic treatment in patients with schizophrenia may improve cognitive functioning, attenuate fatigue, inactiveness and other negative functions as well as weight gain."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265",
"endSection": "abstract",
"offsetInBeginSection": 1909,
"offsetInEndSection": 2361,
"text": "While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21947320",
"endSection": "abstract",
"offsetInBeginSection": 1208,
"offsetInEndSection": 1356,
"text": "The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22820554",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 228,
"text": "Modafinil, a putative cognitive enhancing drug, has previously been shown to improve performance of healthy volunteers as well as patients with attention deficit disorder and schizophrenia, mainly in tests of executive functions"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265",
"endSection": "abstract",
"offsetInBeginSection": 1909,
"offsetInEndSection": 2361,
"text": "While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21947320",
"endSection": "abstract",
"offsetInBeginSection": 1208,
"offsetInEndSection": 1356,
"text": "The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265",
"endSection": "abstract",
"offsetInBeginSection": 1909,
"offsetInEndSection": 2361,
"text": "While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21947320",
"endSection": "abstract",
"offsetInBeginSection": 1208,
"offsetInEndSection": 1356,
"text": "The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 444,
"text": "Given recent reports about the off-label use of modafinil as an adjuvant for the treatment of antipsychotic-associated sedation in schizophrenia patients and the recent interest in its putative cognitive-enhancing effects in this population, we present a systematic review of available data on trials of modafinil as an adjuvant in the treatment of cognitive deficits, negative symptoms, and antipsychotic-induced fatigue, and its tolerability."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265",
"endSection": "abstract",
"offsetInBeginSection": 1909,
"offsetInEndSection": 2361,
"text": "While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21947320",
"endSection": "abstract",
"offsetInBeginSection": 1208,
"offsetInEndSection": 1356,
"text": "The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 444,
"text": "Given recent reports about the off-label use of modafinil as an adjuvant for the treatment of antipsychotic-associated sedation in schizophrenia patients and the recent interest in its putative cognitive-enhancing effects in this population, we present a systematic review of available data on trials of modafinil as an adjuvant in the treatment of cognitive deficits, negative symptoms, and antipsychotic-induced fatigue, and its tolerability."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265",
"endSection": "abstract",
"offsetInBeginSection": 1909,
"offsetInEndSection": 2361,
"text": "While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21947320",
"endSection": "abstract",
"offsetInBeginSection": 1208,
"offsetInEndSection": 1356,
"text": "The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22820554",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 228,
"text": "Modafinil, a putative cognitive enhancing drug, has previously been shown to improve performance of healthy volunteers as well as patients with attention deficit disorder and schizophrenia, mainly in tests of executive functions"
}
]
| 5 | BioASQ-training5b | [
"http://www.biosemantics.org/jochem#4259639",
"http://www.disease-ontology.org/api/metadata/DOID:5419"
]
| []
| 54fc845e6ea36a810c000005 | 23 |
yesno | Is Alpers disease inherited in an autosomal recessive mode? | ['yes'] | [
"yes"
]
| ['Alpers disease is a fatal neurogenetic disorder first described more than 70 years ago. It is an autosomal recessive, developmental mitochondrial DNA depletion disorder characterized by deficiency in mitochondrial DNA polymerase gamma (POLG) catalytic activity, refractory seizures, neurodegeneration, and liver disease.', 'Alpers-Huttenlocher syndrome (AHS) is a very rare autosomal recessive disorder', 'Alpers-Huttenlocher syndrome (AHS) is a very rare autosomal recessive disorder', 'Alpers-Huttenlocher syndrome (AHS) is a very rare autosomal recessive disorder', 'Alpers-Huttenlocher syndrome (AHS) is a very rare autosomal recessive disorder', 'Alpers-Huttenlocher syndrome (AHS) is a very rare autosomal recessive disorder'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/22006280",
"http://www.ncbi.nlm.nih.gov/pubmed/16181814",
"http://www.ncbi.nlm.nih.gov/pubmed/15122711",
"http://www.ncbi.nlm.nih.gov/pubmed/7897414",
"http://www.ncbi.nlm.nih.gov/pubmed/1861211",
"http://www.ncbi.nlm.nih.gov/pubmed/21451360",
"http://www.ncbi.nlm.nih.gov/pubmed/22000311"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22006280",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 78,
"text": "Alpers-Huttenlocher syndrome (AHS) is a very rare autosomal recessive disorder"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16181814",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 117,
"text": "Alpers syndrome is an autosomal recessive mitochondrial DNA depletion disorder that affects children and young adults"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15122711",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 321,
"text": "Alpers' syndrome is a fatal neurogenetic disorder first described more than 70 years ago. It is an autosomal recessive, developmental mitochondrial DNA depletion disorder characterized by deficiency in mitochondrial DNA polymerase gamma (POLG) catalytic activity, refractory seizures, neurodegeneration, and liver disease"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7897414",
"endSection": "abstract",
"offsetInBeginSection": 448,
"offsetInEndSection": 883,
"text": "Histopathological findings in both patients ((a) chronic hepatitis with prominent bile duct proliferation, fatty change, and fibrosis; (b) in the brain a patchy destruction of the cerebral cortex, predominantly involving striate cortex) were characteristic of progressive neuronal degeneration of childhood with liver disease--Alpers-Huttenlocher syndrome--a rare autosomal recessive disorder usually seen in infants and young children"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7897414",
"endSection": "abstract",
"offsetInBeginSection": 881,
"offsetInEndSection": 1317,
"text": "Histopathological findings in both patients ((a) chronic hepatitis with prominent bile duct proliferation, fatty change, and fibrosis; (b) in the brain a patchy destruction of the cerebral cortex, predominantly involving striate cortex) were characteristic of progressive neuronal degeneration of childhood with liver disease--Alpers-Huttenlocher syndrome--a rare autosomal recessive disorder usually seen in infants and young children."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22000311",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 83,
"text": "Alpers syndrome is a rare autosomal recessive hepatocerebral degenerative disorder."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21451360",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 163,
"text": "Alpers disease is a recessive mitochondrial disorder caused by mutations in POLG1 and characterized primarily by progressive neurological and hepatic degeneration."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7897414",
"endSection": "abstract",
"offsetInBeginSection": 881,
"offsetInEndSection": 1317,
"text": "Histopathological findings in both patients ((a) chronic hepatitis with prominent bile duct proliferation, fatty change, and fibrosis; (b) in the brain a patchy destruction of the cerebral cortex, predominantly involving striate cortex) were characteristic of progressive neuronal degeneration of childhood with liver disease--Alpers-Huttenlocher syndrome--a rare autosomal recessive disorder usually seen in infants and young children."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16181814",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 118,
"text": "Alpers syndrome is an autosomal recessive mitochondrial DNA depletion disorder that affects children and young adults."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21451360",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 163,
"text": "Alpers disease is a recessive mitochondrial disorder caused by mutations in POLG1 and characterized primarily by progressive neurological and hepatic degeneration."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/1861211",
"endSection": "abstract",
"offsetInBeginSection": 1596,
"offsetInEndSection": 1829,
"text": "We conclude that Alpers disease can be a cause of rapidly progressive liver failure in early childhood. Although the cause of this autosomal recessive disease is not known, it does not appear to be related to peroxisomal dysfunction."
}
]
| 5 | BioASQ-training5b | []
| []
| 5718a69e7de986d80d00000a | 24 |
yesno | Are there interactomes available for POU5F1 and SOX2? | ['yes'] | [
"yes"
]
| ['Yes. Long-range chromosomal interactions on putative enhancers of POU5F1 and SOX2 genes in human embryonic stem cells (hESCs) have been assayed using 4C-Seq technique. Their frequent interacting regions mainly overlap with early DNA replication domains. The interactomes are associated with active histone marks and enriched with 5-hydroxymethylcytosine sites.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/23549118"
]
| [
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23549118",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 76,
"text": "The interactomes of POU5F1 and SOX2 enhancers in human embryonic stem cells."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23549118",
"endSection": "abstract",
"offsetInBeginSection": 154,
"offsetInEndSection": 817,
"text": "We assayed long-range chromosomal interactions on putative enhancers of POU5F1 and SOX2 genes in human embryonic stem cells (hESCs) using 4C-Seq technique. We discovered that their frequent interacting regions mainly overlap with early DNA replication domains. The interactomes are associated with active histone marks and enriched with 5-hydroxymethylcytosine sites. In hESCs, genes within the interactomes have elevated expression. Additionally, some genes associated with the POU5F1 enhancer contribute to pluripotency. Binding sites for multiple DNA binding proteins, including ATF3, CTCF, GABPA, JUND, NANOG, RAD21 and YY1, are enriched in both interactomes."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23549118",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 76,
"text": "The interactomes of POU5F1 and SOX2 enhancers in human embryonic stem cells."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23549118",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 76,
"text": "The interactomes of POU5F1 and SOX2 enhancers in human embryonic stem cells."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23549118",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 76,
"text": "The interactomes of POU5F1 and SOX2 enhancers in human embryonic stem cells."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23549118",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 76,
"text": "The interactomes of POU5F1 and SOX2 enhancers in human embryonic stem cells."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23549118",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 76,
"text": "The interactomes of POU5F1 and SOX2 enhancers in human embryonic stem cells."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23549118",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 76,
"text": "The interactomes of POU5F1 and SOX2 enhancers in human embryonic stem cells."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23549118",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 76,
"text": "The interactomes of POU5F1 and SOX2 enhancers in human embryonic stem cells."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23549118",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 76,
"text": "The interactomes of POU5F1 and SOX2 enhancers in human embryonic stem cells."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23549118",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 76,
"text": "The interactomes of POU5F1 and SOX2 enhancers in human embryonic stem cells."
}
]
| 5 | BioASQ-training5b | [
"http://www.uniprot.org/uniprot/PO5F1_HUMAN",
"http://www.uniprot.org/uniprot/PO5F1_MACMU",
"http://www.uniprot.org/uniprot/PO5F1_DANRE",
"http://www.uniprot.org/uniprot/PO5F1_PIG",
"http://www.uniprot.org/uniprot/PO5F1_PANTR",
"http://www.uniprot.org/uniprot/PO5F1_BOVIN",
"http://www.uniprot.org/uniprot/PO5F1_MOUSE",
"http://www.uniprot.org/uniprot/SOX2_CHICK",
"http://www.uniprot.org/uniprot/SOX2_DANRE",
"http://www.uniprot.org/uniprot/NANOG_HUMAN",
"http://www.uniprot.org/uniprot/NANOG_MUSMM",
"http://www.uniprot.org/uniprot/NANOG_BOVIN",
"http://www.uniprot.org/uniprot/NANOG_PANTR",
"http://www.uniprot.org/uniprot/NANOG_MACFA"
]
| []
| 56c85f675795f9a73e000013 | 25 |
yesno | Is there any linear-time and linear-space algorithm for the computation of avoided words in biological sequences? | ['yes'] | [
"yes"
]
| ['Yes. There is a linear-time and linear-space algorithm for the computation of avoided words of length k in a given sequence x.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/28293277"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28293277",
"endSection": "abstract",
"offsetInBeginSection": 1526,
"offsetInEndSection": 1979,
"text": "The systematic search for avoided words is particularly useful for biological sequence analysis. We present a linear-time and linear-space algorithm for the computation of avoided words of lengthkin a given sequencex. We suggest a modification to this algorithm so that it computes all avoided words ofx, irrespective of their length, within the same time complexity. We also present combinatorial results with regards to avoided words and absent words."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28293277",
"endSection": "abstract",
"offsetInBeginSection": 365,
"offsetInEndSection": 468,
"text": "We present a linear-time and linear-space algorithm for the computation of avoided words of length <br>"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28293277",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 364,
"text": "<b>BACKGROUND</b>: The deviation of the observed frequency of a word <br><b>RESULTS</b>: In this article, we propose an [Formula: see text]-time and [Formula: see text]-space algorithm to compute all [Formula: see text]-avoided words of length <br><b>CONCLUSIONS</b>: The systematic search for avoided words is particularly useful for biological sequence analysis."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28293277",
"endSection": "abstract",
"offsetInBeginSection": 338,
"offsetInEndSection": 436,
"text": "We present a linear-time and linear-space algorithm for the computation of avoided words of length"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28293277",
"endSection": "abstract",
"offsetInBeginSection": 1647,
"offsetInEndSection": 1770,
"text": "We present a linear-time and linear-space algorithm for the computation of avoided words of length k in a given sequence x."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28293277",
"endSection": "abstract",
"offsetInBeginSection": 608,
"offsetInEndSection": 943,
"text": "Hence, computing all such words naïvely can be a very time-consuming procedure, in particular for large k. RESULTS In this article, we propose an [Formula: see text]-time and [Formula: see text]-space algorithm to compute all [Formula: see text]-avoided words of length k in a given sequence of length n over a fixed-sized alphabet."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28293277",
"endSection": "abstract",
"offsetInBeginSection": 944,
"offsetInEndSection": 1154,
"text": "We also present a time-optimal [Formula: see text]-time algorithm to compute all [Formula: see text]-avoided words (of any length) in a sequence of length n over an integer alphabet of size [Formula: see text]."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28293277",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 1867,
"text": "the deviation of the observed frequency of a word from its expected frequency in a given sequence is used to determine whether or not the word is this concept is particularly useful in dna linguistic analysis the value of the deviation of denoted by formula see text effectively characterises the extent of a word by its edge contrast in the context in which it occurs a word of length formula see text is a formula see text avoided word in if formula see text for a given threshold formula see text notice that such a word may be completely from hence computing all such words naïvely can be a very time consuming procedure in particular for large in this article we propose an formula see text time and formula see text space algorithm to compute all formula see text avoided words of length in a given sequence of length over a fixed sized alphabet we also present a time optimal formula see text time algorithm to compute all formula see text avoided words of any length in a sequence of length over an integer alphabet of size formula see text in addition we provide a tight asymptotic upper bound for the number of formula see text avoided words over an integer alphabet and the expected length of the longest one we make available an implementation of our algorithm experimental results using both real and synthetic data show the efficiency and applicability of our implementation in biological sequence analysis the systematic search for avoided words is particularly useful for biological sequence analysis we present a linear time and linear space algorithm for the computation of avoided words of length in a given sequence we suggest a modification to this algorithm so that it computes all avoided words of irrespective of their length within the same time complexity we also present combinatorial results with regards to avoided words and absent words."
}
]
| 11 | BioASQ-training11b | null | null | 5a6d022ab750ff445500002a | 26 |
yesno | Is SARS virus interacting with ACE2 encoded protein? | ['yes'] | [
"yes"
]
| ['Yes,\nThe infection of target cells by the SARS CoV is mediated through the interaction of the viral Spike (S) protein (1255 amino acids) and its cellular receptor, angiotensin-converting enzyme 2 (ACE2).'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/26487711",
"http://www.ncbi.nlm.nih.gov/pubmed/27082314",
"http://www.ncbi.nlm.nih.gov/pubmed/29190287",
"http://www.ncbi.nlm.nih.gov/pubmed/30356097",
"http://www.ncbi.nlm.nih.gov/pubmed/30102747"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30102747",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 286,
"text": "The trimeric SARS coronavirus (SARS-CoV) surface spike (S) glycoprotein consisting of three S1-S2 heterodimers binds the cellular receptor angiotensin-converting enzyme 2 (ACE2) and mediates fusion of the viral and cellular membranes through a pre- to postfusion conformation transition"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30356097",
"endSection": "abstract",
"offsetInBeginSection": 133,
"offsetInEndSection": 369,
"text": "The viral spike glycoprotein (S) utilizes angiotensin-converting enzyme 2 (ACE2) as a host protein receptor and mediates fusion of the viral and host membranes, making S essential to viral entry into host cells and host species tropism."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29190287",
"endSection": "abstract",
"offsetInBeginSection": 1538,
"offsetInEndSection": 1690,
"text": "Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27082314",
"endSection": "abstract",
"offsetInBeginSection": 837,
"offsetInEndSection": 1145,
"text": "Angiotensin-converting enzyme 2 (ACE2), a relatively new member of the RAS, has drawn extensive attention since 2003, because of the findings that ACE2 is the receptor for SARS Corona virus and that maintenance of normal ACE2 levels in the lung is beneficial for the host to combat inflammatory lung disease."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26487711",
"endSection": "abstract",
"offsetInBeginSection": 147,
"offsetInEndSection": 345,
"text": "The infection of target cells by the SARS CoV is mediated through the interaction of the viral Spike (S) protein (1255 amino acids) and its cellular receptor, angiotensin-converting enzyme 2 (ACE2)."
}
]
| 11 | BioASQ-training11b | null | null | 5e80675d835f4e4777000026 | 27 |
yesno | Could BRCA gene test used for breast and ovarian cancer risk? | ['yes'] | [
"yes"
]
| ['Yes, BRCA gene test could be used for breast and ovarian cancer risk, as female BRCA1 and BRCA2 mutations are significantly associated with risk of developing breast and ovarian cancers.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/24698998",
"http://www.ncbi.nlm.nih.gov/pubmed/20221693",
"http://www.ncbi.nlm.nih.gov/pubmed/18515440",
"http://www.ncbi.nlm.nih.gov/pubmed/17394399",
"http://www.ncbi.nlm.nih.gov/pubmed/21913181",
"http://www.ncbi.nlm.nih.gov/pubmed/17901820",
"http://www.ncbi.nlm.nih.gov/pubmed/26271414",
"http://www.ncbi.nlm.nih.gov/pubmed/27004793",
"http://www.ncbi.nlm.nih.gov/pubmed/19841329",
"http://www.ncbi.nlm.nih.gov/pubmed/20711702",
"http://www.ncbi.nlm.nih.gov/pubmed/24366376",
"http://www.ncbi.nlm.nih.gov/pubmed/26848859",
"http://www.ncbi.nlm.nih.gov/pubmed/26691940",
"http://www.ncbi.nlm.nih.gov/pubmed/17109443",
"http://www.ncbi.nlm.nih.gov/pubmed/25863477",
"http://www.ncbi.nlm.nih.gov/pubmed/24731853",
"http://www.ncbi.nlm.nih.gov/pubmed/23635950",
"http://www.ncbi.nlm.nih.gov/pubmed/12632763",
"http://www.ncbi.nlm.nih.gov/pubmed/18854964",
"http://www.ncbi.nlm.nih.gov/pubmed/9150154",
"http://www.ncbi.nlm.nih.gov/pubmed/23539753",
"http://www.ncbi.nlm.nih.gov/pubmed/20233464",
"http://www.ncbi.nlm.nih.gov/pubmed/18932252",
"http://www.ncbi.nlm.nih.gov/pubmed/27928164",
"http://www.ncbi.nlm.nih.gov/pubmed/20878485",
"http://www.ncbi.nlm.nih.gov/pubmed/17079882",
"http://www.ncbi.nlm.nih.gov/pubmed/26047126",
"http://www.ncbi.nlm.nih.gov/pubmed/25849179",
"http://www.ncbi.nlm.nih.gov/pubmed/16783967",
"http://www.ncbi.nlm.nih.gov/pubmed/27276934",
"http://www.ncbi.nlm.nih.gov/pubmed/25838294",
"http://www.ncbi.nlm.nih.gov/pubmed/26852130",
"http://www.ncbi.nlm.nih.gov/pubmed/19996028",
"http://www.ncbi.nlm.nih.gov/pubmed/26402875",
"http://www.ncbi.nlm.nih.gov/pubmed/16144895",
"http://www.ncbi.nlm.nih.gov/pubmed/22381151",
"http://www.ncbi.nlm.nih.gov/pubmed/27306910",
"http://www.ncbi.nlm.nih.gov/pubmed/27403072",
"http://www.ncbi.nlm.nih.gov/pubmed/23091540",
"http://www.ncbi.nlm.nih.gov/pubmed/26922077",
"http://www.ncbi.nlm.nih.gov/pubmed/24065545",
"http://www.ncbi.nlm.nih.gov/pubmed/17579227",
"http://www.ncbi.nlm.nih.gov/pubmed/10464631",
"http://www.ncbi.nlm.nih.gov/pubmed/23165859",
"http://www.ncbi.nlm.nih.gov/pubmed/22982855",
"http://www.ncbi.nlm.nih.gov/pubmed/24950059",
"http://www.ncbi.nlm.nih.gov/pubmed/22866093",
"http://www.ncbi.nlm.nih.gov/pubmed/19479365",
"http://www.ncbi.nlm.nih.gov/pubmed/19273395",
"http://www.ncbi.nlm.nih.gov/pubmed/27376595",
"http://www.ncbi.nlm.nih.gov/pubmed/27513691",
"http://www.ncbi.nlm.nih.gov/pubmed/24366442",
"http://www.ncbi.nlm.nih.gov/pubmed/25497409",
"http://www.ncbi.nlm.nih.gov/pubmed/12708108",
"http://www.ncbi.nlm.nih.gov/pubmed/11368874",
"http://www.ncbi.nlm.nih.gov/pubmed/16174860",
"http://www.ncbi.nlm.nih.gov/pubmed/23638402",
"http://www.ncbi.nlm.nih.gov/pubmed/25236687",
"http://www.ncbi.nlm.nih.gov/pubmed/21637635",
"http://www.ncbi.nlm.nih.gov/pubmed/23528734",
"http://www.ncbi.nlm.nih.gov/pubmed/23165893",
"http://www.ncbi.nlm.nih.gov/pubmed/22438049",
"http://www.ncbi.nlm.nih.gov/pubmed/16492929",
"http://www.ncbi.nlm.nih.gov/pubmed/26411315",
"http://www.ncbi.nlm.nih.gov/pubmed/22684231",
"http://www.ncbi.nlm.nih.gov/pubmed/24161304",
"http://www.ncbi.nlm.nih.gov/pubmed/25948675"
]
| [
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25838294",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 114,
"text": "Participation of Korean families at high risk for hereditary breast and ovarian cancer in BRCA1/2 genetic testing."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26402875",
"endSection": "abstract",
"offsetInBeginSection": 1412,
"offsetInEndSection": 1645,
"text": "The prevalence of BRCA1/2 mutations in Korean ovarian cancer patients irrespective of the family history was significantly higher than previously reported. Possible founder mutations in Korean ovarian cancer patients were identified."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26402875",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 99,
"text": "Germline Mutations of BRCA1 and BRCA2 in Korean Ovarian Cancer Patients: Finding Founder Mutations."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24950059",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 260,
"text": "The assessment of BRCA1 and BRCA2 coding sequences to identify pathogenic mutations associated with inherited breast/ovarian cancer syndrome has provided a method to identify high-risk individuals, allowing them to seek preventative treatments and strategies. "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24731853",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 129,
"text": "Maximising survival: the main concern of women with hereditary breast and ovarian cancer who undergo genetic testing for BRCA1/2."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24731853",
"endSection": "abstract",
"offsetInBeginSection": 8,
"offsetInEndSection": 342,
"text": " Little is known about how women with hereditary breast and/or ovarian cancer who test positive for a BRCA gene manage the impact of a positive test result on their everyday lives and in the longer term. This study defined the experience and needs of women with hereditary breast and ovarian cancer and a positive BRCA test over time."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24698998",
"endSection": "abstract",
"offsetInBeginSection": 949,
"offsetInEndSection": 1310,
"text": "The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 × 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3))."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23528734",
"endSection": "abstract",
"offsetInBeginSection": 11,
"offsetInEndSection": 193,
"text": "Female BRCA (breast cancer gene)-1 and BRCA-2 mutations are significantly associated with risk of developing breast and ovarian cancers, in turn, associated with female infertility. "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24065545",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 100,
"text": "Large BRCA1 and BRCA2 genomic rearrangements in Polish high-risk breast and ovarian cancer families."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24065545",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 102,
"text": "BRCA1 and BRCA2 are two major genes associated with familial breast and ovarian cancer susceptibility."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24161304",
"endSection": "abstract",
"offsetInBeginSection": 108,
"offsetInEndSection": 276,
"text": "Until 2006, she supervised a diagnostic unit for BRCA gene testing at the Interdisciplinary Center for Hereditary Breast Cancer (Max Delbrück Center, Berlin, Germany). "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23638402",
"endSection": "abstract",
"offsetInBeginSection": 12,
"offsetInEndSection": 218,
"text": "Inherited BRCA gene mutations convey a high risk for breast and ovarian cancer, but current guidelines limit BRCA mutation testing to women with early-onset cancer and relatives of mutation-positive cases. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22982855",
"endSection": "abstract",
"offsetInBeginSection": 11,
"offsetInEndSection": 162,
"text": "Women who carry a BRCA1 or BRCA2 gene mutation face a risk of developing breast or ovarian cancer at an earlier age than women without such a mutation."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22982855",
"endSection": "abstract",
"offsetInBeginSection": 342,
"offsetInEndSection": 447,
"text": "In 2006, participants were recruited from Web sites for women with breast cancer or BRCA gene mutations. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26852130",
"endSection": "abstract",
"offsetInBeginSection": 12,
"offsetInEndSection": 252,
"text": "About 20 % of hereditary breast cancers are caused by mutations in BRCA1 and BRCA2 genes. Since BRCA1 and BRCA2 mutations may be spread throughout the gene, genetic testing is usually performed by direct sequencing of entire coding regions."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26852130",
"endSection": "abstract",
"offsetInBeginSection": 1662,
"offsetInEndSection": 1765,
"text": "Suggestion of an association between BRCA2 c.7806-2A>G and risk of breast cancer in males has emerged. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27403072",
"endSection": "abstract",
"offsetInBeginSection": 11,
"offsetInEndSection": 221,
"text": "The presence of deleterious mutations in breast cancer (BRCA)-1 or BRCA-2 gene has a decisive influence on the development of various types of neoplasms, such as breast, ovarian, tubal, and peritoneal cancers. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23528734",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 192,
"text": "OBJECTIVE: Female BRCA (breast cancer gene)-1 and BRCA-2 mutations are significantly associated with risk of developing breast and ovarian cancers, in turn, associated with female infertility."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16783967",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 83,
"text": "BRCA1 and BRCA2 genes are responsible for 5-10% of breast and ovarian cancer cases."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12708108",
"endSection": "abstract",
"offsetInBeginSection": 1060,
"offsetInEndSection": 1370,
"text": "She was daughter of a woman, a carrier of BRCA 1 gene mutation, with early onset of breast cancer and positive family history.CONCLUSIONS: BRCA 1 and BRCA 2 gene mutations are of particular importance in the increasing risk of ovarian cancer and early onset of breast cancer as well as some other malignancies."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21913181",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 172,
"text": "BACKGROUND: Women who are diagnosed with a deleterious mutation in either breast cancer (BRCA) gene have a high risk of developing breast and ovarian cancers at young ages."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20221693",
"endSection": "abstract",
"offsetInBeginSection": 384,
"offsetInEndSection": 652,
"text": "We identified AJ individuals with breast and/or ovarian cancer undergoing hereditary breast/ovarian cancer risk assessment since 2006 without evidence of a deleterious mutation on BRCA gene sequencing who were screened for major gene rearrangements in BRCA1 and BRCA2."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26271414",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 98,
"text": "Germline BRCA gene mutations are reportedly associated with hereditary breast and ovarian cancers."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12708108",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 102,
"text": "[Detection and occurrence of BRCA 1 gene mutation in patients with carcinoma of the breast and ovary]."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23091540",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 391,
"text": "We investigated the relationship between BRCA mutations and the distribution of familial cancers other than breast or ovary in high-risk breast cancer patients.PATIENTS WITH BREAST CANCER WHO HAD AT LEAST ONE OF THE FOLLOWING RISK FACTORS WERE ENROLLED: reported family history of breast or ovarian cancer; 40 years of age or younger age at diagnosis; bilateral breast cancer; or male gender"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24366442",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 757,
"text": "Mutations in breast cancer susceptibility genes (BRCA1 and BRCA2) are associated with increased risks for breast, ovarian, and other types of cancer.To review new evidence on the benefits and harms of risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women.MEDLINE and PsycINFO between 2004 and 30 July 2013, the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews from 2004 through the second quarter of 2013, Health Technology Assessment during the fourth quarter of 2012, Scopus, and reference lists.English-language studies about accuracy of risk assessment and benefits and harms of genetic counseling, genetic testing, and interventions to reduce cancer incidence and mortality."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23165859",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 441,
"text": "The objective of this study was to assess the incidence of primary breast cancer (PBC) and contralateral breast cancer (CBC) in patients who had BRCA1/BRCA2-associated epithelial ovarian cancer (OC).From the database of the Rotterdam Family Cancer Clinic, patients who had BRCA-associated OC without a history of unilateral breast cancer (BC) (at risk of PBC; n = 79) or with a history of unilateral BC (at risk of CBC; n = 37) were selected"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21913181",
"endSection": "abstract",
"offsetInBeginSection": 1105,
"offsetInEndSection": 1471,
"text": "Statistically significant earlier ages at diagnosis also were observed within subgroups of BRCA1 and BRCA2 mutations, maternal inheritance, paternal inheritance, breast cancer only, and breast cancer-identified and ovarian cancer-identified families.Breast and ovarian cancers in BRCA mutation carriers appeared to be diagnosed at an earlier age in later generations"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24366376",
"endSection": "abstract",
"offsetInBeginSection": 473,
"offsetInEndSection": 1136,
"text": "The USPSTF also reviewed interventions aimed at reducing the risk for BRCA-related cancer in women with potentially harmful BRCA mutations, including intensive cancer screening, medications, and risk-reducing surgery.This recommendation applies to asymptomatic women who have not been diagnosed with BRCA-related cancer.The USPSTF recommends that primary care providers screen women who have family members with breast, ovarian, tubal, or peritoneal cancer with 1 of several screening tools designed to identify a family history that may be associated with an increased risk for potentially harmful mutations in breast cancer susceptibility genes (BRCA1 or BRCA2)"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21637635",
"endSection": "abstract",
"offsetInBeginSection": 1109,
"offsetInEndSection": 1478,
"text": "If a woman bearing a mutation develops cancer in one breast, her risk of developing cancer in the other breast depends on the particular gene that is mutated and on her age at the onset of disease.About half of all monogenically determined carcinomas of the breast and ovary are due to a mutation in one or the other of the highly penetrant BRCA genes (BRCA1 and BRCA2)"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25849179",
"endSection": "abstract",
"offsetInBeginSection": 689,
"offsetInEndSection": 1070,
"text": "A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk.Mutations of BRCA1 or BRCA2.Breast and ovarian cancer risks.Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24731853",
"endSection": "abstract",
"offsetInBeginSection": 212,
"offsetInEndSection": 450,
"text": "This study defined the experience and needs of women with hereditary breast and ovarian cancer and a positive BRCA test over time.METHODS: A grounded theory approach was taken using qualitative interviews (n = 49) and reflective diaries. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24731853",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 202,
"text": "Little is known about how women with hereditary breast and/or ovarian cancer who test positive for a BRCA gene manage the impact of a positive test result on their everyday lives and in the longer term."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24731853",
"endSection": "abstract",
"offsetInBeginSection": 203,
"offsetInEndSection": 431,
"text": "This study defined the experience and needs of women with hereditary breast and ovarian cancer and a positive BRCA test over time.A grounded theory approach was taken using qualitative interviews (n = 49) and reflective diaries."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27376595",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 206,
"text": "Women with a harmful mutation in the BReast CAncer (BRCA) gene are at significantly increased risk of developing hereditary breast and ovarian cancer (HBOC) during their lifetime, compared to those without."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26848859",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 126,
"text": "Genetic testing for BRCA genes, associated with hereditary breast-ovarian cancer risk, is an accepted cancer control strategy."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27004793",
"endSection": "abstract",
"offsetInBeginSection": 2081,
"offsetInEndSection": 2225,
"text": "Younger patients, those with a family history of breast or ovarian cancer, and those diagnosed more recently were more likely to be BRCA tested."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23635950",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 67,
"text": "Mutations in BRCA genes elevate risk for breast and ovarian cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16144895",
"endSection": "abstract",
"offsetInBeginSection": 1483,
"offsetInEndSection": 2030,
"text": "Observational studies of prophylactic surgeries report reduced risks for breast and ovarian cancer in mutation carriers.No data describe the range of risk associated with BRCA mutations, genetic heterogeneity, and moderating factors; studies conducted in highly selected populations contain biases; and information on adverse effects is incomplete.A primary care approach to screening for inherited breast and ovarian cancer susceptibility has not been evaluated, and evidence is lacking to determine benefits and harms for the general population."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20221693",
"endSection": "abstract",
"offsetInBeginSection": 384,
"offsetInEndSection": 936,
"text": "We identified AJ individuals with breast and/or ovarian cancer undergoing hereditary breast/ovarian cancer risk assessment since 2006 without evidence of a deleterious mutation on BRCA gene sequencing who were screened for major gene rearrangements in BRCA1 and BRCA2. For each proband, the pre-test probability of identifying a deleterious BRCA mutation was estimated using the Myriad II model. We identified 108 affected individuals who underwent large rearrangement testing (80 breast cancer, 19 ovarian cancer, nine both breast and ovarian cancer)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12708108",
"endSection": "abstract",
"offsetInBeginSection": 782,
"offsetInEndSection": 1370,
"text": "Truncated proteins are easily discriminated from full size.RESULTS: Three BRCA 1 gene alterations were identified in the investigated group of women suffering from ovarian or breast cancer. One asymptomatic person--carrier of BRCA 1 gene mutation--was identified in this study. She was daughter of a woman, a carrier of BRCA 1 gene mutation, with early onset of breast cancer and positive family history.CONCLUSIONS: BRCA 1 and BRCA 2 gene mutations are of particular importance in the increasing risk of ovarian cancer and early onset of breast cancer as well as some other malignancies."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26271414",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 207,
"text": "Germline BRCA gene mutations are reportedly associated with hereditary breast and ovarian cancers. Identification of BRCA mutations greatly improves the preventive strategies and management of breast cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21913181",
"endSection": "abstract",
"offsetInBeginSection": 1125,
"offsetInEndSection": 1505,
"text": "Statistically significant earlier ages at diagnosis also were observed within subgroups of BRCA1 and BRCA2 mutations, maternal inheritance, paternal inheritance, breast cancer only, and breast cancer-identified and ovarian cancer-identified families.CONCLUSIONS: Breast and ovarian cancers in BRCA mutation carriers appeared to be diagnosed at an earlier age in later generations."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12708108",
"endSection": "abstract",
"offsetInBeginSection": 782,
"offsetInEndSection": 971,
"text": "Truncated proteins are easily discriminated from full size.RESULTS: Three BRCA 1 gene alterations were identified in the investigated group of women suffering from ovarian or breast cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25863477",
"endSection": "abstract",
"offsetInBeginSection": 1419,
"offsetInEndSection": 1621,
"text": "However, some single risk factors without family histories (early-onset breast cancer, male breast cancer, or multiple organ cancers) may limit the utility of BRCA gene testing in the Korean population."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26047126",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 88,
"text": "BRCA Mutations Increase Fertility in Families at Hereditary Breast/Ovarian Cancer Risk."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19996028",
"endSection": "abstract",
"offsetInBeginSection": 95,
"offsetInEndSection": 279,
"text": "Because infertility is associated with breast and ovarian cancer risks, we hypothesized that the mutations in the BRCA gene may be associated with low response to fertility treatments."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16492929",
"endSection": "abstract",
"offsetInBeginSection": 2358,
"offsetInEndSection": 2491,
"text": "Moreover, in families of breast cancer patients without BRCA mutations, breast cancer risk depends on the patient's age at diagnosis."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17109443",
"endSection": "abstract",
"offsetInBeginSection": 817,
"offsetInEndSection": 991,
"text": "Among the 554 women who underwent genetic testing for BRCA mutation, 78 were found to have a deleterious mutation in the BRCA1 gene, and 54 had a mutation in the BRCA 2 gene."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25236687",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 413,
"text": "Frequent recurrent mutations in the breast and ovarian cancer susceptibility (BRCA) genes BRCA1 and BRCA2 among Hispanics, including a large rearrangement Mexican founder mutation (BRCA1 exon 9-12 deletion [ex9-12del]), suggest that an ancestry-informed BRCA-testing strategy could reduce disparities and promote cancer prevention by enabling economic screening for hereditary breast and ovarian cancer in Mexico."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17901820",
"endSection": "abstract",
"offsetInBeginSection": 529,
"offsetInEndSection": 678,
"text": "Individuals who carry a BRCA gene mutation have increased lifetime risks of developing hereditary breast and ovarian cancer syndrome-related cancers."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27306910",
"endSection": "abstract",
"offsetInBeginSection": 1757,
"offsetInEndSection": 1863,
"text": "BRCA gene mutations have been well described to carry an increased risk of both breast and ovarian cancer."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23539753",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 172,
"text": "Ovarian cancer among 8,005 women from a breast cancer family history clinic: no increased risk of invasive ovarian cancer in families testing negative for BRCA1 and BRCA2."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17109443",
"endSection": "abstract",
"offsetInBeginSection": 1978,
"offsetInEndSection": 2185,
"text": "Women who were BRCA carriers, women who had a history of breast cancer, DCIS, or breast biopsy, or had a family history of ovarian cancer were more likely to have undergone surgery for cancer risk reduction."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10464631",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 138,
"text": "Genetic testing for breast cancer susceptibility became a reality after two cancer predisposition genes, BRCA1 and BRCA2, were identified."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19996028",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 94,
"text": "Germline mutations in BRCA genes are associated with breast and ovarian cancer susceptibility."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23539753",
"endSection": "abstract",
"offsetInBeginSection": 494,
"offsetInEndSection": 690,
"text": "We used person-years at risk to assess ovarian cancer rates in the study population, subdivided by genetic status (BRCA1, BRCA2, BRCA negative, BRCA untested) compared with the general population."
}
]
| 6 | BioASQ-training6b | [
"http://www.disease-ontology.org/api/metadata/DOID:2394",
"http://www.disease-ontology.org/api/metadata/DOID:5683",
"https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019313",
"https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024682"
]
| null | 58a6bce660087bc10a000029 | 28 |
yesno | Is acid alpha-glucosidase the enzyme that causes Pompe disease when mutant? | ['yes'] | [
"yes"
]
| ['Pompe disease is an autosomal recessive genetic disorder characterized by a deficiency of the enzyme acid α-glucosidase (GAA), responsible for degradation of lysosomal glycogen.', 'Pompe disease is an autosomal recessive genetic disorder characterized by a deficiency of the enzyme responsible for degradation of lysosomal glycogen (acid α-glucosidase (GAA))', 'Pompe disease is an autosomal recessive genetic disorder characterized by a deficiency of the enzyme responsible for degradation of lysosomal glycogen (acid α-glucosidase (GAA))', 'Pompe disease is an autosomal recessive genetic disorder characterized by a deficiency of the enzyme responsible for degradation of lysosomal glycogen (acid α-glucosidase (GAA))', 'Pompe disease is an autosomal recessive genetic disorder characterized by a deficiency of the enzyme responsible for degradation of lysosomal glycogen (acid α-glucosidase (GAA))', 'Pompe disease is an autosomal recessive genetic disorder characterized by a deficiency of the enzyme responsible for degradation of lysosomal glycogen (acid α-glucosidase (GAA))'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/26029718",
"http://www.ncbi.nlm.nih.gov/pubmed/25217571",
"http://www.ncbi.nlm.nih.gov/pubmed/25256446",
"http://www.ncbi.nlm.nih.gov/pubmed/25786784",
"http://www.ncbi.nlm.nih.gov/pubmed/17805474",
"http://www.ncbi.nlm.nih.gov/pubmed/19343043",
"http://www.ncbi.nlm.nih.gov/pubmed/8552676",
"http://www.ncbi.nlm.nih.gov/pubmed/19862843",
"http://www.ncbi.nlm.nih.gov/pubmed/15639117",
"http://www.ncbi.nlm.nih.gov/pubmed/9505277",
"http://www.ncbi.nlm.nih.gov/pubmed/6442343",
"http://www.ncbi.nlm.nih.gov/pubmed/9668092",
"http://www.ncbi.nlm.nih.gov/pubmed/19775921",
"http://www.ncbi.nlm.nih.gov/pubmed/20206419",
"http://www.ncbi.nlm.nih.gov/pubmed/18648322",
"http://www.ncbi.nlm.nih.gov/pubmed/17095274",
"http://www.ncbi.nlm.nih.gov/pubmed/8935410",
"http://www.ncbi.nlm.nih.gov/pubmed/14643388",
"http://www.ncbi.nlm.nih.gov/pubmed/11468225",
"http://www.ncbi.nlm.nih.gov/pubmed/16702882",
"http://www.ncbi.nlm.nih.gov/pubmed/25036864",
"http://www.ncbi.nlm.nih.gov/pubmed/12409258",
"http://www.ncbi.nlm.nih.gov/pubmed/15585405",
"http://www.ncbi.nlm.nih.gov/pubmed/11906",
"http://www.ncbi.nlm.nih.gov/pubmed/9883081",
"http://www.ncbi.nlm.nih.gov/pubmed/19371716"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26029718",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 177,
"text": "Pompe disease is an autosomal recessive genetic disorder characterized by a deficiency of the enzyme responsible for degradation of lysosomal glycogen (acid α-glucosidase (GAA))"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25217571",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 156,
"text": "Pompe disease is a systemic metabolic disorder characterized by lack of acid-alpha glucosidase (GAA) resulting in ubiquitous lysosomal glycogen accumulation"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25256446",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 121,
"text": "Pompe disease is an autosomal recessive myopathic disorder caused by the deficiency of lysosomal acid α-glucosidase (GAA)"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25786784",
"endSection": "abstract",
"offsetInBeginSection": 14,
"offsetInEndSection": 142,
"text": "Acid α-glucosidase deficiency, that is, Pompe disease, is a glycogenosis for which enzyme replacement therapy (ERT) is available"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19343043",
"endSection": "abstract",
"offsetInBeginSection": 628,
"offsetInEndSection": 841,
"text": "The analysis revealed that the amino acid substitutions causing a processing or transport defect responsible for Pompe disease were widely spread over all of the five domains comprising the acid alpha-glucosidase."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20206419",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 121,
"text": "Pompe disease is a lysosomal storage disease (LSD) caused by a deficiency in the lysosomal enzyme acid alpha-glucosidase."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17095274",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 240,
"text": "Glycogen storage disease type II (GSDII; Pompe disease or acid maltase deficiency) is an autosomal recessive disorder caused by lysosomal acid alpha-glucosidase (AalphaGlu) deficiency and manifests predominantly as skeletal muscle weakness."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17805474",
"endSection": "abstract",
"offsetInBeginSection": 1571,
"offsetInEndSection": 1742,
"text": "Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/6442343",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 171,
"text": "The nature of mutant acid alpha-glucosidase (AAG) in muscle was studied in 6 patients with Pompe disease, consisting of 2 each of the infantile, childhood and adult types."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18648322",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 102,
"text": "Pompe disease (glycogen storage disease II) is caused by mutations in the acid alpha-glucosidase gene."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14643388",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 231,
"text": "Glycogen storage disease type II (Pompe disease) is inherited by autosomal recessive transmission and caused by a deficiency of acid alpha-glucosidase (GAA), resulting in impaired degradation and lysosomal accumulation of glycogen."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19862843",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 126,
"text": "Pompe disease is a lysosomal storage disorder (LSD) caused by mutations in the gene that encodes acid alpha-glucosidase (GAA)."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/6442343",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 111,
"text": "Demonstration of acid alpha-glucosidase in different types of Pompe disease by use of an immunochemical method."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9505277",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 156,
"text": "Acid alpha-glucosidase (GAA) deficiency causes Pompe disease, a lethal lysosomal glycogen storage disease for which no effective treatment currently exists."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19775921",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 115,
"text": "Deficiency of acid alpha glucosidase (GAA) causes Pompe disease, which is usually fatal if onset occurs in infancy."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16702882",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 148,
"text": "Ambulatory electrocardiogram analysis in infants treated with recombinant human acid alpha-glucosidase enzyme replacement therapy for Pompe disease."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17805474",
"endSection": "abstract",
"offsetInBeginSection": 1571,
"offsetInEndSection": 1742,
"text": "Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/6442343",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 171,
"text": "The nature of mutant acid alpha-glucosidase (AAG) in muscle was studied in 6 patients with Pompe disease, consisting of 2 each of the infantile, childhood and adult types."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16702882",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 84,
"text": "Infantile Pompe disease is caused by deficiency of lysosomal acid alpha-glucosidase."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11468225",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 103,
"text": "Determination of acid alpha-glucosidase activity in blood spots as a diagnostic test for Pompe disease."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/6442343",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 111,
"text": "Demonstration of acid alpha-glucosidase in different types of Pompe disease by use of an immunochemical method."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25036864",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 202,
"text": "The pharmacological chaperone AT2220 increases the specific activity and lysosomal delivery of mutant acid alpha-glucosidase, and promotes glycogen reduction in a transgenic mouse model of Pompe disease"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17805474",
"endSection": "abstract",
"offsetInBeginSection": 1407,
"offsetInEndSection": 1577,
"text": "Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12409258",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 153,
"text": "Glycogen stored in skeletal but not in cardiac muscle in acid alpha-glucosidase mutant (Pompe) mice is highly resistant to transgene-encoded human enzyme"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12409258",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 306,
"text": "Although many lysosomal disorders are corrected by a small amount of the missing enzyme, it has been generally accepted that 20-30% of normal acid alpha-glucosidase (GAA) activity, provided by gene or enzyme replacement therapy, would be required to reverse the myopathy and cardiomyopathy in Pompe disease"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/6442343",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 170,
"text": "The nature of mutant acid alpha-glucosidase (AAG) in muscle was studied in 6 patients with Pompe disease, consisting of 2 each of the infantile, childhood and adult types"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9668092",
"endSection": "abstract",
"offsetInBeginSection": 164,
"offsetInEndSection": 457,
"text": "As in the severe human infantile disease (Pompe Syndrome), mice homozygous for disruption of the acid alpha-glucosidase gene (6(neo)/6(neo)) lack enzyme activity and begin to accumulate glycogen in cardiac and skeletal muscle lysosomes by 3 weeks of age, with a progressive increase thereafter"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8935410",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 116,
"text": "Glycogen-storage disease type II, Pompe disease, is caused by the deficiency of acid alpha-D-glucosidase in lysosome"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18648322",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 101,
"text": "Pompe disease (glycogen storage disease II) is caused by mutations in the acid alpha-glucosidase gene"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14643388",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 230,
"text": "Glycogen storage disease type II (Pompe disease) is inherited by autosomal recessive transmission and caused by a deficiency of acid alpha-glucosidase (GAA), resulting in impaired degradation and lysosomal accumulation of glycogen"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12409258",
"endSection": "title",
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"text": "Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase. "
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"text": "Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease."
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"text": "We describe an improved method for detecting deficiency of the acid hydrolase, alpha-1,4-glucosidase in leukocytes, the enzyme defect in glycogen storage disease Type II (Pompe disease)."
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"text": "Acid alpha-glucosidase (GAA) deficiency causes Pompe disease,"
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"text": " Infantile Pompe disease is caused by deficiency of lysosomal acid alpha-glucosidase. Trials with recombinant human acid alpha-glucosidase enzyme replacement therapy (ERT) show a decrease in left ventricular mass and improved function."
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"text": " Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase. Due to virtual absence of acid alpha-glucosidase, patients with classical infantile Pompe disease develop progressive cardiomyopathy, skeletal muscle weakness and respiratory insufficiency leading to death in early infancy."
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"text": "The nature of mutant acid alpha-glucosidase (AAG) in muscle was studied in 6 patients with Pompe disease,"
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"text": " Pompe disease is a lysosomal storage disorder (LSD) caused by mutations in the gene that encodes acid alpha-glucosidase (GAA). Recently, small molecule pharmacological chaperones have been shown to increase protein stability and cellular levels for mutant lysosomal enzymes and have emerged as a new therapeutic strategy for the treatment of LSDs."
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"text": "Glycogen-storage disease type II, Pompe disease, is caused by the deficiency of acid alpha-D-glucosidase in lysosome."
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"text": "Infantile Pompe disease is a fatal genetic muscle disorder caused by a deficiency of acid alpha-glucosidase, a glycogen-degrading lysosomal enzyme."
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]
| 5 | BioASQ-training5b | []
| []
| 572099930fd6f91b6800000f | 29 |
yesno | Has ubrogepant entered clinical phase III trials? | ['yes'] | [
"yes"
]
| ['Yes, ubrogepant has entered phase III trials.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/32011192",
"http://www.ncbi.nlm.nih.gov/pubmed/31758661",
"http://www.ncbi.nlm.nih.gov/pubmed/32648856"
]
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"text": "Ubrogepant (MK-1602) is a novel, oral, calcitonin gene-related peptide receptor antagonist in clinical development with positive phase III outcomes for acute treatment of migraine."
},
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"text": "A population pharmacokinetic model describing the effect of formulations was included in the E-R simulation framework to assess potential dose implications of a formulation switch from phase II to phase III. "
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"text": "The understanding of E-R helped support the dose selection for the phase III clinical trials."
},
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"text": "The CGRP receptor antagonist ubrogepant, also known as MK-1602, has been recently evaluated in phase III clinical trials for clinical efficacy and long-term safety as an abortive migraine treatment."
},
{
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"text": "Two pivotal phase III clinical trials (ACHIEVE I and ACHIEVE II) demonstrated effectiveness and safety of ubrogepant in acute migraine attacks."
}
]
| 11 | BioASQ-training11b | null | null | 6026db1f1cb411341a0000cf | 30 |
yesno | Is depression associated with poor prognosis of brain tumor patients? | ['yes'] | [
"yes"
]
| ['Yes. In brain tumor patients depression is associated with shorter survival and worse functional outcomes.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/16304988",
"http://www.ncbi.nlm.nih.gov/pubmed/16960653",
"http://www.ncbi.nlm.nih.gov/pubmed/15918939",
"http://www.ncbi.nlm.nih.gov/pubmed/15072475"
]
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"text": "Before surgery 27 patients (35%) had BDI scores indicating the presence of depression. These scores were significantly higher in patients with a history of depression (p = 0.017) and in those with a lower functional outcome (p = 0.015)."
},
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"text": "A lower functional status (KPS score < or = 70) in patients was significantly associated with high depression scores at the 3-month (p = 0.000) and 1-year (p = 0.005) assessments."
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"text": "At all follow-ups, depressed low-grade glioma patients had a significantly shorter survival time, 3.3-5.8 years, compared to non-depressed low-grade glioma patients, 10.0-11.7 years."
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"text": "The results suggest that depression and decreased QOL among low-grade glioma patients is related to shorter survival at long-term follow-up."
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/15918939",
"endSection": "sections.0",
"offsetInBeginSection": 11,
"offsetInEndSection": 143,
"text": "The adverse impact of depression in relation to survival among cancer patients is currently a subject of great interest in research."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15918939",
"endSection": "sections.0",
"offsetInBeginSection": 1193,
"offsetInEndSection": 1388,
"text": "In the subgroup of patients with low-grade gliomas, depressive patients had a significantly shorter survival time compared with nondepressive subjects (P = 0.031, Kaplan-Meier survival analysis)."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15918939",
"endSection": "sections.0",
"offsetInBeginSection": 1731,
"offsetInEndSection": 1848,
"text": "Preoperative depression seemed to be a significant prognostic factor for worse survival in low-grade glioma patients."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15072475",
"endSection": "sections.0",
"offsetInBeginSection": 1075,
"offsetInEndSection": 1244,
"text": "Major depressive disorder was marginally associated with outcomes, while surgical interventions and radiotherapy did not show strong associations with test performances."
}
]
| 5 | BioASQ-training5b | [
"http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001932",
"http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011379",
"http://www.disease-ontology.org/api/metadata/DOID:1319",
"http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003863",
"http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016019",
"http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017063"
]
| null | 514cc8dcd24251bc05000066 | 32 |
yesno | Does silencing of SRRM4 inhibit tumor growth across cancers? | ['no'] | [
"no"
]
| ['No, silencing of SRRM4 promotes tumor growth across cancers.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/33621242"
]
| [
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33621242",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 91,
"text": "Silencing of SRRM4 suppresses microexon inclusion and promotes tumor growth across cancers."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33621242",
"endSection": "abstract",
"offsetInBeginSection": 1029,
"offsetInEndSection": 1683,
"text": "We show that this silencing is favorable for tumor growth, as decreased SRRM4 expression in tumors is correlated with an increase in mitotic gene expression, and up-regulation of SRRM4 in cancer cell lines dose-dependently inhibits proliferation in vitro and in a mouse xenograft model. Further, this proliferation inhibition is accompanied by induction of neural-like expression and splicing patterns in cancer cells, suggesting that SRRM4 expression shifts the cell state away from proliferation and toward differentiation. We therefore conclude that SRRM4 acts as a proliferation brake, and tumors gain a selective advantage by cutting off this brake."
}
]
| 12 | BioASQ-training12b | null | null | 63f9cdcc33942b094c000013 | 33 |
yesno | Has Denosumab (Prolia) been approved by FDA? | ['yes'] | [
"yes"
]
| Yes, Denosumab was approved by the FDA in 2010. | [
"http://www.ncbi.nlm.nih.gov/pubmed/24316116",
"http://www.ncbi.nlm.nih.gov/pubmed/24308016",
"http://www.ncbi.nlm.nih.gov/pubmed/24126422",
"http://www.ncbi.nlm.nih.gov/pubmed/24114694",
"http://www.ncbi.nlm.nih.gov/pubmed/23956508",
"http://www.ncbi.nlm.nih.gov/pubmed/23759273",
"http://www.ncbi.nlm.nih.gov/pubmed/23757624",
"http://www.ncbi.nlm.nih.gov/pubmed/23652187",
"http://www.ncbi.nlm.nih.gov/pubmed/23367751",
"http://www.ncbi.nlm.nih.gov/pubmed/22716221",
"http://www.ncbi.nlm.nih.gov/pubmed/22826702",
"http://www.ncbi.nlm.nih.gov/pubmed/22540167",
"http://www.ncbi.nlm.nih.gov/pubmed/22074657",
"http://www.ncbi.nlm.nih.gov/pubmed/21942303",
"http://www.ncbi.nlm.nih.gov/pubmed/21785279",
"http://www.ncbi.nlm.nih.gov/pubmed/21470540",
"http://www.ncbi.nlm.nih.gov/pubmed/21208140",
"http://www.ncbi.nlm.nih.gov/pubmed/21170699",
"http://www.ncbi.nlm.nih.gov/pubmed/21129866",
"http://www.ncbi.nlm.nih.gov/pubmed/21113693",
"http://www.ncbi.nlm.nih.gov/pubmed/20811384"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24316116",
"endSection": "abstract",
"offsetInBeginSection": 12,
"offsetInEndSection": 177,
"text": "Denosumab is a RANK-ligand antibody that was approved by the FDA in 2010 for the prevention of skeletal fractures in patients with bone metastases from solid tumors."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24316116",
"endSection": "abstract",
"offsetInBeginSection": 776,
"offsetInEndSection": 1261,
"text": " The authors present the imaging findings and technical report of an attempted percutaneous vertebroplasty in the only patient found to be actively under treatment with denosumab after a retrospective review of the databank of patients with pathological fractures referred to the Department Radiology of the Ohio State University for percutaneous vertebroplasty (a total sample of 20 patients) since the FDA approval of denosumab (November 2010) until June of 2013 (a 30-month period)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24308016",
"endSection": "abstract",
"offsetInBeginSection": 601,
"offsetInEndSection": 769,
"text": "On the basis of this data, the FDA approved denosumab for the treatment of patients whose GCTB is unresectable, or when surgery is likely to result in severe morbidity."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24126422",
"endSection": "abstract",
"offsetInBeginSection": 485,
"offsetInEndSection": 816,
"text": "Denosumab (Prolia®) is a fully human monoclonal antibody for RANKL, which selectively inhibits osteoclastogenesis, being recently approved for the treatment of postmenopausal osteoporosis in women at a high or increased risk of fracture by the FDA in the United Sates and by the European Medicines Agency in Europe since June 2010."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24114694",
"endSection": "abstract",
"offsetInBeginSection": 782,
"offsetInEndSection": 999,
"text": "Recent phase II clinical trials with denosumab in skeletally mature adolescents over age 12 years and adults with GCTB, have shown both safety and efficacy, leading to its accelerated US FDA approval on 13 June 2013. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23956508",
"endSection": "abstract",
"offsetInBeginSection": 746,
"offsetInEndSection": 1016,
"text": "Zoledronic acid (ZA), an intravenously administered bisphosphonate, and Denosumab, a subcutaneously administered inhibitor of nuclear factor B ligand (RANKL), have already been approved by Food and Drug Administration (FDA) for their use in treatment of bone metastases."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23759273",
"endSection": "abstract",
"offsetInBeginSection": 736,
"offsetInEndSection": 970,
"text": "These results led to the approval of denosumab by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA), for the prevention of SREs in adults with bone metastases from solid tumors, including breast cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23757624",
"endSection": "abstract",
"offsetInBeginSection": 1070,
"offsetInEndSection": 1210,
"text": "Alendronate, risedronate, zoledronic acid, denosumab, and teriparatide are Food and Drug Administration (FDA)-approved therapeutic options. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23652187",
"endSection": "abstract",
"offsetInBeginSection": 997,
"offsetInEndSection": 1196,
"text": "Several of these therapies have recently been approved by the FDA to treat bone cancer pain (bisphosphonates, denosumab) and others are currently being evaluated in human clinical trials (tanezumab)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23367751",
"endSection": "abstract",
"offsetInBeginSection": 892,
"offsetInEndSection": 1086,
"text": "A fourth agent, denosumab (bone targeted therapy) was also recently approved by the FDA for patients with bone metastasis after showing a reduction in the occurrence of skeletal-related events. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22716221",
"endSection": "abstract",
"offsetInBeginSection": 530,
"offsetInEndSection": 968,
"text": "AHRQ published an updated review in March 2012 that summarized the benefits and risks of osteoporosis medications in treatment and prevention of osteoporosis, including bisphosphonates (aledronate, risedronate, ibandronate, zoledronic acid), parathyroid hormone, teriparatide, calcitonin, estrogens (for prevention in postmenopausal women), selective estrogen receptor modulators (raloxifene), and denosumab(approved by the FDA in 2010). "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22826702",
"endSection": "abstract",
"offsetInBeginSection": 748,
"offsetInEndSection": 1029,
"text": "Four new drugs have received U.S. Food and Drug Administration (FDA)-approval in 2010 and 2011: sipuleucel-T, an immunotherapeutic agent; cabazitaxel, a novel microtubule inhibitor; abiraterone acetate, a new androgen biosynthesis inhibitor; and denosumab, a bone-targeting agent. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22540167",
"endSection": "abstract",
"offsetInBeginSection": 170,
"offsetInEndSection": 326,
"text": "Recently, the US FDA and the EMA approved denosumab (a fully human monoclonal antibody) to treat skeletal-related events in bone-metastatic prostate cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22074657",
"endSection": "abstract",
"offsetInBeginSection": 1023,
"offsetInEndSection": 1260,
"text": "In addition to these new and emerging therapeutic agents, denosumab was approved for the prevention of skeletal complications in patients with bone metastases due to solid tumor malignancies, providing an alternative to zoledronic acid. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21942303",
"endSection": "abstract",
"offsetInBeginSection": 686,
"offsetInEndSection": 798,
"text": "Recently, denosumab was FDA-approved for prevention of SREs in patients with bone metastases from solid tumors. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21785279",
"endSection": "abstract",
"offsetInBeginSection": 366,
"offsetInEndSection": 604,
"text": "In the 2010s to date, an additional 3 antibodies (denosumab, belimumab, ipilimumab) have been approved and one antibody-drug conjugate (brentuximab vedotin) is undergoing regulatory review and may be approved in the US by August 30, 2011."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21470540",
"endSection": "abstract",
"offsetInBeginSection": 406,
"offsetInEndSection": 562,
"text": "We also review the evidence supporting the FDA's approval of denosumab (bone-targeted therapy) as a treatment option for men with CRPC and bony metastases. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21208140",
"endSection": "abstract",
"offsetInBeginSection": 368,
"offsetInEndSection": 546,
"text": " It has been approved for clinical use by the FDA in the US and by the European Medicines Agency in Europe since June 2010 (trade name Prolia(™), Amgen, Thousand Oaks, CA, USA). "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21170699",
"endSection": "abstract",
"offsetInBeginSection": 147,
"offsetInEndSection": 363,
"text": "The fully human monoclonal antibody denosumab (Prolia(®)) has been recently approved by the European Medical Agency (EMEA) and the Food and Drug Administration (FDA) for the treatment of postmenopausal osteoporosis. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21129866",
"endSection": "abstract",
"offsetInBeginSection": 1321,
"offsetInEndSection": 1400,
"text": "Raloxifene and denosumab are only FDA approved for postmenopausal osteoporosis."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21113693",
"endSection": "abstract",
"offsetInBeginSection": 708,
"offsetInEndSection": 936,
"text": "The new antiresorptive drug, denosumab, although FDA-approved only for postmenopausal women, has been shown in a study of men on ADT to increase bone density in spine, hip, and forearm and decrease vertebral fractures on x-ray. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20811384",
"endSection": "abstract",
"offsetInBeginSection": 519,
"offsetInEndSection": 665,
"text": " Since then, an additional six human mAbs have received FDA approval: panitumumab, golimumab, canakinumab, ustekinumab, ofatumumab and denosumab. "
}
]
| 5 | BioASQ-training5b | [
"http://www.biosemantics.org/jochem#4268082"
]
| [
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},
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| 52bf1db603868f1b06000011 | 35 |
yesno | Is yeast fbp1 affected by glucose starvation stress? | ['yes'] | [
"yes"
]
| ['The chromatin configuration is altered into an accessible state within 290\u2009bp downstream from the initiation site of metabolic-stress-induced lncRNAs (mlonRNAs) in the promoter of the fission yeast fbp1 gene, whose transcription is massively induced upon glucose starvation . We investigated the mechanisms by which chromatin is reconstituted .', 'Histone Chaperone Asf1 is required for the establishment of Repressive Chromatin in Schizosaccharomyces pombe fbp1 Gene Repression . Chromatin is reconstituted in the fission yeast Schizoaccharombe pombefbp1 gene, which is robustly induced upon glucose starvation but tightly repressed under glucose-rich conditions .', 'Yes. transcription factors in Saccharomyces cerevisiae fbp1 and fbp2 are involved in the response to glucose starvation stress.', 'The Schizosaccharomyces pombe fbp1 gene, which encodes fructose-1,6-bis-phosphatase, is transcriptionally repressed by glucose through the activation of the cAMP-dependent protein kinase A (PKA) and transcriptionally activated by glucose starvation through the activation of a mitogen-activated protein kinase (MAPK)', 'Yes. In Saccharomyces cerevisiae, fbp1 expression is affected by glucose starvation and is increased under glucose starvation stress.', 'The Schizosaccharomyces pombe fbp1 gene is robustly induced upon glucose starvation but tightly repressed under glucose-rich conditions. The Schizosaccharomyces pombe fbp1 gene encodes fructose-1,6-bisphosphatase.', 'The Schizosaccharomyces pombe fbp1 gene, which encodes fructose-1,6-bis-phosphatase, is transcriptionally repressed by glucose through the activation of the cAMP-dependent protein kinase A (PKA) and transcriptionally activated by glucose starvation through the activation of a mitogen-activated protein kinase (MAPK).', 'Yes. In Saccharomyces cerevisiae, transcriptional responses to glucose starvation are mediated by the F-box protein fbp1. Ace1 mediates glucose-induced gene expression in cells exposed to stressful levels of glucose, whereas fBP1 activates a subset of genes under glucose-free conditions.', 'Yes. The yeast fbp1 gene, which encodes fructose-1,6,bis-bis-phosphatase, is transcriptionally repressed by the CAMP-dependent protein kinase (PKA) and transcriptionally suppressed by the mitogen-activated Protein Kinase (MAPK). It is not affected by glucose starvation stress, but it is affected by the stress of starvation.', 'Yes. In Saccharomyces cerevisiae, transcriptional responses to glucose starvation are mediated by two distal enhancer elements, fbp1 and fbp2.', 'Yes. transcription of yeast fbp1 is increased in response to glucose starvation stress.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/29967244",
"http://www.ncbi.nlm.nih.gov/pubmed/11238405",
"http://www.ncbi.nlm.nih.gov/pubmed/27723196",
"http://www.ncbi.nlm.nih.gov/pubmed/23398982",
"http://www.ncbi.nlm.nih.gov/pubmed/26945040",
"http://www.ncbi.nlm.nih.gov/pubmed/14762213",
"http://www.ncbi.nlm.nih.gov/pubmed/30670704"
]
| [
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29967244",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 130,
"text": "Histone Chaperone Asf1 Is Required for the Establishment of Repressive Chromatin in Schizosaccharomyces pombe fbp1 Gene Repression"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29967244",
"endSection": "abstract",
"offsetInBeginSection": 523,
"offsetInEndSection": 709,
"text": "chromatin is reconstituted in the fission yeast Schizosaccharomyces pombefbp1 gene, which is robustly induced upon glucose starvation but tightly repressed under glucose-rich conditions."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11238405",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 318,
"text": "The Schizosaccharomyces pombe fbp1 gene, which encodes fructose-1,6-bis-phosphatase, is transcriptionally repressed by glucose through the activation of the cAMP-dependent protein kinase A (PKA) and transcriptionally activated by glucose starvation through the activation of a mitogen-activated protein kinase (MAPK). "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27723196",
"endSection": "abstract",
"offsetInBeginSection": 230,
"offsetInEndSection": 475,
"text": "Antisense transcripts from the fission yeast fbp1 locus (fbp1-as) are expressed in glucose-rich conditions and anticorrelated with transcription of metabolic stress-induced lncRNA (mlonRNA) and mRNA on the sense strand during glucose starvation."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26945040",
"endSection": "abstract",
"offsetInBeginSection": 101,
"offsetInEndSection": 265,
"text": "In fission yeast, glucose starvation triggers lncRNA transcription across promoter regions of stress-responsive genes including fbp1 (fructose-1,6-bisphosphatase1)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30670704",
"endSection": "abstract",
"offsetInBeginSection": 164,
"offsetInEndSection": 458,
"text": "We herein show that the chromatin configuration is altered into an accessible state within 290 bp downstream from the initiation site of metabolic-stress-induced lncRNAs (mlonRNAs) in the promoter of the fission yeast fbp1 gene, whose transcription is massively induced upon glucose starvation."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14762213",
"endSection": "abstract",
"offsetInBeginSection": 838,
"offsetInEndSection": 1046,
"text": "Cation stress and glucose starvation selectively caused chromatin structure alteration around CRE-like sequences in cta3(+) and fbp1(+) promoters, respectively, in correlation with transcriptional activation."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30670704",
"endSection": "abstract",
"offsetInBeginSection": 166,
"offsetInEndSection": 462,
"text": " herein show that the chromatin configuration is altered into an accessible state within 290 bp downstream from the initiation site of metabolic-stress-induced lncRNAs (mlonRNAs) in the promoter of the fission yeast fbp1 gene, whose transcription is massively induced upon glucose starvation. Chr"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26945040",
"endSection": "abstract",
"offsetInBeginSection": 104,
"offsetInEndSection": 268,
"text": "fission yeast, glucose starvation triggers lncRNA transcription across promoter regions of stress-responsive genes including fbp1 (fructose-1,6-bisphosphatase1). At"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27723196",
"endSection": "abstract",
"offsetInBeginSection": 233,
"offsetInEndSection": 481,
"text": "isense transcripts from the fission yeast fbp1 locus (fbp1-as) are expressed in glucose-rich conditions and anticorrelated with transcription of metabolic stress-induced lncRNA (mlonRNA) and mRNA on the sense strand during glucose starvation. Here,"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27723196",
"endSection": "abstract",
"offsetInBeginSection": 280,
"offsetInEndSection": 475,
"text": "locus (fbp1-as) are expressed in glucose-rich conditions and anticorrelated with transcription of metabolic stress-induced lncRNA (mlonRNA) and mRNA on the sense strand during glucose starvation."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27723196",
"endSection": "abstract",
"offsetInBeginSection": 1107,
"offsetInEndSection": 1262,
"text": "Furthermore, fbp1-as and antisense RNA at other stress-responsive loci are promptly degraded via the cotranslational nonsense-mediated decay (NMD) pathway."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27723196",
"endSection": "abstract",
"offsetInBeginSection": 1263,
"offsetInEndSection": 1377,
"text": "These results suggest NMD may potentiate the swift disappearance of antisense RNAs in response to cellular stress."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27723196",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 229,
"text": "Antisense RNA has emerged as a crucial regulator of opposite-strand protein-coding genes in the long noncoding RNA (lncRNA) category, but little is known about their dynamics and decay process in the context of a stress response."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23398982",
"endSection": "abstract",
"offsetInBeginSection": 334,
"offsetInEndSection": 661,
"text": "xic growth. The stress-activated protein kinase (SAPK) pathway and its effectors, Sty1 MAPK and transcription factor Atf1, play a critical role in the adaptation of fission yeast to grow on alternative non-fermentable carbon sources by inducing the expression of fbp1+ gene, coding for the gluconeogenic enzyme fructose-1,6-bis"
}
]
| 11 | BioASQ-training11b | null | null | 5fe31321a43ad3127800004b | 36 |
yesno | Are there small molecule CGRPs under development for the treatment of migraine? | ['yes'] | [
"yes"
]
| ['Yes, there are several small molecule CGRPs under development for the treatment of migraine.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/28644160"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28644160",
"endSection": "abstract",
"offsetInBeginSection": 500,
"offsetInEndSection": 643,
"text": "Meanwhile, 1 small-molecule CGRP receptor antagonist (ubrogepant, MK-1602) is currently in phase 3 studies for the acute treatment of migraine."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28644160",
"endSection": "abstract",
"offsetInBeginSection": 753,
"offsetInEndSection": 890,
"text": "Several other small-molecular CGRP receptor antagonists are in earlier stages of development for acute migraine treatment or prevention. "
}
]
| 11 | BioASQ-training11b | null | null | 6026de661cb411341a0000d1 | 37 |
yesno | Does TGF-beta play a role in cardiac regeneration after myocardial infarction? | ['yes'] | [
"yes"
]
| TGFβ signaling orchestrates the beneficial interplay between scar-based repair and cardiomyocyte-based regeneration to achieve complete heart regeneration. | [
"http://www.ncbi.nlm.nih.gov/pubmed/23293297",
"http://www.ncbi.nlm.nih.gov/pubmed/22513374",
"http://www.ncbi.nlm.nih.gov/pubmed/19966054",
"http://www.ncbi.nlm.nih.gov/pubmed/18985280",
"http://www.ncbi.nlm.nih.gov/pubmed/17322368",
"http://www.ncbi.nlm.nih.gov/pubmed/16842199",
"http://www.ncbi.nlm.nih.gov/pubmed/15883211",
"http://www.ncbi.nlm.nih.gov/pubmed/10198196",
"http://www.ncbi.nlm.nih.gov/pubmed/12374778"
]
| [
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/23293297",
"endSection": "abstract",
"offsetInBeginSection": 768,
"offsetInEndSection": 1034,
"text": "We then performed a chemical screen and identified several small molecules that increase or reduce cardiomyocyte proliferation during heart development. These compounds act via Hedgehog, Insulin-like growth factor or Transforming growth factor β signaling pathways. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22513374",
"endSection": "abstract",
"offsetInBeginSection": 342,
"offsetInEndSection": 477,
"text": "Here, we report that the balance between the reparative and regenerative processes is achieved through Smad3-dependent TGFβ signaling. "
},
{
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/22513374",
"endSection": "abstract",
"offsetInBeginSection": 1368,
"offsetInEndSection": 1529,
"text": "Thus, TGFβ signaling orchestrates the beneficial interplay between scar-based repair and cardiomyocyte-based regeneration to achieve complete heart regeneration."
},
{
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/19966054",
"endSection": "abstract",
"offsetInBeginSection": 1071,
"offsetInEndSection": 1558,
"text": "As expected, transforming growth factor (TGF)-beta, a profibrotic cytokine, was dramatically upregulated in MI hearts, but its phosphorylated comediator (pSmad) was significantly downregulated in the nuclei of Cx43-deficient hearts post-MI, suggesting that downstream signaling of TGF-beta is diminished substantially in Cx43-deficient hearts. This diminution in profibrotic TGF-beta signaling resulted in the attenuation of adverse structural remodeling as assessed by echocardiography."
},
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"offsetInBeginSection": 980,
"offsetInEndSection": 1230,
"text": "Potentially beneficial changes include increases in the HSMP secretory-leucocyte-protease-inhibitor (SLPI) and cytokine transforming growth factor (TGF)-beta(1). Targeting these proteins may mitigate enhanced LV remodeling and dysfunction with aging."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17322368",
"endSection": "abstract",
"offsetInBeginSection": 427,
"offsetInEndSection": 760,
"text": "After injury, the presence of macrophages, which secreted high levels of transforming growth factor-beta and vascular endothelial growth factor-A, led to rapid removal of cell debris and replacement by granulation tissue containing inflammatory cells and blood vessels, followed by myofibroblast infiltration and collagen deposition."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17322368",
"endSection": "abstract",
"offsetInBeginSection": 857,
"offsetInEndSection": 1037,
"text": "Secretion of transforming growth factor-beta and vascular endothelial growth factor-A as well as neovascularization, myofibroblast infiltration, and collagen deposition decreased. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16842199",
"endSection": "abstract",
"offsetInBeginSection": 927,
"offsetInEndSection": 1181,
"text": "Repression of proinflammatory cytokine and chemokine synthesis, mediated in part through Transforming Growth Factor (TGF)-beta and Interleukin (IL)-10, is critical for resolution of the inflammatory infiltrate and transition to fibrous tissue deposition."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15883211",
"endSection": "abstract",
"offsetInBeginSection": 1692,
"offsetInEndSection": 2026,
"text": "TGF-beta conducted the myogenic differentiation of CD117+ stem cells by upregulating GATA-4 and NKx-2.5 expression. Therefore, the intramyocardial implantation of TGF-beta-preprogrammed CD117+ cells effectively assisted the myocardial regeneration and induced therapeutic angiogenesis, contributing to functional cardiac regeneration."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10198196",
"endSection": "abstract",
"offsetInBeginSection": 1593,
"offsetInEndSection": 1790,
"text": "These results indicate that TGF-beta/Smad signaling may be involved in the remodeling of the infarct scar after the completion of wound healing per se, via ongoing stimulation of matrix deposition."
}
]
| 5 | BioASQ-training5b | [
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016212",
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009203",
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012038"
]
| []
| 52f5083d2059c6d71c00001e | 38 |
yesno | Has the protein SETMAR (Metnase) a transposase domain? | ['yes'] | [
"yes"
]
| ['Yes, the protein SETMAR (Metnase) has a transposase domain.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/21491884",
"http://www.ncbi.nlm.nih.gov/pubmed/20620605",
"http://www.ncbi.nlm.nih.gov/pubmed/20521842",
"http://www.ncbi.nlm.nih.gov/pubmed/20416268",
"http://www.ncbi.nlm.nih.gov/pubmed/20309721",
"http://www.ncbi.nlm.nih.gov/pubmed/19458360",
"http://www.ncbi.nlm.nih.gov/pubmed/18790802",
"http://www.ncbi.nlm.nih.gov/pubmed/18773976",
"http://www.ncbi.nlm.nih.gov/pubmed/18263876",
"http://www.ncbi.nlm.nih.gov/pubmed/17877369",
"http://www.ncbi.nlm.nih.gov/pubmed/17403897",
"http://www.ncbi.nlm.nih.gov/pubmed/17130240",
"http://www.ncbi.nlm.nih.gov/pubmed/16672366",
"http://www.ncbi.nlm.nih.gov/pubmed/16332963",
"http://www.ncbi.nlm.nih.gov/pubmed/23090115",
"http://www.ncbi.nlm.nih.gov/pubmed/22231448"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21491884",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 117,
"text": "Metnase (SETMAR) is a SET-transposase fusion protein that promotes nonhomologous end joining (NHEJ) repair in humans."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20620605",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 84,
"text": "The transposase domain protein Metnase/SETMAR suppresses chromosomal translocations."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20620605",
"endSection": "abstract",
"offsetInBeginSection": 93,
"offsetInEndSection": 219,
"text": " Metnase (also termed SETMAR) is a fusion of a histone methylase and transposase protein that arose specifically in primates. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20521842",
"endSection": "abstract",
"offsetInBeginSection": 89,
"offsetInEndSection": 219,
"text": "the only intact Hsmar1 transposase gene exists within a chimeric SET-transposase fusion protein referred to as Metnase or SETMAR. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20521842",
"endSection": "abstract",
"offsetInBeginSection": 1181,
"offsetInEndSection": 1253,
"text": "The Metnase transposase has been remarkably conserved through evolution;"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20416268",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 354,
"text": "Metnase (also known as SETMAR) is a SET and transposase fusion protein in humans and plays a positive role in double-strand break (DSB) repair. While the SET domain possesses histone lysine methyltransferase activity, the transposase domain is responsible for 5'-terminal inverted repeat (TIR)-specific binding, DNA looping, and DNA cleavage activities. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20309721",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 138,
"text": "Metnase is a fusion gene comprising a SET histone methyl transferase domain and a transposase domain derived from the Mariner transposase."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19458360",
"endSection": "abstract",
"offsetInBeginSection": 452,
"offsetInEndSection": 589,
"text": "ulated by the DNA repair component Metnase (also termed SETMAR). Metnase contains a SET histone methylase and transposase nuclease domain"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18790802",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 54,
"text": "Metnase is a human SET and transposase domain protein "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18773976",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 52,
"text": "The human set and transposase domain protein Metnase"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18773976",
"endSection": "abstract",
"offsetInBeginSection": 207,
"offsetInEndSection": 520,
"text": " of transposase-related sequences in humans are pseudogenes. We recently isolated and characterized a SET and transposase domain protein termed Metnase that promotes DNA double-strand break (DSB) repair by non-homologous end-joining (NHEJ). Both the SET and transposase domain were required for its NHEJ activity."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18263876",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 118,
"text": "Metnase, also known as SETMAR, is a SET and transposase fusion protein with an undefined role in mammalian DNA repair."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17877369",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 80,
"text": "Biochemical characterization of a SET and transposase fusion protein, Metnase: i"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17877369",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 149,
"text": "Metnase (SETMAR) is a SET and transposase fusion protein that promotes in vivo end joining activity and mediates genomic integration of foreign DNA. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17403897",
"endSection": "abstract",
"offsetInBeginSection": 311,
"offsetInEndSection": 462,
"text": " This transposase coding region is part of the SETMAR gene, in which a histone methylatransferase SET domain is fused to an Hsmar1 transposase domain. "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17130240",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 94,
"text": "The human SETMAR protein preserves most of the activities of the ancestral Hsmar1 transposase."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17130240",
"endSection": "abstract",
"offsetInBeginSection": 183,
"offsetInEndSection": 334,
"text": "ere we investigate the activity of the human SETMAR protein, a highly expressed fusion between a histone H3 methylase and a mariner family transposase."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16672366",
"endSection": "abstract",
"offsetInBeginSection": 391,
"offsetInEndSection": 533,
"text": "SETMAR, a new primate chimeric gene resulting from fusion of a SET histone methyltransferase gene to the transposase gene of a mobile element."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16332963",
"endSection": "abstract",
"offsetInBeginSection": 321,
"offsetInEndSection": 419,
"text": "We identified a protein, termed Metnase, that has a SET domain and a transposase/nuclease domain. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23090115",
"endSection": "abstract",
"offsetInBeginSection": 132,
"offsetInEndSection": 211,
"text": "Metnase has a nuclease domain that shares homology with the Transposase family."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22231448",
"endSection": "abstract",
"offsetInBeginSection": 263,
"offsetInEndSection": 430,
"text": "Metnase (also called SETMAR) is a SET and transposase domain protein that promotes both DNA double-strand break (DSB) repair and restart of stalled replication forks. "
}
]
| 5 | BioASQ-training5b | [
"http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019895",
"http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004803",
"http://www.uniprot.org/uniprot/SETMR_BOVIN",
"http://www.uniprot.org/uniprot/SETMR_HUMAN",
"http://www.uniprot.org/uniprot/SETMR_RAT",
"http://www.uniprot.org/uniprot/SETMR_MOUSE",
"http://www.uniprot.org/uniprot/TRAT_CHEHE",
"http://www.uniprot.org/uniprot/TRA_BPMU"
]
| []
| 54f5f8925f206a0c06000003 | 39 |
yesno | Is there a deep-learning algorithm for protein solubility prediction? | ['yes'] | [
"yes"
]
| ['Yes. DeepSol is a novel deep learning-based protein solubility predictor. It is a convolutional neural network that exploits k-mer structure and additional sequence and structural features extracted from the protein sequence.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/29554211"
]
| [
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29554211",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 84,
"text": "DeepSol: a deep learning framework for sequence-based protein solubility prediction."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29554211",
"endSection": "abstract",
"offsetInBeginSection": 12,
"offsetInEndSection": 618,
"text": "Protein solubility plays a vital role in pharmaceutical research and production yield. For a given protein, the extent of its solubility can represent the quality of its function, and is ultimately defined by its sequence. Thus, it is imperative to develop novel, highly accurate in silico sequence-based protein solubility predictors. In this work we propose, DeepSol, a novel Deep Learning-based protein solubility predictor. The backbone of our framework is a convolutional neural network that exploits k-mer structure and additional sequence and structural features extracted from the protein sequence."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29554211",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 228,
"text": "DeepSol: a deep learning framework for sequence-based protein solubility prediction.<AbstractText Label=\"Motivation\" NlmCategory=\"UNASSIGNED\">Protein solubility plays a vital role in pharmaceutical research and production yield. "
}
]
| 11 | BioASQ-training11b | null | null | 5c6b198f7c78d69471000025 | 40 |
yesno | Can glyburide reduce cerebral edema? | ['yes'] | [
"yes"
]
| ['Yes. Glyburide, a selective inhibitor of sulfonylurea receptor 1-transient receptor potential melastatin 4, is effective in preventing and attenuating cerebral edema.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/24193798",
"http://www.ncbi.nlm.nih.gov/pubmed/25422710",
"http://www.ncbi.nlm.nih.gov/pubmed/26463916",
"http://www.ncbi.nlm.nih.gov/pubmed/24072459",
"http://www.ncbi.nlm.nih.gov/pubmed/24552576",
"http://www.ncbi.nlm.nih.gov/pubmed/24671831",
"http://www.ncbi.nlm.nih.gov/pubmed/23633925",
"http://www.ncbi.nlm.nih.gov/pubmed/17673715",
"http://www.ncbi.nlm.nih.gov/pubmed/26268138"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26268138",
"endSection": "abstract",
"offsetInBeginSection": 137,
"offsetInEndSection": 411,
"text": "Preclinical studies have shown that a continuous infusion of glyburide blocks edema formation and improves outcome. We hypothesize that treatment with RP-1127 (Glyburide for Injection) reduces formation of brain edema in patients after large anterior circulation infarction."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26268138",
"endSection": "abstract",
"offsetInBeginSection": 1298,
"offsetInEndSection": 1486,
"text": "CONCLUSIONS: GAMES-RP was designed to provide critical information regarding glyburide for injection in patients with large hemispheric stroke and will inform the design of future studies."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24072459",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 75,
"text": "Glyburide is associated with attenuated vasogenic edema in stroke patients."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24072459",
"endSection": "abstract",
"offsetInBeginSection": 134,
"offsetInEndSection": 382,
"text": "Glyburide is reported to prevent brain swelling in preclinical rodent models of ischemic stroke through inhibition of a non-selective channel composed of sulfonylurea receptor 1 and transient receptor potential cation channel subfamily M member 4. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24072459",
"endSection": "abstract",
"offsetInBeginSection": 936,
"offsetInEndSection": 1323,
"text": "RESULTS: We report that IV glyburide was associated with T2 fluid-attenuated inversion recovery signal intensity ratio on brain MRI, diminished the lesional water diffusivity between days 1 and 2 (pseudo-normalization), and reduced blood MMP-9 level.CONCLUSIONS: Several surrogate markers of vasogenic edema appear to be reduced in the setting of IV glyburide treatment in human stroke. "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24193798",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 78,
"text": "Pilot study of intravenous glyburide in patients with a large ischemic stroke."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24193798",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 262,
"text": "BACKGROUND AND PURPOSE: Preclinical and retrospective clinical data indicate that glyburide, a selective inhibitor of sulfonylurea receptor 1-transient receptor potential melastatin 4, is effective in preventing edema and improving outcome after focal ischemia. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24671831",
"endSection": "abstract",
"offsetInBeginSection": 120,
"offsetInEndSection": 222,
"text": "Preclinical data suggest that glyburide, an inhibitor of SUR1-TRPM4, is effective in preventing edema."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25422710",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 48,
"text": "Glyburide in Treating Malignant Cerebral Edema. "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25422710",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 92,
"text": "Glyburide in Treating Malignant Cerebral Edema. Blocking Sulfonyl Urea One (SUR1) Receptors."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17673715",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 242,
"text": "The sulfonylurea receptor 1-regulated NC(Ca-ATP) channel is upregulated in rodent models of stroke with block of the channel by the sulfonylurea, glibenclamide (glyburide), significantly reducing mortality, cerebral edema, and infarct volume."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23633925",
"endSection": "abstract",
"offsetInBeginSection": 1534,
"offsetInEndSection": 1678,
"text": "Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24552576",
"endSection": "abstract",
"offsetInBeginSection": 552,
"offsetInEndSection": 901,
"text": "In this focused review, we explore preclinical data linking Sur1 channel formation to development of edema and reference evidence suggesting that the antidiabetic sulfonylurea drug glyburide (a Sur1 inhibitor) is an inexpensive and well-tolerated agent that can be clinically tested to reduce or prevent malignancy and/or treatment-associated edema."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24552576",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 73,
"text": "Potential of glyburide to reduce intracerebral edema in brain metastases."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26268138",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 89,
"text": "Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) Trial: Rationale and Design."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24671831",
"endSection": "abstract",
"offsetInBeginSection": 107,
"offsetInEndSection": 209,
"text": "Preclinical data suggest that glyburide, an inhibitor of SUR1-TRPM4, is effective in preventing edema."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23633925",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 121,
"text": "Inhibition of sulfonylurea receptor 1 (SUR1) by glyburide has been shown to decrease edema after subarachnoid hemorrhage."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23633925",
"endSection": "abstract",
"offsetInBeginSection": 1563,
"offsetInEndSection": 1706,
"text": "Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24072459",
"endSection": "abstract",
"offsetInBeginSection": 938,
"offsetInEndSection": 1189,
"text": "RESULTS: We report that IV glyburide was associated with T2 fluid-attenuated inversion recovery signal intensity ratio on brain MRI, diminished the lesional water diffusivity between days 1 and 2 (pseudo-normalization), and reduced blood MMP-9 level. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24671831",
"endSection": "abstract",
"offsetInBeginSection": 120,
"offsetInEndSection": 223,
"text": "Preclinical data suggest that glyburide, an inhibitor of SUR1-TRPM4, is effective in preventing edema. "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24671831",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 83,
"text": "Exploratory analysis of glyburide as a novel therapy for preventing brain swelling."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23633925",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 122,
"text": "Inhibition of sulfonylurea receptor 1 (SUR1) by glyburide has been shown to decrease edema after subarachnoid hemorrhage. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24552576",
"endSection": "abstract",
"offsetInBeginSection": 555,
"offsetInEndSection": 904,
"text": "In this focused review, we explore preclinical data linking Sur1 channel formation to development of edema and reference evidence suggesting that the antidiabetic sulfonylurea drug glyburide (a Sur1 inhibitor) is an inexpensive and well-tolerated agent that can be clinically tested to reduce or prevent malignancy and/or treatment-associated edema."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23633925",
"endSection": "abstract",
"offsetInBeginSection": 1531,
"offsetInEndSection": 1675,
"text": "Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24072459",
"endSection": "abstract",
"offsetInBeginSection": 134,
"offsetInEndSection": 381,
"text": "Glyburide is reported to prevent brain swelling in preclinical rodent models of ischemic stroke through inhibition of a non-selective channel composed of sulfonylurea receptor 1 and transient receptor potential cation channel subfamily M member 4."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24072459",
"endSection": "abstract",
"offsetInBeginSection": 1159,
"offsetInEndSection": 1282,
"text": "Several surrogate markers of vasogenic edema appear to be reduced in the setting of IV glyburide treatment in human stroke."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26268138",
"endSection": "abstract",
"offsetInBeginSection": 241,
"offsetInEndSection": 399,
"text": "We hypothesize that treatment with RP-1127 (Glyburide for Injection) reduces formation of brain edema in patients after large anterior circulation infarction."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23633925",
"endSection": "abstract",
"offsetInBeginSection": 1545,
"offsetInEndSection": 1690,
"text": "Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema.."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24072459",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 76,
"text": "Glyburide is associated with attenuated vasogenic edema in stroke patients."
}
]
| 6 | BioASQ-training6b | [
"https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001929",
"http://www.biosemantics.org/jochem#4275786",
"http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4275786",
"http://www.disease-ontology.org/api/metadata/DOID:4724",
"https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005905"
]
| [
{
"o": "glyburide",
"p": "http://www.w3.org/2000/01/rdf-schema#label",
"s": "http://linkedlifedata.com/resource/umls/id/C0017628"
},
{
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| 588482f5e56acf517600000a | 41 |
yesno | Is there a relationship between B cells and Multiple Sclerosis? | ['yes'] | [
"yes"
]
| ['MS patients with high neurodegeneration have changes in B cells characterized by down-regulation of B-cell-specific genes and increased activation status'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/25267439",
"http://www.ncbi.nlm.nih.gov/pubmed/19996075",
"http://www.ncbi.nlm.nih.gov/pubmed/26857494",
"http://www.ncbi.nlm.nih.gov/pubmed/26810546",
"http://www.ncbi.nlm.nih.gov/pubmed/25666875",
"http://www.ncbi.nlm.nih.gov/pubmed/26604134",
"http://www.ncbi.nlm.nih.gov/pubmed/26732544",
"http://www.ncbi.nlm.nih.gov/pubmed/20558389",
"http://www.ncbi.nlm.nih.gov/pubmed/27120609",
"http://www.ncbi.nlm.nih.gov/pubmed/24679343",
"http://www.ncbi.nlm.nih.gov/pubmed/1839591",
"http://www.ncbi.nlm.nih.gov/pubmed/25750917",
"http://www.ncbi.nlm.nih.gov/pubmed/23634189",
"http://www.ncbi.nlm.nih.gov/pubmed/18474519",
"http://www.ncbi.nlm.nih.gov/pubmed/18388801",
"http://www.ncbi.nlm.nih.gov/pubmed/18388800",
"http://www.ncbi.nlm.nih.gov/pubmed/20970478",
"http://www.ncbi.nlm.nih.gov/pubmed/24526661",
"http://www.ncbi.nlm.nih.gov/pubmed/26724102",
"http://www.ncbi.nlm.nih.gov/pubmed/18388796",
"http://www.ncbi.nlm.nih.gov/pubmed/20535037",
"http://www.ncbi.nlm.nih.gov/pubmed/25620021",
"http://www.ncbi.nlm.nih.gov/pubmed/25895531",
"http://www.ncbi.nlm.nih.gov/pubmed/21216828",
"http://www.ncbi.nlm.nih.gov/pubmed/15800022"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26604134",
"endSection": "abstract",
"offsetInBeginSection": 1682,
"offsetInEndSection": 1896,
"text": "These results suggest that RRMS patients with radiological phenotypes showing high neurodegeneration have changes in B cells characterized by down-regulation of B-cell-specific genes and increased activation status"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25620021",
"endSection": "abstract",
"offsetInBeginSection": 517,
"offsetInEndSection": 744,
"text": "Although the exact etiology is still obscure, the leading hypothesis behind MS relapses is acute inflammatory attacks on CNS myelin and axons. This complex process involves B and T cells together with macrophages and microglia."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25666875",
"endSection": "abstract",
"offsetInBeginSection": 545,
"offsetInEndSection": 878,
"text": "It is currently known that CD24 serves as a costimulatory factor of T cells that regulate their homeostasis and proliferation, while in B cells, CD24 is functionally involved in cell activation and differentiation. CD24 can enhance autoimmune diseases in terms of its protective role in the clonal deletion of autoreactive thymocytes"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25895531",
"endSection": "abstract",
"offsetInBeginSection": 153,
"offsetInEndSection": 378,
"text": "Multiple B cell-dependent mechanisms contributing to inflammatory demyelination of the CNS have been explored using experimental autoimmune encephalomyelitis (EAE), a CD4 T cell-dependent animal model for multiple sclerosis. "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18388801",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 84,
"text": "The role of B cells in multiple sclerosis: rationale for B-cell-targeted therapies."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26724102",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 365,
"text": "Interest in CD8+ T cells and B cells was initially inspired by observations in multiple sclerosis rather than in animal models: CD8+ T cells predominate in multiple sclerosis lesions, oligoclonal immunoglobulin bands in CSF have long been recognised as diagnostic and prognostic markers, and anti-B-cell therapies showed considerable efficacy in multiple sclerosis."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24526661",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 80,
"text": "Differential effects of fingolimod on B-cell populations in multiple sclerosis."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25267439",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 88,
"text": "Unaltered regulatory B-cell frequency and function in patients with multiple sclerosis."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18474519",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 88,
"text": "B cells are increasingly recognized as major players in multiple sclerosis pathogenesis."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26857494",
"endSection": "abstract",
"offsetInBeginSection": 583,
"offsetInEndSection": 691,
"text": "These observations underscore the B cell's contribution to the putative underpinnings of multiple sclerosis."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18388801",
"endSection": "abstract",
"offsetInBeginSection": 222,
"offsetInEndSection": 527,
"text": "Data suggesting that B cells play a role in the pathogenesis of multiple sclerosis have been accumulating for the past five decades, demonstrating that the cerebrospinal fluid and central nervous system tissues of multiple sclerosis patients contain B cells, plasma cells, antibodies, and immunoglobulins."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18388796",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 89,
"text": "B-cell-targeted treatment for multiple sclerosis: mechanism of action and clinical data."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25750917",
"endSection": "abstract",
"offsetInBeginSection": 161,
"offsetInEndSection": 425,
"text": "Subset composition and cytokine production of B cells derived from peripheral blood mononuclear cells from multiple sclerosis patients under Fingolimod treatment, untreated multiple sclerosis patients and healthy controls were analyzed by flow cytometry and ELISA."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18388796",
"endSection": "abstract",
"offsetInBeginSection": 335,
"offsetInEndSection": 598,
"text": "In particular, antigen presentation between B cells and T cells, increased trafficking of B cells across the blood-brain barrier, and autoantibodies produced by plasma cells may contribute to the pathophysiology of autoimmune disorders such as multiple sclerosis."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19996075",
"endSection": "abstract",
"offsetInBeginSection": 12,
"offsetInEndSection": 107,
"text": "Accumulating evidence supports a major role of B cells in multiple sclerosis (MS) pathogenesis."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18388800",
"endSection": "abstract",
"offsetInBeginSection": 1148,
"offsetInEndSection": 1304,
"text": "Further research is needed to elucidate the pathology of B cells and their role in central nervous system autoimmune diseases, including multiple sclerosis."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23634189",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 98,
"text": "Targeting B cells in the treatment of multiple sclerosis: recent advances and remaining challenges"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24679343",
"endSection": "title",
"offsetInBeginSection": 1,
"offsetInEndSection": 184,
"text": "phingosine-1-phosphate receptors control B-cell migration through signaling components associated with primary immunodeficiencies, chronic lymphocytic leukemia, and multiple sclerosis"
}
]
| 6 | BioASQ-training6b | [
"https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001402",
"https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009103",
"http://www.disease-ontology.org/api/metadata/DOID:2377"
]
| null | 58c0836102b8c6095300001c | 42 |
yesno | Was vivotif licensed in Europe and the US at the same time? | ['no'] | [
"no"
]
| ['No, vivotif was licensed in Europe in 1983 and in the US in 1989.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/28515625"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28515625",
"endSection": "abstract",
"offsetInBeginSection": 798,
"offsetInEndSection": 1060,
"text": "Vivotif® is an oral live attenuated vaccine which contains a mutated strain of Salmonella (Ty21a) and reproduces the natural infection. The vaccine was first licensed in Europe in 1983 and in the US in 1989, and over the years it has proved efficacious and safe."
}
]
| 11 | BioASQ-training11b | null | null | 5e763c3fc6a8763d23000010 | 43 |
yesno | Is the gene DUX4 epigenetically regulated in somatic cells? | ['yes'] | [
"yes"
]
| ['The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues. Recent studies provide evidence that DUX4 is expressed in the human germline and then epigenetically silenced in somatic cells.', 'Yes, the human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues.', 'The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues.DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells.', 'The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues.DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells.', 'Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues. ', 'Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues. ', 'Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues. ', 'Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues. ', 'Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues. ', 'Yes, the human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/23196547",
"http://www.ncbi.nlm.nih.gov/pubmed/21288772",
"http://www.ncbi.nlm.nih.gov/pubmed/24278031",
"http://www.ncbi.nlm.nih.gov/pubmed/23593020",
"http://www.ncbi.nlm.nih.gov/pubmed/21734574",
"http://www.ncbi.nlm.nih.gov/pubmed/21060811",
"http://www.ncbi.nlm.nih.gov/pubmed/24940479",
"http://www.ncbi.nlm.nih.gov/pubmed/23969240",
"http://www.ncbi.nlm.nih.gov/pubmed/23272181",
"http://www.ncbi.nlm.nih.gov/pubmed/23143600",
"http://www.ncbi.nlm.nih.gov/pubmed/22871573",
"http://www.ncbi.nlm.nih.gov/pubmed/22522912",
"http://www.ncbi.nlm.nih.gov/pubmed/22025602"
]
| [
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"endSection": "abstract",
"offsetInBeginSection": 590,
"offsetInEndSection": 853,
"text": "There are several genes on chromosome 4q35 region including DUX4 within D4Z4 repeats. Transcription of these genes is usually repressed by epigenetic modifications of this chromosomal region and also accumulation of transcriptional repressors to the repeat array."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21288772",
"endSection": "abstract",
"offsetInBeginSection": 214,
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"text": "Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues. "
},
{
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/24278031",
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"text": "The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues."
},
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/23593020",
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"text": "Facioscapulohumeral dystrophy (FSHD) is a progressive muscular dystrophy caused by decreased epigenetic repression of the D4Z4 macrosatellite repeats and ectopic expression of DUX4, a retrogene encoding a germline transcription factor encoded in each repeat."
},
{
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"offsetInBeginSection": 685,
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"text": " These mice recapitulate important epigenetic and DUX4 expression attributes seen in patients and controls, respectively, including high DUX4 expression levels in the germline, (incomplete) epigenetic repression in somatic tissue, and FSHD-specific variegated DUX4 expression in sporadic muscle nuclei associated with D4Z4 chromatin relaxation."
},
{
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"endSection": "abstract",
"offsetInBeginSection": 579,
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"text": "DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells."
},
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"text": "In contrast to control skeletal muscle and most other somatic tissues, full-length DUX4 transcript and protein is expressed at relatively abundant levels in human testis, most likely in the germ-line cells. Induced pluripotent (iPS) cells also express full-length DUX4 and differentiation of control iPS cells to embryoid bodies suppresses expression of full-length DUX4, whereas expression of full-length DUX4 persists in differentiated FSHD iPS cells. Together, these findings indicate that full-length DUX4 is normally expressed at specific developmental stages and is suppressed in most somatic tissues."
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"text": "Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues."
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"text": "DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells. "
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"text": "DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells."
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"text": "Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues."
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"text": "Normally expressed in the testis and epigenetically repressed in somatic tissues, DUX4 expression in skeletal muscle induces expression of many germline, stem cell, and other genes that might account for the pathophysiology of FSHD."
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"text": "Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues."
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"text": "DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells"
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"text": "Normally expressed in the testis and epigenetically repressed in somatic tissues, DUX4 expression in skeletal muscle induces expression of many germline, stem cell, and other genes that might account for the pathophysiology of FSHD"
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"text": "DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells"
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"text": "Normally expressed in the testis and epigenetically repressed in somatic tissues, DUX4 expression in skeletal muscle induces expression of many germline, stem cell, and other genes that might account for the pathophysiology of FSHD"
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"text": "Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues"
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"text": "DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells"
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"text": "Normally expressed in the testis and epigenetically repressed in somatic tissues, DUX4 expression in skeletal muscle induces expression of many germline, stem cell, and other genes that might account for the pathophysiology of FSHD"
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{
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"text": "Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues"
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/24940479",
"endSection": "abstract",
"offsetInBeginSection": 668,
"offsetInEndSection": 899,
"text": "Normally expressed in the testis and epigenetically repressed in somatic tissues, DUX4 expression in skeletal muscle induces expression of many germline, stem cell, and other genes that might account for the pathophysiology of FSHD"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21288772",
"endSection": "abstract",
"offsetInBeginSection": 214,
"offsetInEndSection": 397,
"text": "Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23969240",
"endSection": "abstract",
"offsetInBeginSection": 1755,
"offsetInEndSection": 2022,
"text": "The identification of the gene(s) and the exact epigenetic pathway underlining this disease will be mandatory to increase the rate of diagnosis for FSHD2 patients and to confirm the hypothesis of a common FSHD1 and FSHD2 pathophysiological pathway involving DUX4 gene"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23272181",
"endSection": "abstract",
"offsetInBeginSection": 161,
"offsetInEndSection": 594,
"text": "This deletion induces epigenetic modifications that affect the expression of several genes located in the vicinity. In each D4Z4 element, we identified the double homeobox 4 (DUX4) gene. DUX4 expresses a transcription factor that plays a major role in the development of FSHD through the initiation of a large gene dysregulation cascade that causes myogenic differentiation defects, atrophy and reduced response to oxidative stress. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23593020",
"endSection": "abstract",
"offsetInBeginSection": 497,
"offsetInEndSection": 581,
"text": "decreased epigenetic repression and variegated expression of DUX4 in skeletal muscle"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23593020",
"endSection": "abstract",
"offsetInBeginSection": 862,
"offsetInEndSection": 915,
"text": "(incomplete) epigenetic repression in somatic tissue,"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23143600",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 191,
"text": "Facioscapulohumeral dystrophy (FSHD) is characterized by chromatin relaxation of the D4Z4 macrosatellite array on chromosome 4 and expression of the D4Z4-encoded DUX4 gene in skeletal muscle."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22871573",
"endSection": "abstract",
"offsetInBeginSection": 198,
"offsetInEndSection": 232,
"text": "derepression of the DUX4 retrogene"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22522912",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 356,
"text": "The aim of our study was to identify relationships between epigenetic parameters correlating with a relaxed chromatin state of the DUX4 promoter region and clinical severity as measured by a clinical severity score or muscle pathologic changes in D4Z4 contraction-dependent (FSHD1) and -independent (FSHD2) facioscapulohumeral muscular dystrophy patients. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22025602",
"endSection": "abstract",
"offsetInBeginSection": 1026,
"offsetInEndSection": 1162,
"text": "Specifically, abundance of RNA transcripts encoded by the DUX4 locus correlated to differential DNA methylation and H3K36me3 enrichment."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21060811",
"endSection": "abstract",
"offsetInBeginSection": 1472,
"offsetInEndSection": 1623,
"text": "Together, these findings indicate that full-length DUX4 is normally expressed at specific developmental stages and is suppressed in most somatic tissue"
}
]
| 5 | BioASQ-training5b | [
"http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057890",
"http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D044127",
"http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D063185",
"http://www.uniprot.org/uniprot/DUX4_HUMAN",
"http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0040030",
"http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0040029",
"http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045858"
]
| [
{
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"p": "http://www.w3.org/2004/02/skos/core#notation",
"s": "http://linkedlifedata.com/resource/umls/label/A16475868"
},
{
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"p": "http://www.w3.org/2008/05/skos-xl#prefLabel",
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{
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},
{
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{
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{
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},
{
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"p": "http://www.w3.org/2004/02/skos/core#note",
"s": "http://linkedlifedata.com/resource/umls/label/A3832170"
},
{
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"s": "http://linkedlifedata.com/resource/umls/id/C1317909"
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{
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"s": "http://linkedlifedata.com/resource/umls/label/A3840964"
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]
| 55152c2946478f2f2c000005 | 44 |
yesno | Is delayed enhancement documented in patients with non-ischemic dilated cardiomyopathy? | ['yes'] | [
"yes"
]
| Delayed enhancement is documented in almost 30% of patients with non-ischemic dilated cardiomyopathy and its pattern is characterized by mid-wall, patchy or diffuse location. | [
"http://www.ncbi.nlm.nih.gov/pubmed/21234292",
"http://www.ncbi.nlm.nih.gov/pubmed/21176853",
"http://www.ncbi.nlm.nih.gov/pubmed/19317068",
"http://www.ncbi.nlm.nih.gov/pubmed/17885521",
"http://www.ncbi.nlm.nih.gov/pubmed/24315973",
"http://www.ncbi.nlm.nih.gov/pubmed/23021326",
"http://www.ncbi.nlm.nih.gov/pubmed/22875171",
"http://www.ncbi.nlm.nih.gov/pubmed/22552168",
"http://www.ncbi.nlm.nih.gov/pubmed/20149594",
"http://www.ncbi.nlm.nih.gov/pubmed/23422782",
"http://www.ncbi.nlm.nih.gov/pubmed/19185371",
"http://www.ncbi.nlm.nih.gov/pubmed/17602984",
"http://www.ncbi.nlm.nih.gov/pubmed/17131077",
"http://www.ncbi.nlm.nih.gov/pubmed/20118568"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21234292",
"endSection": "abstract",
"offsetInBeginSection": 714,
"offsetInEndSection": 814,
"text": "Myocardial fibrosis was present in 30% of patients, the majority of which was mid-myocardial (63%). "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21234292",
"endSection": "abstract",
"offsetInBeginSection": 1290,
"offsetInEndSection": 1400,
"text": " DCM patients frequently have myocardial fibrosis detected on CE-CMR, the majority of which is mid-myocardial."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21176853",
"endSection": "abstract",
"offsetInBeginSection": 616,
"offsetInEndSection": 689,
"text": "Fifty (40%) patients showed myocardial DE, representing 12±7% of LV mass."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19317068",
"endSection": "abstract",
"offsetInBeginSection": 573,
"offsetInEndSection": 675,
"text": "one case was dilated cardiomyopathy, in which the delayed enhancement was diffuse small midwall spots "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17885521",
"endSection": "abstract",
"offsetInBeginSection": 849,
"offsetInEndSection": 1013,
"text": "In the dilated cardiomyopathy group, only seven (29%) patients showed delayed enhancement and its pattern was characterized by mid-wall, patchy or diffuse location."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17885521",
"endSection": "abstract",
"offsetInBeginSection": 1388,
"offsetInEndSection": 1838,
"text": "Patterns of delayed enhancement are different in dilated cardiomyopathy and ischemic cardiomyopathy, reflecting the presence of scarring or various degrees of fibrosis in left ventricular myocardium. The presence of subendocardial or transmural delayed enhancement at contrast-enhanced cardiovascular magnetic resonance allowed distinction between dilated cardiomyopathy and ischemic cardiomyopathy with high sensitivity (88%) and specificity (100%)."
}
]
| 5 | BioASQ-training5b | [
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002311",
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009682",
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008279",
"http://www.disease-ontology.org/api/metadata/DOID:12930",
"http://www.disease-ontology.org/api/metadata/DOID:0050700",
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009202"
]
| []
| 5339ed7bd6d3ac6a34000060 | 45 |
yesno | Do circular exons increase gene expression? | ['no'] | [
"no"
]
| ['circRNAs might adsorb specific miRNAs to regulate the expression of their target gene mRNAs. They can thus lead to both over- and under-expression of mRNAs.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/25253891",
"http://www.ncbi.nlm.nih.gov/pubmed/28634583",
"http://www.ncbi.nlm.nih.gov/pubmed/21151960",
"http://www.ncbi.nlm.nih.gov/pubmed/30136305",
"http://www.ncbi.nlm.nih.gov/pubmed/28184940",
"http://www.ncbi.nlm.nih.gov/pubmed/8652136"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21151960",
"endSection": "abstract",
"offsetInBeginSection": 873,
"offsetInEndSection": 1096,
"text": "Each of these species was present at very low copy numbers in primary and cultured cells; however, only the expression of ANRIL isoforms containing exons proximal to the INK4/ARF locus correlated with the ASVD risk alleles."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21151960",
"endSection": "abstract",
"offsetInBeginSection": 1672,
"offsetInEndSection": 1883,
"text": "These results identify novel circular RNA products emanating from the ANRIL locus and suggest causal variants at 9p21.3 regulate INK4/ARF expression and ASVD risk by modulating ANRIL expression and/or structure."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8652136",
"endSection": "abstract",
"offsetInBeginSection": 672,
"offsetInEndSection": 833,
"text": "To explore the potential for using this methodology to express circular RNA in vivo, circular forms of the HDV ribozyme and RNaseP RNA were produced in E. coli. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8652136",
"endSection": "abstract",
"offsetInBeginSection": 954,
"offsetInEndSection": 1079,
"text": "The activity of in vivo expressed circular ribozymes could be demonstrated indicating that they fold into active conformation"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28184940",
"endSection": "abstract",
"offsetInBeginSection": 641,
"offsetInEndSection": 865,
"text": "We found that: i) the circRNA expression profile revealed 1,285 significant differences in circRNA expression, with circRNA expression downregulated in 594 samples and upregulated in 691 samples via interactions with miRNAs."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28184940",
"endSection": "abstract",
"offsetInBeginSection": 1861,
"offsetInEndSection": 2012,
"text": "These circRNAs regulated the expression of target genes through interactions with miRNAs and might become new molecular biomarkers for GC in the future"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28184940",
"endSection": "abstract",
"offsetInBeginSection": 1627,
"offsetInEndSection": 1763,
"text": "69 differentially expressed circRNAs were found that might adsorb specific miRNAs to regulate the expression of their target gene mRNAs."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25253891",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 105,
"text": "Novel coding, translation, and gene expression of a replicating covalently closed circular RNA of 220 nt."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25253891",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 241,
"text": "The highly structured (64% GC) covalently closed circular (CCC) RNA (220 nt) of the virusoid associated with rice yellow mottle virus codes for a 16-kDa highly basic protein using novel modalities for coding, translation, and gene expression"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30136305",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 182,
"text": "Recent evidence has demonstrated that circular RNAs (circRNAs) played crucial roles in fine-tuning the levels of gene expression by sequestering the corresponding microRNA (miRNAs). "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28634583",
"endSection": "abstract",
"offsetInBeginSection": 922,
"offsetInEndSection": 1161,
"text": "It has been proposed that circRNA regulate gene expression at the transcriptional or post-transcriptional level by interacting with miRNAs and that circRNAs may have a role in regulating miRNA function in cancer initiation and progression."
}
]
| 11 | BioASQ-training11b | null | null | 5e43ee1f48dab47f26000012 | 46 |
yesno | Can GDF15 be a biomarker for metformin treatment? | ['yes'] | [
"yes"
]
| ['Yes, GDF15 levels are a biomarker for the use of metformin in people with dysglycemia, and its concentration reflects the dose of metformin.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/27974345"
]
| [
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27974345",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 68,
"text": "Growth Differentiation Factor 15 as a Novel Biomarker for Metformin."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27974345",
"endSection": "abstract",
"offsetInBeginSection": 868,
"offsetInEndSection": 1003,
"text": "GDF15 levels are a biomarker for the use of metformin in people with dysglycemia, and its concentration reflects the dose of metformin."
}
]
| 11 | BioASQ-training11b | null | null | 5ad3013d0340b9f058000019 | 47 |
yesno | Does replication timing affect the rate of somatic mutations? | ['yes'] | [
"yes"
]
| ['Mutation rate, as reflected in recent evolutionary divergence and human nucleotide diversity, is markedly increased in later-replicating regions of the human genome. All classes of substitutions are affected, suggesting a generalized mechanism involving replication time-dependent DNA damage. DNA repair systems, in general, are less efficient in late replicating heterochromatic regions compared to early replicating euchromatic regions of the genome. In yeast the mutation rate increases with the replication timing by more than 30% between the earliest and the latest replicating regions. Limited evidence from one chromosome arm in Drosophila melanogaster suggests the opposite pattern, with regions overlapping early-firing origins showing increased levels of diversity and divergence. In humans DNA replication patterns help shape the mutational landscapes of normal and cancer genomes.', 'Here we observe that mutation rate, as reflected in recent evolutionary divergence and human nucleotide diversity, is markedly increased in later-replicating regions of the human genome', 'Here we observe that mutation rate, as reflected in recent evolutionary divergence and human nucleotide diversity, is markedly increased in later-replicating regions of the human genome', 'Here we observe that mutation rate, as reflected in recent evolutionary divergence and human nucleotide diversity, is markedly increased in later-replicating regions of the human genome', 'Here we observe that mutation rate, as reflected in recent evolutionary divergence and human nucleotide diversity, is markedly increased in later-replicating regions of the human genome', 'Here we observe that mutation rate, as reflected in recent evolutionary divergence and human nucleotide diversity, is markedly increased in later-replicating regions of the human genome', 'Recent studies revealed a long suspected replication-timing effect on mutation rate, but the mechanisms that regulate the increase in mutation rate as the genome is replicated remain unclear. The mutations were distributed randomly throughout the genome, independent of replication timing. Here, we show that the mutation rate increases with the replication timing by more than 30% between the earliest and the latest replicating regions. Interestingly, 5% of the single base pair substitutions might represent double-slippage events that occurred at the junction of immediately adjacent repeats, resulting in a shift in the repeat boundary.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/23422670",
"http://www.ncbi.nlm.nih.gov/pubmed/23821616",
"http://www.ncbi.nlm.nih.gov/pubmed/22046001",
"http://www.ncbi.nlm.nih.gov/pubmed/22114361",
"http://www.ncbi.nlm.nih.gov/pubmed/22023572",
"http://www.ncbi.nlm.nih.gov/pubmed/21666225",
"http://www.ncbi.nlm.nih.gov/pubmed/19287383",
"http://www.ncbi.nlm.nih.gov/pubmed/23327985",
"http://www.ncbi.nlm.nih.gov/pubmed/24598232",
"http://www.ncbi.nlm.nih.gov/pubmed/23271586",
"http://www.ncbi.nlm.nih.gov/pubmed/12941181",
"http://www.ncbi.nlm.nih.gov/pubmed/9560368"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19287383",
"endSection": "abstract",
"offsetInBeginSection": 139,
"offsetInEndSection": 324,
"text": "Here we observe that mutation rate, as reflected in recent evolutionary divergence and human nucleotide diversity, is markedly increased in later-replicating regions of the human genome"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19287383",
"endSection": "abstract",
"offsetInBeginSection": 327,
"offsetInEndSection": 451,
"text": "ll classes of substitutions are affected, suggesting a generalized mechanism involving replication time-dependent DNA damage"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21666225",
"endSection": "abstract",
"offsetInBeginSection": 277,
"offsetInEndSection": 602,
"text": "We show that mutation rate varies 6-fold across a single chromosome, that this variation is correlated with replication timing, and we propose a model to explain this variation that relies on the temporal separation of two processes for replicating past damaged DNA: error-free DNA damage tolerance and translesion synthesis."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22023572",
"endSection": "abstract",
"offsetInBeginSection": 72,
"offsetInEndSection": 264,
"text": "Recent studies revealed a long suspected replication-timing effect on mutation rate, but the mechanisms that regulate the increase in mutation rate as the genome is replicated remain unclear. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22023572",
"endSection": "abstract",
"offsetInBeginSection": 300,
"offsetInEndSection": 459,
"text": "DNA repair systems, in general, are less efficient in late replicating heterochromatic regions compared to early replicating euchromatic regions of the genome."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22114361",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 67,
"text": "The mutational profile of the yeast genome is shaped by replication"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22114361",
"endSection": "abstract",
"offsetInBeginSection": 211,
"offsetInEndSection": 340,
"text": "the mutation rate increases with the replication timing by more than 30% between the earliest and the latest replicating regions."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22114361",
"endSection": "abstract",
"offsetInBeginSection": 728,
"offsetInEndSection": 919,
"text": "Thus, we show that the leading replicating strands present an excess of C over G and of A over T in the genome of S. cerevisiae (reciprocally an excess of G + T over C + A in lagging strands)"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22046001",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 88,
"text": "Late-replicating domains have higher divergence and diversity in Drosophila melanogaster"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22046001",
"endSection": "abstract",
"offsetInBeginSection": 286,
"offsetInEndSection": 382,
"text": "Recent evidence also suggests that late replication is associated with high mutability in yeast."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22046001",
"endSection": "abstract",
"offsetInBeginSection": 480,
"offsetInEndSection": 677,
"text": "Limited evidence from one chromosome arm in Drosophila melanogaster suggests the opposite pattern, with regions overlapping early-firing origins showing increased levels of diversity and divergence"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23821616",
"endSection": "abstract",
"offsetInBeginSection": 731,
"offsetInEndSection": 981,
"text": "The mutation rate for DNA mismatch repair null strains was approximately 1 mutation per genome per generation, 225-fold greater than the wild-type rate. The mutations were distributed randomly throughout the genome, independent of replication timing."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23422670",
"endSection": "abstract",
"offsetInBeginSection": 81,
"offsetInEndSection": 218,
"text": "Many single-nucleotide substitutions in cancer genomes arise because of errors in DNA replication, which is spatio-temporally stratified."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23422670",
"endSection": "abstract",
"offsetInBeginSection": 219,
"offsetInEndSection": 330,
"text": "Here we propose that DNA replication patterns help shape the mutational landscapes of normal and cancer genomes"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23422670",
"endSection": "abstract",
"offsetInBeginSection": 332,
"offsetInEndSection": 603,
"text": "Using data on five fully sequenced cancer types and two personal genomes, we determined that the frequency of intergenic single-nucleotide substitution is significantly higher in late DNA replication timing regions, even after controlling for a number of genomic features"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23422670",
"endSection": "abstract",
"offsetInBeginSection": 770,
"offsetInEndSection": 930,
"text": "we found that genomic regions in close spatial proximity to late-replicating domains display similar mutation spectra as the late-replicating regions themselves"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23271586",
"endSection": "abstract",
"offsetInBeginSection": 1047,
"offsetInEndSection": 1439,
"text": "In addition, certain chromosome rearrangements found in cancer cells and in cells exposed to ionizing radiation display a significant delay in replication timing of >3 hours that affects the entire chromosome(2,3). Recent work from our lab indicates that disruption of discrete cis-acting autosomal loci result in an extremely late replicating phenotype that affects the entire chromosome(4)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12941181",
"endSection": "abstract",
"offsetInBeginSection": 166,
"offsetInEndSection": 510,
"text": "A conservative estimate is that at least 1-2% of new deleterious mutations affect some aspect of DNA replication, repair, or chromosome segregation. Since deleterious mutations can have an effect even as heterozygotes, this mutation accumulation can create an inherited background of late-acting mutations that themselves enhance mutation rate."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9560368",
"endSection": "abstract",
"offsetInBeginSection": 650,
"offsetInEndSection": 972,
"text": "Drake calculates that lytic RNA viruses display spontaneous mutation rates of approximately one per genome while most have mutation rates that are approximately 0.1 per genome (Drake 1993). This constancy of germline mutation rates among microbial species need not necessarily mean constancy of the somatic mutation rates."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24598232",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 116,
"text": "A recent flurry of reports correlates replication timing (RT) with mutation rates during both evolution and cancer."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23327985",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 146,
"text": "DNA replication timing, genome stability and cancer: late and/or delayed DNA replication timing is associated with increased genomic instability."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24598232",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 116,
"text": "A recent flurry of reports correlates replication timing (RT) with mutation rates during both evolution and cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12941181",
"endSection": "abstract",
"offsetInBeginSection": 315,
"offsetInEndSection": 510,
"text": "Since deleterious mutations can have an effect even as heterozygotes, this mutation accumulation can create an inherited background of late-acting mutations that themselves enhance mutation rate."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24598232",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 116,
"text": "A recent flurry of reports correlates replication timing (RT) with mutation rates during both evolution and cancer."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23327985",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 146,
"text": "DNA replication timing, genome stability and cancer: late and/or delayed DNA replication timing is associated with increased genomic instability."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23271586",
"endSection": "abstract",
"offsetInBeginSection": 2048,
"offsetInEndSection": 2229,
"text": "In addition, this method allows for the unambiguous identification of chromosomal rearrangements that correlate with changes in replication timing that affect the entire chromosome."
}
]
| 5 | BioASQ-training5b | []
| []
| 5710dd61cf1c32585100002e | 48 |
yesno | Is Tofacitinib effective for Ulcerative Colitis? | ['yes'] | [
"yes"
]
| ['Yes. Tofacitinib, an oral small-molecule Janus kinase inhibitor, is effective in the treatment of moderate-severe ulcerative colitis. It is also effective treatment of rheumatoid arthritis and autoimmune encephalomyelitis.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/22894574",
"http://www.ncbi.nlm.nih.gov/pubmed/28467869",
"http://www.ncbi.nlm.nih.gov/pubmed/27663846",
"http://www.ncbi.nlm.nih.gov/pubmed/28503977",
"http://www.ncbi.nlm.nih.gov/pubmed/28164724",
"http://www.ncbi.nlm.nih.gov/pubmed/28158411",
"http://www.ncbi.nlm.nih.gov/pubmed/27140405",
"http://www.ncbi.nlm.nih.gov/pubmed/27699641",
"http://www.ncbi.nlm.nih.gov/pubmed/28601639",
"http://www.ncbi.nlm.nih.gov/pubmed/28790099",
"http://www.ncbi.nlm.nih.gov/pubmed/25651782",
"http://www.ncbi.nlm.nih.gov/pubmed/28475384",
"http://www.ncbi.nlm.nih.gov/pubmed/26608188"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28158411",
"endSection": "abstract",
"offsetInBeginSection": 879,
"offsetInEndSection": 1027,
"text": "Tofacitinib, inhibiting signalling via all Janus kinase family members, was effective in phase 2 and 3 trials in moderate-severe ulcerative colitis."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28164724",
"endSection": "abstract",
"offsetInBeginSection": 243,
"offsetInEndSection": 564,
"text": "Among them, Janus kinase (JAK) inhibitors seem to have the lead, since tofacitinib has received regulatory approval in 2012 for the treatment of rheumatoid arthritis, and also it has shown a favorable risk-benefit ratio in phase 3 studies for ulcerative colitis, both in anti-TNF naïve and anti-TNF experienced patients. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28475384",
"endSection": "abstract",
"offsetInBeginSection": 1023,
"offsetInEndSection": 1116,
"text": "Near future conventional drug options include oral agents such as tofacitinib and mongersen. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28503977",
"endSection": "abstract",
"offsetInBeginSection": 717,
"offsetInEndSection": 781,
"text": "Tofacitinib showed dose related efficacy for induction therapy. "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 72,
"text": "Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 174,
"text": "BACKGROUND: Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869",
"endSection": "abstract",
"offsetInBeginSection": 2243,
"offsetInEndSection": 2404,
"text": "CONCLUSIONS: In patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28601639",
"endSection": "abstract",
"offsetInBeginSection": 96,
"offsetInEndSection": 295,
"text": "Tofacitinib (CP-690,550), an oral small-molecule Janus kinase inhibitor, has been shown to be effective in the treatment of rheumatoid arthritis, autoimmune encephalomyelitis and ulcerative colitis. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 161,
"text": "Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 180,
"text": "<b>BACKGROUND</b>: Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869",
"endSection": "abstract",
"offsetInBeginSection": 1932,
"offsetInEndSection": 2444,
"text": "Across all three trials, adjudicated nonmelanoma skin cancer occurred in five patients who received tofacitinib and in one who received placebo, and adjudicated cardiovascular events occurred in five who received tofacitinib and in none who received placebo; as compared with placebo, tofacitinib was associated with increased lipid levels.<br><b>CONCLUSIONS</b>: In patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28601639",
"endSection": "abstract",
"offsetInBeginSection": 96,
"offsetInEndSection": 294,
"text": "Tofacitinib (CP-690,550), an oral small-molecule Janus kinase inhibitor, has been shown to be effective in the treatment of rheumatoid arthritis, autoimmune encephalomyelitis and ulcerative colitis."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22894574",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 74,
"text": "Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28790099",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 166,
"text": "Tofacitinib, a non-selective Janus kinase (JAK) inhibitor, is effective in inducing clinical and endoscopic remission in patients with active ulcerative colitis (UC)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 172,
"text": "BACKGROUND Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25651782",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 198,
"text": "BACKGROUND Tofacitinib, a novel, oral Janus kinase inhibitor, demonstrated a dose-dependent efficacy for induction of clinical response and remission in patients with active ulcerative colitis (UC)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869",
"endSection": "abstract",
"offsetInBeginSection": 2249,
"offsetInEndSection": 2409,
"text": "CONCLUSIONS In patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27663846",
"endSection": "abstract",
"offsetInBeginSection": 199,
"offsetInEndSection": 409,
"text": "Tofacitinib, an oral janus kinase inhibitor, is a new biologic that has shown promise in the treatment of ulcerative colitis and may be effective in the treatment of Crohn's disease according to phase 2 trials."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22894574",
"endSection": "abstract",
"offsetInBeginSection": 2066,
"offsetInEndSection": 2252,
"text": "CONCLUSIONS Patients with moderately to severely active ulcerative colitis treated with tofacitinib were more likely to have clinical response and remission than those receiving placebo."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22894574",
"endSection": "abstract",
"offsetInBeginSection": 1996,
"offsetInEndSection": 2285,
"text": "Three patients treated with tofacitinib had an absolute neutrophil count of less than 1500.<br><b>CONCLUSIONS</b>: Patients with moderately to severely active ulcerative colitis treated with tofacitinib were more likely to have clinical response and remission than those receiving placebo."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 2467,
"text": "tofacitinib an oral small molecule janus kinase inhibitor was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial we further evaluated the efficacy of tofacitinib as induction and maintenance therapy we conducted three phase 3 randomized double blind placebo controlled trials of tofacitinib therapy in adults with ulcerative colitis in the octave induction 1 and 2 trials 598 and 541 patients respectively who had moderately to severely active ulcerative colitis despite previous conventional therapy or therapy with a tumor necrosis factor antagonist were randomly assigned to receive induction therapy with tofacitinib 10 mg twice daily or placebo for 8 weeks the primary end point was remission at 8 weeks in the octave sustain trial 593 patients who had a clinical response to induction therapy were randomly assigned to receive maintenance therapy with tofacitinib either 5 mg or 10 mg twice daily or placebo for 52 weeks the primary end point was remission at 52 weeks in the octave induction 1 trial remission at 8 weeks occurred in 18 5 of the patients in the tofacitinib group versus 8 2 in the placebo group p 0 007 in the octave induction 2 trial remission occurred in 16 6 versus 3 6 p 0 001 in the octave sustain trial remission at 52 weeks occurred in 34 3 of the patients in the 5 mg tofacitinib group and 40 6 in the 10 mg tofacitinib group versus 11 1 in the placebo group p 0 001 for both comparisons with placebo in the octave induction 1 and 2 trials the rates of overall infection and serious infection were higher with tofacitinib than with placebo in the octave sustain trial the rate of serious infection was similar across the three treatment groups and the rates of overall infection and herpes zoster infection were higher with tofacitinib than with placebo across all three trials adjudicated nonmelanoma skin cancer occurred in five patients who received tofacitinib and in one who received placebo and adjudicated cardiovascular events occurred in five who received tofacitinib and in none who received placebo as compared with placebo tofacitinib was associated with increased lipid levels in patients with moderately to severely active ulcerative colitis tofacitinib was more effective as induction and maintenance therapy than placebo funded by pfizer octave induction 1 octave induction 2 and octave sustain clinicaltrials gov numbers nct01465763 nct01458951 and nct01458574 respectively."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22894574",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 2176,
"text": "ulcerative colitis is a chronic inflammatory disease of the colon for which current treatments are not universally effective one additional treatment may be tofacitinib cp 690 550 an oral inhibitor of janus kinases 1 2 and 3 with in vitro functional specificity for kinases 1 and 3 over kinase 2 which is expected to block signaling involving gamma chain containing cytokines including interleukins 2 4 7 9 15 and 21 these cytokines are integral to lymphocyte activation function and proliferation in a double blind placebo controlled phase 2 trial we evaluated the efficacy of tofacitinib in 194 adults with moderately to severely active ulcerative colitis patients were randomly assigned to receive tofacitinib at a dose of 0 5 mg 3 mg 10 mg or 15 mg or placebo twice daily for 8 weeks the primary outcome was a clinical response at 8 weeks defined as an absolute decrease from baseline in the score on the mayo scoring system for assessment of ulcerative colitis activity possible score 0 to 12 with higher scores indicating more severe disease of 3 or more and a relative decrease from baseline of 30 or more with an accompanying decrease in the rectal bleeding subscore of 1 point or more or an absolute rectal bleeding subscore of 0 or 1 the primary outcome clinical response at 8 weeks occurred in 32 48 61 and 78 of patients receiving tofacitinib at a dose of 0 5 mg p 0 39 3 mg p 0 55 10 mg p 0 10 and 15 mg p 0 001 respectively as compared with 42 of patients receiving placebo clinical remission defined as a mayo score 2 with no subscore 1 at 8 weeks occurred in 13 33 48 and 41 of patients receiving tofacitinib at a dose of 0 5 mg p 0 76 3 mg p 0 01 10 mg p 0 001 and 15 mg p 0 001 respectively as compared with 10 of patients receiving placebo there was a dose dependent increase in both low density and high density lipoprotein cholesterol three patients treated with tofacitinib had an absolute neutrophil count of less than 1500 patients with moderately to severely active ulcerative colitis treated with tofacitinib were more likely to have clinical response and remission than those receiving placebo funded by pfizer clinicaltrials gov number nct00787202."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27699641",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 851,
"text": "recently several medical treatments for ulcerative colitis uc have been developed including 5 aminosalicylic acids 5 asas corticosteroids thiopurine calcineurin inhibitors and anti tumor necrosis factor tnf α treatments treatment options including calcineurin inhibitors and anti tnf treatment for refractory uc are discussed in this article furthermore upcoming treatments are introduced such as golimumab vedolizumab ajm300 tofacitinib budesonide foamwill be used as one treatment option in patients with distal colitis herbal medicine such as qing dai is also effective for active uc and may be useful for patients who are refractory to anti tnfα treatments in the near future physicians will able to use many different treatments for uc patients however we should not forget 5 asa and corticosteroids as the fundamental treatments for uc patients."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26608188",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 1420,
"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."
}
]
| 11 | BioASQ-training11b | [
"http://www.disease-ontology.org/api/metadata/DOID:8577",
"https://meshb.nlm.nih.gov/record/ui?ui=D016896",
"https://meshb.nlm.nih.gov/record/ui?ui=D003093"
]
| null | 5a723edd2dc08e987e00000c | 49 |
yesno | Can botulism poisoning of a pregnant woman harm her fetus? | ['no'] | [
"no"
]
| ['Botulinum toxin, which causes botulism, is not expected to be present in systemic circulation following proper intramuscular or intradermal injection. Moreover, botulinum toxin has a high molecular weight, and does not appear to cross the placenta. Based on the study cases reported in the literature, botulism poisoning during pregnancy does not appear to increase the risk of adverse outcome in the fetus.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/24235190",
"http://www.ncbi.nlm.nih.gov/pubmed/23735780"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23735780",
"endSection": "abstract",
"offsetInBeginSection": 632,
"offsetInEndSection": 871,
"text": "Two botulism outbreaks were attributed to commercial ready-to-eat meat products and 3 to foods served in restaurants; several cases were attributed to non-Native home-prepared foods. Three affected pregnant women delivered healthy infants."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24235190",
"endSection": "abstract",
"offsetInBeginSection": 192,
"offsetInEndSection": 610,
"text": "Botulinum toxin is not expected to be present in systemic circulation following proper intramuscular or intradermal injection. Moreover, BTX-A, which has a high molecular weight, does not appear to cross the placenta. From the 38 pregnancies reported in the literature, including women who had botulism poisoning during pregnancy, exposure to BTX-A does not appear to increase the risk of adverse outcome in the fetus."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24235190",
"endSection": "abstract",
"offsetInBeginSection": 393,
"offsetInEndSection": 593,
"text": "From the 38 pregnancies reported in the literature, including women who had botulism poisoning during pregnancy, exposure to BTX-A does not appear to increase the risk of adverse outcome in the fetus."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24235190",
"endSection": "abstract",
"offsetInBeginSection": 393,
"offsetInEndSection": 593,
"text": "From the 38 pregnancies reported in the literature, including women who had botulism poisoning during pregnancy, exposure to BTX-A does not appear to increase the risk of adverse outcome in the fetus."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24235190",
"endSection": "abstract",
"offsetInBeginSection": 393,
"offsetInEndSection": 593,
"text": "From the 38 pregnancies reported in the literature, including women who had botulism poisoning during pregnancy, exposure to BTX-A does not appear to increase the risk of adverse outcome in the fetus."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24235190",
"endSection": "abstract",
"offsetInBeginSection": 393,
"offsetInEndSection": 593,
"text": "From the 38 pregnancies reported in the literature, including women who had botulism poisoning during pregnancy, exposure to BTX-A does not appear to increase the risk of adverse outcome in the fetus."
}
]
| 5 | BioASQ-training5b | [
"http://www.disease-ontology.org/api/metadata/DOID:11976",
"http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037841",
"http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005333",
"http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014930",
"http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011041",
"http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011042"
]
| []
| 554763f0f35db75526000002 | 50 |
yesno | Does amiodarone affect thyroid hormone receptors in the myocardium? | ['yes'] | [
"yes"
]
| ['Yes'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/17535870",
"http://www.ncbi.nlm.nih.gov/pubmed/10445678",
"http://www.ncbi.nlm.nih.gov/pubmed/9781936",
"http://www.ncbi.nlm.nih.gov/pubmed/7598731"
]
| [
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17535870",
"endSection": "sections.0",
"offsetInBeginSection": 732,
"offsetInEndSection": 845,
"text": "AM and Dron affected TR expression in the RA similarly by decreasing TRalpha 1 and beta 1 expression by about 50%"
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17535870",
"endSection": "sections.0",
"offsetInBeginSection": 847,
"offsetInEndSection": 933,
"text": "In the LVW, AM and Dron decreased TRbeta 1 and, interestingly, AM increased TRalpha 1."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17535870",
"endSection": "sections.0",
"offsetInBeginSection": 935,
"offsetInEndSection": 975,
"text": "n the apex, AM also increased TRalpha 2."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10445678",
"endSection": "sections.0",
"offsetInBeginSection": 1080,
"offsetInEndSection": 1324,
"text": "Both in treated and untreated mice, TRalpha2 mRNA had the highest density in mouse heart, whereas TRbeta2 mRNA had the lowest density. Amiodarone dose-dependently downregulated the levels of TRalpha1 and beta1 mRNA in comparison to the control."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10445678",
"endSection": "sections.0",
"offsetInBeginSection": 1537,
"offsetInEndSection": 1648,
"text": "amiodarone subtype selectively downregulates the TR mRNA levels in mouse myocardium in a dose-dependent manner."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9781936",
"endSection": "sections.0",
"offsetInBeginSection": 1613,
"offsetInEndSection": 1691,
"text": "Western blot analysis revealed no change in the expression of the ThR protein."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7598731",
"endSection": "sections.0",
"offsetInBeginSection": 830,
"offsetInEndSection": 1094,
"text": "Amiodarone and T3, respectively, downregulated T3R alpha 1, T3R beta 1, T3R beta 2 (p < 0.05), but did not affect the levels of T3R alpha 2. Amiodarone and T3, added together, upregulated T3R alpha 2 and T3R beta 1 (p < 0.05) as compared to amiodarone or T3 alone."
}
]
| 5 | BioASQ-training5b | [
"http://www.uniprot.org/uniprot/THB_PAROL",
"http://www.uniprot.org/uniprot/THB_DANRE",
"http://www.uniprot.org/uniprot/THB_MOUSE",
"http://www.uniprot.org/uniprot/THB_HUMAN",
"http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042",
"http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021",
"http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988",
"http://www.uniprot.org/uniprot/THA_LITCT",
"http://www.uniprot.org/uniprot/THA_SPAAU",
"http://www.uniprot.org/uniprot/THA_ONCMY",
"http://www.uniprot.org/uniprot/THA_SALSA",
"http://www.uniprot.org/uniprot/THB_LITCT",
"http://www.uniprot.org/uniprot/THB_SHEEP",
"http://www.uniprot.org/uniprot/THBA_XENLA",
"http://www.uniprot.org/uniprot/THB_RAT",
"http://www.uniprot.org/uniprot/THB_CAIMO",
"http://www.uniprot.org/uniprot/THB_CHICK",
"http://www.uniprot.org/uniprot/THA_MOUSE",
"http://www.uniprot.org/uniprot/THA_APTPA",
"http://www.uniprot.org/uniprot/THAA_DANRE",
"http://www.uniprot.org/uniprot/THA_CAIMO",
"http://www.uniprot.org/uniprot/THA_NECMA",
"http://www.uniprot.org/uniprot/THAA_PAROL",
"http://www.uniprot.org/uniprot/THA_ELECQ",
"http://www.uniprot.org/uniprot/THA_CHICK",
"http://www.uniprot.org/uniprot/THA_SHEEP",
"http://www.uniprot.org/uniprot/THA_HUMAN",
"http://www.uniprot.org/uniprot/THA_PIG",
"http://www.uniprot.org/uniprot/THA_RAT",
"http://www.uniprot.org/uniprot/THAA_XENLA",
"http://www.uniprot.org/uniprot/THA_HIPHI",
"http://www.uniprot.org/uniprot/THA_PYGAD",
"http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963",
"http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000638",
"http://www.biosemantics.org/jochem#4274241"
]
| null | 516d5baa298dcd4e51000078 | 51 |
yesno | Does thyroid hormone regulate calcium transient in the myocardium? | ['yes'] | [
"yes"
]
| ['YES'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/19298522",
"http://www.ncbi.nlm.nih.gov/pubmed/9875761",
"http://www.ncbi.nlm.nih.gov/pubmed/9773867",
"http://www.ncbi.nlm.nih.gov/pubmed/2428004"
]
| [
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19298522",
"endSection": "sections.0",
"offsetInBeginSection": 0,
"offsetInEndSection": 249,
"text": "3-iodothyronamine (T(1)AM) is a novel endogenous relative of thyroid hormone, able to interact with trace amine-associated receptors, a class of plasma membrane G protein-coupled receptors, and to produce a negative inotropic and chronotropic effect"
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19298522",
"endSection": "sections.0",
"offsetInBeginSection": 455,
"offsetInEndSection": 580,
"text": "In adult rat cardiomyocytes acute exposure to 20 microM T(1)AM decreased the amplitude and duration of the calcium transient."
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9875761",
"endSection": "sections.0",
"offsetInBeginSection": 1520,
"offsetInEndSection": 1869,
"text": "In normal porcine myocardium T3 had no effect on the extent of isometric force generation but accelerated the time course of force development (p < 0.05) and increased the calcium transient (p < 0.001). After induction of myocardial depression by epinephrine exposure T3 accelerated the intracellular calcium transients and reduced diastolic calcium"
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9773867",
"endSection": "sections.0",
"offsetInBeginSection": 2162,
"offsetInEndSection": 2428,
"text": "The experimental data showing increased force amplitudes at unaltered amplitudes of the intracellular calcium transient and an even-reduced calcium time integral provide strong evidence for a sensitization of the contractile apparatus for calcium by triiodothyronine"
},
{
"beginSection": "sections.0",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2428004",
"endSection": "sections.0",
"offsetInBeginSection": 1313,
"offsetInEndSection": 1525,
"text": "hese results indicate that the thyroid state influences the time course of the calcium transient and are consistent with the abbreviation in the duration of contraction that is observed in the hyperthyroid state."
}
]
| 5 | BioASQ-training5b | [
"http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963",
"http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0070327",
"http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0070324",
"http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988",
"http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004887",
"http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010861",
"http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021",
"http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042",
"http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014284",
"http://www.uniprot.org/uniprot/THB_RAT",
"http://www.uniprot.org/uniprot/THB_DANRE",
"http://www.uniprot.org/uniprot/THB_MOUSE",
"http://www.uniprot.org/uniprot/THB_HUMAN",
"http://www.uniprot.org/uniprot/THB_PAROL",
"http://www.uniprot.org/uniprot/THB_SHEEP",
"http://www.uniprot.org/uniprot/THB_CAIMO",
"http://www.uniprot.org/uniprot/THB_CHICK",
"http://www.uniprot.org/uniprot/THA_MOUSE",
"http://www.uniprot.org/uniprot/THA_APTPA",
"http://www.uniprot.org/uniprot/THAA_DANRE",
"http://www.uniprot.org/uniprot/THAA_PAROL",
"http://www.uniprot.org/uniprot/THA_ONCMY",
"http://www.uniprot.org/uniprot/THA_HUMAN",
"http://www.uniprot.org/uniprot/THA_LITCT",
"http://www.uniprot.org/uniprot/THA_SPAAU",
"http://www.uniprot.org/uniprot/THB_LITCT",
"http://www.uniprot.org/uniprot/THBA_XENLA",
"http://www.uniprot.org/uniprot/THA_CHICK",
"http://www.uniprot.org/uniprot/THA_ELECQ",
"http://www.uniprot.org/uniprot/THAA_XENLA",
"http://www.uniprot.org/uniprot/THA_CAIMO",
"http://www.uniprot.org/uniprot/THA_NECMA",
"http://www.uniprot.org/uniprot/THA_PIG",
"http://www.uniprot.org/uniprot/THA_RAT",
"http://www.uniprot.org/uniprot/THA_SALSA",
"http://www.uniprot.org/uniprot/THA_HIPHI",
"http://www.uniprot.org/uniprot/THA_PYGAD",
"http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009206"
]
| null | 515ac533d24251bc050000a9 | 53 |
yesno | Can you computationally predict Molecular Recognition Features (MoRFs) regions in Intrinsically Disordered Proteins (IDPs)? | ['yes'] | [
"yes"
]
| ['Yes. There are various tools available in the literature that enable computational identification of Molecular Recognition Features (MoRFs) regions in intrinsically disordered protein sequences.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/30324701",
"http://www.ncbi.nlm.nih.gov/pubmed/30298407",
"http://www.ncbi.nlm.nih.gov/pubmed/25637562",
"http://www.ncbi.nlm.nih.gov/pubmed/26517836",
"http://www.ncbi.nlm.nih.gov/pubmed/29360926",
"http://www.ncbi.nlm.nih.gov/pubmed/29042212"
]
| [
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30298407",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 58,
"text": "Predicting Functions of Disordered Proteins with MoRFpred."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30298407",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 949,
"text": "Intrinsically disordered proteins and regions are involved in a wide range of cellular functions, and they often facilitate protein-protein interactions. Molecular recognition features (MoRFs) are segments of intrinsically disordered regions that bind to partner proteins, where binding is concomitant with a transition to a structured conformation. MoRFs facilitate translation, transport, signaling, and regulatory processes and are found across all domains of life. A popular computational tool, MoRFpred, accurately predicts MoRFs in protein sequences. MoRFpred is implemented as a user-friendly web server that is freely available at http://biomine.cs.vcu.edu/servers/MoRFpred/ . We describe this predictor, explain how to run the web server, and show how to interpret the results it generates. We also demonstrate the utility of this web server based on two case studies, focusing on the relevance of evolutionary conservation of MoRF regions."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29042212",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 124,
"text": "MoRFPred-plus: Computational Identification of MoRFs in Protein Sequences using Physicochemical Properties and HMM profiles."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29042212",
"endSection": "abstract",
"offsetInBeginSection": 12,
"offsetInEndSection": 1777,
"text": "Intrinsically Disordered Proteins (IDPs) lack stable tertiary structure and they actively participate in performing various biological functions. These IDPs expose short binding regions called Molecular Recognition Features (MoRFs) that permit interaction with structured protein regions. Upon interaction they undergo a disorder-to-order transition as a result of which their functionality arises. Predicting these MoRFs in disordered protein sequences is a challenging task.METHOD: In this study, we present MoRFpred-plus, an improved predictor over our previous proposed predictor to identify MoRFs in disordered protein sequences. Two separate independent propensity scores are computed via incorporating physicochemical properties and HMM profiles, these scores are combined to predict final MoRF propensity score for a given residue. The first score reflects the characteristics of a query residue to be part of MoRF region based on the composition and similarity of assumed MoRF and flank regions. The second score reflects the characteristics of a query residue to be part of MoRF region based on the properties of flanks associated around the given residue in the query protein sequence. The propensity scores are processed and common averaging is applied to generate the final prediction score of MoRFpred-plus.RESULTS: Performance of the proposed predictor is compared with available MoRF predictors, MoRFchibi, MoRFpred, and ANCHOR. Using previously collected training and test sets used to evaluate the mentioned predictors, the proposed predictor outperforms these predictors and generates lower false positive rate. In addition, MoRFpred-plus is a downloadable predictor, which makes it useful as it can be used as input to other computational tools."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29360926",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 79,
"text": "OPAL: prediction of MoRF regions in intrinsically disordered protein sequences."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29360926",
"endSection": "abstract",
"offsetInBeginSection": 12,
"offsetInEndSection": 1433,
"text": "Intrinsically disordered proteins lack stable 3-dimensional structure and play a crucial role in performing various biological functions. Key to their biological function are the molecular recognition features (MoRFs) located within long disordered regions. Computationally identifying these MoRFs from disordered protein sequences is a challenging task. In this study, we present a new MoRF predictor, OPAL, to identify MoRFs in disordered protein sequences. OPAL utilizes two independent sources of information computed using different component predictors. The scores are processed and combined using common averaging method. The first score is computed using a component MoRF predictor which utilizes composition and sequence similarity of MoRF and non-MoRF regions to detect MoRFs. The second score is calculated using half-sphere exposure (HSE), solvent accessible surface area (ASA) and backbone angle information of the disordered protein sequence, using information from the amino acid properties of flanks surrounding the MoRFs to distinguish MoRF and non-MoRF residues.Results: OPAL is evaluated using test sets that were previously used to evaluate MoRF predictors, MoRFpred, MoRFchibi and MoRFchibi-web. The results demonstrate that OPAL outperforms all the available MoRF predictors and is the most accurate predictor available for MoRF prediction. It is available at http://www.alok-ai-lab.com/tools/opal/."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30324701",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 85,
"text": "OPAL+: Length-Specific MoRF Prediction in Intrinsically Disordered Protein Sequences."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30324701",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 972,
"text": "Intrinsically disordered proteins (IDPs) contain long unstructured regions, which play an important role in their function. These intrinsically disordered regions (IDRs) participate in binding events through regions called molecular recognition features (MoRFs). Computational prediction of MoRFs helps identify the potentially functional regions in IDRs. In this study, OPAL+, a novel MoRF predictor, is presented. OPAL+ uses separate models to predict MoRFs of varying lengths along with incorporating the hidden Markov model (HMM) profiles and physicochemical properties of MoRFs and their flanking regions. Together, these features help OPAL+ achieve a marginal performance improvement of 0.4-0.7% over its predecessor for diverse MoRF test sets. This performance improvement comes at the expense of increased run time as a result of the requirement of HMM profiles. OPAL+ is available for download at https://github.com/roneshsharma/OPAL-plus/wiki/OPAL-plus-Download."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26517836",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 104,
"text": "Computational Identification of MoRFs in Protein Sequences Using Hierarchical Application of Bayes Rule."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26517836",
"endSection": "abstract",
"offsetInBeginSection": 131,
"offsetInEndSection": 1810,
"text": "Key to their regulatory function is often the binding to globular protein domains via sequence elements known as molecular recognition features (MoRFs). Development of computational tools for the identification of candidate MoRF locations in amino acid sequences is an important task and an area of growing interest. Given the relative sparseness of MoRFs in protein sequences, the accuracy of the available MoRF predictors is often inadequate for practical usage, which leaves a significant need and room for improvement. In this work, we introduce MoRFCHiBi_Web, which predicts MoRF locations in protein sequences with higher accuracy compared to current MoRF predictors.METHODS: Three distinct and largely independent property scores are computed with component predictors and then combined to generate the final MoRF propensity scores. The first score reflects the likelihood of sequence windows to harbour MoRFs and is based on amino acid composition and sequence similarity information. It is generated by MoRFCHiBi using small windows of up to 40 residues in size. The second score identifies long stretches of protein disorder and is generated by ESpritz with the DisProt option. Lastly, the third score reflects residue conservation and is assembled from PSSM files generated by PSI-BLAST. These propensity scores are processed and then hierarchically combined using Bayes rule to generate the final MoRFCHiBi_Web predictions.RESULTS: MoRFCHiBi_Web was tested on three datasets. Results show that MoRFCHiBi_Web outperforms previously developed predictors by generating less than half the false positive rate for the same true positive rate at practical threshold values."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25637562",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 59,
"text": "Computational identification of MoRFs in protein sequences."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25637562",
"endSection": "abstract",
"offsetInBeginSection": 429,
"offsetInEndSection": 1580,
"text": "In this study, we introduce MoRFCHiBi, a new computational approach for fast and accurate prediction of MoRFs in protein sequences. MoRFCHiBi combines the outcomes of two support vector machine (SVM) models that take advantage of two different kernels with high noise tolerance. The first, SVMS, is designed to extract maximal information from the general contrast in amino acid compositions between MoRFs, their surrounding regions (Flanks), and the remainders of the sequences. The second, SVMT, is used to identify similarities between regions in a query sequence and MoRFs of the training set.RESULTS: We evaluated the performance of our predictor by comparing its results with those of two currently available MoRF predictors, MoRFpred and ANCHOR. Using three test sets that have previously been collected and used to evaluate MoRFpred and ANCHOR, we demonstrate that MoRFCHiBi outperforms the other predictors with respect to different evaluation metrics. In addition, MoRFCHiBi is downloadable and fast, which makes it useful as a component in other computational prediction tools.AVAILABILITY AND IMPLEMENTATION: http://www.chibi.ubc.ca/morf/."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29360926",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 137,
"text": "OPAL: prediction of MoRF regions in intrinsically disordered protein sequences.Supplementary data are available at Bioinformatics online."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30324701",
"endSection": "abstract",
"offsetInBeginSection": 263,
"offsetInEndSection": 355,
"text": "Computational prediction of MoRFs helps identify the potentially functional regions in IDRs."
}
]
| 11 | BioASQ-training11b | null | null | 5c6d9a157c78d69471000041 | 55 |
yesno | Is tumor expression of Topoisomerase I a biomarker of response to irinotecan in colorectal cancer patients therapy? | ['yes'] | [
"yes"
]
| ['Based on the provided abstracts, it appears that topoisomerase I (TOP1) copy number alterations may be associated with response to irinotecan in metastatic colorectal cancer patients. In one study, a borderline significant association was observed between increasing TOP1 copy number and objective response to irinotecan. However, the ratios of TOP1/CEN-20 and TOP1/CEN-2 did not provide additional information for patient stratification. Another study developed an immunohistochemistry-based predictive test, P-topoI-Dx, which demonstrated good sensitivity and specificity in identifying patients who responded to camptothecin-based therapy, including irinotecan. Overall, tumor expression of TOP1 may be a promising biomarker of response to irinotecan in colorectal cancer patients, but further validation is needed.', 'Based on the provided information, the role of topoisomerase I (Topo I) expression as a predictive biomarker for response to irinotecan (CPT-11) in colorectal cancer patients remains controversial and inconclusive.\n\nSome studies suggest that higher Topo I expression in tumor tissue may be associated with better response to irinotecan-based therapy. For example, one study found that responding patients had significantly higher Topo I expression compared to non-responders. Another study showed a borderline significant association between increased Topo I levels and objective response.\n\nHowever, other studies did not find a significant difference in response rates between tumors with high and low Topo I expression. One study concluded that clinical response and prognosis did not differ based on Topo I expression levels.\n\nIn summary, while preliminary data suggests a potential role for Topo I as a predictive biomarker, the evidence is mixed and controversial. Larger, well-designed studies, preferably in a randomized setting, are needed to clarify the utility of Topo I expression in guiding irinotecan treatment decisions in colorectal cancer patients.', 'Based on the provided information, tumor expression of Topoisomerase I (Topo I) may serve as a potential biomarker of response to irinotecan therapy in colorectal cancer patients, but the evidence is not conclusive.\n\nSome studies suggest that higher Topo I expression in tumor tissue is associated with better response to irinotecan-based therapy. For example, one study found that biopsies from responding patients had significantly higher Topo I expression compared to non-responders. Another showed a borderline significant association between increasing Topo I levels and objective response.\n\nHowever, other studies did not find a significant difference in response rates between tumors with high vs low Topo I expression. One concluded that prognosis did not differ based on Topo I levels in patients treated with irinotecan.\n\nIn summary, while preliminary data indicates Topo I expression could be a predictive biomarker for irinotecan response, the results are mixed and controversial. More research, ideally in larger randomized trials, is needed to validate Topo I as a reliable biomarker to guide irinotecan therapy decisions in colorectal cancer patients. Currently, the evidence is suggestive but not definitive.', 'The expression level of topoisomerase-I (Topo I) in colorectal cancer (CRC) tumors has been studied as a potential biomarker for predicting response to irinotecan-based therapy. Preliminary data suggests that higher Topo I expression in untreated tumor tissue may be associated with a better response to irinotecan-based chemoradiation. However, other studies have not found a significant association between Topo I expression and response to irinotecan-based therapy. Therefore, the use of Topo I expression as a biomarker for predicting response to irinotecan in CRC patients is still a topic of ongoing research and not yet established in clinical practice.', 'Based on the abstract, yes, tumor expression of Topoisomerase I (Topo I) is associated with improved outcome in patients with resected colorectal cancer treated with irinotecan-containing adjuvant chemotherapy. In the multivariate analysis, Topo I expression was found to be associated with a reduced risk of death (HR = 0.61, p = 0.009). Moreover, in the subgroup of patients who received irinotecan-containing chemotherapy, those with Topo I expression had better overall survival (HR = 0.47, p = 0.033). These findings suggest that Topo I tumor expression may be a biomarker for predicting response to irinotecan therapy in colorectal cancer patients. However, as the authors conclude, randomized prospective trials are needed to confirm these results.', 'In summary, tumor expression of Topoisomerase I (Topo I) is suggested as a biomarker for response to irinotecan in colorectal cancer patients receiving adjuvant chemotherapy. Patients with resected CRC expressing Topo I tend to benefit from this treatment and may have improved outcomes, potentially guiding personalized treatment decisions.', 'Yes, tumor expression of Topoisomerase I (Top1) has been identified as a potential biomarker for response to irinotecan therapy in colorectal cancer patients. Preliminary data suggest that gene expression levels of Top1 may be predictive of response to therapy with irinotecan. In a study, the biopsies of the untreated tumor tissue of responding patients showed a significant higher expression of Top1 compared with nonresponding patients. Another study demonstrated a borderline significant association between a stepwise increase in the TOP1 signal count and objective response. Despite limitations of the study, the positive associations between TOP1 and objective response suggest that further analysis in larger tumor material is warranted. However, it is controversial whether the response to irinotecan could be predicted by the expression level of Top1.', 'Based on the abstracts provided, there is evidence suggesting that tumor expression of Topoisomerase I (TOP1) may be a biomarker of response to irinotecan-based therapy in colorectal cancer patients. In one study, TOP1 expression was significantly higher in responding patients with rectal cancer who received neoadjuvant chemoradiation with irinotecan and capecitabine. Additionally, TOP1 expression decreased significantly during treatment in responders. Another study found a borderline significant association between increasing TOP1 copy number and objective response to irinotecan therapy in breast cancer patients. While the evidence is not yet conclusive, these findings suggest that TOP1 may be a useful biomarker for predicting response to irinotecan-based therapy in certain patient populations.', 'Yes, tumor expression of Topoisomerase I (Top1) has been identified as a potential biomarker for response to irinotecan therapy in colorectal cancer patients. Irinotecan is a topoisomerase inhibitor that blocks the Top1 enzyme, leading to DNA damage and cell death. The inhibition of Top1 by irinotecan is achieved by trapping a subset of Top1-DNA cleavage complexes, specifically those with a guanine +1 in the DNA sequence. Top1 is a DNA topoisomerase that controls and alters the topologic states of DNA during transcription. It is encoded by the TOP1 gene, which is located on chromosome 20. The enzyme catalyzes the transient breaking and rejoining of a single strand of DNA, allowing the broken strand to rotate around the intact strand and altering the topology of DNA. Irinotecan inactivation of Top1 has been shown to be synthetically lethal in combination with deficiencies in expression of specific DNA repair genes, such as the DNA repair WRN gene and the DNA repair MRE11 gene. This synthetic lethality has been observed in patients with colon cancer, with irinotecan being more strongly beneficial for patients with hypermethylated WRN promoters compared to those with unmethylated WRN promoters. In addition, irinotecan inactivation of Top1 may be synthetically lethal with deficient expression of DNA repair gene ATM, which is frequently hypermethylated in many cancers. A 2016 study showed that low expression of the ATM protein in gastric cancer cells in vitro and in a mouse model caused increased sensitivity to inactivation by irinotecan compared to cells with high expression of ATM. Overall, the evidence suggests that Top1 expression may be a useful biomarker for predicting response to irinotecan therapy in colorectal cancer patients, particularly in those with deficiencies in specific DNA repair genes. However, further research is needed to confirm these findings and determine the clinical utility of Top1 expression as a biomarker.', 'Yes, the expression of Topoisomerase I (Topo I) in resected colorectal cancer (CRC) seems to be a biomarker of response to irinotecan therapy. Patients with CRC expressing Topo I appear to benefit from irinotecan-containing adjuvant chemotherapy.', 'Tumor expression of Topoisomerase I (Topo I) may serve as a biomarker for predicting response to irinotecan in colorectal cancer patients, indicating that those with resected CRC expressing Topo I are more likely to benefit from irinotecan-containing adjuvant chemotherapy. This suggests the potential use of Topo I expression as a personalized treatment guide for irinotecan therapy in CRC patients.', 'Based on the provided snippet, yes, tumor expression of Topoisomerase I (Topo I) appears to be a biomarker of response to irinotecan in colorectal cancer (CRC) patients. The snippet suggests that patients with resected CRC who express Topo I tend to benefit from irinotecan-containing adjuvant chemotherapy. This implies that Topo I expression is associated with improved treatment outcomes in CRC patients receiving irinotecan-based therapy. As a biomarker, Topo I expression could potentially identify patients who are more likely to respond to irinotecan and guide personalized treatment decisions.', 'Tumor expression of topoisomerase I (TOPO-1) may be a potential biomarker of response to irinotecan-based chemotherapy in patients with metastatic colorectal cancer (mCRC). In a study of 98 mCRC patients, high expression of TOPO-1 was found to be positively correlated with better curative effect and longer progression-free survival (PFS) and overall survival (OS) in patients who underwent irinotecan chemotherapy. However, TOPO-1 expression was not significantly correlated with age, gender, tumor site, tumor grade, or metastatic sites in mCRC patients. Additionally, a separate study examining biomarker-guided treatment for patients with colon cancer found that patients with high ABCG2 expression and low TOP-1 expression had worse recurrence-free survival (RFS) and overall survival (OS) when treated with irinotecan-based therapy. These findings suggest that TOPO-1 expression may be a useful biomarker for predicting response to irinotecan-based therapy in mCRC patients.', 'The association between tumor expression of Topoisomerase I and a clinical response to irinotecan therapy in colorectal cancer patients has not been demonstrated. However, Topoisomerase I overexpression in colorectal cancer has been associated with a poor prognosis, and the activity of irinotecan can be predicted by Topoisomerase I levels in colorectal cancer cells.', 'Yes, tumor expression of Topoisomerase I is a biomarker of response to irinotecan in colorectal cancer patients therapy. Patients with resected CRC expressing Topo I seem to benefit from irinotecan-containing adjuvant chemotherapy.', 'Patients with resected CRC expressing Topo I seem to benefit from irinotecan-containing adjuvant chemotherapy.', "Yes, tumor expression of Topoisomerase I is a biomarker of response to irinotecan in colorectal cancer patients, as patients with resected CRC expressing Topo I seem to benefit from irinotecan-containing adjuvant chemotherapy. \n\nPlease go ahead and ask your question. I'll do my best to provide a concise answer based on the context. \n\n(Note: You can ask multiple questions, and I'll respond accordingly.)"] | [
"http://www.ncbi.nlm.nih.gov/pubmed/22108516",
"https://pubmed.ncbi.nlm.nih.gov/22788763/",
"http://www.ncbi.nlm.nih.gov/pubmed/24256029",
"http://www.ncbi.nlm.nih.gov/pubmed/33790151",
"http://www.ncbi.nlm.nih.gov/pubmed/38016427",
"http://www.ncbi.nlm.nih.gov/pubmed/16184927",
"http://www.ncbi.nlm.nih.gov/pubmed/11177741",
"http://www.ncbi.nlm.nih.gov/pubmed/28077117",
"http://www.ncbi.nlm.nih.gov/pubmed/36678550",
"https://pubmed.ncbi.nlm.nih.gov/21874414/",
"http://www.ncbi.nlm.nih.gov/pubmed/19775480",
"http://www.ncbi.nlm.nih.gov/pubmed/26542057",
"http://www.ncbi.nlm.nih.gov/pubmed/28880238",
"http://www.ncbi.nlm.nih.gov/pubmed/37176164",
"http://www.ncbi.nlm.nih.gov/pubmed/15197779",
"http://www.ncbi.nlm.nih.gov/pubmed/19436196",
"https://pubmed.ncbi.nlm.nih.gov/19436196/",
"http://www.ncbi.nlm.nih.gov/pubmed/29261002",
"http://www.ncbi.nlm.nih.gov/pubmed/31196001",
"http://www.ncbi.nlm.nih.gov/pubmed/33731288",
"http://www.ncbi.nlm.nih.gov/pubmed/28870917",
"http://www.ncbi.nlm.nih.gov/pubmed/32326511",
"http://www.ncbi.nlm.nih.gov/pubmed/32764831",
"http://www.ncbi.nlm.nih.gov/pubmed/24966994",
"http://www.ncbi.nlm.nih.gov/pubmed/15160997",
"http://www.ncbi.nlm.nih.gov/pubmed/21874414"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19775480",
"endSection": "abstract",
"offsetInBeginSection": 1475,
"offsetInEndSection": 1585,
"text": "Patients with resected CRC expressing Topo I seem to benefit from irinotecan-containing adjuvant chemotherapy."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28077117",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 109,
"text": "Topoisomerase I copy number alterations as biomarker for irinotecan efficacy in metastatic colorectal cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29261002",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36678550",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32326511",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28870917",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31196001",
"endSection": "abstract",
"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 ≥4 or a TOP1/CEN20 ratio of ≥2. Patients were treated with irinotecan +/- trastuzumab weekly for 4 weeks following 2 weeks break, until progression or unacceptable toxicities. Evaluation scans were performed every 6 weeks. Primary endpoint was clinical benefit rate defined as the fraction of patients with stable disease for ≥4 months.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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33731288",
"endSection": "abstract",
"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 = 79) and a validation cohort (n = 27) of gastric cancer (GC) patients, and 8 cohorts of colorectal cancer (CRC) patient tissue (n = 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 = 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 = 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 = 176), the 40% threshold demonstrated 87.5% (78-94) sensitivity; 70.0% (59-79) specificity; PPV "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33790151",
"endSection": "abstract",
"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 Ⅰ(topo Ⅰ)is an important step for irinotecan resistance. We have developed an immunohistochemical staining-based biomarker; topo Ⅰ-pS10, for predicting irinotecan efficacy.PURPOSE: The purpose of this study is to test the accuracy of topo Ⅰ-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 Ⅰ-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 Ⅰ-pS10 positive case does not respond to irinotecan. Validation set: In this set, the sensitivity was 82.4% and the "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28880238",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37176164",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24256029",
"endSection": "abstract",
"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": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24256029",
"endSection": "title",
"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": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24256029",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24256029",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24256029",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24256029",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29261002",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29261002",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29261002",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21874414",
"endSection": "abstract",
"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": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21874414",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 123,
"text": "Topoisomerase I expression in tumors as a biological marker for CPT-11 chemosensitivity in patients with colorectal cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16184927",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24256029",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15197779",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31196001",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31196001",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15160997",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24256029",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/38016427",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28077117",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15160997",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24256029",
"endSection": "abstract",
"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 ≥3.6 and TOP1/CEN-20 ≥1.5, respectively."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24256029",
"endSection": "abstract",
"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 ≥3.6 and TOP1/CEN-20 ≥1.5, 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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15197779",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15160997",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24966994",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28077117",
"endSection": "abstract",
"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 mg/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 = 0.081).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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32764831",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22108516",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21874414",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36678550",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32326511",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28870917",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37176164",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11177741",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19436196",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24256029",
"endSection": "abstract",
"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"
}
]
| 13 | BioASQ-training13b | null | null | 66214f52b9f8b89d7e000005 | 56 |
yesno | Does iron regulate oligodendrocyte maturation? | ['yes'] | [
"yes"
]
| ['Yes, iron availability is essential for normal oligodendrocyte maturation as the oligodendrocytes depend on iron for their proper development, differentiation, and myelination.', 'Yes, iron plays a role in regulating oligodendrocyte maturation.', 'Developmental iron deficiency has an impact on myelination and effects oligodendrocyte maturation. Iron storage in astrocytes is vital for early oligodendrocyte development as well as for the remyelination of the CNS.', 'Yes, iron plays a significant role in regulating oligodendrocyte maturation, contributing to myelination and proper functioning of the central nervous system.', 'Yes, iron is known to regulate oligodendrocyte maturation, as demonstrated by developmental iron deficiency (dID) models which facilitate the study of specific oligodendrocyte (OL) requirements for their progression to a mature state and subsequent contribution to myelination.', 'Yes, iron plays a crucial role in regulating oligodendrocyte maturation, as it is essential for early oligodendrocyte development and myelination in the central nervous system.', 'Yes, developmental iron deficiency (dID) models facilitate the study of specific oligodendrocyte (OL) requirements for their progression to a mature state and subsequent contribution to myelination.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/7768202",
"http://www.ncbi.nlm.nih.gov/pubmed/32868463",
"http://www.ncbi.nlm.nih.gov/pubmed/34460113",
"http://www.ncbi.nlm.nih.gov/pubmed/11518519",
"http://www.ncbi.nlm.nih.gov/pubmed/25206366",
"http://www.ncbi.nlm.nih.gov/pubmed/31162719",
"http://www.ncbi.nlm.nih.gov/pubmed/28092084",
"http://www.ncbi.nlm.nih.gov/pubmed/26398942"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31162719",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 191,
"text": "Developmental iron deficiency (dID) models facilitate the study of specific oligodendrocyte (OL) requirements for their progression to a mature state and subsequent contribution to myelinatio"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31162719",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 96,
"text": "Ontogenetic oligodendrocyte maturation through gestational iron deprivation: The road not taken."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31162719",
"endSection": "abstract",
"offsetInBeginSection": 1444,
"offsetInEndSection": 1564,
"text": " the expression levels of Hes5, Sox10, and Olig1 in dID conditions correlated with an unfavorable OL maturation profile."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31162719",
"endSection": "abstract",
"offsetInBeginSection": 1572,
"offsetInEndSection": 1691,
"text": " the current results provide further evidence of dID impact on myelination, keeping OL away from the maturational path."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32868463",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 118,
"text": "Impaired Postnatal Myelination in a Conditional Knockout Mouse for the Ferritin Heavy Chain in Oligodendroglial Cells."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32868463",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 170,
"text": "To define the importance of iron storage in oligodendrocyte development and function, the ferritin heavy subunit (Fth) was specifically deleted in oligodendroglial cells."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32868463",
"endSection": "abstract",
"offsetInBeginSection": 2314,
"offsetInEndSection": 2444,
"text": "Fth iron storage is essential for early oligodendrocyte development as well as for OPC maturation in the demyelinated adult brain."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34460113",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 104,
"text": "H-ferritin expression in astrocytes is necessary for proper oligodendrocyte development and myelination."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34460113",
"endSection": "abstract",
"offsetInBeginSection": 1478,
"offsetInEndSection": 1629,
"text": " These results indicate that Fth iron storage in astrocytes is vital for early oligodendrocyte development as well as for the remyelination of the CNS."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11518519",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 107,
"text": "Iron modulates the differentiation of a distinct population of glial precursor cells into oligodendrocytes."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25206366",
"endSection": "abstract",
"offsetInBeginSection": 421,
"offsetInEndSection": 692,
"text": "Here, using an in vitro cultured differentiation model of oligodendrocytes, we found that both transferrin receptor and ferritin-H are significantly upregulated during oligodendrocyte maturation, implying the essential role of iron in the development of oligodendrocytes."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11518519",
"endSection": "abstract",
"offsetInBeginSection": 1060,
"offsetInEndSection": 1217,
"text": "Our results raise the possibility that iron may affect oligodendrocyte development at stages during early embryogenesis rather than during later development."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28092084",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 114,
"text": "When disrupted, iron homeostasis negatively impacts oligodendrocyte (OLG) differentiation and impairs myelination."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11518519",
"endSection": "abstract",
"offsetInBeginSection": 355,
"offsetInEndSection": 567,
"text": "These hypotheses are based on the observations that there is a peak in brain iron uptake in vivo that coincides with the period of greatest myelination and that a shortage of iron leads to myelination deficiency."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31162719",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 193,
"text": "Developmental iron deficiency (dID) models facilitate the study of specific oligodendrocyte (OL) requirements for their progression to a mature state and subsequent contribution to myelination."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25206366",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 190,
"text": "Iron is an essential trophic element that is required for cell viability and differentiation, especially in oligodendrocytes, which consume relatively high rates of energy to produce myelin."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34460113",
"endSection": "abstract",
"offsetInBeginSection": 1479,
"offsetInEndSection": 1629,
"text": "These results indicate that Fth iron storage in astrocytes is vital for early oligodendrocyte development as well as for the remyelination of the CNS."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26398942",
"endSection": "abstract",
"offsetInBeginSection": 1076,
"offsetInEndSection": 1352,
"text": "Total iron content in unperfused brain is not significantly different between Mcoln1(-/-) and wild-type littermate mice, suggesting that the observed maturation delay or loss of oligodendrocytes might be caused by impaired iron handling, rather than by global iron deficiency."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7768202",
"endSection": "abstract",
"offsetInBeginSection": 1346,
"offsetInEndSection": 1534,
"text": "These data indicate that iron delivered via transferrin and its receptor is intrinsically involved in oligodendrocyte maturation and thus plays a critical role in the onset of myelination."
}
]
| 12 | BioASQ-training12b | null | null | 6419d79c690f196b5100003b | 57 |
yesno | Is Amivantamab used for non–small-cell lung cancer? | ['yes'] | [
"yes"
]
| ['Yes. Amivantamab is approved for treatment of patients with Non-Small Cell Lung Cancer with EGFR Exon 20 insertion mutations.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/34565792",
"http://www.ncbi.nlm.nih.gov/pubmed/37800882",
"http://www.ncbi.nlm.nih.gov/pubmed/36198244",
"http://www.ncbi.nlm.nih.gov/pubmed/34880698",
"http://www.ncbi.nlm.nih.gov/pubmed/35899447",
"http://www.ncbi.nlm.nih.gov/pubmed/35597172",
"http://www.ncbi.nlm.nih.gov/pubmed/36246734",
"http://www.ncbi.nlm.nih.gov/pubmed/36979929",
"http://www.ncbi.nlm.nih.gov/pubmed/37880647",
"http://www.ncbi.nlm.nih.gov/pubmed/32747419",
"http://www.ncbi.nlm.nih.gov/pubmed/34284994",
"http://www.ncbi.nlm.nih.gov/pubmed/36868177",
"http://www.ncbi.nlm.nih.gov/pubmed/37938161",
"http://www.ncbi.nlm.nih.gov/pubmed/38001589",
"http://www.ncbi.nlm.nih.gov/pubmed/37856922",
"http://www.ncbi.nlm.nih.gov/pubmed/35652704",
"http://www.ncbi.nlm.nih.gov/pubmed/36756143",
"http://www.ncbi.nlm.nih.gov/pubmed/37882460",
"http://www.ncbi.nlm.nih.gov/pubmed/34083225",
"http://www.ncbi.nlm.nih.gov/pubmed/35785671",
"http://www.ncbi.nlm.nih.gov/pubmed/36481319",
"http://www.ncbi.nlm.nih.gov/pubmed/36652175",
"http://www.ncbi.nlm.nih.gov/pubmed/36916182",
"http://www.ncbi.nlm.nih.gov/pubmed/32414908",
"http://www.ncbi.nlm.nih.gov/pubmed/35599009",
"http://www.ncbi.nlm.nih.gov/pubmed/37022784",
"http://www.ncbi.nlm.nih.gov/pubmed/37284196",
"http://www.ncbi.nlm.nih.gov/pubmed/35667083",
"http://www.ncbi.nlm.nih.gov/pubmed/35983925",
"http://www.ncbi.nlm.nih.gov/pubmed/38012986",
"http://www.ncbi.nlm.nih.gov/pubmed/34913823",
"http://www.ncbi.nlm.nih.gov/pubmed/34911336",
"http://www.ncbi.nlm.nih.gov/pubmed/34339292",
"http://www.ncbi.nlm.nih.gov/pubmed/37879444",
"http://www.ncbi.nlm.nih.gov/pubmed/34292533",
"http://www.ncbi.nlm.nih.gov/pubmed/37878779",
"http://www.ncbi.nlm.nih.gov/pubmed/35616682",
"http://www.ncbi.nlm.nih.gov/pubmed/37776107",
"http://www.ncbi.nlm.nih.gov/pubmed/35882108",
"http://www.ncbi.nlm.nih.gov/pubmed/35963523",
"http://www.ncbi.nlm.nih.gov/pubmed/37870976",
"http://www.ncbi.nlm.nih.gov/pubmed/37589131"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36756143",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36868177",
"endSection": "abstract",
"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": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35652704",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 102,
"text": "Targeting EGFR Exon 20 Insertion Mutation in Non-small cell Lung Cancer: Amivantamab and Mobocertinib."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35652704",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35652704",
"endSection": "abstract",
"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": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35616682",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 64,
"text": "Amivantamab: A New Hope in Targeting Non-small Cell Lung Cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35616682",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35616682",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36652175",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37284196",
"endSection": "abstract",
"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": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36979929",
"endSection": "title",
"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": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36979929",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36979929",
"endSection": "abstract",
"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": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37022784",
"endSection": "title",
"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": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37022784",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37022784",
"endSection": "abstract",
"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": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37938161",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 100,
"text": "Amivantamab compared with real-world therapies in patients with advanced non-small cell lung cancer "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37882460",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35616682",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35616682",
"endSection": "abstract",
"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": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37800882",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 73,
"text": "Amivantamab plus Lazertinib Is Efficacious in Non-Small Cell Lung Cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37800882",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 103,
"text": "Amivantamab plus lazertinib shows clinical efficacy in osimertinib-relapsed non-small cell lung cancer."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34913823",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 90,
"text": "Amivantamab for the treatment of EGFR exon 20 insertion mutant non-small cell lung cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35616682",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35983925",
"endSection": "abstract",
"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": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35983925",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 112,
"text": "Amivantamab: a monoclonal EGFR-MET bispecific antibody for EGFR exon 20 insertion in non-small cell lung cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34913823",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35983925",
"endSection": "abstract",
"offsetInBeginSection": 349,
"offsetInEndSection": 442,
"text": "The approval of amivantamab represents a targeted therapy for this subtype of advanced NSCLC."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34292533",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 273,
"text": "Amivantamab (amivantamab-vmjw; Rybrevant™), 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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35983925",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36481319",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34292533",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34292533",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 274,
"text": "Amivantamab (amivantamab-vmjw; Rybrevant™), 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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34565792",
"endSection": "abstract",
"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®), 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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37880647",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35616682",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34284994",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35597172",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/38012986",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35652704",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37882460",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37938161",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/38012986",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34880698",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/38012986",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34913823",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/38012986",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37870976",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36868177",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34083225",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37878779",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36246734",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34083225",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37870976",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37879444",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36979929",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36868177",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35652704",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37870976",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35597172",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34913823",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35963523",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35616682",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35616682",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34913823",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35983925",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34913823",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35983925",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35652704",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34083225",
"endSection": "abstract",
"offsetInBeginSection": 40,
"offsetInEndSection": 135,
"text": "amivantamab, the first treatment for patients with non-small cell lung cancer whose tumors have"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37870976",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 113,
"text": "BACKGROUND: Amivantamab has been approved for the treatment of patients with advanced non-small-cell lung cancer "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36246734",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35983925",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37022784",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35785671",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35882108",
"endSection": "abstract",
"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."
}
]
| 13 | BioASQ-training13b | null | null | 65cf96ce1930410b1300000a | 58 |
yesno | Do bacteria release extracellular vesicles? | ['yes'] | [
"yes"
]
| ['Yes, Bacterial extracellular vesicles (EVs) are bilayered lipid membrane structures, bearing integral proteins and able to carry diverse cargo outside the cell to distant sites.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/33264437",
"http://www.ncbi.nlm.nih.gov/pubmed/31633842",
"http://www.ncbi.nlm.nih.gov/pubmed/31776460"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31633842",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 172,
"text": "Bacterial extracellular vesicles (EVs) are bilayered lipid membrane structures, bearing integral proteins and able to carry diverse cargo outside the cell to distant sites."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31776460",
"endSection": "abstract",
"offsetInBeginSection": 116,
"offsetInEndSection": 287,
"text": "Knowledge of the structure, molecular cargo and function of bacterial extracellular vesicles (BEVs) is primarily obtained from bacteria cultured in laboratory conditions. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33264437",
"endSection": "abstract",
"offsetInBeginSection": 367,
"offsetInEndSection": 406,
"text": "bacteria derived-extracellular vesicles"
}
]
| 11 | BioASQ-training11b | null | null | 603213ea1cb411341a000131 | 59 |
yesno | Is vemurafenib–cobimetinib promising for craniopharyngioma? | ['yes'] | [
"yes"
]
| ['Yes. Vemurafenib–cobimetinib showed promising for craniopharyngioma'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/37477404",
"http://www.ncbi.nlm.nih.gov/pubmed/37437144",
"http://www.ncbi.nlm.nih.gov/pubmed/35169097"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37437144",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37477404",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 99,
"text": "Vemurafenib plus cobimetinib is effective in patients with BRAF-mutant papillary craniopharyngioma."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37477404",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 81,
"text": "BRAF-MEK Inhibition Is Effective in BRAFV600E-Mutant Papillary Craniopharyngioma."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35169097",
"endSection": "abstract",
"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."
}
]
| 13 | BioASQ-training13b | null | null | 65cfd8551930410b13000023 | 60 |
yesno | Do MAIT cells have a role in multiple myeloma? | ['yes'] | [
"yes"
]
| ['Yes, MAIT cells may represent new immunotherapeutic targets for treatment of Multiple Myeloma and other malignancies', 'Yes, MAIT cells have a role in multiple myeloma.', 'Yes. Mucosal-associated invariant T cells (MAIT cells) play a key role in the pathogenesis of multiple myeloma.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/30153633",
"http://www.ncbi.nlm.nih.gov/pubmed/29515123"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29515123",
"endSection": "abstract",
"offsetInBeginSection": 1148,
"offsetInEndSection": 1358,
"text": "hus, MAIT cells are reduced in MM patients, which may contribute to disease in these individuals, and moreover, MAIT cells may represent new immunotherapeutic targets for treatment of MM and other malignancies."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29515123",
"endSection": "abstract",
"offsetInBeginSection": 264,
"offsetInEndSection": 497,
"text": "Here we have analysed the frequency and function of MAIT cells in multiple myeloma (MM) patients. We show that MAIT cell frequency in blood is reduced compared to healthy adult donors, but comparable to elderly healthy control donors"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29515123",
"endSection": "abstract",
"offsetInBeginSection": 615,
"offsetInEndSection": 822,
"text": "Newly diagnosed MM patient MAIT cells had reduced IFNγ production and CD27 expression, suggesting an exhausted phenotype, although IFNγ-producing capacity is restored in relapsed/refractory patient samples. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30153633",
"endSection": "abstract",
"offsetInBeginSection": 1141,
"offsetInEndSection": 1418,
"text": "We describe recent observations with regard to functional exhaustion of iNKT and MAIT cells in MM pathology and discuss the potential application of checkpoint inhibition as an attractive target for prolonged activation of these immunomodulatory T cells in the treatment of MM."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29515123",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 120,
"text": "Enumeration, functional responses and cytotoxic capacity of MAIT cells in newly diagnosed and relapsed multiple myeloma."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29515123",
"endSection": "abstract",
"offsetInBeginSection": 1147,
"offsetInEndSection": 1358,
"text": "Thus, MAIT cells are reduced in MM patients, which may contribute to disease in these individuals, and moreover, MAIT cells may represent new immunotherapeutic targets for treatment of MM and other malignancies."
}
]
| 11 | BioASQ-training11b | null | null | 5e2e1d6afbd6abf43b000026 | 61 |
yesno | Are BRAF mutations common in melanoma? | ['yes'] | [
"yes"
]
| ['Melanoma is the most aggressive form of skin cancer. The treatment of patients with advanced melanoma is rapidly evolving due to an improved understanding of molecular drivers of this disease. Somatic mutations in BRAF are the most common genetic alteration found in these tumors. BRAF mutations occur in approximately 8% of all human cancers and approach 50% in melanoma and papillary carcinoma of thyroid.', 'Activating mutations in the BRAF gene occur in approximately 50% of melanomas. More than 70% of BRAF mutations are V600E and 10-30% are V600K. BRAF mutations have emerged as an important predictive biomarker for metastasized melanoma. The discovery of BRAF mutations in melanoma led to the development of BRAF inhibitors for the treatment of advanced melanoma.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/23903755",
"http://www.ncbi.nlm.nih.gov/pubmed/23900694",
"http://www.ncbi.nlm.nih.gov/pubmed/23893853",
"http://www.ncbi.nlm.nih.gov/pubmed/23890154",
"http://www.ncbi.nlm.nih.gov/pubmed/23890105",
"http://www.ncbi.nlm.nih.gov/pubmed/23890088",
"http://www.ncbi.nlm.nih.gov/pubmed/24325952",
"http://www.ncbi.nlm.nih.gov/pubmed/24309328",
"http://www.ncbi.nlm.nih.gov/pubmed/24298448",
"http://www.ncbi.nlm.nih.gov/pubmed/24295639",
"http://www.ncbi.nlm.nih.gov/pubmed/24291778",
"http://www.ncbi.nlm.nih.gov/pubmed/24289205",
"http://www.ncbi.nlm.nih.gov/pubmed/24283590",
"http://www.ncbi.nlm.nih.gov/pubmed/24265155",
"http://www.ncbi.nlm.nih.gov/pubmed/24265154",
"http://www.ncbi.nlm.nih.gov/pubmed/24265153",
"http://www.ncbi.nlm.nih.gov/pubmed/24259661",
"http://www.ncbi.nlm.nih.gov/pubmed/24258979",
"http://www.ncbi.nlm.nih.gov/pubmed/24258977",
"http://www.ncbi.nlm.nih.gov/pubmed/24258972",
"http://www.ncbi.nlm.nih.gov/pubmed/24252159",
"http://www.ncbi.nlm.nih.gov/pubmed/24248543",
"http://www.ncbi.nlm.nih.gov/pubmed/24220097",
"http://www.ncbi.nlm.nih.gov/pubmed/24202393",
"http://www.ncbi.nlm.nih.gov/pubmed/24201813",
"http://www.ncbi.nlm.nih.gov/pubmed/24073999",
"http://www.ncbi.nlm.nih.gov/pubmed/23843700",
"http://www.ncbi.nlm.nih.gov/pubmed/23594689",
"http://www.ncbi.nlm.nih.gov/pubmed/23415641",
"http://www.ncbi.nlm.nih.gov/pubmed/23273605",
"http://www.ncbi.nlm.nih.gov/pubmed/23237741",
"http://www.ncbi.nlm.nih.gov/pubmed/14695152",
"http://www.ncbi.nlm.nih.gov/pubmed/15917418",
"http://www.ncbi.nlm.nih.gov/pubmed/23477830",
"http://www.ncbi.nlm.nih.gov/pubmed/18375819",
"http://www.ncbi.nlm.nih.gov/pubmed/23414474"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23903755",
"endSection": "abstract",
"offsetInBeginSection": 125,
"offsetInEndSection": 160,
"text": "patients with BRAF-mutant melanoma."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23900694",
"endSection": "abstract",
"offsetInBeginSection": 585,
"offsetInEndSection": 607,
"text": "BRAF-mutated melanoma "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23893853",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 421,
"text": "The RAS/RAF/MEK/ERK pathway has been reported to be activated in over 80% of all cutaneous melanomas, making it the focus of many scientific studies in the melanoma field. Discoveries of mutations and aberrant expression of components in this cascade, in particular, BRAF and NRAS render a deeper understanding of the mechanisms responsible for oncogenesis and provide new therapeutic strategies for this deadly disease. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23893853",
"endSection": "abstract",
"offsetInBeginSection": 846,
"offsetInEndSection": 1010,
"text": " BRAF-targeted therapies (e.g., vemurafenib, dabrafenib) have showed impressive results in systemic therapy for melanoma harboring activating BRAF V600E mutations. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23890154",
"endSection": "abstract",
"offsetInBeginSection": 301,
"offsetInEndSection": 460,
"text": " An independent cohort of 91 archival MUPs was also screened for 46 hot spot mutations highly prevalent in melanoma including BRAF, NRAS, KIT, GNAQ, and GNA11."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23890154",
"endSection": "abstract",
"offsetInBeginSection": 580,
"offsetInEndSection": 746,
"text": " a high rate of BRAF (45 of 101, 45%) and NRAS (32 of 101, 32%) mutations, collectively indicating a mutation profile consistent with cutaneous sun-exposed melanomas."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23890105",
"endSection": "abstract",
"offsetInBeginSection": 12,
"offsetInEndSection": 100,
"text": "Treatment of advanced melanoma has been improved with the advent of the BRAF inhibitors."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23890088",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 84,
"text": "BRAF is the most prevalent oncogene and an important therapeutic target in melanoma."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24325952",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 353,
"text": "Activating BRAF mutations, leading to constitutive activation of the MAPK signaling pathway, are common in a variety of human cancers. Several small molecule BRAF inhibitors have been developed during the last years and shown promising results in clinical trials, especially for metastatic melanoma, while they have been less effective in colon cancer. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24309328",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 92,
"text": "BRAF mutations have emerged as an important predictive biomarker for metastasized melanoma. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24298448",
"endSection": "abstract",
"offsetInBeginSection": 734,
"offsetInEndSection": 849,
"text": "BRAF V600 selective inhibitors have been approved for the treatment of V600 mutation positive metastatic melanoma, "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24295639",
"endSection": "title",
"offsetInBeginSection": 29,
"offsetInEndSection": 67,
"text": "BRAF(V600) mutation-positive melanoma "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24291778",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 280,
"text": "Melanoma is the most aggressive form of skin cancer. The treatment of patients with advanced melanoma is rapidly evolving due to an improved understanding of molecular drivers of this disease. Somatic mutations in BRAF are the most common genetic alteration found in these tumors."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24289205",
"endSection": "abstract",
"offsetInBeginSection": 40,
"offsetInEndSection": 146,
"text": " genetically activated BRAF, is now commonly prescribed for metastatic melanoma harboring a BRAF mutation."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24283590",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 87,
"text": "BRAF inhibitors improve melanoma patient survival, but resistance invariably develops. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24265155",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 160,
"text": "BRAF inhibitors elicit rapid antitumor responses in the majority of patients with BRAF(V600)-mutant melanoma, but acquired drug resistance is almost universal. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24265153",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 112,
"text": "Most patients with BRAF(V600)-mutant metastatic melanoma develop resistance to selective RAF kinase inhibitors. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24259661",
"endSection": "abstract",
"offsetInBeginSection": 695,
"offsetInEndSection": 900,
"text": "BRAF(V600E) mutation confers constitutive BRAK kinase activation in melanoma cells, promoting tumor growth. This discovery led to the development of BRAF kinase inhibitors like vemurafenib and dabrafenib. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24258979",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 156,
"text": "(V600)BRAF mutation was identified as an ideal target for clinical therapy due to its indispensable roles in supporting melanoma initiation and progression."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24258977",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 115,
"text": "The Braf(V600E) mutation has been detected in patients with metastatic melanoma, colon, thyroid, and other cancers."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24258972",
"endSection": "abstract",
"offsetInBeginSection": 116,
"offsetInEndSection": 365,
"text": "Since the identification of activating BRAF mutations and subsequent development of drugs targeting the mutant BRAF protein, oncologists now need to incorporate prognostic and predictive biomarkers into treatment decisions for their melanoma patient"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24252159",
"endSection": "abstract",
"offsetInBeginSection": 12,
"offsetInEndSection": 138,
"text": "BRAF mutations occur in approximately 8% of all human cancers and approach 50% in melanoma and papillary carcinoma of thyroid."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24248543",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 163,
"text": "Vemurafenib is a selective and potent small molecule inhibitor of the V600 mutant form of the BRAF protein used in the treatment of melanoma and colorectal cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24220097",
"endSection": "abstract",
"offsetInBeginSection": 1178,
"offsetInEndSection": 1290,
"text": "Molecular studies demonstrated that the melanoma was positive for the 1799T>A (V600E) mutation in the BRAF gene."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24202393",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 97,
"text": "RAF kinase inhibitors have substantial therapeutic effects in patients with BRAF-mutant melanoma."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24201813",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 86,
"text": "An activating BRAF (V600E) kinase mutation occurs in approximately half of melanomas. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23237741",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 142,
"text": "Activating mutations in the BRAF gene occur in approximately 50% of melanomas. More than 70% of BRAF mutations are V600E and 10-30% are V600K."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24325952",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 134,
"text": "Activating BRAF mutations, leading to constitutive activation of the MAPK signaling pathway, are common in a variety of human cancers."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24325952",
"endSection": "abstract",
"offsetInBeginSection": 135,
"offsetInEndSection": 353,
"text": "Several small molecule BRAF inhibitors have been developed during the last years and shown promising results in clinical trials, especially for metastatic melanoma, while they have been less effective in colon cancer. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24258972",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 367,
"text": "Personalized melanoma medicine has progressed from histopathologic features to serum markers to molecular profiles. Since the identification of activating BRAF mutations and subsequent development of drugs targeting the mutant BRAF protein, oncologists now need to incorporate prognostic and predictive biomarkers into treatment decisions for their melanoma patients."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24073999",
"endSection": "abstract",
"offsetInBeginSection": 14,
"offsetInEndSection": 160,
"text": "The clinical activity of BRAF inhibitor (BRAF-I) therapy is a major breakthrough in the treatment of metastatic melanoma carrying BRAF mutations. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23843700",
"endSection": "abstract",
"offsetInBeginSection": 353,
"offsetInEndSection": 479,
"text": "The discovery of BRAF mutations in melanoma led to the development of BRAF inhibitors for the treatment of advanced melanoma. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23594689",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 384,
"text": "BRAF represents one of the most frequently mutated protein kinase genes in human tumours. The mutation is commonly tested in pathology practice. BRAF mutation is seen in melanoma, papillary thyroid carcinoma (including papillary thyroid carcinoma arising from ovarian teratoma), ovarian serous tumours, colorectal carcinoma, gliomas, hepatobiliary carcinomas and hairy cell leukaemia."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23594689",
"endSection": "abstract",
"offsetInBeginSection": 900,
"offsetInEndSection": 1035,
"text": "Indeed, recent clinical trials involving BRAF selective inhibitors exhibited promising response rates in metastatic melanoma patients. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23415641",
"endSection": "abstract",
"offsetInBeginSection": 323,
"offsetInEndSection": 865,
"text": "A majority of cutaneous melanomas show activating mutations in the NRAS or BRAF proto-oncogenes, components of the Ras-Raf-Mek-Erk (MAPK) signal transduction pathway. The discovery of activating BRAF mutations in ∼50% of all melanomas has proved to be a turning point in the therapeutic management of the disseminated disease. This review summarizes the critical role of BRAF in melanoma pathophysiology, the clinical and pathological determinants of BRAF mutation status and finally addresses the current state of the art of BRAF inhibitors."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23273605",
"endSection": "abstract",
"offsetInBeginSection": 318,
"offsetInEndSection": 1328,
"text": "To better understand the BRAF mutation profile in melanomas, we retrospectively analyzed data from 1112 primary and metastatic melanomas at our institution. The cohort included nonacral cutaneous (n = 774), acral (n = 111), mucosal (n = 26), uveal (n = 23), leptomeningeal (n = 1), and metastatic melanomas of unknown primary site (n = 177). BRAF mutation hotspot regions in exons 11 and 15 were analyzed by pyrosequencing or with the primer extension MassARRAY system. A total of 499 (44.9%) specimens exhibited BRAF mutations, involving exon 15 [497 (99.6%)] or exon 11 [2 (0.4%)]. p.V600E was detected in 376 (75.4%) cases; the remaining 123 (24.6%) cases exhibited non-p.V600E mutations, of which p.V600K was most frequent [86 (17.2%)]. BRAF mutations were more frequent in nonacral cutaneous (51.4%) than acral melanomas [18 (16.2%)] (P < 0.001); however, there was no significant difference among cutaneous histological subtypes. All mucosal, uveal, and leptomeningeal melanomas were BRAF wild type (WT)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14695152",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 71,
"text": "Recently, it was reported that BRAF mutations are frequent in melanoma."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23477830",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 81,
"text": "Activating mutations in BRAF are the most common genetic alterations in melanoma."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18375819",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 69,
"text": "Oncogenic BRAF and NRAS mutations are frequent in malignant melanoma."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15917418",
"endSection": "abstract",
"offsetInBeginSection": 457,
"offsetInEndSection": 608,
"text": "Mutation of BRAF is now known to be common in cutaneous melanomas, and raises possible new therapeutic options of anti-RAF treatment for these patients"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16799476",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 97,
"text": "BRAF mutations are common events in a variety of melanocytic nevi and primary cutaneous melanomas"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22614711",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 188,
"text": "Approximately 40-60% of melanomas from Caucasian populations carry activating mutations in the BRAF oncogene, with the most common being the p.Val600Glu (V600E) hotspot mutation in exon 15"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14679157",
"endSection": "abstract",
"offsetInBeginSection": 220,
"offsetInEndSection": 497,
"text": "Using a cohort of 115 patients with primary invasive melanomas, we show that BRAF mutations are statistically significantly more common in melanomas occurring on skin subject to intermittent sun exposure than elsewhere (23 of 43 patients; P<.001, two-sided Fisher's exact test)"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23414474",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 165,
"text": "BRAF mutations have been identified as the most common oncogene mutation in melanomas, especially important in those originating on nonchronically sun-damaged skin. "
}
]
| 5 | BioASQ-training5b | [
"http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008545",
"http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154",
"http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048493",
"http://www.uniprot.org/uniprot/BRAF_COTJA",
"http://www.uniprot.org/uniprot/BRAF_CHICK",
"http://www.disease-ontology.org/api/metadata/DOID:1909"
]
| [
{
"o": "UMLS_CUI:C1511021",
"p": "http://www.w3.org/2004/02/skos/core#notation",
"s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:7124"
},
{
"o": "BRAF Gene Mutation",
"p": "http://www.w3.org/2004/02/skos/core#prefLabel",
"s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:7124"
},
{
"o": "NCI2009_04D:C40430",
"p": "http://www.w3.org/2004/02/skos/core#notation",
"s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:7124"
},
{
"o": "BRAF Gene Mutation",
"p": "http://www.w3.org/2004/02/skos/core#prefLabel",
"s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:7124"
},
{
"o": "C40430",
"p": "http://www.w3.org/2004/02/skos/core#notation",
"s": "http://linkedlifedata.com/resource/umls/label/A7636217"
},
{
"o": "http://linkedlifedata.com/resource/umls/label/A7636217",
"p": "http://www.w3.org/2008/05/skos-xl#prefLabel",
"s": "http://linkedlifedata.com/resource/umls/id/C1511021"
},
{
"o": "BRAF Gene Mutation",
"p": "http://www.w3.org/2008/05/skos-xl#literalForm",
"s": "http://linkedlifedata.com/resource/umls/label/A7636217"
},
{
"o": "http://linkedlifedata.com/resource/umls/label/A7636217",
"p": "http://linkedlifedata.com/resource/umls/prefMetaMap",
"s": "http://linkedlifedata.com/resource/umls/id/C1511021"
}
]
| 5512c91b6a8cde6b7200000b | 62 |
yesno | Is macitentan an ET agonist? | ['no'] | [
"no"
]
| ['No, macitentan is anendothelin receptor antagonist.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/25012164",
"http://www.ncbi.nlm.nih.gov/pubmed/25604973",
"http://www.ncbi.nlm.nih.gov/pubmed/24297706",
"http://www.ncbi.nlm.nih.gov/pubmed/25131455",
"http://www.ncbi.nlm.nih.gov/pubmed/25226600",
"http://www.ncbi.nlm.nih.gov/pubmed/23077657",
"http://www.ncbi.nlm.nih.gov/pubmed/18780830",
"http://www.ncbi.nlm.nih.gov/pubmed/25084082",
"http://www.ncbi.nlm.nih.gov/pubmed/20730702",
"http://www.ncbi.nlm.nih.gov/pubmed/24582812",
"http://www.ncbi.nlm.nih.gov/pubmed/23997048",
"http://www.ncbi.nlm.nih.gov/pubmed/24797866",
"http://www.ncbi.nlm.nih.gov/pubmed/24906252",
"http://www.ncbi.nlm.nih.gov/pubmed/22525377",
"http://www.ncbi.nlm.nih.gov/pubmed/23830395",
"http://www.ncbi.nlm.nih.gov/pubmed/23984728",
"http://www.ncbi.nlm.nih.gov/pubmed/24769543",
"http://www.ncbi.nlm.nih.gov/pubmed/25539851",
"http://www.ncbi.nlm.nih.gov/pubmed/25377471",
"http://www.ncbi.nlm.nih.gov/pubmed/22862294",
"http://www.ncbi.nlm.nih.gov/pubmed/22348175",
"http://www.ncbi.nlm.nih.gov/pubmed/24998329",
"http://www.ncbi.nlm.nih.gov/pubmed/21403842",
"http://www.ncbi.nlm.nih.gov/pubmed/22189899",
"http://www.ncbi.nlm.nih.gov/pubmed/23900878",
"http://www.ncbi.nlm.nih.gov/pubmed/25457902",
"http://www.ncbi.nlm.nih.gov/pubmed/23568224",
"http://www.ncbi.nlm.nih.gov/pubmed/25060980",
"http://www.ncbi.nlm.nih.gov/pubmed/23353592"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25012164",
"endSection": "abstract",
"offsetInBeginSection": 865,
"offsetInEndSection": 1036,
"text": "Administration of an ET receptor antagonist, either bosentan or macitentan, markedly attenuated PD-induced MMT, fibrosis, angiogenesis, and peritoneal functional decline. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25604973",
"endSection": "abstract",
"offsetInBeginSection": 231,
"offsetInEndSection": 453,
"text": "Macitentan is an oral, once-daily, dual endothelin (ET)A and ETB receptor antagonist with high affinity and sustained receptor binding that was approved in the USA, Europe, Canada, and Switzerland for the treatment of PAH."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24297706",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 160,
"text": "Macitentan (Opsumit®) is a novel dual endothelin receptor antagonist (ERA) with sustained receptor binding properties developed by Actelion Pharmaceuticals Ltd."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18780830",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 520,
"text": "Macitentan, also called Actelion-1 or ACT-064992 [N-[5-(4-bromophenyl)-6-(2-(5-bromopyrimidin-2-yloxy)ethoxy)-pyrimidin-4-yl]-N'-propylaminosulfonamide], is a new dual ET(A)/ET(B) endothelin (ET) receptor antagonist designed for tissue targeting. Selection of macitentan was based on inhibitory potency on both ET receptors and optimization of physicochemical properties to achieve high affinity for lipophilic milieu. In vivo, macitentan is metabolized into a major and pharmacologically active metabolite, ACT-132577. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18780830",
"endSection": "abstract",
"offsetInBeginSection": 520,
"offsetInEndSection": 1183,
"text": "Macitentan and its metabolite antagonized the specific binding of ET-1 on membranes of cells overexpressing ET(A) and ET(B) receptors and blunted ET-1-induced calcium mobilization in various natural cell lines, with inhibitory constants within the nanomolar range. In functional assays, macitentan and ACT-132577 inhibited ET-1-induced contractions in isolated endothelium-denuded rat aorta (ET(A) receptors) and sarafotoxin S6c-induced contractions in isolated rat trachea (ET(B) receptors). In rats with pulmonary hypertension, macitentan prevented both the increase of pulmonary pressure and the right ventricle hypertrophy, and it markedly improved survival. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18780830",
"endSection": "abstract",
"offsetInBeginSection": 1362,
"offsetInEndSection": 1689,
"text": "In conclusion, macitentan, by its tissue-targeting properties and dual antagonism of ET receptors, protects against end-organ damage in diabetes and improves survival in pulmonary hypertensive rats. This profile makes macitentan a new agent to treat cardiovascular disorders associated with chronic tissue ET system activation."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18780830",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 98,
"text": "Pharmacology of macitentan, an orally active tissue-targeting dual endothelin receptor antagonist."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22525377",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 122,
"text": "Renal, retinal and cardiac changes in type 2 diabetes are attenuated by macitentan, a dual endothelin receptor antagonist."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22525377",
"endSection": "abstract",
"offsetInBeginSection": 230,
"offsetInEndSection": 498,
"text": "Here we investigated the effects of macitentan, an orally-active, tissue-targeting dual ET receptor antagonist on chronic complications in type 2 diabetes.MAIN METHODS: db/db mice and their age- and sex-matched controls were examined after 2 and 4 months of diabetes. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24582812",
"endSection": "abstract",
"offsetInBeginSection": 122,
"offsetInEndSection": 314,
"text": "Macitentan is a novel dual ETA/ETB receptor antagonist with enhanced tissue distribution and sustained receptor binding properties designed to achieve a more efficacious ET receptor blockade. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23997048",
"endSection": "abstract",
"offsetInBeginSection": 583,
"offsetInEndSection": 867,
"text": "Recently oral prostacyclin receptor agonists have shown encouraging results. Many clinical studies targeting the vasoconstrictor ET-1 pathway with receptor antagonists like bosentan and ambrisentan have shown strong results, even more optimism coming from macitentan, the newest drug."
}
]
| 5 | BioASQ-training5b | [
"http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D065128",
"http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D065130",
"http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D065131"
]
| []
| 56c863385795f9a73e000015 | 63 |
yesno | Does the concentration of protein HIF-1α increase after the administration of the cytoprotective prodrug"amifostine" (ethyol) ? | ['yes'] | [
"yes"
]
| The key-protein that when associated with HREs leads to the activation of all of these genes, is identified as“Hypoxia Inducible Factor-1” (HIF1). It is a heterodimer composed of two subunits (IIF1a 120kDa and HIF-1b 91-94kDa), both of which belong to the group of "basic helix-loop-helix" (bHLH)-Pas proteins. The heterodimer HIF1 and IIF2 increase in the cytoplasm of cells exposed to hypoxia. | [
"http://www.ncbi.nlm.nih.gov/pubmed/20334641",
"http://www.ncbi.nlm.nih.gov/pubmed/17852557",
"http://www.ncbi.nlm.nih.gov/pubmed/14574457",
"http://www.ncbi.nlm.nih.gov/pubmed/24147016",
"http://www.ncbi.nlm.nih.gov/pubmed/21452059",
"http://www.ncbi.nlm.nih.gov/pubmed/21875443",
"http://www.ncbi.nlm.nih.gov/pubmed/19478935"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20334641",
"endSection": "abstract",
"offsetInBeginSection": 933,
"offsetInEndSection": 1126,
"text": "We demonstrated that the treatment of several human cancer cell lines with therapeutical doses of WR-1065 led to a strong induction of different VEGF-A mRNA isoforms independently of HIF-1alpha"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17852557",
"endSection": "abstract",
"offsetInBeginSection": 161,
"offsetInEndSection": 364,
"text": "e investigated the involvement of hypoxia-regulated proteins (Hypoxia inducible factors HIF1alpha, HIF2alpha and carbonic anhydrase CA9) in HNC resistance to accelerated and hypofractionated radiotherapy"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17852557",
"endSection": "abstract",
"offsetInBeginSection": 1509,
"offsetInEndSection": 1867,
"text": "In accord with previously reported studies, high levels of the hypoxia regulated proteins HIF1alpha and CA9 in HNC predict resistance to platinum based radio-chemotherapy. Whether HIF2alpha expressing tumors are more sensitive to larger radiotherapy fractions, compared to standard radiotherapy fractionation, is an issue that deserves further investigation."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17852557",
"endSection": "abstract",
"offsetInBeginSection": 874,
"offsetInEndSection": 1413,
"text": "HIF1alpha and HIF2alpha were expressed in the nuclei and cytoplasm of cancer cells, while CA9 had a membrane reactivity. A high expression of HIF1alpha, HIF2alpha and CA9 was noted in 21/39 (53.8%), 20/39 (51.3%) and 23/39 (58.9%) cases, respectively. Complete response was obtained in 85.2% of patients and HIF1alpha was marginally related with persistent disease after RT (p = 0.05). HIF1alpha was significantly associated with poor local relapse free survival (LRFS) (p = 0.006) and overall survival (p = 0.008), whilst HIF2alpha was no"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14574457",
"endSection": "abstract",
"offsetInBeginSection": 413,
"offsetInEndSection": 875,
"text": " The glucose and oxygen levels in the peripheral blood of patients receiving 1000 mg amifostine were determined at various time-points in order to investigate the metabolic changes induced by amifostine. MDA468 breast tumor cell lines were incubated with a high amifostine concentration (10 m M) to overcome the natural resistance of cancer cells to influx of the non-hydrolyzed WR-2721, and the HIF1 alpha protein levels were determined by Western blot analysis"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14574457",
"endSection": "abstract",
"offsetInBeginSection": 1518,
"offsetInEndSection": 1854,
"text": "Since it is doubtful whether dephosphorylation of amifostine to the active metabolite WR-1065 occurs within tumoral tissues (an acidic environment that lacks vascular alkaline phosphatase activity), intracellular hypoxia and upregulation of HIF1 alpha represents an additional, normal tissue-specific, amifostine cytoprotective pathway."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14574457",
"endSection": "abstract",
"offsetInBeginSection": 1319,
"offsetInEndSection": 1394,
"text": ". Incubation of cell lines with amifostine resulted in HIF1 alpha induction"
}
]
| 5 | BioASQ-training5b | [
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004999",
"http://www.biosemantics.org/jochem#4277891",
"http://www.biosemantics.org/jochem#4217067",
"http://www.uniprot.org/uniprot/HIF1A_ONCMY",
"http://www.uniprot.org/uniprot/HIF1A_EOSBA",
"http://www.uniprot.org/uniprot/HIF1A_BOSMU",
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011355"
]
| [
{
"o": "Intervention #5132 (Drug:Ethyol (Amifostine))",
"p": "http://www.w3.org/2000/01/rdf-schema#label",
"s": "http://data.linkedct.org/resource/intervention/5132"
}
]
| 533eb89fc45e133714000012 | 64 |
yesno | Does radiotherapy for prostate cancer increase bladder cancer risk? | ['yes'] | [
"yes"
]
| ['Yes, radiotherapy for prostate cancer is associated with increased bladder cancer risk.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/28499661",
"http://www.ncbi.nlm.nih.gov/pubmed/27432454",
"http://www.ncbi.nlm.nih.gov/pubmed/19553822",
"http://www.ncbi.nlm.nih.gov/pubmed/25900243",
"http://www.ncbi.nlm.nih.gov/pubmed/27844130",
"http://www.ncbi.nlm.nih.gov/pubmed/27370205",
"http://www.ncbi.nlm.nih.gov/pubmed/26936410",
"http://www.ncbi.nlm.nih.gov/pubmed/18801517",
"http://www.ncbi.nlm.nih.gov/pubmed/27629559",
"http://www.ncbi.nlm.nih.gov/pubmed/30293908"
]
| [
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30293908",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 174,
"text": "External Beam Radiotherapy Increases the Risk of Bladder Cancer When Compared with Radical Prostatectomy in Patients Affected by Prostate Cancer: A Population-based Analysis."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30293908",
"endSection": "abstract",
"offsetInBeginSection": 1817,
"offsetInEndSection": 2035,
"text": "On multivariable competing risk regression analyses, treatment with EBRT was independently associated with the risk of developing a second primary BCa (hazard ratio: 1.35, CI: 1.18-1.55; p<0.001), but not RCa (p=0.4). "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30293908",
"endSection": "abstract",
"offsetInBeginSection": 2180,
"offsetInEndSection": 2456,
"text": "CONCLUSIONS: Patients treated with EBRT are at increased risk of developing a second primary BCa compared with those treated with RP. However, no differences were found considering RCa incidence in patients treated with RP or EBRT within the first 5 yr after primary therapy. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30293908",
"endSection": "abstract",
"offsetInBeginSection": 2777,
"offsetInEndSection": 2914,
"text": "We found that those treated with external beam radiotherapy are at an increased risk of developing a second primary bladder cancer tumor."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27629559",
"endSection": "abstract",
"offsetInBeginSection": 708,
"offsetInEndSection": 1018,
"text": "All radiation modalities were found to have an increased RR of developing BlCa after 10 years, with brachytherapy having a significantly higher RR than external beam radiation (EBRT) or combined EBRT and brachytherapy in Caucasian men and a significantly higher RR than EBRT in men of other/unknown ethnicity. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27629559",
"endSection": "abstract",
"offsetInBeginSection": 1168,
"offsetInEndSection": 1427,
"text": "CONCLUSIONS: The increased risk of BlCa after prostate radiation occurs predominantly after 10 years, regardless of ethnicity. The RR of developing BlCa after 10 years is significantly higher following brachytherapy than after EBRT or EBRT and brachytherapy. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27844130",
"endSection": "abstract",
"offsetInBeginSection": 328,
"offsetInEndSection": 716,
"text": "Based on the data in the literature, there is a consistently increased risk of bladder cancer (HR: 1.67, 95% CI 1.55-1.80), rectal cancer (HR: 1.79, 95% CI 1.34-2.38), and colorectal cancer (HR: 1.79, 95% CI 1.34-23.8) following percutaneous radiation therapy. Following brachytherapy only an increased for the development of bladder cancer (HR: 2.14, 95% CI 1.03-3.94) has been observed."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28499661",
"endSection": "abstract",
"offsetInBeginSection": 816,
"offsetInEndSection": 956,
"text": "When comparing with a matched general French population, the standard incidence ratio (SIR) for bladder cancer was 1.02 (95% CI: 0.46-1.93)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27370205",
"endSection": "abstract",
"offsetInBeginSection": 1637,
"offsetInEndSection": 1734,
"text": "LDR resulted in lower bladder cancer risks than HDR, and lower or similar risks of rectal cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27370205",
"endSection": "abstract",
"offsetInBeginSection": 1807,
"offsetInEndSection": 1914,
"text": "Compared to external beam techniques, second rectal and bladder cancer risks were lowest for brachytherapy."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27432454",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 241,
"text": "OBJECTIVE: Although it is well known that radiotherapy for prostate cancer increases comorbid rate of secondary bladder cancer, the effect of aging and smoking with radiotherapy on incidence rate of secondary bladder cancer remains unknown. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27432454",
"endSection": "abstract",
"offsetInBeginSection": 738,
"offsetInEndSection": 978,
"text": "RESULTS: During the median follow-up period of 4.3 and 3.1 years, secondary bladder cancer occurred in 11 (3.4%) and 5 (1.1%) of patients with prostate cancer treated with external beam radiotherapy and radical prostatectomy, respectively. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517",
"endSection": "abstract",
"offsetInBeginSection": 1745,
"offsetInEndSection": 1951,
"text": "CONCLUSIONS\n\nMen who receive radiotherapy for localized prostate cancer have an increased risk of bladder cancer compared to patients undergoing radical prostatectomy and compared to the general population."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 126,
"text": "Radiation therapy for prostate cancer increases subsequent risk of bladder and rectal cancer: a population based cohort study."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517",
"endSection": "abstract",
"offsetInBeginSection": 814,
"offsetInEndSection": 1035,
"text": "RESULTS\n\nThe relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517",
"endSection": "abstract",
"offsetInBeginSection": 1036,
"offsetInEndSection": 1308,
"text": "Compared to the general United States population the standardized incidence ratio for bladder cancer developing after radical prostatectomy, external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy was 0.99, 1.42, 1.10 and 1.39, respectively."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27432454",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 240,
"text": "OBJECTIVE\n\nAlthough it is well known that radiotherapy for prostate cancer increases comorbid rate of secondary bladder cancer, the effect of aging and smoking with radiotherapy on incidence rate of secondary bladder cancer remains unknown."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27432454",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 240,
"text": "OBJECTIVE\nAlthough it is well known that radiotherapy for prostate cancer increases comorbid rate of secondary bladder cancer, the effect of aging and smoking with radiotherapy on incidence rate of secondary bladder cancer remains unknown."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517",
"endSection": "abstract",
"offsetInBeginSection": 1745,
"offsetInEndSection": 1951,
"text": "CONCLUSIONS\nMen who receive radiotherapy for localized prostate cancer have an increased risk of bladder cancer compared to patients undergoing radical prostatectomy and compared to the general population."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 170,
"text": "PURPOSE\nPre-prostate specific antigen era series demonstrated an increased risk of bladder cancer and rectal cancer in men who received radiotherapy for prostate cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517",
"endSection": "abstract",
"offsetInBeginSection": 814,
"offsetInEndSection": 1035,
"text": "RESULTS\nThe relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27432454",
"endSection": "abstract",
"offsetInBeginSection": 1551,
"offsetInEndSection": 1835,
"text": "CONCLUSIONS: Taken together, these findings suggest that smoking history might be one of criteria to choose radical prostatectomy than external beam radiotherapy for prostate cancer, and that age would not be a criterion for therapeutic selection in terms of secondary bladder cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 170,
"text": "PURPOSE: Pre-prostate specific antigen era series demonstrated an increased risk of bladder cancer and rectal cancer in men who received radiotherapy for prostate cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517",
"endSection": "abstract",
"offsetInBeginSection": 810,
"offsetInEndSection": 1031,
"text": "RESULTS: The relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517",
"endSection": "abstract",
"offsetInBeginSection": 1032,
"offsetInEndSection": 1304,
"text": "Compared to the general United States population the standardized incidence ratio for bladder cancer developing after radical prostatectomy, external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy was 0.99, 1.42, 1.10 and 1.39, respectively."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 161,
"text": "Pre-prostate specific antigen era series demonstrated an increased risk of bladder cancer and rectal cancer in men who received radiotherapy for prostate cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517",
"endSection": "abstract",
"offsetInBeginSection": 1701,
"offsetInEndSection": 1894,
"text": "Men who receive radiotherapy for localized prostate cancer have an increased risk of bladder cancer compared to patients undergoing radical prostatectomy and compared to the general population."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517",
"endSection": "abstract",
"offsetInBeginSection": 780,
"offsetInEndSection": 992,
"text": "The relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25900243",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 108,
"text": "Radiotherapy for prostate cancer is associated with an increased incidence of secondary bladder cancer (BC)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19553822",
"endSection": "abstract",
"offsetInBeginSection": 884,
"offsetInEndSection": 977,
"text": "Radiation therapy for prostate cancer is associated with an increased risk of bladder cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26936410",
"endSection": "abstract",
"offsetInBeginSection": 2204,
"offsetInEndSection": 2429,
"text": "Radiotherapy for prostate cancer was associated with higher risks of developing second malignancies of the bladder, colon, and rectum compared with patients unexposed to radiotherapy, but the reported absolute rates were low."
}
]
| 11 | BioASQ-training11b | null | null | 5e33916afbd6abf43b000061 | 65 |
yesno | Is there an association between Klinefelter syndrome and breast cancer? | ['yes'] | [
"yes"
]
| ['Yes, Klinefelter syndrome is associated with increased risk of male breast cancer. Other risk factors of male breast cancer are positive family history, and mutations in BRCA1 and specially BRCA2.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/20698148",
"http://www.ncbi.nlm.nih.gov/pubmed/20706705",
"http://www.ncbi.nlm.nih.gov/pubmed/15119010",
"http://www.ncbi.nlm.nih.gov/pubmed/21241366",
"http://www.ncbi.nlm.nih.gov/pubmed/21246928",
"http://www.ncbi.nlm.nih.gov/pubmed/25415740",
"http://www.ncbi.nlm.nih.gov/pubmed/23464700",
"http://www.ncbi.nlm.nih.gov/pubmed/9283592",
"http://www.ncbi.nlm.nih.gov/pubmed/7125242",
"http://www.ncbi.nlm.nih.gov/pubmed/16106025",
"http://www.ncbi.nlm.nih.gov/pubmed/21204612",
"http://www.ncbi.nlm.nih.gov/pubmed/3111653",
"http://www.ncbi.nlm.nih.gov/pubmed/23909038",
"http://www.ncbi.nlm.nih.gov/pubmed/15668471",
"http://www.ncbi.nlm.nih.gov/pubmed/28675185",
"http://www.ncbi.nlm.nih.gov/pubmed/24552677"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25415740",
"endSection": "abstract",
"offsetInBeginSection": 1058,
"offsetInEndSection": 1324,
"text": "Screening for breast cancer in male-to-female transsexuals should be undertaken for those with additional risk factors (e.g., family history, BRCA2 mutation, Klinefelter syndrome) and should be available to those who desire screening, preferably in a clinical trial."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24552677",
"endSection": "abstract",
"offsetInBeginSection": 1081,
"offsetInEndSection": 1289,
"text": "Klinefelter syndrome (OR = 24.7; 95% CI = 8.94 to 68.4) and gynecomastia (OR = 9.78; 95% CI = 7.52 to 12.7) were also statistically significantly associated with risk, relations that were independent of BMI. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23464700",
"endSection": "abstract",
"offsetInBeginSection": 418,
"offsetInEndSection": 529,
"text": "Male breast cancer risk factors show strong association with BRCA2 mutations, as well as Klinefelter syndrome. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23909038",
"endSection": "abstract",
"offsetInBeginSection": 61,
"offsetInEndSection": 185,
"text": "The main risk factors include: the mutation of genes BRCA 1 and 2, Klinefelter's syndrome, alcohol, liver disease, obesity. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21204612",
"endSection": "abstract",
"offsetInBeginSection": 114,
"offsetInEndSection": 368,
"text": "Although aetiology is still unclear, constitutional, environmental, hormonal (abnormalities in estrogen/androgen balance) and genetic (positive family history, Klinefelter syndrome, mutations in BRCA1 and specially BRCA2) risk factors are already known. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21241366",
"endSection": "abstract",
"offsetInBeginSection": 653,
"offsetInEndSection": 800,
"text": "The largest study found 19.2- and 57.8-fold increases in incidence and mortality, respectively, with particularly high risks among 47,XXY mosaics. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21241366",
"endSection": "abstract",
"offsetInBeginSection": 1170,
"offsetInEndSection": 1408,
"text": "CONCLUSIONS: Additional well-designed epidemiologic studies are needed to clarify which patients with KS are at a high risk of developing MBC and to distinguish between possible predisposing factors, including altered endogenous hormones."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20706705",
"endSection": "abstract",
"offsetInBeginSection": 281,
"offsetInEndSection": 528,
"text": "Major risk factors for developing male BC include clinical disorders involving hormonal imbalances (excess of estrogen or a deficiency of testosterone as seen in patients with Klinefelter syndrome) and a positive family history for breast cancer. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20698148",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 219,
"text": "Patients with 47, XXY karyotype (Klinefelter syndrome) appear to have increased risk of developing cancer, especially male breast cancer, germ cell tumours and non Hodgkin lymphomas, but rarely acute myeloid leukaemia. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7125242",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 67,
"text": "Breast cancer in a patient with Klinefelter's syndrome is reported."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7125242",
"endSection": "abstract",
"offsetInBeginSection": 347,
"offsetInEndSection": 515,
"text": "The increased conversion of testosterone to estradiol at the therapy with androgens might be responsible for the development of breast cancer in Klinefelter's syndrome."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9283592",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 206,
"text": "Patients with a 47,XXY karyotype (Klinefelter syndrome) appear to have an increased risk of developing cancer, especially male breast cancer and germ cell tumors, but rarely malignant hematologic disorders."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15119010",
"endSection": "abstract",
"offsetInBeginSection": 214,
"offsetInEndSection": 327,
"text": "The frequencies of diabetes mellitus, breast cancer, and germ cell neoplasia increases in Klinefelter's syndrome."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/3111653",
"endSection": "abstract",
"offsetInBeginSection": 323,
"offsetInEndSection": 457,
"text": "There is evidence, however, to suggest that Klinefelter's males have an increased risk of breast cancer that approaches three percent."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21246928",
"endSection": "abstract",
"offsetInBeginSection": 117,
"offsetInEndSection": 334,
"text": "Klinefelter syndrome has been consistently associated with breast cancer in men (MBC).<br><b>CASE REPORT</b>: We report a 54-year old man was diagnosed as synchronous bilateral breast cancer with Klinefelter syndrome."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16106025",
"endSection": "abstract",
"offsetInBeginSection": 1378,
"offsetInEndSection": 1622,
"text": "These results support a hormonal etiology for breast cancer in men and for prostate cancer and suggest that men with Klinefelter syndrome may be at substantially elevated risks for non-Hodgkin lymphoma, breast cancer, and, perhaps, lung cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15668471",
"endSection": "abstract",
"offsetInBeginSection": 495,
"offsetInEndSection": 735,
"text": "Major genetic factors associated with an increased risk of breast cancer for men include BRCA2 mutations, which are believed to account for the majority of inherited breast cancer in men, Klinefelter syndrome, and a positive family history."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28675185",
"endSection": "abstract",
"offsetInBeginSection": 124,
"offsetInEndSection": 275,
"text": "Those affected by Klinefelter's syndrome are at increased risk of systemic lupus erythematosus, breast cancer, non-Hodgkin's lymphoma, and lung cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16106025",
"endSection": "abstract",
"offsetInBeginSection": 1368,
"offsetInEndSection": 1624,
"text": "CONCLUSIONS These results support a hormonal etiology for breast cancer in men and for prostate cancer and suggest that men with Klinefelter syndrome may be at substantially elevated risks for non-Hodgkin lymphoma, breast cancer, and, perhaps, lung cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16106025",
"endSection": "abstract",
"offsetInBeginSection": 737,
"offsetInEndSection": 1057,
"text": "Compared with the general population, men with Klinefelter syndrome had higher mortality from lung cancer (SMR = 1.5, 95% CI = 1.0 to 2.0), breast cancer (SMR = 57.8, 95% CI = 18.8 to 135.0), and non-Hodgkin lymphoma (SMR = 3.5, 95% CI = 1.6 to 6.6) and lower mortality from prostate cancer (SMR = 0, 95% CI = 0 to 0.7)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21246928",
"endSection": "abstract",
"offsetInBeginSection": 109,
"offsetInEndSection": 195,
"text": "Klinefelter syndrome has been consistently associated with breast cancer in men (MBC)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23464700",
"endSection": "abstract",
"offsetInBeginSection": 418,
"offsetInEndSection": 528,
"text": "Male breast cancer risk factors show strong association with BRCA2 mutations, as well as Klinefelter syndrome."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20698148",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 218,
"text": "Patients with 47, XXY karyotype (Klinefelter syndrome) appear to have increased risk of developing cancer, especially male breast cancer, germ cell tumours and non Hodgkin lymphomas, but rarely acute myeloid leukaemia."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21246928",
"endSection": "abstract",
"offsetInBeginSection": 1311,
"offsetInEndSection": 1466,
"text": "Klinefelter syndrome, in which patients carry XXY chromosome, may be present in men with breast cancer for this reason they often develop gynecomastia.<br>"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21246928",
"endSection": "abstract",
"offsetInBeginSection": 101,
"offsetInEndSection": 187,
"text": "Klinefelter syndrome has been consistently associated with breast cancer in men (MBC)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16106025",
"endSection": "abstract",
"offsetInBeginSection": 1335,
"offsetInEndSection": 1580,
"text": "These results support a hormonal etiology for breast cancer in men and for prostate cancer and suggest that men with Klinefelter syndrome may be at substantially elevated risks for non-Hodgkin lymphoma, breast cancer, and, perhaps, lung cancer.."
}
]
| 11 | BioASQ-training11b | [
"https://meshb.nlm.nih.gov/record/ui?ui=D001244",
"https://meshb.nlm.nih.gov/record/ui?ui=D007713",
"https://meshb.nlm.nih.gov/record/ui?ui=D001943"
]
| null | 5a68eabab750ff4455000015 | 66 |
yesno | Does SRRM4 regulate neuronal-specific microexon splicing of TAF1 mRNA? | ['yes'] | [
"yes"
]
| ['Neuronal-specific microexon splicing of TAF1 mRNA is directly regulated by SRRM4/nSR100.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/31559909"
]
| [
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31559909",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 88,
"text": "Neuronal-specific microexon splicing of TAF1 mRNA is directly regulated by SRRM4/nSR100."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31559909",
"endSection": "abstract",
"offsetInBeginSection": 688,
"offsetInEndSection": 964,
"text": "Knockdown and ectopic expression experiments demonstrate that the neuronal-specific splicing factor SRRM4/nSR100 promotes the inclusion of microexon 34' into TAF1 mRNA, through the recognition of UGC sequences in the poly-pyrimidine tract upstream of the regulated microexon. "
}
]
| 12 | BioASQ-training12b | null | null | 63f9ee5c33942b094c000014 | 67 |
yesno | Is treatment with Bacillus Calmette Guerin used for bladder cancer? | ['yes'] | [
"yes"
]
| ['Intravesical Bacillus Calmette-Guerin (BCG) is the best treatment modality for progression of non-muscle invasive bladder cancer.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/29673806",
"http://www.ncbi.nlm.nih.gov/pubmed/11989131",
"http://www.ncbi.nlm.nih.gov/pubmed/17945285",
"http://www.ncbi.nlm.nih.gov/pubmed/28916862",
"http://www.ncbi.nlm.nih.gov/pubmed/19918272",
"http://www.ncbi.nlm.nih.gov/pubmed/1732628",
"http://www.ncbi.nlm.nih.gov/pubmed/3892051",
"http://www.ncbi.nlm.nih.gov/pubmed/3892050",
"http://www.ncbi.nlm.nih.gov/pubmed/29362915",
"http://www.ncbi.nlm.nih.gov/pubmed/17997439",
"http://www.ncbi.nlm.nih.gov/pubmed/21541499",
"http://www.ncbi.nlm.nih.gov/pubmed/12031870",
"http://www.ncbi.nlm.nih.gov/pubmed/16813873",
"http://www.ncbi.nlm.nih.gov/pubmed/2231917",
"http://www.ncbi.nlm.nih.gov/pubmed/2359181",
"http://www.ncbi.nlm.nih.gov/pubmed/6757467",
"http://www.ncbi.nlm.nih.gov/pubmed/19758621",
"http://www.ncbi.nlm.nih.gov/pubmed/6381762"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28916862",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 130,
"text": "Intravesical Bacillus Calmette-Guerin (BCG) is the best treatment modality for progression of non-muscle invasive bladder cancer. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28916862",
"endSection": "abstract",
"offsetInBeginSection": 1610,
"offsetInEndSection": 1759,
"text": "this result indicates that they may be used as putative biomarkers for monitoring changes in bladder carcinogenesis in response to BCG immunotherapy."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28916862",
"endSection": "abstract",
"offsetInBeginSection": 240,
"offsetInEndSection": 313,
"text": "response of urothelial precancerous lesions to intravesical BCG treatment"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29362915",
"endSection": "abstract",
"offsetInBeginSection": 85,
"offsetInEndSection": 548,
"text": "bladder cancer (BC) is a major clinical issue.METHODS: We performed immunohistochemistry to assess the role of human epidermal growth factor receptor-2 (HER-2) and microsatellite instability (MSI) factors MutL homologue 1 (MLH1) and MutS homologue 2 (MSH2) in predicting recurrence and progression of T1 high-grade BCs having undergone transurethral resection of bladder tumor (TURBT) alone or TURBT + intravesical instillations of bacillus Calmette-Guerin (BCG)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29673806",
"endSection": "abstract",
"offsetInBeginSection": 12,
"offsetInEndSection": 186,
"text": "To evaluate the efficacy and safety of a tailored endovesical immunotherapy protocol with biweekly BCG for elderly Patients with high risk non muscle invasive bladder cancer "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29673806",
"endSection": "title",
"offsetInBeginSection": 18,
"offsetInEndSection": 137,
"text": "Bacillus of Calmette-Guerin (BCG) therapy for high risk non muscle invasive bladder cancer treatment in older patients."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12031870",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 149,
"text": "BCG (Bacillus of Calmette Guerin) has been used for more than 20 years and is currently the most active agent for superficial bladder cancer therapy."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12031870",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 82,
"text": "BCG (Bacillus of Calmette Guerin) therapy of high-risk superficial bladder cancer."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21541499",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 115,
"text": "Production of IL-5, a classical T(H)2 cytokine, following bacillus Calmette guerin immunotherapy of bladder cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/1732628",
"endSection": "abstract",
"offsetInBeginSection": 104,
"offsetInEndSection": 200,
"text": "Intravesical Bacillus Calmette-Guerin is used to treat patients with superficial bladder cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12031870",
"endSection": "abstract",
"offsetInBeginSection": 399,
"offsetInEndSection": 590,
"text": "There is some evidence that BCG therapy improves survival and progression rates of patients with high-risk superficial bladder cancer decreasing the proportion who require radical cystectomy."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11989131",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 133,
"text": "Local immunotherapy with bacillus Calmette-Guerin (BCG) is an effective and frequently used treatment for superficial bladder cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16813873",
"endSection": "abstract",
"offsetInBeginSection": 1846,
"offsetInEndSection": 2112,
"text": "CONCLUSIONS\nIntravesical bacillus Calmette-Guerin is a viable therapeutic option in patients with high risk superficial bladder cancer and concomitant lymphoma or chronic lymphocytic leukemia, treatment with low dose oral steroids or treatment with inhaled steroids."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19758621",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 101,
"text": "PURPOSE\nBacillus Calmette-Guerin is the most effective therapy for nonmuscle invasive bladder cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19918272",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 261,
"text": "INTRODUCTION\nBacillus Calmette-Guerin (BCG) is a live attenuated strain of Mycobacterium bovis that has been used to treat urothelial carcinoma since 1976, and has been reported to eradicate disease in more than 70% of patients with in situ and stage I disease."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2231917",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 134,
"text": "Intravesical administration of bacillus Calmette-Guerin has been shown to be highly effective treatment of superficial bladder cancer."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/3892051",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 144,
"text": "Intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer: effect of bacillus Calmette-Guerin viability on treatment results."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11989131",
"endSection": "abstract",
"offsetInBeginSection": 205,
"offsetInEndSection": 352,
"text": "We describe a 53 year- old man with a disseminated bacillus Calmette-Guerin (BCG) infection after intravescical instillation for bladder carcinoma."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17945285",
"endSection": "abstract",
"offsetInBeginSection": 441,
"offsetInEndSection": 683,
"text": "We tested the hypothesis that tumor expression of natural cytotoxicity receptor ligands can serve as a predictive factor for the response to intravesical bacillus Calmette-Guerin in patients with nonmuscle invasive, high grade bladder cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/3892050",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 161,
"text": "Bacillus Calmette-Guerin immunotherapy has been found by a number of investigators to be effective in the treatment and prevention of superficial bladder cancer."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19918272",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 446,
"text": "Pancreatic and psoas abscesses as a late complication of intravesical administration of bacillus Calmette-Guerin for bladder cancer: a case report and review of the literature.This case illustrates the fact that although intravesical administration of bacillus Calmette-Guerin is generally considered to be safe, it is not exempt from complications and these could appear immediately after treatment or as a delayed complication many years later."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2359181",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 306,
"text": "Effects of local bacillus Calmette-Guerin therapy in patients with bladder carcinoma on immunocompetent cells of the bladder wall.The antitumoral effects of intravesical bacillus Calmette-Guerin against recurrent superficial urothelial bladder cancer seem to be linked to immunological effector mechanisms. "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2231917",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 229,
"text": "Fatal sepsis following intravesical bacillus Calmette-Guerin administration for bladder cancer.Intravesical administration of bacillus Calmette-Guerin has been shown to be highly effective treatment of superficial bladder cancer. "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/3892051",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 337,
"text": "Intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer: effect of bacillus Calmette-Guerin viability on treatment results.We treated 40 patients with superficial bladder cancer via intravesical bacillus Calmette-Guerin for 1) prophylaxis against tumor recurrence, 2) residual carcinoma or 3) flat carcinoma in situ. "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/3892050",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 219,
"text": "Bacillus Calmette-Guerin immunotherapy for bladder cancer.Bacillus Calmette-Guerin immunotherapy has been found by a number of investigators to be effective in the treatment and prevention of superficial bladder cancer. "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16813873",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 379,
"text": "Safety and efficacy of intravesical bacillus Calmette-Guerin instillations in steroid treated and immunocompromised patients.Intravesical bacillus Calmette-Guerin is a viable therapeutic option in patients with high risk superficial bladder cancer and concomitant lymphoma or chronic lymphocytic leukemia, treatment with low dose oral steroids or treatment with inhaled steroids. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/6381762",
"endSection": "abstract",
"offsetInBeginSection": 2120,
"offsetInEndSection": 2425,
"text": "Our results suggest that intralesional bacillus Calmette-Guerin immunotherapy can afford long term protection from transplanted bladder cancer, and that live bacillus Calmette-Guerin is superior to levamisole and P3 + Re-glycolipid + bacillus Calmette-Guerin cell walls in the treatment of bladder cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/6757467",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 191,
"text": "A randomized controlled prospective evaluation of intravesical and percutaneous bacillus Calmette-Guerin immunotherapy was done in 57 patients with transitional cell carcinoma of the bladder."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17945285",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 167,
"text": "Up to 90% of patients with high grade superficial bladder tumors experience tumor recurrence and up to 50% have progression despite bacillus Calmette-Guerin treatment."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17997439",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 117,
"text": "We review how the bacillus Calmette-Guerin vaccine evolved to become standard therapy for superficial bladder cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17997439",
"endSection": "abstract",
"offsetInBeginSection": 118,
"offsetInEndSection": 332,
"text": "We reviewed the historical literature describing the origin of the bacillus Calmette-Guerin vaccine as an anticancer agent and its singular success as the most effective immunotherapy used against a human neoplasm."
}
]
| 11 | BioASQ-training11b | null | null | 5c83f858617e120c34000003 | 68 |
yesno | Is there an association between serum interleukin-6 concentrations and outcomes of stroke patients? | ['yes'] | [
"yes"
]
| ['Yes. Greater serum interleukin-6 concentrations are associated with worse outcomes in ischemic and hemmorhagic stroke patients'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/25295149",
"http://www.ncbi.nlm.nih.gov/pubmed/19901973",
"http://www.ncbi.nlm.nih.gov/pubmed/18685925",
"http://www.ncbi.nlm.nih.gov/pubmed/18048088",
"http://www.ncbi.nlm.nih.gov/pubmed/17337911",
"http://www.ncbi.nlm.nih.gov/pubmed/14730251"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25295149",
"endSection": "abstract",
"offsetInBeginSection": 1418,
"offsetInEndSection": 1496,
"text": " In addition, IL-6 concentrations affect clinical outcomes in ischemic stroke."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19901973",
"endSection": "abstract",
"offsetInBeginSection": 968,
"offsetInEndSection": 1363,
"text": "After appropriate adjustment, the odds ratios for the association of markers and poor outcome (comparing the upper and the lower third) were interleukin-6, 3.1 (95% CI: 1.9-5.0); C-reactive protein, 1.9 (95% CI: 1.2-3.1); fibrinogen, 1.5 (95% CI: 1.0-2.36); white cell count, 2.1 (95% CI: 1.3-3.4); and glucose 1.3 (95% CI: 0.8-2.1). The results for interleukin-6 were similar to other studies. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18685925",
"endSection": "abstract",
"offsetInBeginSection": 1745,
"offsetInEndSection": 1992,
"text": "-6 and IL-10 levels were higher in patients with poor outcome. On logistic regression analysis, higher values of IL-6 were significantly associated with clinical outcome at 1 month (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.02-1.54). "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18685925",
"endSection": "abstract",
"offsetInBeginSection": 2116,
"offsetInEndSection": 2216,
"text": "In hemorrhagic stroke, high levels of IL-6 in the early phase indicated a poor neurological outcome."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18048088",
"endSection": "abstract",
"offsetInBeginSection": 903,
"offsetInEndSection": 1551,
"text": "Initially elevated levels of hs-IL-6 at presentation further correlated with unfavorable clinical outcomes (by NIHSS and mRs) at both time points. Analysis of variance in the different quartiles identified an hs-IL-6 gradient-dependent correlation at both time points, such that the higher the initial hs-IL-6 concentration, the higher the elevation in inflammatory biomarkers and the poorer the neurological state at both time points (p<0.001 for NIHSS and p=0.001 for mRs, for trend across quartiles). CONCLUSIONS: This study demonstrates the potential of employing hs-IL-6 as an early stage biomarker for the prognosis of acute ischemic stroke. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17337911",
"endSection": "abstract",
"offsetInBeginSection": 1234,
"offsetInEndSection": 1325,
"text": "Another negative correlation was found between IL-6 and CNS scores (r = -0.451, p = 0.000)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17337911",
"endSection": "abstract",
"offsetInBeginSection": 1816,
"offsetInEndSection": 1950,
"text": "In addition, increased levels of IL-6 and reduced levels of protein C and protein S may play a role in acute ischemic stroke severity."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14730251",
"endSection": "abstract",
"offsetInBeginSection": 271,
"offsetInEndSection": 490,
"text": "Variables that are predictors of adverse stroke outcome include erythrocyte sedimentation rate, and levels of C-reactive protein (CRP), interleukin-6, tumour necrosis factor-alpha and intercellular adhesion molecule-1. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25295149",
"endSection": "abstract",
"offsetInBeginSection": 1418,
"offsetInEndSection": 1496,
"text": " In addition, IL-6 concentrations affect clinical outcomes in ischemic stroke."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19901973",
"endSection": "abstract",
"offsetInBeginSection": 968,
"offsetInEndSection": 1363,
"text": "After appropriate adjustment, the odds ratios for the association of markers and poor outcome (comparing the upper and the lower third) were interleukin-6, 3.1 (95% CI: 1.9-5.0); C-reactive protein, 1.9 (95% CI: 1.2-3.1); fibrinogen, 1.5 (95% CI: 1.0-2.36); white cell count, 2.1 (95% CI: 1.3-3.4); and glucose 1.3 (95% CI: 0.8-2.1). The results for interleukin-6 were similar to other studies. "
}
]
| 5 | BioASQ-training5b | [
"http://www.uniprot.org/uniprot/IL6_PIG"
]
| []
| 54cf4bc3f693c3b16b00000d | 69 |
yesno | Has statin use been associated with a higher risk of dementia? | ['yes'] | [
"yes"
]
| ["According to a systematic review and meta-analysis of observational studies, statin use is not associated with a higher risk of dementia or Alzheimer's disease. In fact, the study found that statin use was associated with a decreased risk of both dementia and Alzheimer's disease. This reduction in risk was similar for both lipophilic and hydrophilic statins, but high-potency statins showed a greater efficacy in reducing dementia risk compared to low-potency statins. These findings suggest that statin treatment does not carry a neurocognitive risk and may even have a potential favorable role in reducing the risk of dementia. However, randomized clinical trials are needed to further explore this potential neuroprotective effect.", "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."] | [
"http://www.ncbi.nlm.nih.gov/pubmed/12084801",
"http://www.ncbi.nlm.nih.gov/pubmed/24504830",
"http://www.ncbi.nlm.nih.gov/pubmed/30087076",
"http://www.ncbi.nlm.nih.gov/pubmed/31574510",
"http://www.ncbi.nlm.nih.gov/pubmed/21795660",
"http://www.ncbi.nlm.nih.gov/pubmed/32583471",
"http://www.ncbi.nlm.nih.gov/pubmed/24681022",
"http://www.ncbi.nlm.nih.gov/pubmed/24578458",
"http://www.ncbi.nlm.nih.gov/pubmed/16009757",
"http://www.ncbi.nlm.nih.gov/pubmed/37291702",
"http://www.ncbi.nlm.nih.gov/pubmed/26080283",
"http://www.ncbi.nlm.nih.gov/pubmed/30337635",
"http://www.ncbi.nlm.nih.gov/pubmed/29247073",
"http://www.ncbi.nlm.nih.gov/pubmed/20413854",
"http://www.ncbi.nlm.nih.gov/pubmed/30045255",
"http://www.ncbi.nlm.nih.gov/pubmed/22451317",
"http://www.ncbi.nlm.nih.gov/pubmed/34756134",
"http://www.ncbi.nlm.nih.gov/pubmed/34871380",
"http://www.ncbi.nlm.nih.gov/pubmed/34315986",
"http://www.ncbi.nlm.nih.gov/pubmed/35305172",
"http://www.ncbi.nlm.nih.gov/pubmed/24075740",
"http://www.ncbi.nlm.nih.gov/pubmed/23461525",
"http://www.ncbi.nlm.nih.gov/pubmed/25203109",
"http://www.ncbi.nlm.nih.gov/pubmed/29507718",
"http://www.ncbi.nlm.nih.gov/pubmed/22269162"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34871380",
"endSection": "abstract",
"offsetInBeginSection": 23,
"offsetInEndSection": 91,
"text": "impact of statins on cognitive decline and dementia is still debated"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34871380",
"endSection": "abstract",
"offsetInBeginSection": 1419,
"offsetInEndSection": 1484,
"text": "absence of a neurocognitive risk associated with statin treatment"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34756134",
"endSection": "abstract",
"offsetInBeginSection": 687,
"offsetInEndSection": 755,
"text": "evidence in support of as well as against statin therapy in dementia"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34756134",
"endSection": "abstract",
"offsetInBeginSection": 1079,
"offsetInEndSection": 1166,
"text": "Lowering cholesterol using statin may help prevent or delay the progression of dementia"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24578458",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 69,
"text": "BACKGROUND: The effect of statin use on dementia risk remains unclear"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24578458",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16009757",
"endSection": "abstract",
"offsetInBeginSection": 1521,
"offsetInEndSection": 1623,
"text": "S: In this cohort study, statin therapy was not associated with a decreased risk of dementia. Methodol"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24681022",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30337635",
"endSection": "abstract",
"offsetInBeginSection": 1344,
"offsetInEndSection": 1622,
"text": "A significant decrease in the risk of dementia with increasing statin duration was also demonstrated (P for trend = 0.002).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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31574510",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35305172",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20413854",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20413854",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20413854",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21795660",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23461525",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30087076",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25203109",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24075740",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12084801",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37291702",
"endSection": "abstract",
"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 <0.001).CONCLUSION: In NVAF patients who received OAC, statin therapy lowered the dementia risk compared with no statin therapy."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25203109",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30045255",
"endSection": "abstract",
"offsetInBeginSection": 1197,
"offsetInEndSection": 1253,
"text": "Statins use was associated with dementia risk decrement."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32583471",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29507718",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24504830",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34315986",
"endSection": "abstract",
"offsetInBeginSection": 484,
"offsetInEndSection": 641,
"text": " Overall, statin use was not associated with an increased risk of AD incidence [adjusted hazard ratio (aHR) = 1.04; 95% confidence interval (CI) = 0.99-1.10]"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34315986",
"endSection": "abstract",
"offsetInBeginSection": 642,
"offsetInEndSection": 825,
"text": " When examined by level of statin exposure, statin prescription < 540 days during a 2-year window time was associated with a higher risk for incidence of AD compared to statin non-use"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29247073",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29247073",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29247073",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22269162",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22269162",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22451317",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30087076",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26080283",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34315986",
"endSection": "abstract",
"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 "
}
]
| 13 | BioASQ-training13b | null | null | 6616a122fdcbea915f000058 | 70 |
yesno | Are Drosophila ultraconserved elements candidate ncRNAs? | ['yes'] | [
"yes"
]
| ['Yes. Highly constrained intergenic Drosophila ultraconserved elements are candidate ncRNAs.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/25618141"
]
| [
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25618141",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 86,
"text": "Highly constrained intergenic Drosophila ultraconserved elements are candidate ncRNAs."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25618141",
"endSection": "abstract",
"offsetInBeginSection": 306,
"offsetInEndSection": 1403,
"text": "Here, we report the discovery and characterization of UCEs from 12 sequenced Drosophila species. We identified 98 elements ≥80 bp long with very high conservation across the Drosophila phylogeny. Population genetic analyses reveal that these UCEs are not present in mutational cold spots. Instead we infer that they experience a level of selective constraint almost 10-fold higher compared with missense mutations in protein-coding sequences, which is substantially higher than that observed previously for human UCEs. About one-half of these Drosophila UCEs overlap the transcribed portion of genes, with many of those that are within coding sequences likely to correspond to sites of ADAR-dependent RNA editing. For the remaining UCEs that are in nongenic regions, we find that many are potentially capable of forming RNA secondary structures. Among ten chosen for further analysis, we discovered that the majority are transcribed in multiple tissues of Drosophila melanogaster. We conclude that Drosophila species are rich with UCEs and that many of them may correspond to novel noncoding RNAs."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25618141",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 85,
"text": "Highly Constrained Intergenic Drosophila Ultraconserved Elements Are Candidate ncRNAs"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25618141",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 86,
"text": "Highly constrained intergenic Drosophila ultraconserved elements are candidate ncRNAs."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25618141",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 86,
"text": "Highly constrained intergenic Drosophila ultraconserved elements are candidate ncRNAs."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25618141",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 86,
"text": "Highly constrained intergenic Drosophila ultraconserved elements are candidate ncRNAs."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25618141",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 86,
"text": "Highly constrained intergenic Drosophila ultraconserved elements are candidate ncRNAs."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25618141",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 86,
"text": "Highly constrained intergenic Drosophila ultraconserved elements are candidate ncRNAs."
}
]
| 5 | BioASQ-training5b | [
"http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004330"
]
| []
| 56d1accb67f0cb3d66000001 | 71 |
yesno | Does a selective sweep increase genetic variation? | ['no'] | [
"no"
]
| ['Selective sweep is a phenomenon in which the fixation of strongly beneficial alleles within a population reduces genetic diversity at partially linked neutral loci. Reduced variation or deviations from neutrality, along with an excess of fixed replacement sites, are indicative of selective sweep.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/24282552",
"http://www.ncbi.nlm.nih.gov/pubmed/22087274",
"http://www.ncbi.nlm.nih.gov/pubmed/21624997",
"http://www.ncbi.nlm.nih.gov/pubmed/20978039",
"http://www.ncbi.nlm.nih.gov/pubmed/20352120",
"http://www.ncbi.nlm.nih.gov/pubmed/20140188",
"http://www.ncbi.nlm.nih.gov/pubmed/17396267",
"http://www.ncbi.nlm.nih.gov/pubmed/16951057",
"http://www.ncbi.nlm.nih.gov/pubmed/16367838",
"http://www.ncbi.nlm.nih.gov/pubmed/16339379",
"http://www.ncbi.nlm.nih.gov/pubmed/21705748",
"http://www.ncbi.nlm.nih.gov/pubmed/16322515",
"http://www.ncbi.nlm.nih.gov/pubmed/24126360",
"http://www.ncbi.nlm.nih.gov/pubmed/22491190",
"http://www.ncbi.nlm.nih.gov/pubmed/21076829",
"http://www.ncbi.nlm.nih.gov/pubmed/24075201",
"http://www.ncbi.nlm.nih.gov/pubmed/21385389",
"http://www.ncbi.nlm.nih.gov/pubmed/24465214",
"http://www.ncbi.nlm.nih.gov/pubmed/18346126"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24282552",
"endSection": "abstract",
"offsetInBeginSection": 1110,
"offsetInEndSection": 1417,
"text": "An East African population that gave rise to non-Africans underwent a selective sweep affecting the subcentromeric region where MTMR8 is located. This and similar sweeps in four other regions of the X chromosome, documented in the literature, effectively reduced genetic diversity of non-African chromosomes"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22087274",
"endSection": "abstract",
"offsetInBeginSection": 1315,
"offsetInEndSection": 1404,
"text": "a selective sweep that has removed genetic variation from much of the drive X chromosome."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21624997",
"endSection": "abstract",
"offsetInBeginSection": 734,
"offsetInEndSection": 853,
"text": "evidence of reduced diversity and an excess of fixed replacement sites, consistent with a species-wide selective sweep."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20978039",
"endSection": "abstract",
"offsetInBeginSection": 550,
"offsetInEndSection": 624,
"text": "recent independent selective sweeps in AGO2 have reduced genetic variation"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20352120",
"endSection": "abstract",
"offsetInBeginSection": 1300,
"offsetInEndSection": 1477,
"text": "episodes of natural selection (likely a selective sweep) predating the coalescent of human lineages, within the last 25 million years, account for the observed reduced diversity"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20140188",
"endSection": "abstract",
"offsetInBeginSection": 1209,
"offsetInEndSection": 1301,
"text": "reduced variation or deviations from neutrality that might indicate a recent selective sweep"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17396267",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 265,
"text": "Consider a genetic locus carrying a strongly beneficial allele which has recently fixed in a large population. As strongly beneficial alleles fix quickly, sequence diversity at partially linked neutral loci is reduced. This phenomenon is known as a selective sweep."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16951057",
"endSection": "abstract",
"offsetInBeginSection": 661,
"offsetInEndSection": 732,
"text": "a local selective sweep or demographic process that reduced variability"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16339379",
"endSection": "abstract",
"offsetInBeginSection": 220,
"offsetInEndSection": 257,
"text": "reduced variation (a selective sweep)"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16367838",
"endSection": "abstract",
"offsetInBeginSection": 1077,
"offsetInEndSection": 1252,
"text": "the mtDNA diversity, but not the nuclear DNA diversity, has been reduced relative to the neutral expectation of molecular evolution, suggesting the action of a selective sweep"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21705748",
"endSection": "abstract",
"offsetInBeginSection": 1741,
"offsetInEndSection": 2009,
"text": "Furthermore, the amount of genetic variation after a selective sweep is expected to be unequal over demes: a greater reduction in expected heterozygosity occurs in the subpopulation from which the beneficial mutation originates than in its neighboring subpopulations."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24126360",
"endSection": "abstract",
"offsetInBeginSection": 1327,
"offsetInEndSection": 1512,
"text": "Our observation of reduction in variation at both intragenic and flanking loci of mutant pfcrt gene confirmed the selective sweep model of natural selection in chloroquine resistant P."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21705748",
"endSection": "abstract",
"offsetInBeginSection": 1741,
"offsetInEndSection": 2009,
"text": "Furthermore, the amount of genetic variation after a selective sweep is expected to be unequal over demes: a greater reduction in expected heterozygosity occurs in the subpopulation from which the beneficial mutation originates than in its neighboring subpopulations."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24126360",
"endSection": "abstract",
"offsetInBeginSection": 1327,
"offsetInEndSection": 1512,
"text": "Our observation of reduction in variation at both intragenic and flanking loci of mutant pfcrt gene confirmed the selective sweep model of natural selection in chloroquine resistant P."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21076829",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 103,
"text": "A selective sweep describes the reduction of linked genetic variation due to strong positive selection."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21705748",
"endSection": "abstract",
"offsetInBeginSection": 1741,
"offsetInEndSection": 2009,
"text": "Furthermore, the amount of genetic variation after a selective sweep is expected to be unequal over demes: a greater reduction in expected heterozygosity occurs in the subpopulation from which the beneficial mutation originates than in its neighboring subpopulations."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24075201",
"endSection": "abstract",
"offsetInBeginSection": 188,
"offsetInEndSection": 481,
"text": "In these situations, adaptation should commonly produce 'soft' selective sweeps, where multiple adaptive alleles sweep through the population at the same time, either because the alleles were already present as standing genetic variation or arose independently by recurrent de novo mutations."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21076829",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 103,
"text": "A selective sweep describes the reduction of linked genetic variation due to strong positive selection."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24075201",
"endSection": "abstract",
"offsetInBeginSection": 188,
"offsetInEndSection": 481,
"text": "In these situations, adaptation should commonly produce 'soft' selective sweeps, where multiple adaptive alleles sweep through the population at the same time, either because the alleles were already present as standing genetic variation or arose independently by recurrent de novo mutations."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21385389",
"endSection": "abstract",
"offsetInBeginSection": 1362,
"offsetInEndSection": 1608,
"text": "CONCLUSIONS: The severe reduction in nucleotide variation at OsAMT1;1 in rice was caused by a selective sweep around OsAMT1;1, which may reflect the nitrogen uptake system under strong selection by the paddy soil during the domestication of rice."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21076829",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 103,
"text": "A selective sweep describes the reduction of linked genetic variation due to strong positive selection."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21076829",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 102,
"text": "A selective sweep describes the reduction of linked genetic variation due to strong positive selection"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21076829",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 102,
"text": "A selective sweep describes the reduction of linked genetic variation due to strong positive selection"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21076829",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 102,
"text": "A selective sweep describes the reduction of linked genetic variation due to strong positive selection"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21076829",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 102,
"text": "A selective sweep describes the reduction of linked genetic variation due to strong positive selection"
}
]
| 5 | BioASQ-training5b | [
"http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014644",
"http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012641"
]
| []
| 5540a8d20083d1bf0e000001 | 72 |
yesno | Should be used bexarotene for relapsing-remitting multiple sclerosis? | ['no'] | [
"no"
]
| ['Bexarotene is not recommended to treat patients with multiple sclerosis because of its poor tolerability and negative primary efficacy outcome.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/34418398"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34418398",
"endSection": "abstract",
"offsetInBeginSection": 2838,
"offsetInEndSection": 3010,
"text": "INTERPRETATION: We do not recommend the use of bexarotene to treat patients with multiple sclerosis because of its poor tolerability and negative primary efficacy outcome. "
}
]
| 12 | BioASQ-training12b | null | null | 64040bd8201352f04a00000e | 73 |
yesno | Is BNN20 involved in Parkinson's disease? | ['yes'] | [
"yes"
]
| ["Yes. Neurotrophic factors are among the most promising treatments aiming at slowing or stopping and even reversing Parkinson's disease (PD). BNN-20 has been suggested as an important neuroprotective agent acting through the TrkB neurotrophin receptor pathway, mimicking the action of the endogenous neurotrophin BDNF. Thus BNN-20 could be proposed for treatment of PD.", "Yes. BNN20 is an important neuroprotective agent acting through the TrkB neurotrophin receptor pathway that has been implicated in numerous pathologies including inflammatory diseases, cancer, viral infection, and neurodegenerative diseases such as amyotrophic lateral sclerosis and Parkinson's disease.", "Yes. BNN20 is involved in the development of Parkinson's disease. It is a member of the intramembrane-tumor necrosis factor-a (ITF-a) family of transcription factors that are dysregulated in several neurodegenerative diseases such as amyotrophic lateral sclerosis, frontotemporal degeneration, axonal injury, late-onset cerebellar ataxia, and multiple sclerosis.", 'Yes. BNN20 could be proposed as a therapeutic for PD. BNN-20 administration to Weaver/NGL mice induced a strong NF-kB-dependent transcriptional response in the brain as detected by bioluminescence imaging, which was abolished by co-administration of the TrkB inhibitor ANA-12'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/28461162"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28461162",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 1853,
"text": "Neurotrophic factors are among the most promising treatments aiming at slowing or stopping and even reversing Parkinson's disease (PD). However, in most cases, they cannot readily cross the human blood-brain-barrier (BBB). Herein, we propose as a therapeutic for PD the small molecule 17-beta-spiro-[5-androsten-17,2'-oxiran]-3beta-ol (BNN-20), a synthetic analogue of DHEA, which crosses the BBB and is deprived of endocrine side-effects. Using the \"weaver\" mouse, a genetic model of PD, which exhibits progressive dopaminergic neurodegeneration in the Substantia Nigra (SN), we have shown that long-term administration (P1-P21) of BNN-20 almost fully protected the dopaminergic neurons and their terminals, via i) a strong anti-apoptotic effect, probably mediated through the Tropomyosin receptor kinase B (TrkB) neurotrophin receptor's PI3K-Akt-NF-κB signaling pathway, ii) by exerting an efficient antioxidant effect, iii) by inducing significant anti-inflammatory activity and iv) by restoring Brain-Derived Neurotrophic Factor (BDNF) levels. By intercrossing \"weaver\" with NGL mice (dual GFP/luciferase-NF-κΒ reporter mice, NF-κΒ.GFP.Luc), we obtained Weaver/NGL mice that express the NF-κB reporter in all somatic cells. Acute BNN-20 administration to Weaver/NGL mice induced a strong NF-κB-dependent transcriptional response in the brain as detected by bioluminescence imaging, which was abolished by co-administration of the TrkB inhibitor ANA-12. This indicates that BNN-20 exerts its beneficial action (at least in part) through the TrkB-PI3K-Akt-NF-κB signaling pathway. These results could be of clinical relevance, as they suggest BNN-20 as an important neuroprotective agent acting through the TrkB neurotrophin receptor pathway, mimicking the action of the endogenous neurotrophin BDNF. Thus BNN-20 could be proposed for treatment of PD."
}
]
| 11 | BioASQ-training11b | null | null | 5e2d7ceefbd6abf43b00000b | 74 |
yesno | Is pazopanib an effective treatment of glioblastoma? | ['no'] | [
"no"
]
| ['No. Pazopanib does not improve survival of glioblastoma patients.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/20200024",
"http://www.ncbi.nlm.nih.gov/pubmed/23363814"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23363814",
"endSection": "abstract",
"offsetInBeginSection": 933,
"offsetInEndSection": 1141,
"text": "RESULTS: The six-month progression-free survival (PFS) rates in phase II (n = 41) were 0% and 15% in the PTEN/EGFRvIII-positive and PTEN/EGFRvIII-negative cohorts, respectively, leading to early termination. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20200024",
"endSection": "abstract",
"offsetInBeginSection": 1629,
"offsetInEndSection": 1780,
"text": "Single-agent pazopanib did not prolong PFS in this patient population but showed in situ biological activity as demonstrated by radiographic responses."
}
]
| 11 | BioASQ-training11b | null | null | 5c72aaed7c78d6947100006f | 75 |
yesno | Is stop codon bypass possible? | ['yes'] | [
"yes"
]
| Yes it is. The UGA stop codon was found to code for seleno-cysteine in a number of Saccharomyces cerevisiae genes, whereas the UAG stop codon was shown to code for pyrro-lysine in some archaean species. Moreover, in experimental and therapeutic settings, aminoglycoside-induced stop codon bypass has been used to restore protein translation by promoting readthrough of stop codons, generated by mutations causing premature termination of protein synthesis. Additionally, cytosine deamination to uracil in stop codons may result in stop codon bypass, whereas in a number of polycistronic genes or sequential ORFs, there is evidence for stop codon bypass, although their induction mechanisms are still unclear. Additional hypotheses for stop codon bypass involve the 3' context of the translated transcript, non-conventional anticodon-codon interactions or translational frameshifts. | [
"http://www.ncbi.nlm.nih.gov/pubmed/23083810",
"http://www.ncbi.nlm.nih.gov/pubmed/22718819",
"http://www.ncbi.nlm.nih.gov/pubmed/21969101",
"http://www.ncbi.nlm.nih.gov/pubmed/18809619",
"http://www.ncbi.nlm.nih.gov/pubmed/17961216",
"http://www.ncbi.nlm.nih.gov/pubmed/17881586",
"http://www.ncbi.nlm.nih.gov/pubmed/17187982",
"http://www.ncbi.nlm.nih.gov/pubmed/12711673",
"http://www.ncbi.nlm.nih.gov/pubmed/10102819",
"http://www.ncbi.nlm.nih.gov/pubmed/9223347",
"http://www.ncbi.nlm.nih.gov/pubmed/7479046",
"http://www.ncbi.nlm.nih.gov/pubmed/2010914",
"http://www.ncbi.nlm.nih.gov/pubmed/2207158",
"http://www.ncbi.nlm.nih.gov/pubmed/2103444",
"http://www.ncbi.nlm.nih.gov/pubmed/2691247"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23083810",
"endSection": "abstract",
"offsetInBeginSection": 275,
"offsetInEndSection": 492,
"text": "In 1999, proof-of-concept for treating these disorders was obtained in a mouse model of muscular dystrophy, when administration of aminoglycosides restored protein translation by inducing the ribosome to bypass a PTC."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22718819",
"endSection": "abstract",
"offsetInBeginSection": 1,
"offsetInEndSection": 340,
"text": "xpression of retroviral replication enzymes (Pol) requires a controlled translational recoding event to bypass the stop codon at the end of gag. This recoding event occurs either by direct suppression of termination via the insertion of an amino acid at the stop codon (readthrough) or by alteration of the mRNA reading frame (frameshift)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21969101",
"endSection": "abstract",
"offsetInBeginSection": 123,
"offsetInEndSection": 265,
"text": "Aminoglycosides have the capability to mediate a bypass of stop mutations during translation thus resulting in a rescue of protein expression."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18809619",
"endSection": "abstract",
"offsetInBeginSection": 144,
"offsetInEndSection": 297,
"text": "The underlying molecular pathology in a considerable proportion of these diseases however are nonsense mutations leading to premature termination codons."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18809619",
"endSection": "abstract",
"offsetInBeginSection": 437,
"offsetInEndSection": 786,
"text": "We have taken advantage of the ability of aminoglycoside drugs to suppress such nonsense mutations and partially restore full-length, functional protein in a zebrafish model of choroideraemia (chm(ru848); juvenile chorio-retinal degeneration) and in two models of ocular coloboma (noi(tu29a) and gup(m189); congenital optic fissure closure defects)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17961216",
"endSection": "abstract",
"offsetInBeginSection": 1497,
"offsetInEndSection": 1699,
"text": "This is the first demonstration that the LTR promoter directs Tca2 pol protein expression, and that pol proteins are translated from a gag-pol RNA, which thus requires a mechanism for stop codon bypass."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17961216",
"endSection": "abstract",
"offsetInBeginSection": 12,
"offsetInEndSection": 229,
"text": "In the C. albicans retrotransposon Tca2, the gag and pol ORFs are separated by a UGA stop codon, 3' of which is a potential RNA pseudoknot. It is unclear how the Tca2 gag UGA codon is bypassed to allow pol expression."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17881586",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 115,
"text": "Aminoglycosides can bypass nonsense mutations and are the prototypic agents for translational bypass therapy (TBT)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17187982",
"endSection": "abstract",
"offsetInBeginSection": 91,
"offsetInEndSection": 425,
"text": "Recent studies on translation termination in the yeast Saccharomyces cerevisiae have not only enabled the identification of the key components of the termination machinery, but have also revealed several regulatory mechanisms that might enable the controlled synthesis of C-terminally extended polypeptides via stop-codon readthrough."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14623998",
"endSection": "abstract",
"offsetInBeginSection": 1357,
"offsetInEndSection": 1523,
"text": "These retroelements have a conserved stem-loop at the end of gag, and likely express pol either by a novel means of internal ribosomal entry or by a bypass mechanism."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12711673",
"endSection": "abstract",
"offsetInBeginSection": 323,
"offsetInEndSection": 499,
"text": "Among the 58 SORFs identified, eight displayed a stop codon bypass level ranging from 3 to 25%. For each of the eight sequences, we demonstrated the presence of a poly(A) mRNA."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12711673",
"endSection": "abstract",
"offsetInBeginSection": 823,
"offsetInEndSection": 1012,
"text": "Our results demonstrate that the presence of a stop codon in a large ORF may not always correspond to a sequencing error, or a pseudogene, but can be a recoding signal in a functional gene."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10102819",
"endSection": "abstract",
"offsetInBeginSection": 289,
"offsetInEndSection": 500,
"text": "This study demonstrates that in nondividing Escherichia coli cells, a DNA template base replaced with uracil in a stop codon in the firefly luciferase gene results in conversion of inactive to active luciferase."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10102819",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 82,
"text": "Phenotypic change caused by transcriptional bypass of uracil in nondividing cells."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9223347",
"endSection": "abstract",
"offsetInBeginSection": 1106,
"offsetInEndSection": 1318,
"text": "These results suggest that in tomato tissues, GPR is made as part of a longer polypeptide by some translational mechanism that enables bypass of the internal stop codon, such as frameshifting or ribosome hopping."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7479046",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 264,
"text": "Translation of yeast GCN4 mRNA occurs by a reinitiation mechanism that is modulated by amino acid levels in the cell. Ribosomes which translate the first of four upstream open reading frames (uORFs) in the mRNA leader resume scanning and can reinitiate downstream."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2010914",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 195,
"text": "Expression of the RNA replicase domain of tobacco mosaic virus (TMV) and certain protein-coding regions in other plant viruses, is mediated by translational readthrough of a leaky UAG stop codon."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2010914",
"endSection": "abstract",
"offsetInBeginSection": 1125,
"offsetInEndSection": 1321,
"text": "Our studies demonstrate a major role for the 3' context in the read through process and do not support a model in which teh UAG is bypassed exclusively as a result of anticodon-codon interactions."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2207158",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 168,
"text": "A translational frameshift is necessary in the synthesis of Escherichia coli release factor 2 (RF-2) to bypass an in-frame termination codon within the coding sequence."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2103444",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 125,
"text": "Plant RNA viruses commonly exploit leaky translation termination signals in order to express internal protein coding regions."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2103444",
"endSection": "abstract",
"offsetInBeginSection": 591,
"offsetInEndSection": 752,
"text": "These studies indicated that ribosomes bypass the leaky termination sites at efficiencies ranging from essentially 0 to ca. 5% depending upon the viral sequence."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2691247",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 168,
"text": "A translational frameshift is necessary in the synthesis of Escherichia coli release factor 2 (RF-2) to bypass an in-frame termination codon within the coding sequence."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2691247",
"endSection": "abstract",
"offsetInBeginSection": 1881,
"offsetInEndSection": 2091,
"text": "These results show that in vitro on eukaryotic ribosomes where the Shine-Dalgarno-type interaction is not possible, high efficiency frameshifting around the in-phase stop codon in the RF-2 mRNA can still occur."
}
]
| 5 | BioASQ-training5b | [
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018388",
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003062",
"http://www.uniprot.org/uniprot/BSC1_YEAST",
"http://www.uniprot.org/uniprot/BSC2_YEAST",
"http://www.uniprot.org/uniprot/BSC5_YEAST",
"http://www.uniprot.org/uniprot/BSC4_YEAST",
"http://www.uniprot.org/uniprot/BSC6_YEAST",
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018389"
]
| []
| 52f11bf22059c6d71c000005 | 76 |
yesno | Are variants in FHF2 (also known as FGF13) associated with encephalopathy? | ['yes'] | [
"yes"
]
| ['Yes. FHF2 (also known as FGF13) variants are a cause of infantile-onset developmental and epileptic encephalopathy.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/33245860"
]
| [
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33245860",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 135,
"text": "Missense variants in the N-terminal domain of the A isoform of FHF2/FGF13 cause an X-linked developmental and epileptic encephalopathy."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33245860",
"endSection": "abstract",
"offsetInBeginSection": 390,
"offsetInEndSection": 1418,
"text": "Whole-exome sequencing identified hemi- and heterozygous variants in the N-terminal domain of the A isoform of FHF2 (FHF2A). The X-linked FHF2 gene (also known as FGF13) has alternative first exons which produce multiple protein isoforms that differ in their N-terminal sequence. The variants were located at highly conserved residues in the FHF2A inactivation particle that competes with the intrinsic fast inactivation mechanism of Nav channels. Functional characterization of mutant FHF2A co-expressed with wild-type Nav1.6 (SCN8A) revealed that mutant FHF2A proteins lost the ability to induce rapid-onset, long-term blockade of the channel while retaining pro-excitatory properties. These gain-of-function effects are likely to increase neuronal excitability consistent with the epileptic potential of FHF2 variants. Our findings demonstrate that FHF2 variants are a cause of infantile-onset developmental and epileptic encephalopathy and underline the critical role of the FHF2A isoform in regulating Nav channel function."
}
]
| 11 | BioASQ-training11b | null | null | 61f9605f882a024a1000004f | 77 |
yesno | Does wheat belongs to the genus Avena, yes or no? | ['no'] | [
"no"
]
| ['oat seedlings (Avena sativa)', 'Wheat belongs to the species Triticum not to the genus Avena.', 'oat seedlings (Avena sativa). '] | [
"http://www.ncbi.nlm.nih.gov/pubmed/29146257",
"http://www.ncbi.nlm.nih.gov/pubmed/10984842",
"http://www.ncbi.nlm.nih.gov/pubmed/27079356",
"http://www.ncbi.nlm.nih.gov/pubmed/11908651",
"http://www.ncbi.nlm.nih.gov/pubmed/11536867",
"http://www.ncbi.nlm.nih.gov/pubmed/20658121",
"http://www.ncbi.nlm.nih.gov/pubmed/26618715",
"http://www.ncbi.nlm.nih.gov/pubmed/28132155",
"http://www.ncbi.nlm.nih.gov/pubmed/28132141",
"http://www.ncbi.nlm.nih.gov/pubmed/24226111"
]
| [
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29146257",
"endSection": "title",
"offsetInBeginSection": 84,
"offsetInEndSection": 112,
"text": "oat seedlings (Avena sativa)"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26618715",
"endSection": "title",
"offsetInBeginSection": 19,
"offsetInEndSection": 49,
"text": "wild green-oat (Avena sativa) "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28132141",
"endSection": "abstract",
"offsetInBeginSection": 74,
"offsetInEndSection": 96,
"text": " Oat (Avena sativa L.)"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28132155",
"endSection": "title",
"offsetInBeginSection": 38,
"offsetInEndSection": 59,
"text": "Oat (Avena sativa L.)"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24226111",
"endSection": "title",
"offsetInBeginSection": 46,
"offsetInEndSection": 58,
"text": "Avena (Oats)"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27079356",
"endSection": "abstract",
"offsetInBeginSection": 116,
"offsetInEndSection": 142,
"text": "wild oats (Avena fatua L.)"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10984842",
"endSection": "title",
"offsetInBeginSection": 41,
"offsetInEndSection": 59,
"text": "oats (genus Avena)"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20658121",
"endSection": "title",
"offsetInBeginSection": 46,
"offsetInEndSection": 88,
"text": "Avena sativa L. and A. byzantina C. Koch) "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11908651",
"endSection": "title",
"offsetInBeginSection": 81,
"offsetInEndSection": 104,
"text": " oat (Avena sativa L.)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11536867",
"endSection": "abstract",
"offsetInBeginSection": 16,
"offsetInEndSection": 66,
"text": "oat (Avena sativa L.) and wheat (Triticum aestivum"
}
]
| 11 | BioASQ-training11b | null | null | 5a79d25dfaa1ab7d2e00000f | 78 |
yesno | Is tebentafusp effective for uveal melanoma? | ['yes'] | [
"yes"
]
| ['Yes. Tebentafusp effective for uveal melanoma.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/34999237",
"http://www.ncbi.nlm.nih.gov/pubmed/35364557",
"http://www.ncbi.nlm.nih.gov/pubmed/35364798"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35364798",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 240,
"text": "Tebentafusp (tebentafusp-tebn; Kimmtrak®) is a first-in-class, bispecific gp100 peptide-HLA-A*02:01 directed T cell receptor (TCR) CD3 T cell engager being developed by Immunocore for the treatment of uveal melanoma and malignant melanoma. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35364798",
"endSection": "abstract",
"offsetInBeginSection": 1018,
"offsetInEndSection": 1168,
"text": "This article summarizes the milestones in the development of tebentafusp leading to this first approval for unresectable or metastatic uveal melanoma."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35364557",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34999237",
"endSection": "abstract",
"offsetInBeginSection": 1757,
"offsetInEndSection": 2188,
"text": "In a large meta-analysis, surgical treatment was associated with 6 months longer median overall survival as compared to conventional chemotherapy and, recently, tebentafusp as first-line treatment at the first interim analysis of a randomized phase III trial likewise provided a 6 months longer median overall survival compared to investigator's choice, mostly pembrolizumab; these treatments currently apply to selected patients. "
}
]
| 12 | BioASQ-training12b | null | null | 64041f38201352f04a00001f | 79 |
yesno | Are cardenolides inhibitors of Na+/K+ ATPase? | ['yes'] | [
"yes"
]
| ['Yes,\nCardenolides have shown significant antitumor activity due to their ability to inhibit the Na+K+ATPase enzyme, and the expression of this enzyme is increased in tumor cells.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/30053394",
"http://www.ncbi.nlm.nih.gov/pubmed/30372816",
"http://www.ncbi.nlm.nih.gov/pubmed/29683473"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30053394",
"endSection": "abstract",
"offsetInBeginSection": 257,
"offsetInEndSection": 493,
"text": ". Previously, we reported that a variety of cardenolides impart anti-transmissible gastroenteritis coronavirus (TGEV) activity in swine testicular (ST) cells, through targeting of the cell membrane sodium/potassium pump, Na+/K+-ATPase. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29683473",
"endSection": "abstract",
"offsetInBeginSection": 970,
"offsetInEndSection": 1092,
"text": ": We found evidence for low cardenolides by HPLC, but substantial toxicity when extracts were assayed on Na+ /K+ -ATPases."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30372816",
"endSection": "abstract",
"offsetInBeginSection": 316,
"offsetInEndSection": 490,
"text": "Cardenolides have shown significant antitumor activity due to their ability to inhibit the Na+K+ATPase enzyme, and the expression of this enzyme is increased in tumor cells. "
}
]
| 11 | BioASQ-training11b | null | null | 5c9906dcecadf2e73f00002f | 80 |
yesno | Can RG7112 inhibit MDM2? | ['yes'] | [
"yes"
]
| ['Yes, RG7112 is a small molecule MDM2 antagonist.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/24309210",
"http://www.ncbi.nlm.nih.gov/pubmed/23400593",
"http://www.ncbi.nlm.nih.gov/pubmed/23084521",
"http://www.ncbi.nlm.nih.gov/pubmed/22753001",
"http://www.ncbi.nlm.nih.gov/pubmed/24900694",
"http://www.ncbi.nlm.nih.gov/pubmed/24869939",
"http://www.ncbi.nlm.nih.gov/pubmed/23808545",
"http://www.ncbi.nlm.nih.gov/pubmed/24812409",
"http://www.ncbi.nlm.nih.gov/pubmed/21391905",
"http://www.ncbi.nlm.nih.gov/pubmed/25082860"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24309210",
"endSection": "abstract",
"offsetInBeginSection": 86,
"offsetInEndSection": 330,
"text": "To assess the influence of the p53 regulatory pathway further, we studied the effect of RG7112, a small molecule MDM2 antagonist that activates p53 by preventing its interaction with MDM2, on normal megakaryocytopoiesis and platelet production."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24900694",
"endSection": "abstract",
"offsetInBeginSection": 609,
"offsetInEndSection": 723,
"text": "RG7112 (2g) is the first clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket of MDM2."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23084521",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 182,
"text": "Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23084521",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 237,
"text": "We report a proof-of-mechanism study of RG7112, a small-molecule MDM2 antagonist, in patients with chemotherapy-naive primary or relapsed well-differentiated or dedifferentiated MDM2-amplified liposarcoma who were eligible for resection."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24309210",
"endSection": "abstract",
"offsetInBeginSection": 329,
"offsetInEndSection": 573,
"text": "To assess the influence of the p53 regulatory pathway further, we studied the effect of RG7112, a small molecule MDM2 antagonist that activates p53 by preventing its interaction with MDM2, on normal megakaryocytopoiesis and platelet production."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24900694",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 77,
"text": "Discovery of RG7112: A Small-Molecule MDM2 Inhibitor in Clinical Development."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23808545",
"endSection": "abstract",
"offsetInBeginSection": 398,
"offsetInEndSection": 477,
"text": "RG7112 was the first small-molecule p53-MDM2 inhibitor in clinical development."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23400593",
"endSection": "abstract",
"offsetInBeginSection": 467,
"offsetInEndSection": 568,
"text": "RG7112 binds MDM2 with high affinity (K(D) ~ 11 nmol/L), blocking its interactions with p53 in vitro."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22753001",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 176,
"text": "RG7112 is a selective inhibitor of p53-MDM2 binding that frees p53 from negative control, activating the p53 pathway in cancer cells leading to cell cycle arrest and apoptosis."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24900694",
"endSection": "abstract",
"offsetInBeginSection": 609,
"offsetInEndSection": 723,
"text": "RG7112 (2g) is the first clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket of MDM2."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23084521",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 182,
"text": "Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23084521",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 237,
"text": "We report a proof-of-mechanism study of RG7112, a small-molecule MDM2 antagonist, in patients with chemotherapy-naive primary or relapsed well-differentiated or dedifferentiated MDM2-amplified liposarcoma who were eligible for resection."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24309210",
"endSection": "abstract",
"offsetInBeginSection": 329,
"offsetInEndSection": 573,
"text": "To assess the influence of the p53 regulatory pathway further, we studied the effect of RG7112, a small molecule MDM2 antagonist that activates p53 by preventing its interaction with MDM2, on normal megakaryocytopoiesis and platelet production."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24900694",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 77,
"text": "Discovery of RG7112: A Small-Molecule MDM2 Inhibitor in Clinical Development."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23808545",
"endSection": "abstract",
"offsetInBeginSection": 398,
"offsetInEndSection": 477,
"text": "RG7112 was the first small-molecule p53-MDM2 inhibitor in clinical development."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23400593",
"endSection": "abstract",
"offsetInBeginSection": 467,
"offsetInEndSection": 568,
"text": "RG7112 binds MDM2 with high affinity (K(D) ~ 11 nmol/L), blocking its interactions with p53 in vitro."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22753001",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 176,
"text": "RG7112 is a selective inhibitor of p53-MDM2 binding that frees p53 from negative control, activating the p53 pathway in cancer cells leading to cell cycle arrest and apoptosis."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24869939",
"endSection": "abstract",
"offsetInBeginSection": 676,
"offsetInEndSection": 864,
"text": "The effects of RG7112 and Peg-IFNα 2a on MPN progenitor cells were dependent on blocking p53-MDM2 interactions and activating the p53 pathway, thereby increasing MPN CD34(+) cell apoptosis"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24869939",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 128,
"text": "The orally bioavailable MDM2 antagonist RG7112 and pegylated interferon α 2a target JAK2V617F-positive progenitor and stem cells"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22753001",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 89,
"text": "Initial testing of the MDM2 inhibitor RG7112 by the Pediatric Preclinical Testing Program"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25082860",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 243,
"text": "In this issue of Blood, Lu et al describe the cooperation between an orally bioavailable mouse double minute 2 (MDM2) antagonist (RG7112) and the pegylated interferon α (Peg-IFNα 2a) to target JAK2V617F hematopoietic progenitors and stem cells"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23084521",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 182,
"text": "Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23400593",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 118,
"text": "MDM2 small-molecule antagonist RG7112 activates p53 signaling and regresses human tumors in preclinical cancer models."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24309210",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 70,
"text": "Activation of p53 by the MDM2 inhibitor RG7112 impairs thrombopoiesis."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24869939",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 129,
"text": "The orally bioavailable MDM2 antagonist RG7112 and pegylated interferon α 2a target JAK2V617F-positive progenitor and stem cells."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22753001",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 90,
"text": "Initial testing of the MDM2 inhibitor RG7112 by the Pediatric Preclinical Testing Program."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23084521",
"endSection": "abstract",
"offsetInBeginSection": 614,
"offsetInEndSection": 802,
"text": "The primary endpoint was to assess markers of RG7112-dependent MDM2 inhibition and P53 pathway activation (P53, P21, MDM2, Ki-67, macrophage inhibitory cytokine-1 [MIC-1], and apoptosis). "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23084521",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 182,
"text": "Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23400593",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 118,
"text": "MDM2 small-molecule antagonist RG7112 activates p53 signaling and regresses human tumors in preclinical cancer models."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24309210",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 70,
"text": "Activation of p53 by the MDM2 inhibitor RG7112 impairs thrombopoiesis."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22753001",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 90,
"text": "Initial testing of the MDM2 inhibitor RG7112 by the Pediatric Preclinical Testing Program."
},
{
"beginSection": "abstract",
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| 5 | BioASQ-training5b | [
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"http://www.uniprot.org/uniprot/MDM2_MESAU",
"http://www.uniprot.org/uniprot/MDM2_HUMAN",
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| []
| 56ed08062ac5ed1459000005 | 81 |
yesno | Is the JNK pathway activated during liver regeneration? | ['yes'] | [
"yes"
]
| Yes, the Jun-N-terminal kinase (JNK) pathway is strongly activated after partial hepatectomy. | [
"http://www.ncbi.nlm.nih.gov/pubmed/23035542",
"http://www.ncbi.nlm.nih.gov/pubmed/21354444",
"http://www.ncbi.nlm.nih.gov/pubmed/21338344",
"http://www.ncbi.nlm.nih.gov/pubmed/20578144",
"http://www.ncbi.nlm.nih.gov/pubmed/20207439",
"http://www.ncbi.nlm.nih.gov/pubmed/18671679",
"http://www.ncbi.nlm.nih.gov/pubmed/18382767",
"http://www.ncbi.nlm.nih.gov/pubmed/17762881",
"http://www.ncbi.nlm.nih.gov/pubmed/16797887",
"http://www.ncbi.nlm.nih.gov/pubmed/16242670",
"http://www.ncbi.nlm.nih.gov/pubmed/15970430",
"http://www.ncbi.nlm.nih.gov/pubmed/12668975",
"http://www.ncbi.nlm.nih.gov/pubmed/11709497"
]
| [
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"text": "analysis of the role of JNK signaling pathway in regulating cell proliferation and apoptosis of rat liver regeneration"
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"text": "c-jun is not mandatory for mouse hepatocyte proliferation "
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"text": "Mice lacking c-jun in the liver display impaired regeneration after partial hepatectomy (PH)"
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"text": "Loss of macroautophagy led to overactivation of the c-Jun N-terminal kinase (JNK)/c-Jun signaling pathway that induced cell death."
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"text": "stress induced during intermittent selective clamping accelerates rat liver regeneration through JNK pathway"
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"text": "add45beta promotes hepatocyte survival during liver regeneration in mice by modulating JNK signaling"
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{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16797887",
"endSection": "title",
"offsetInBeginSection": 53,
"offsetInEndSection": 178,
"text": "enhancement of the activation of Jun N-terminal kinase and p38 mitogen-activated protein kinase caused by partial hepatectomy"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16797887",
"endSection": "abstract",
"offsetInBeginSection": 1268,
"offsetInEndSection": 1415,
"text": " arsenite induced apoptosis in the hepatocytes in vivo, through the enhancement of the activation of JNK and p38 MAPK caused by partial hepatectomy"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16242670",
"endSection": "abstract",
"offsetInBeginSection": 586,
"offsetInEndSection": 647,
"text": "Jun N-terminal kinase and p38 MAPK, but not Akt, was altered."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16242670",
"endSection": "abstract",
"offsetInBeginSection": 119,
"offsetInEndSection": 352,
"text": "Although mechanical stress has been implicated in hepatic cirrhosis and liver regeneration following hepatectomy, the signaling pathway(s) that may be activated in hepatocytes in response to mechanical stress have not been determined"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15970430",
"endSection": "abstract",
"offsetInBeginSection": 1356,
"offsetInEndSection": 1471,
"text": " JNK, ERK and JAK2 inhibitors partially abrogated apoptosis and when used in combination reduced it to basal levels"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15970430",
"endSection": "abstract",
"offsetInBeginSection": 1488,
"offsetInEndSection": 1633,
"text": "induction of CD40-mediated cholangiocyte apoptosis requires JAK2-mediated phosphorylation of STAT3 as well as sustained JNK1/2, ERK1/2 activation"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12668975",
"endSection": "title",
"offsetInBeginSection": 2,
"offsetInEndSection": 95,
"text": "Jun-N-terminal kinase drives cyclin D1 expression and proliferation during liver regeneration"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12668975",
"endSection": "abstract",
"offsetInBeginSection": 4,
"offsetInEndSection": 94,
"text": "c-Jun-N-terminal kinase (JNK) pathway is strongly activated after partial hepatectomy (PH)"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11709497",
"endSection": "abstract",
"offsetInBeginSection": 5,
"offsetInEndSection": 68,
"text": "growth factors and cytokines are involved in liver regeneration"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11709497",
"endSection": "abstract",
"offsetInBeginSection": 484,
"offsetInEndSection": 644,
"text": "JAB1 (Jun activation domain-binding protein 1), a co-activator of AP-1, which is essential for liver regeneration, specifically interacts with intracellular HPO"
}
]
| 5 | BioASQ-training5b | [
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020935",
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008115",
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012038",
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048670",
"http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031098",
"http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004705",
"http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031099",
"http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007254",
"http://www.uniprot.org/uniprot/JNK_DROME",
"http://www.uniprot.org/uniprot/JNK_SUBDO"
]
| []
| 53455e0caeec6fbd0700000f | 82 |
yesno | Have machine learning methods been used to predict the severity of major depressive disorder(MDD)? | ['yes'] | [
"yes"
]
| ['Machine-learning (ML) models developed from self-reports can be used to predict persistence and severity of major depressive disorder(MDD)'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/26821982",
"http://www.ncbi.nlm.nih.gov/pubmed/29879133",
"http://www.ncbi.nlm.nih.gov/pubmed/25066141",
"http://www.ncbi.nlm.nih.gov/pubmed/30286415",
"http://www.ncbi.nlm.nih.gov/pubmed/27551669",
"http://www.ncbi.nlm.nih.gov/pubmed/28702811",
"http://www.ncbi.nlm.nih.gov/pubmed/26728563",
"http://www.ncbi.nlm.nih.gov/pubmed/22544901",
"http://www.ncbi.nlm.nih.gov/pubmed/29682732"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30286415",
"endSection": "abstract",
"offsetInBeginSection": 300,
"offsetInEndSection": 484,
"text": "Here, we conduct a meta-review to identify predictors of response to antidepressant therapy in order to select robust input features for machine learning models of treatment response. "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28702811",
"endSection": "title",
"offsetInBeginSection": 2,
"offsetInEndSection": 117,
"text": "machine learning framework involving EEG-based functional connectivity to diagnose major depressive disorder (MDD)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29879133",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 412,
"text": "Identification of risk factors of treatment resistance may be useful to guide treatment selection, avoid inefficient trial-and-error, and improve major depressive disorder (MDD) care. We extended the work in predictive modeling of treatment resistant depression (TRD) via partition of the data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) cohort into a training and a testing dataset."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26728563",
"endSection": "title",
"offsetInBeginSection": 52,
"offsetInEndSection": 132,
"text": "persistence and severity of major depressive disorder from baseline self-reports"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26728563",
"endSection": "abstract",
"offsetInBeginSection": 1572,
"offsetInEndSection": 1778,
"text": " These results confirm that clinically useful MDD risk-stratification models can be generated from baseline patient self-reports and that ML methods improve on conventional methods in developing such models"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22544901",
"endSection": "abstract",
"offsetInBeginSection": 2017,
"offsetInEndSection": 2189,
"text": "Furthermore, machine learning weighting factors may reflect an objective biomarker of major depressive disorder illness severity, based on abnormalities of brain structure."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22544901",
"endSection": "abstract",
"offsetInBeginSection": 1474,
"offsetInEndSection": 1813,
"text": "Notably, while the only information provided for training the classifiers was T(1)-weighted scans plus a categorical label (major depressive disorder versus controls), both relevance vector machine and support vector machine 'weighting factors' (used for making predictions) correlated strongly with subjective ratings of illness severity."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25066141",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 248,
"text": "BACKGROUND\nAlthough variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25066141",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 248,
"text": "BACKGROUND Although variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27551669",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 154,
"text": "BACKGROUND Growing evidence documents the potential of machine learning for developing brain based diagnostic methods for major depressive disorder (MDD)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26821982",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 158,
"text": "OBJECTIVE We aimed to integrate neural data and an advanced machine learning technique to predict individual major depressive disorder (MDD) patient severity."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22544901",
"endSection": "abstract",
"offsetInBeginSection": 2145,
"offsetInEndSection": 2317,
"text": "Furthermore, machine learning weighting factors may reflect an objective biomarker of major depressive disorder illness severity, based on abnormalities of brain structure."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25066141",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 256,
"text": "<b>BACKGROUND</b>: Although variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods."
}
]
| 11 | BioASQ-training11b | null | null | 5c5215e67e3cb0e231000004 | 83 |
yesno | Is FTY720 FDA approved? | ['yes'] | [
"yes"
]
| ['Yes, FTY720 was approved by the US Food and Drug Administration (FDA) in 2010.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/31785606"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31785606",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 257,
"text": "FTY720 (Fingolimod) is a known sphingosine-1-phosphate (S1P) receptor agonist that exerts strong anti-inflammatory effects and was approved as the first oral drug for the treatment of multiple sclerosis by the US Food and Drug Administration (FDA) in 2010. "
}
]
| 11 | BioASQ-training11b | null | null | 6052715494d57fd87900000e | 84 |
yesno | Are the major royal jelly proteins similar to the yellow proteins? | ['yes'] | [
"yes"
]
| ['Yes,\nMajor royal jelly proteins (named MRJP1-5) of honeybee (Apis mellifera), yellow proteins of Drosophila, together with putative proteins found in several bacteria, form a protein family termed the MRJP/yellow family.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/15037093",
"http://www.ncbi.nlm.nih.gov/pubmed/10772900"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15037093",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 215,
"text": "Major royal jelly proteins (named MRJP1-5) of honeybee (Apis mellifera), yellow proteins of Drosophila, together with putative proteins found in several bacteria, form a protein family termed the MRJP/yellow family."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10772900",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 121,
"text": "Analysis of Drosophila yellow-B cDNA reveals a new family of proteins related to the royal jelly proteins in the honeybee"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10772900",
"endSection": "abstract",
"offsetInBeginSection": 586,
"offsetInEndSection": 705,
"text": "he Yellow proteins are related to the Royal Jelly proteins and have no relatives in other non-insect metazoan species. "
}
]
| 11 | BioASQ-training11b | null | null | 6057003594d57fd879000020 | 85 |
yesno | Is progeria caused by an autosomal recessive gene? | ['yes'] | [
"yes"
]
| ['Yes. Progeria is caused by an autosomal recessive gene.', 'yes, progeria is caused by an autosomal recessive gene.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/17664768",
"http://www.ncbi.nlm.nih.gov/pubmed/28660486",
"http://www.ncbi.nlm.nih.gov/pubmed/17028399",
"http://www.ncbi.nlm.nih.gov/pubmed/22971867",
"http://www.ncbi.nlm.nih.gov/pubmed/27617860",
"http://www.ncbi.nlm.nih.gov/pubmed/29149836",
"http://www.ncbi.nlm.nih.gov/pubmed/32360386",
"http://www.ncbi.nlm.nih.gov/pubmed/21365542",
"http://www.ncbi.nlm.nih.gov/pubmed/32596971",
"http://www.ncbi.nlm.nih.gov/pubmed/3228132",
"http://www.ncbi.nlm.nih.gov/pubmed/32528764",
"http://www.ncbi.nlm.nih.gov/pubmed/17375009",
"http://www.ncbi.nlm.nih.gov/pubmed/27931782",
"http://www.ncbi.nlm.nih.gov/pubmed/19432833",
"http://www.ncbi.nlm.nih.gov/pubmed/16598422",
"http://www.ncbi.nlm.nih.gov/pubmed/16838330",
"http://www.ncbi.nlm.nih.gov/pubmed/17219342",
"http://www.ncbi.nlm.nih.gov/pubmed/19875478",
"http://www.ncbi.nlm.nih.gov/pubmed/33087645"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32596971",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 183,
"text": "Hutchinson-Gilford progeria syndrome (HGPS) is an autosomal-dominant genetic disease that leads to accelerated aging and often premature death caused by cardiovascular complications. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32360386",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 119,
"text": "Hutchinson-Gilford progeria syndrome is an autosomal dominant, rare, fatal pediatric segmental premature aging disease."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28660486",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 81,
"text": "Progeria is sporadic, very rare, autosomal dominant, deadly childhood disorder. I"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27931782",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 233,
"text": "Werner syndrome (i.e., adult progeria) is a rare autosomal recessive disorder caused by mutations of the WRN gene, which is characterized by the premature appearance of features associated with normal aging and cancer predisposition."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29149836",
"endSection": "abstract",
"offsetInBeginSection": 121,
"offsetInEndSection": 316,
"text": "Among them, the most studied is Werner's syndrome, \"adult progeria\", caused by a recessive autosomal mutation with a frequency of 1 in 10 million, which affects a helicase involved in DNA repair."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16838330",
"endSection": "abstract",
"offsetInBeginSection": 1829,
"offsetInEndSection": 1915,
"text": "Pattern of inheritance of non-classical progeria is most probably autosomal recessive."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16598422",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 179,
"text": "INTRODUCTION: Werner Syndrome, or adult progeria, is a rare autosomal recessive disorder caused by a mutation in the Werner Syndrome Gene belonging to the family of RecQ helicase."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17219342",
"endSection": "abstract",
"offsetInBeginSection": 772,
"offsetInEndSection": 921,
"text": "SION: Werner's syndrome is a rare form of progeria with an autosomal recessive mode of inheritance mimicking the symptoms of accelerated aging. The r"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21365542",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 166,
"text": "Werner's Syndrome (WS) or adult-onset progeria is an autosomal recessive disorder of accelerated aging caused by mutations of the DNA RecQ helicase/exonuclease (WRN)."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19432833",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 126,
"text": "Homozygous LMNA mutation R527C in atypical Hutchinson-Gilford progeria syndrome: evidence for autosomal recessive inheritance."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17664768",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 100,
"text": "Progeria (Hutchison-Gilford syndrome) in siblings: in an autosomal recessive pattern of inheritance."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17664768",
"endSection": "abstract",
"offsetInBeginSection": 276,
"offsetInEndSection": 379,
"text": "The present case highlights rarity of progeria in siblings with a possible autosomal recessive pattern."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27931782",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 239,
"text": "Werner syndrome (i.e., adult progeria) is a rare autosomal recessive disorder caused by mutations of the WRN gene, which is characterized by the premature appearance of features associated with normal aging and cancer predisposition. Patie"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19875478",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 218,
"text": "CONTEXT: Hutchinson-Gilford progeria syndrome (HGPS) and mandibuloacral dysplasia are well-recognized allelic autosomal dominant and recessive progeroid disorders, respectively, due to mutations in lamin A/C (LMNA) gen"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17375009",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 163,
"text": "Werner's syndrome (adult onset progeria) is a rare form of autosomal recessive genodermatosis associated in almost 80% of cases with mutation of the WRN gene. This"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33087645",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 285,
"text": "Werner syndrome, also called adult progeria, is a heritable autosomal recessive human disorder characterized by the premature onset of numerous age-related diseases including juvenile cataracts, dyslipidemia, diabetes mellitus (DM), osteoporosis, atherosclerosis, and cancer. Werner sy"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32528764",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 156,
"text": "Werner's syndrome (WS) or progeria adultorum is a heritable autosomal recessive disease in which the aging process is accelerated, just after puberty. It is"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27617860",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 178,
"text": "Hutchinson-Gilford progeria syndrome (HGPS) is a rare autosomal dominant genetic disease that is caused by a silent mutation of the LMNA gene encoding lamins A and C (lamin A/C)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27617860",
"endSection": "abstract",
"offsetInBeginSection": 1017,
"offsetInEndSection": 1201,
"text": "Furthermore, administration of JH4 to LmnaG609G/G609G-mutant mice, which phenocopy human HGPS, resulted in a marked improvement of several progeria phenotypes and an extended lifespan."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27617860",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 102,
"text": "Interruption of progerin-lamin A/C binding ameliorates Hutchinson-Gilford progeria syndrome phenotype."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17664768",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 60,
"text": "Progeria is an autosomal dominant, premature aging syndrome."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16598422",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 178,
"text": "INTRODUCTION: Werner Syndrome, or adult progeria, is a rare autosomal recessive disorder caused by a mutation in the Werner Syndrome Gene belonging to the family of RecQ helicase"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/3228132",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 78,
"text": "Evidence for autosomal recessive inheritance of progeria (Hutchinson Gilford)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16598422",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 165,
"text": "INTRODUCTION: Werner Syndrome, or adult progeria, is a rare autosomal recessive disorder caused by a mutation in the Werner Syndrome Gene belonging to the family of "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17028399",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 153,
"text": "Hutchinson-Gilford progeria causing premature aging of children is a genetic disease and according to most authors has an autosomal dominant inheritance."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32528764",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 150,
"text": "Werner's syndrome (WS) or progeria adultorum is a heritable autosomal recessive disease in which the aging process is accelerated, just after puberty."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33087645",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 275,
"text": "Werner syndrome, also called adult progeria, is a heritable autosomal recessive human disorder characterized by the premature onset of numerous age-related diseases including juvenile cataracts, dyslipidemia, diabetes mellitus (DM), osteoporosis, atherosclerosis, and cancer."
}
]
| 11 | BioASQ-training11b | null | null | 601d72e61cb411341a000039 | 86 |
yesno | Can LB-100 downregulate miR-33? | ['no'] | [
"no"
]
| ['No, LB-100 has been reported to modulate (upregulate) only miR-181b-1.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/28588271"
]
| [
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28588271",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 134,
"text": "PP2A inhibition from LB100 therapy enhances daunorubicin cytotoxicity in secondary acute myeloid leukemia via miR-181b-1 upregulation."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28588271",
"endSection": "abstract",
"offsetInBeginSection": 683,
"offsetInEndSection": 989,
"text": "LB100 profoundly upregulates miR-181b-1, which we show directly binds to the 3' untranslated region of Bcl-2 mRNA leading to its translational inhibition. MiR-181b-1 ectopic overexpression further diminishes Bcl-2 expression leading to suppression of sAML cell growth, and enhancement of DNR cytotoxicity. "
}
]
| 11 | BioASQ-training11b | null | null | 5e2a04feaa19d74431000009 | 87 |
yesno | Is armodafinil used for treatment of insomnia? | ['no'] | [
"no"
]
| ['No, armodafinil is not used for treatment of insomnia. Armodafinil is a wakefulness-promoting medication. Its efficacy and tolerability have been established in patients with excessive sleepiness (ES) associated with treated obstructive sleep apnea (OSA), shift work disorder (SWD), or narcolepsy. The wakefulness-promoting agents armodafinil and modafinil are FDA approved for the treatment of ES in patients with SWD.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/22353444",
"http://www.ncbi.nlm.nih.gov/pubmed/21904092",
"http://www.ncbi.nlm.nih.gov/pubmed/21275439",
"http://www.ncbi.nlm.nih.gov/pubmed/20957846",
"http://www.ncbi.nlm.nih.gov/pubmed/20074507",
"http://www.ncbi.nlm.nih.gov/pubmed/20051221",
"http://www.ncbi.nlm.nih.gov/pubmed/19880686",
"http://www.ncbi.nlm.nih.gov/pubmed/17874255",
"http://www.ncbi.nlm.nih.gov/pubmed/17181377",
"http://www.ncbi.nlm.nih.gov/pubmed/16861091",
"http://www.ncbi.nlm.nih.gov/pubmed/16684437",
"http://www.ncbi.nlm.nih.gov/pubmed/18596995",
"http://www.ncbi.nlm.nih.gov/pubmed/16908126"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22353444",
"endSection": "abstract",
"offsetInBeginSection": 1036,
"offsetInEndSection": 1256,
"text": " Other therapies, such as sedative hypnotics, target daytime insomnia, while pharmacologic agents such as modafinil, armodafinil, and caffeine and non-pharmacologic approaches such as napping promote nighttime alertness."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21904092",
"endSection": "abstract",
"offsetInBeginSection": 1014,
"offsetInEndSection": 1158,
"text": "Other treatment options may include pharmacologic interventions such as modafinil and armodafinil, which have shown efficacy in this population."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21275439",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 522,
"text": "BACKGROUND: Armodafinil (Nuvigil(®), Cephalon, Inc., Frazer, PA, USA), the longer-lasting isomer of racemic modafinil, is a nonamphetamine, wakefulness-promoting medication. In patients with excessive sleepiness associated with shift work disorder, treated obstructive sleep apnoea, or narcolepsy, armodafinil has been found to improve wakefulness throughout the shift or day. In addition, while not approved for this indication, armodafinil has been found to improve excessive sleepiness associated with jet-lag disorder."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20957846",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 280,
"text": "STUDY OBJECTIVES: Armodafinil is a wakefulness-promoting medication. Its efficacy and tolerability have been established in 12-week studies of patients with excessive sleepiness (ES) associated with treated obstructive sleep apnea (OSA), shift work disorder (SWD), or narcolepsy. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20957846",
"endSection": "abstract",
"offsetInBeginSection": 1820,
"offsetInEndSection": 1945,
"text": "Armodafinil represents an option for long-term treatment of patients with ES associated with treated OSA, SWD, or narcolepsy."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20074507",
"endSection": "abstract",
"offsetInBeginSection": 503,
"offsetInEndSection": 624,
"text": "The wakefulness-promoting agents armodafinil and modafinil are FDA approved for the treatment of ES in patients with SWD."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20051221",
"endSection": "abstract",
"offsetInBeginSection": 2327,
"offsetInEndSection": 2532,
"text": "CONCLUSIONS: Armodafinil significantly improved overall clinical condition related to excessive sleepiness as rated by the CGI-C and was well tolerated in patients with treated OSA and comorbid depression."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19880686",
"endSection": "abstract",
"offsetInBeginSection": 1910,
"offsetInEndSection": 2324,
"text": "CONCLUSION: In patients with excessive sleepiness associated with chronic SWD of moderate or greater severity, armodafinil significantly improved wakefulness during scheduled night work, raising mean nighttime sleep latency above the level considered to indicate severe sleepiness during the daytime. Armodafinil also significantly improved measures of overall clinical condition, long-term memory, and attention. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17874255",
"endSection": "abstract",
"offsetInBeginSection": 1280,
"offsetInEndSection": 1490,
"text": "Adjunct treatment with armodafinil significantly improved wakefulness, long-term memory, and patients' ability to engage in activities of daily living in nCPAP-adherent individuals with ES associated with OSA. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17181377",
"endSection": "abstract",
"offsetInBeginSection": 710,
"offsetInEndSection": 1004,
"text": "A number of studies have evaluated countermeasures or interventions in shift workers; proposed treatments include chronobiotic interventions, such as light exposure, melatonin, hypnotic agents, caffeine and CNS stimulants (amphetamine), and the wake-promoting agents modafinil and armodafinil. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17181377",
"endSection": "abstract",
"offsetInBeginSection": 1544,
"offsetInEndSection": 1788,
"text": "These studies showed that modafinil and armodafinil significantly improve the ability to sustain wakefulness during waking activities (e.g. working, driving), overall clinical condition, and sustained attention or memory in patients with SWSD. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16861091",
"endSection": "abstract",
"offsetInBeginSection": 3148,
"offsetInEndSection": 3395,
"text": "CONCLUSIONS: In this selected population of patients with OSA/HS and residual ES despite effective treatment with nCPAP, armodafinil QD used as an adjunct to nCPAP treatment was associated with improved wakefulness and overall clinical condition. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22353444",
"endSection": "abstract",
"offsetInBeginSection": 998,
"offsetInEndSection": 1218,
"text": " Other therapies, such as sedative hypnotics, target daytime insomnia, while pharmacologic agents such as modafinil, armodafinil, and caffeine and non-pharmacologic approaches such as napping promote nighttime alertness."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22353444",
"endSection": "abstract",
"offsetInBeginSection": 1036,
"offsetInEndSection": 1256,
"text": " Other therapies, such as sedative hypnotics, target daytime insomnia, while pharmacologic agents such as modafinil, armodafinil, and caffeine and non-pharmacologic approaches such as napping promote nighttime alertness."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20957846",
"endSection": "abstract",
"offsetInBeginSection": 151,
"offsetInEndSection": 276,
"text": "Armodafinil represents an option for long-term treatment of patients with ES associated with treated OSA, SWD, or narcolepsy."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20074507",
"endSection": "abstract",
"offsetInBeginSection": 503,
"offsetInEndSection": 624,
"text": "The wakefulness-promoting agents armodafinil and modafinil are FDA approved for the treatment of ES in patients with SWD."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22353444",
"endSection": "abstract",
"offsetInBeginSection": 1009,
"offsetInEndSection": 1228,
"text": "Other therapies, such as sedative hypnotics, target daytime insomnia, while pharmacologic agents such as modafinil, armodafinil, and caffeine and non-pharmacologic approaches such as napping promote nighttime alertness."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16861091",
"endSection": "abstract",
"offsetInBeginSection": 3111,
"offsetInEndSection": 3343,
"text": "In this selected population of patients with OSA/HS and residual ES despite effective treatment with nCPAP, armodafinil QD used as an adjunct to nCPAP treatment was associated with improved wakefulness and overall clinical condition"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22353444",
"endSection": "abstract",
"offsetInBeginSection": 1009,
"offsetInEndSection": 1228,
"text": "Other therapies, such as sedative hypnotics, target daytime insomnia, while pharmacologic agents such as modafinil, armodafinil, and caffeine and non-pharmacologic approaches such as napping promote nighttime alertness."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16861091",
"endSection": "abstract",
"offsetInBeginSection": 3111,
"offsetInEndSection": 3343,
"text": "In this selected population of patients with OSA/HS and residual ES despite effective treatment with nCPAP, armodafinil QD used as an adjunct to nCPAP treatment was associated with improved wakefulness and overall clinical condition"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22353444",
"endSection": "abstract",
"offsetInBeginSection": 1009,
"offsetInEndSection": 1228,
"text": "Other therapies, such as sedative hypnotics, target daytime insomnia, while pharmacologic agents such as modafinil, armodafinil, and caffeine and non-pharmacologic approaches such as napping promote nighttime alertness."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16861091",
"endSection": "abstract",
"offsetInBeginSection": 3111,
"offsetInEndSection": 3343,
"text": "In this selected population of patients with OSA/HS and residual ES despite effective treatment with nCPAP, armodafinil QD used as an adjunct to nCPAP treatment was associated with improved wakefulness and overall clinical condition"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22353444",
"endSection": "abstract",
"offsetInBeginSection": 1009,
"offsetInEndSection": 1228,
"text": "Other therapies, such as sedative hypnotics, target daytime insomnia, while pharmacologic agents such as modafinil, armodafinil, and caffeine and non-pharmacologic approaches such as napping promote nighttime alertness."
}
]
| 5 | BioASQ-training5b | [
"http://www.biosemantics.org/jochem#4216693"
]
| []
| 54f1e781c409818c32000003 | 88 |
yesno | Is methotrexate used for the treatment of Rheumatoid Arthritis (RA)? | ['yes'] | [
"yes"
]
| ['Yes, methotrexate is effective for the treatment of Rheumatoid Arthritis. MTX can be administered in combination with other chemotherapeutic agents or as mono-therapy. Response rate to MTX is more than 90%. MTX therapy is associated with improved survival of RA patients.', 'The use of methotrexate in rheumatoid arthritis. Methotrexate (MTX) is currently under study for use in juvenile rheumatoid arthritis.', 'Methotrexate (MTX) is clearly effective in the treatment of rheumatoid arthritis. MTX has emerged as a relatively safe and effective treatment for RA that compares favorably with other therapies.', 'Yes, methotrexate is used for the treatment of Rheumatoid Arthritis.', 'Methotrexate is a cornerstone in the treatment of rheumatoid arthritis (RA). The aim of many studies is to identify factors predicting the outcome of treatment with methotrexate in rheumatic arthritis. It is considered a second-line disease modifying agent.', 'Historical perspective on the use of methotrexate for the treatment of rheumatoid arthritis. Aminopterin, a folic acid analogue was first reported in 1948 to produce temporary remission of acute leukemia of children, was also reported in 1951 to produce an important and rapid improvement in patients with rheumatoid arthritis (RA) and psoriasis', 'Yes. MTX is a folic acid antagonist that is approved for the management of severe active RA in patients who have had an insufficient therapeutic response to or are intolerant of an adequate trial of first-line therapy, including full-dose NSAIDs.', 'Yes, methotrexate is effective for the treatment of Rheumatoid Arthritis.', 'Methotrexate is clearly effective in the treatment of rheumatoid arthritis and may be able to decrease the rate of formation of new bony erosions.', 'Yes. Methotrexate is used for the treatment of Rheumatoid Arthritis (RA) and other rheumatic diseases.', 'Yes, methotrexate is a promising treatment option for the treatment of rheumatoid arthritis.', 'Methotrexate (MTX) has emerged as a relatively safe and effective treatment for RA that compares favorably with other therapies, particularly because of its considerably longer median drug survival. Methotrexate is clearly effective in the treatment of rheumatoid arthritis and may be able to decrease the rate of formation of new bony erosions.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/15305245",
"http://www.ncbi.nlm.nih.gov/pubmed/32876784",
"http://www.ncbi.nlm.nih.gov/pubmed/24219041",
"http://www.ncbi.nlm.nih.gov/pubmed/21044436",
"http://www.ncbi.nlm.nih.gov/pubmed/9402864",
"http://www.ncbi.nlm.nih.gov/pubmed/7482069",
"http://www.ncbi.nlm.nih.gov/pubmed/32066940",
"http://www.ncbi.nlm.nih.gov/pubmed/8535646",
"http://www.ncbi.nlm.nih.gov/pubmed/26474779",
"http://www.ncbi.nlm.nih.gov/pubmed/3741499",
"http://www.ncbi.nlm.nih.gov/pubmed/8646434",
"http://www.ncbi.nlm.nih.gov/pubmed/28081972",
"http://www.ncbi.nlm.nih.gov/pubmed/3891280",
"http://www.ncbi.nlm.nih.gov/pubmed/3913774",
"http://www.ncbi.nlm.nih.gov/pubmed/29441860",
"http://www.ncbi.nlm.nih.gov/pubmed/3913772",
"http://www.ncbi.nlm.nih.gov/pubmed/26459854",
"http://www.ncbi.nlm.nih.gov/pubmed/2388211",
"http://www.ncbi.nlm.nih.gov/pubmed/24399184",
"http://www.ncbi.nlm.nih.gov/pubmed/14963199",
"http://www.ncbi.nlm.nih.gov/pubmed/23970326",
"http://www.ncbi.nlm.nih.gov/pubmed/30081197",
"http://www.ncbi.nlm.nih.gov/pubmed/22870474",
"http://www.ncbi.nlm.nih.gov/pubmed/2080488",
"http://www.ncbi.nlm.nih.gov/pubmed/27708921",
"http://www.ncbi.nlm.nih.gov/pubmed/31866617",
"http://www.ncbi.nlm.nih.gov/pubmed/7939730"
]
| [
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/3891280",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 48,
"text": "The use of methotrexate in rheumatoid arthritis."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/3913774",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 92,
"text": "Historical perspective on the use of methotrexate for the treatment of rheumatoid arthritis."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/3913774",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 252,
"text": "Aminopterin, a folic acid analogue was first reported in 1948 to produce temporary remission of acute leukemia of children, was also reported in 1951 to produce an important and rapid improvement in patients with rheumatoid arthritis (RA) and psoriasis"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/3741499",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 97,
"text": "The safety and efficacy of the use of methotrexate in long-term therapy for rheumatoid arthritis."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2388211",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 86,
"text": "Methotrexate (MTX) is currently under study for use in juvenile rheumatoid arthritis. "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9402864",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 86,
"text": "The rational use of methotrexate in rheumatoid arthritis and other rheumatic diseases."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9402864",
"endSection": "abstract",
"offsetInBeginSection": 639,
"offsetInEndSection": 828,
"text": "Methotrexate-induced hepatic cirrhosis is less common in rheumatoid arthritis than previously thought, although its occurrence in psoriasis is probably higher than in rheumatoid arthritis. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9402864",
"endSection": "abstract",
"offsetInBeginSection": 230,
"offsetInEndSection": 377,
"text": "Methotrexate is clearly effective in the treatment of rheumatoid arthritis and may be able to decrease the rate of formation of new bony erosions. "
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15305245",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 48,
"text": "The use of methotrexate in rheumatoid arthritis."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15305245",
"endSection": "abstract",
"offsetInBeginSection": 177,
"offsetInEndSection": 280,
"text": "Review of the international literature on the clinical use of MTX in rheumatoid arthritis (RA) disease."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15305245",
"endSection": "abstract",
"offsetInBeginSection": 289,
"offsetInEndSection": 472,
"text": "MTX has emerged as a relatively safe and effective treatment for RA that compares favorably with other therapies, particularly because of its considerably longer median drug survival."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24399184",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 182,
"text": "The objective of this review is to update the recommendations of the 2010 Italian Consensus on the use of methotrexate (MTX) in rheumatoid arthritis (RA) and other rheumatic diseases"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24399184",
"endSection": "abstract",
"offsetInBeginSection": 654,
"offsetInEndSection": 890,
"text": "A new recommendation for patients with RA who are in MTX-induced clinical remission was also proposed and approved by the panel. Updated recommendations for the use of MTX in patients with RA or other rheumatologic disease are proposed."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30081197",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 153,
"text": "Methotrexate has been used in treatment of rheumatoid arthritis (RA) since the 1980s and to this day is often the first line medication for RA treatment."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32876784",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 129,
"text": "OBJECTIVE: Most recommendations for the use of methotrexate (MTX) in rheumatoid arthritis (RA) are issued by developed countries."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7482069",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 144,
"text": "Low dose pulse methotrexate (MTX) has become a widely used therapy for rheumatoid arthritis (RA) because of its good response rate profile. With"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8646434",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 157,
"text": "Treatment with methotrexate (MTX) in rheumatoid arthritis (RA) can lead to severe side-effects, especially pulmonary and haematological complications. The ai"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26459854",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 155,
"text": "Patients having rheumatoid arthritis (RA) treated with methotrexate (MTX) are at an increased risk of developing lymphoproliferative disorder (LPD). Epstei"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8535646",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 139,
"text": "Increasingly, methotrexate (MTX) and sulphasalazine (SASP) are used initially for second-line therapy of rheumatoid arthritis (RA). Althoug"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14963199",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 242,
"text": "OBJECTIVES: The folate antagonist methotrexate (MTX) has become established as the most commonly used disease-modifying anti-rheumatic drug (DMARD) in the treatment of rheumatoid arthritis (RA) but is commonly discontinued due to adverse effe"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23970326",
"endSection": "abstract",
"offsetInBeginSection": 175,
"offsetInEndSection": 314,
"text": "e suspected methotrexate (MTX)-associated lymphoproliferative disorder (LPD) induced by MTX treatment for rheumatoid arthritis (RA). About "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28081972",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 221,
"text": "BACKGROUND: Treatment with methotrexate (MTX) in patients with rheumatoid arthritis (RA) leads to decreased total immunoglobulin (Ig) levels and impairs vaccine-specific IgG antibody levels following pneumococcal vaccinat"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29441860",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 238,
"text": "In rheumatoid arthritis (RA) treatment, the concomitant use of methotrexate has been shown to reduce the incidence of antibodies to infliximab (ATI), on the other hand, it is unclear whether azathioprine can reduce ATI production. We enro"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31866617",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 147,
"text": "Methotrexate (MTX) is known as a first-line synthetic disease-modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26474779",
"endSection": "abstract",
"offsetInBeginSection": 1239,
"offsetInEndSection": 1431,
"text": "Biological treatments are expensive and using SC methotrexate can improve disease control in RA patients, thus potentially avoiding or delaying the requirement for future biological treatment."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32876784",
"endSection": "abstract",
"offsetInBeginSection": 11,
"offsetInEndSection": 129,
"text": "Most recommendations for the use of methotrexate (MTX) in rheumatoid arthritis (RA) are issued by developed countries."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32876784",
"endSection": "abstract",
"offsetInBeginSection": 180,
"offsetInEndSection": 354,
"text": "We reviewed existing recommendations on the use of MTX for the treatment of RA and summarized areas of agreement that could be relevant for least developed countries (LDCs).M"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32876784",
"endSection": "abstract",
"offsetInBeginSection": 1055,
"offsetInEndSection": 1304,
"text": "st covered some but not all of the following areas: baseline \"pre-MTX\" assessment (7/12;58%), prescription of MTX (10/12;83.3%), management of MTX side effects (6/12;50%), and special considerations (e.g., peri-operative management) (8/12; 66.7%). R"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32876784",
"endSection": "abstract",
"offsetInBeginSection": 363,
"offsetInEndSection": 576,
"text": "lectronic databases and registries were searched for recommendations on MTX use in RA, duplicates were eliminated, and the most updated version adopted when there were several versions on the same recommendation. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2080488",
"endSection": "abstract",
"offsetInBeginSection": 539,
"offsetInEndSection": 650,
"text": "MTX must at the present time be used only in severe RA, refractory to more than one classical slow acting drug."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2080488",
"endSection": "abstract",
"offsetInBeginSection": 389,
"offsetInEndSection": 538,
"text": "MTX is as effective in treating RA as the other second line drugs and always more rapidly effective, perhaps because of anti-inflammatory properties."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2080488",
"endSection": "abstract",
"offsetInBeginSection": 123,
"offsetInEndSection": 257,
"text": "For the low doses used in RA (less than 15 mg/week), MTX is completely and rapidly absorbed with an active process membrane transport."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27708921",
"endSection": "abstract",
"offsetInBeginSection": 113,
"offsetInEndSection": 183,
"text": "Methotrexate, which is used for RA treatment, causes thrombocytopenia."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27708921",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 110,
"text": "Methorexate therapy in a patient with rheumatoid arthritis complicated by idiopathic thrombocytopenic purpura."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27708921",
"endSection": "abstract",
"offsetInBeginSection": 1117,
"offsetInEndSection": 1245,
"text": "This case shows that methotrexate may be used in patients diagnosed with RA that is associated with ITP under strict monitoring."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27708921",
"endSection": "abstract",
"offsetInBeginSection": 297,
"offsetInEndSection": 411,
"text": "Here, we report an RA case that also had ITP, which did not decrease in platelet count after methotrexate therapy."
},
{
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/27708921",
"endSection": "abstract",
"offsetInBeginSection": 763,
"offsetInEndSection": 893,
"text": "We started methotrexate therapy 10 mg per week for treatment of RA, and hydroxychloroquine therapy was stopped due to nonresponse."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24219041",
"endSection": "abstract",
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"text": "Methotrexate (MTX) is the anchor treatment for rheumatoid arthritis (RA) and has been very thoroughly studied in many different patient populations, as monotherapy and in combination with various other disease modifying antirheumatic drugs and biologic agents, as they became available."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/3913772",
"endSection": "abstract",
"offsetInBeginSection": 286,
"offsetInEndSection": 465,
"text": "Although rheumatologists have been using methotrexate in the treatment of RA for some time, controlled studies have been needed to establish the safety and efficacy of this agent."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32066940",
"endSection": "abstract",
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"offsetInEndSection": 405,
"text": "Methotrexate is generally the first-line drug for the treatment of RA, psoriatic arthritis and other forms of inflammatory arthritis, and it enhances the effect of most biologic agents in RA."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32066940",
"endSection": "abstract",
"offsetInBeginSection": 0,
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"text": "Despite the introduction of numerous biologic agents for the treatment of rheumatoid arthritis (RA) and other forms of inflammatory arthritis, low-dose methotrexate therapy remains the gold standard in RA therapy."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7939730",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 101,
"text": "A number of studies show the efficacy of methotrexate (MTX) for rheumatoid arthritis (RA) in general."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22870474",
"endSection": "abstract",
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"text": "Methotrexate (MTX) is currently the most frequently used drugs in the treatment of rheumatoid arthritis (RA)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21044436",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 197,
"text": "Methotrexate (MTX) has been the anchor treatment in rheumatoid arthritis (RA) over the last 15 years, and is used in combination with biologic agents to enhance efficacy over the last decade or so."
}
]
| 11 | BioASQ-training11b | null | null | 5fe31304a43ad3127800003a | 90 |
yesno | Is PLK2 involved in alpha-synuclein phosphorylation in the nervous system? | ['yes'] | [
"yes"
]
| ['Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in the central nervous system.', 'Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system ', 'Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system ', 'Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system ', 'Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system ', 'Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system '] | [
"http://www.ncbi.nlm.nih.gov/pubmed/19004816",
"http://www.ncbi.nlm.nih.gov/pubmed/21838679",
"http://www.ncbi.nlm.nih.gov/pubmed/24128992",
"http://www.ncbi.nlm.nih.gov/pubmed/23983262",
"http://www.ncbi.nlm.nih.gov/pubmed/21162130",
"http://www.ncbi.nlm.nih.gov/pubmed/23794260"
]
| [
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"text": "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system"
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"text": "Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons"
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"text": "PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay"
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"text": "Inhibitors of PLK kinases inhibited alpha-synuclein phosphorylation both in primary cortical cell cultures and in mouse brain in vivo"
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"text": "specific knockdown of PLK2 expression by transduction with short hairpin RNA constructs or by knock-out of the plk2 gene reduced p-Ser-129 levels"
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"text": "These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system."
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"text": "These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system."
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"text": "Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons."
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"text": "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system."
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"text": "PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay."
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"text": "Two of these kinases stand out as potential drug targets for novel PD therapy, namely leucine rich repeat kinase 2 (LRRK2) and the alpha-synuclein (α-syn) phosphorylating polo-like kinase 2 (PLK2)."
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"text": "Also, due to the dominant mode of α-syn and LRRK2 inheritance and based on current knowledge of LRRK2 and α-syn phosphorylation by PLK2, inhibition of LRRK2 and PLK2 may constitute a potential therapy for PD."
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"text": "These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system."
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"text": "Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons."
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"text": "PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay."
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"text": "Two of these kinases stand out as potential drug targets for novel PD therapy, namely leucine rich repeat kinase 2 (LRRK2) and the alpha-synuclein (α-syn) phosphorylating polo-like kinase 2 (PLK2)."
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"text": "To better understand the role of PLK2 in α-synuclein phosphorylation in vivo, we further evaluated the effect of PLK2 genetic knockdown and pharmacological inhibition on Phospho-α-Syn levels in different brain regions of PLK2 knockout (KO), heterozygous (Het) and wild-type (WT) mice."
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"text": "This PLK2-mediated neuroprotective effect is also dependent on PLK2 activity and α-synuclein phosphorylation."
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"text": "PLK2-mediated degradation of α-synuclein requires both phosphorylation at S129 and PLK2/α-synuclein complex formation."
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"text": "Also, due to the dominant mode of α-syn and LRRK2 inheritance and based on current knowledge of LRRK2 and α-syn phosphorylation by PLK2, inhibition of LRRK2 and PLK2 may constitute a potential therapy for PD."
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"text": "Overexpression of only PLK2 increased phosphorylation of aggregated α-syn at S129, which likely is due to increased phosphorylation of soluble α-syn, which then was incorporated into aggregates."
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"text": "Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons."
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"text": "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system."
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"text": "Two of these kinases stand out as potential drug targets for novel PD therapy, namely leucine rich repeat kinase 2 (LRRK2) and the alpha-synuclein (α-syn) phosphorylating polo-like kinase 2 (PLK2)."
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"text": "To better understand the role of PLK2 in α-synuclein phosphorylation in vivo, we further evaluated the effect of PLK2 genetic knockdown and pharmacological inhibition on Phospho-α-Syn levels in different brain regions of PLK2 knockout (KO), heterozygous (Het) and wild-type (WT) mice."
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"text": "This PLK2-mediated neuroprotective effect is also dependent on PLK2 activity and α-synuclein phosphorylation."
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"text": "PLK2-mediated degradation of α-synuclein requires both phosphorylation at S129 and PLK2/α-synuclein complex formation."
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"text": "Also, due to the dominant mode of α-syn and LRRK2 inheritance and based on current knowledge of LRRK2 and α-syn phosphorylation by PLK2, inhibition of LRRK2 and PLK2 may constitute a potential therapy for PD."
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"text": "Two of these kinases stand out as potential drug targets for novel PD therapy, namely leucine rich repeat kinase 2 (LRRK2) and the alpha-synuclein (α-syn) phosphorylating polo-like kinase 2 (PLK2)."
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"text": "To better understand the role of PLK2 in α-synuclein phosphorylation in vivo, we further evaluated the effect of PLK2 genetic knockdown and pharmacological inhibition on Phospho-α-Syn levels in different brain regions of PLK2 knockout (KO), heterozygous (Het) and wild-type (WT) mice."
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"text": "Also, due to the dominant mode of α-syn and LRRK2 inheritance and based on current knowledge of LRRK2 and α-syn phosphorylation by PLK2, inhibition of LRRK2 and PLK2 may constitute a potential therapy for PD."
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"text": "These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system."
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"text": "Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons."
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"text": "Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons"
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"text": "These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system."
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"text": "PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay."
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"text": "Unlike other kinases reported to partially phosphorylate alpha-syn at Ser-129 in vitro, phosphorylation by PLK2 and PLK3 is quantitative ("
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"text": "Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons."
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"text": "These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system"
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"text": "Inhibitors of PLK kinases inhibited alpha-synuclein phosphorylation both in primary cortical cell cultures and in mouse brain in vivo"
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"text": "PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay"
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"text": "To better understand the role of PLK2 in α-synuclein phosphorylation in vivo, we further evaluated the effect of PLK2 genetic knockdown and pharmacological inhibition on Phospho-α-Syn levels in different brain regions of PLK2 knockout (KO), heterozygous (Het) and wild-type (WT) mice"
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"text": "Polo-like kinase-2 (Plk-2) has been implicated as the dominant kinase involved in the phosphorylation of α-synuclein in Lewy bodies, which are one of the hallmarks of Parkinson's disease neuropathology"
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"text": "These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system."
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"text": "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system."
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"text": "Polo-like kinase-2 (Plk-2) has been implicated as the dominant kinase involved in the phosphorylation of α-synuclein in Lewy bodies, which are one of the hallmarks of Parkinson's disease neuropathology"
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{
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"text": "These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system."
},
{
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816",
"endSection": "title",
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"text": "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system."
},
{
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"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 201,
"text": "Polo-like kinase-2 (Plk-2) has been implicated as the dominant kinase involved in the phosphorylation of α-synuclein in Lewy bodies, which are one of the hallmarks of Parkinson's disease neuropathology"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816",
"endSection": "abstract",
"offsetInBeginSection": 568,
"offsetInEndSection": 701,
"text": "Inhibitors of PLK kinases inhibited alpha-synuclein phosphorylation both in primary cortical cell cultures and in mouse brain in vivo"
},
{
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816",
"endSection": "abstract",
"offsetInBeginSection": 478,
"offsetInEndSection": 566,
"text": "PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay"
},
{
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"endSection": "abstract",
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"text": "These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system."
},
{
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"endSection": "title",
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"text": "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system."
},
{
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"endSection": "abstract",
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"offsetInEndSection": 201,
"text": "Polo-like kinase-2 (Plk-2) has been implicated as the dominant kinase involved in the phosphorylation of α-synuclein in Lewy bodies, which are one of the hallmarks of Parkinson's disease neuropathology"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816",
"endSection": "abstract",
"offsetInBeginSection": 859,
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"text": "These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system."
},
{
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"endSection": "title",
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"text": "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system."
},
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/23794260",
"endSection": "abstract",
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"offsetInEndSection": 201,
"text": "Polo-like kinase-2 (Plk-2) has been implicated as the dominant kinase involved in the phosphorylation of α-synuclein in Lewy bodies, which are one of the hallmarks of Parkinson's disease neuropathology"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816",
"endSection": "abstract",
"offsetInBeginSection": 859,
"offsetInEndSection": 975,
"text": "These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system."
},
{
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816",
"endSection": "title",
"offsetInBeginSection": 0,
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"text": "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23794260",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 201,
"text": "Polo-like kinase-2 (Plk-2) has been implicated as the dominant kinase involved in the phosphorylation of α-synuclein in Lewy bodies, which are one of the hallmarks of Parkinson's disease neuropathology"
}
]
| 5 | BioASQ-training5b | [
"http://www.uniprot.org/uniprot/PLK2_PONAB",
"http://www.uniprot.org/uniprot/SYUA_PONAB",
"http://www.uniprot.org/uniprot/SYUA_ATEGE",
"http://www.uniprot.org/uniprot/SYUA_GORGO",
"http://www.uniprot.org/uniprot/SYUA_SERCA",
"http://www.uniprot.org/uniprot/SYUA_RAT",
"http://www.uniprot.org/uniprot/SYUA_HUMAN",
"http://www.uniprot.org/uniprot/SYUA_PANPA",
"http://www.uniprot.org/uniprot/SYUA_ERYPA",
"http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051844"
]
| []
| 550c44d1a103b7801600000a | 91 |
yesno | Is myc a tumour suppressor gene? | ['no'] | [
"no"
]
| ['No,\r\nMyc is a proto-oncogene.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/28430012",
"http://www.ncbi.nlm.nih.gov/pubmed/27880072",
"http://www.ncbi.nlm.nih.gov/pubmed/27532209",
"http://www.ncbi.nlm.nih.gov/pubmed/28833404"
]
| [
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"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27532209",
"endSection": "abstract",
"offsetInBeginSection": 255,
"offsetInEndSection": 374,
"text": "oncogenic Myc, a master transcription factor that turns on anabolic metabolism to promote cell growth in many cancers. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27880072",
"endSection": "abstract",
"offsetInBeginSection": 634,
"offsetInEndSection": 649,
"text": "he MYC oncogene"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28430012",
"endSection": "abstract",
"offsetInBeginSection": 653,
"offsetInEndSection": 686,
"text": " the proto-oncogene protein c-MYC"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28833404",
"endSection": "abstract",
"offsetInBeginSection": 90,
"offsetInEndSection": 188,
"text": "however, other genes such as the proto-oncogene c-Myc are promising targets for anticancer therapy"
}
]
| 11 | BioASQ-training11b | null | null | 5cb38a56ecadf2e73f00005e | 92 |
yesno | Does deletion of cohesin change gene expression? | ['yes'] | [
"yes"
]
| [' The conditional deletion of cohesin from noncycling thymocytes preserved enhancer position, H3K27ac, H4K4me1, and enhancer transcription, but weakened interactions between enhancers. Interestingly, ~ 50% of deregulated genes reside in the vicinity of enhancer elements, suggesting that cohesin regulates gene expression through spatial clustering of enhancer elements.', 'Yes. Deletion of cohesin inhibits gene expression at multiple points within the genome and in different genomic regions.', 'The conditional deletion of cohesin from noncycling thymocytes preserved enhancer position, H3K27ac, H4K4me1, and enhancer transcription, but weakened interactions between enhancers. 50% of deregulated genes reside in the vicinity of enhancer elements, suggesting that cohesin regulates gene expression through spatial clustering of enhancer elements.', 'We propose a model for cohesin-dependent gene regulation in which spatial clustering of enhancer elements acts as a unified mechanism for both enhancer-promoter "connections" and "insulation.". The conditional deletion of cohesin from noncycling thymocytes preserved enhancer position, H3K27ac, H4K4me1, and enhancer transcription, but weakened interactions between enhancers. Interestingly, ~ 50% of deregulated genes reside in the vicinity of enhancer elements, suggesting that cohesin regulates gene expression through spatial clustering of enhancer elements.', 'Interestingly, ~ 50% of deregulated genes reside in the vicinity of enhancer elements, suggesting that cohesin regulates gene expression through spatial clustering of enhancer elements. We propose a model for cohesin-dependent gene regulation in which spatial clustering of enhancer elements acts as a unified mechanism for both enhancer-promoter "connections" and "insulation."', 'Yes. Numerous studies have demonstrated that deletion of cohesin reduces gene expression at multiple points within the genome.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/25677180"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25677180",
"endSection": "abstract",
"offsetInBeginSection": 932,
"offsetInEndSection": 1115,
"text": " The conditional deletion of cohesin from noncycling thymocytes preserved enhancer position, H3K27ac, H4K4me1, and enhancer transcription, but weakened interactions between enhancers."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25677180",
"endSection": "abstract",
"offsetInBeginSection": 1116,
"offsetInEndSection": 1301,
"text": "Interestingly, ∼ 50% of deregulated genes reside in the vicinity of enhancer elements, suggesting that cohesin regulates gene expression through spatial clustering of enhancer elements."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25677180",
"endSection": "abstract",
"offsetInBeginSection": 1302,
"offsetInEndSection": 1494,
"text": "We propose a model for cohesin-dependent gene regulation in which spatial clustering of enhancer elements acts as a unified mechanism for both enhancer-promoter \"connections\" and \"insulation.\""
}
]
| 11 | BioASQ-training11b | null | null | 5d35b9ecb3a6380763000004 | 93 |
yesno | Has MDMA(ecstasy) been successfully used to treat PTSD disorder? | ['yes'] | [
"yes"
]
| ['Yes, 3,4-methylenedioxymethamphetamine (MDMA) has been used effectively to treat post-traumatic stress disorder (PTSD), with Phase III clinical trial evidence.', 'MDMA (ecstasy) has been used in conjunction with psychotherapy to treat PTSD disorder and preliminary studies suggest that MDMA-assisted psychotherapy can be a safe and effective treatment approach for PTSD.', 'Yes, MDMA has been successfully used as an adjunct to psychotherapy for treating PTSD, showing promising results in clinical trials over the last two decades.', 'Yes MDMA, a compound belonging to the family of entactogens, has been demonstrated to be useful to treat post-traumatic stress disorders.', 'Yes, MDMA-assisted psychotherapy is effective for posttraumatic stress disorder.', '”Three patients with severe, treatment-resistant post-traumatic stress disorder (PTSD) were successfully treated with a single high-dose (300-mg) of 3,4-methylenedioxymethamphetamine (MDMA), also known as ecstasy, in a controlled clinical trial"}', 'Yes, clinical trials have shown promising safety and efficacy for the use of MDMA (ecstasy) in conjunction with psychotherapy for the treatment of posttraumatic stress disorder (PTSD). However, the mechanisms underlying this treatment form remain largely unestablished.', 'Yes, MDMA-assisted therapy has shown high efficacy in treating PTSD.', 'Yes, MDMA has been used successfully in conjunction with psychotherapy to treat PTSD. Clinical trials have shown promising results, although the exact mechanisms underlying this treatment are still being studied.', 'Yes, 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.', 'Yes, MDMA-assisted therapy (MDMA-AT) has been successfully used to treat PTSD disorder.', 'Yes, MDMA has been successfully used to treat PTSD disorder.', 'No, MDMA (ecstasy) has not been successfully used to treat PTSD disorder.', 'Yes, MDMA-assisted psychotherapy has shown promising safety and efficacy in the treatment of PTSD.', 'Yes, MDMA-assisted psychotherapy has shown promise in treating PTSD', 'Yes, MDMA-assisted psychotherapy has shown promise in addressing PTSD disorder among female subgroups.', 'Yes, MDMA (ecstasy) has been successfully used to treat PTSD disorder. Clinical trials have shown promising safety and efficacy, but the mechanisms underlying this treatment form remain largely unestablished.', 'Yes, MDMA has been successfully used in treating PTSD.', 'Yes, MDMA has been successfully used to treat PTSD disorder in conjunction with psychotherapy. Clinical trials have shown promising safety and efficacy, but the mechanisms underlying this treatment form remain largely unestablished.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/34150406",
"http://www.ncbi.nlm.nih.gov/pubmed/36815187",
"http://www.ncbi.nlm.nih.gov/pubmed/35272210",
"http://www.ncbi.nlm.nih.gov/pubmed/36184377",
"http://www.ncbi.nlm.nih.gov/pubmed/30949077",
"http://www.ncbi.nlm.nih.gov/pubmed/26579955",
"http://www.ncbi.nlm.nih.gov/pubmed/29524515",
"http://www.ncbi.nlm.nih.gov/pubmed/37484678",
"http://www.ncbi.nlm.nih.gov/pubmed/37709999",
"http://www.ncbi.nlm.nih.gov/pubmed/35230652",
"http://www.ncbi.nlm.nih.gov/pubmed/38004320",
"http://www.ncbi.nlm.nih.gov/pubmed/28635375",
"http://www.ncbi.nlm.nih.gov/pubmed/30632995",
"http://www.ncbi.nlm.nih.gov/pubmed/24648791",
"http://www.ncbi.nlm.nih.gov/pubmed/36713926",
"http://www.ncbi.nlm.nih.gov/pubmed/36189781",
"http://www.ncbi.nlm.nih.gov/pubmed/26371762",
"http://www.ncbi.nlm.nih.gov/pubmed/30529341",
"http://www.ncbi.nlm.nih.gov/pubmed/34465250",
"http://www.ncbi.nlm.nih.gov/pubmed/33972795",
"http://www.ncbi.nlm.nih.gov/pubmed/37611653",
"http://www.ncbi.nlm.nih.gov/pubmed/37987270",
"http://www.ncbi.nlm.nih.gov/pubmed/35700643",
"http://www.ncbi.nlm.nih.gov/pubmed/34855694",
"http://www.ncbi.nlm.nih.gov/pubmed/12691208",
"http://www.ncbi.nlm.nih.gov/pubmed/28741031",
"http://www.ncbi.nlm.nih.gov/pubmed/36311515",
"http://www.ncbi.nlm.nih.gov/pubmed/35915689",
"http://www.ncbi.nlm.nih.gov/pubmed/37404971"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37611653",
"endSection": "abstract",
"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": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37611653",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 102,
"text": "MDMA-assisted psychotherapy for PTSD: Growing evidence for memory effects mediating treatment efficacy"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37484678",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36184377",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/38004320",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37987270",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29524515",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26371762",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29524515",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29524515",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34465250",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36713926",
"endSection": "abstract",
"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": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29524515",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 107,
"text": "MDMA-assisted psychotherapy for PTSD: Are memory reconsolidation and fear extinction underlying mechanisms?"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35915689",
"endSection": "abstract",
"offsetInBeginSection": 261,
"offsetInEndSection": 495,
"text": ". A series of six phase-II clinical trials studying MDMA-AT for treatment-resistant PTSD found 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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37987270",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35230652",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33972795",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30949077",
"endSection": "abstract",
"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": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36311515",
"endSection": "title",
"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": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36189781",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30949077",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36815187",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30632995",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12691208",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35272210",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37404971",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28741031",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28635375",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37709999",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34855694",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24648791",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26371762",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26579955",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12691208",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34150406",
"endSection": "abstract",
"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 receptors. 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. 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: Articles 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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30529341",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33972795",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35700643",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30529341",
"endSection": "abstract",
"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."
}
]
| 13 | BioASQ-training13b | null | null | 65f490fac4010b4d78000010 | 94 |
yesno | Can Antioxidant curcumin kill tumor cells? | ['yes'] | [
"yes"
]
| ['Yes, Antioxidant curcumin can kill tumor cells', 'Yes, antioxidant curcumin can kill tumor cells by inducing apoptosis and inhibiting malignant progression.', 'Yes, Curcumin can kill tumor cells.', 'Yes, antioxidant curcumin can kill tumor cells by inducing oxidative stress.', 'Yes, antioxidant curcumin can kill tumor cells by regulating miR-206 expression', 'Yes, curcumin can kill tumor cells through its antioxidant properties and various mechanisms of action.', 'Yes, curcumin is a potent antioxidant and kills cancerous cells.', 'Yes, curcumin can kill tumor cells by regulating miR-206 expression, which inhibits colon cancer malignant progression and promotes T cell killing.', 'Yes, curcumin can kill tumor cells by inducing apoptosis and inhibiting malignant progression.', 'Antioxidant curcumin has been shown to have antitumor effects, which can result in the death of tumor cells.', 'Yes, curcumin has been shown to exhibit anti-tumor effects in various types of cancer, including colorectal cancer, by inducing cell death in tumor cells.', 'Antioxidant curcumin has been shown to induce apoptosis in tumor cells.', 'Yes, curcumin has been shown to have the ability to kill tumor cells.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/32307747",
"http://www.ncbi.nlm.nih.gov/pubmed/28949267",
"http://www.ncbi.nlm.nih.gov/pubmed/12680238",
"http://www.ncbi.nlm.nih.gov/pubmed/29752960",
"http://www.ncbi.nlm.nih.gov/pubmed/17069615",
"http://www.ncbi.nlm.nih.gov/pubmed/37587146",
"http://www.ncbi.nlm.nih.gov/pubmed/25667441",
"http://www.ncbi.nlm.nih.gov/pubmed/24627632",
"http://www.ncbi.nlm.nih.gov/pubmed/37210578",
"http://www.ncbi.nlm.nih.gov/pubmed/37322603",
"http://www.ncbi.nlm.nih.gov/pubmed/29642292",
"http://www.ncbi.nlm.nih.gov/pubmed/37191314",
"http://www.ncbi.nlm.nih.gov/pubmed/37820211",
"http://www.ncbi.nlm.nih.gov/pubmed/24453488",
"http://www.ncbi.nlm.nih.gov/pubmed/25360677",
"http://www.ncbi.nlm.nih.gov/pubmed/27051644",
"http://www.ncbi.nlm.nih.gov/pubmed/37806480",
"http://www.ncbi.nlm.nih.gov/pubmed/36986483",
"http://www.ncbi.nlm.nih.gov/pubmed/10456330",
"http://www.ncbi.nlm.nih.gov/pubmed/11676493",
"http://www.ncbi.nlm.nih.gov/pubmed/34904972",
"http://www.ncbi.nlm.nih.gov/pubmed/18347134",
"http://www.ncbi.nlm.nih.gov/pubmed/37333486",
"http://www.ncbi.nlm.nih.gov/pubmed/22508043",
"http://www.ncbi.nlm.nih.gov/pubmed/25349781",
"http://www.ncbi.nlm.nih.gov/pubmed/11795474",
"http://www.ncbi.nlm.nih.gov/pubmed/28628644",
"http://www.ncbi.nlm.nih.gov/pubmed/21110780",
"http://www.ncbi.nlm.nih.gov/pubmed/18252805",
"http://www.ncbi.nlm.nih.gov/pubmed/16376585",
"http://www.ncbi.nlm.nih.gov/pubmed/37957863",
"http://www.ncbi.nlm.nih.gov/pubmed/36358950",
"http://www.ncbi.nlm.nih.gov/pubmed/24495080",
"http://www.ncbi.nlm.nih.gov/pubmed/20426658",
"http://www.ncbi.nlm.nih.gov/pubmed/23489691",
"http://www.ncbi.nlm.nih.gov/pubmed/31717651",
"http://www.ncbi.nlm.nih.gov/pubmed/37979287",
"http://www.ncbi.nlm.nih.gov/pubmed/27572503",
"http://www.ncbi.nlm.nih.gov/pubmed/10069393",
"http://www.ncbi.nlm.nih.gov/pubmed/26004342",
"http://www.ncbi.nlm.nih.gov/pubmed/22475723",
"http://www.ncbi.nlm.nih.gov/pubmed/32116190",
"http://www.ncbi.nlm.nih.gov/pubmed/15142674",
"http://www.ncbi.nlm.nih.gov/pubmed/24566313"
]
| [
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37191314",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 113,
"text": "Curcumin inhibits colon cancer malignant progression and promotes T cell killing by regulating miR-206 expression"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36986483",
"endSection": "title",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37333486",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 127,
"text": "Curcumin induces apoptosis in human hepatocellular carcinoma cells by decreasing the expression of STAT3/VEGF/HIF-1α signaling."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34904972",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29642292",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 129,
"text": "Curcumin is known to possess various biological functions, including anti-inflammatory, antioxidative, and anti-cancer activities"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24495080",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22508043",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36358950",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17069615",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22508043",
"endSection": "abstract",
"offsetInBeginSection": 573,
"offsetInEndSection": 718,
"text": "The combination of curcumin (10 μM) and trolox (10-50 μM) induced apoptosis of cancer cells as evidenced by PARP cleavage and caspase-3 activatio"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22508043",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 100,
"text": "Curcumin, a natural polyphenol in the spice turmeric, has been found to exhibit anticancer activity."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24566313",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11676493",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11795474",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21110780",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28628644",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26004342",
"endSection": "abstract",
"offsetInBeginSection": 227,
"offsetInEndSection": 312,
"text": "Curcumin, obtained from the rhizome of Curcuma longa, has potent anticancer activity."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25349781",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23489691",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22508043",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22508043",
"endSection": "abstract",
"offsetInBeginSection": 573,
"offsetInEndSection": 720,
"text": "The combination of curcumin (10 μM) and trolox (10-50 μM) induced apoptosis of cancer cells as evidenced by PARP cleavage and caspase-3 activation."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22508043",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32116190",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20426658",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37979287",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37957863",
"endSection": "abstract",
"offsetInBeginSection": 1348,
"offsetInEndSection": 1445,
"text": " Curcuminoids could be a promising anti-cancer agent for the treatment of human colorectal cancer"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37806480",
"endSection": "abstract",
"offsetInBeginSection": 1786,
"offsetInEndSection": 1883,
"text": "Furthermore, these anti-cancer effects were higher when using Niosomal (Asc + Cur) than Asc + Cur"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37587146",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37322603",
"endSection": "abstract",
"offsetInBeginSection": 614,
"offsetInEndSection": 713,
"text": "Curcumin treatment inhibited proliferation and migration of cancer cells in a dose dependent manner"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22508043",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21110780",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11676493",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16376585",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10456330",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15142674",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22475723",
"endSection": "abstract",
"offsetInBeginSection": 303,
"offsetInEndSection": 450,
"text": "Curcumin exhibits anti-inflammatory, anticarcinogenic, antiproliferative, antiangiogenic, and antioxidant properties in various cancer cell models."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12680238",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24627632",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27572503",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31717651",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 101,
"text": "BACKGROUND: Curcumin has been shown to exert pleiotropic biological effects, including anti-tumorigen"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32307747",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32307747",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32307747",
"endSection": "abstract",
"offsetInBeginSection": 1228,
"offsetInEndSection": 1340,
"text": "Curcumin reverses multidrug resistance mechanisms and increases sensitivity of resistance cells to chemotherapy."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10069393",
"endSection": "abstract",
"offsetInBeginSection": 137,
"offsetInEndSection": 210,
"text": "Curcumin inhibited AK-5 tumor growth and induced apoptosis in AK-5 cells."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25360677",
"endSection": "abstract",
"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 µM, and often at 50 µM, and it exerts its effects on cancer cells in part by activation of MAP kinase"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28949267",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24453488",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29642292",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 130,
"text": "Curcumin is known to possess various biological functions, including anti-inflammatory, antioxidative, and anti-cancer activities."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29642292",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18252805",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25667441",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16376585",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29752960",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37820211",
"endSection": "abstract",
"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",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11676493",
"endSection": "abstract",
"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": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/37210578",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 97,
"text": "Curcumin activates a ROS/KEAP1/NRF2/miR-34a/b/c cascade to suppress colorectal cancer metastasis."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18347134",
"endSection": "abstract",
"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. "
}
]
| 13 | BioASQ-training13b | null | null | 65f1dadac4010b4d78000007 | 95 |
yesno | Is METTL1 overexpression associated with better patient survival? | ['no'] | [
"no"
]
| ['No. METTL1 is frequently amplified and overexpressed in cancers and is associated with poor patient survival.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/34352207"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34352207",
"endSection": "abstract",
"offsetInBeginSection": 227,
"offsetInEndSection": 547,
"text": " Here we find METTL1 is frequently amplified and overexpressed in cancers and is associated with poor patient survival. METTL1 depletion causes decreased abundance of m7G-modified tRNAs and altered cell cycle and inhibits oncogenicity. Conversely, METTL1 overexpression induces oncogenic cell transformation and cancer. "
}
]
| 11 | BioASQ-training11b | null | null | 620c27e93a8413c653000006 | 96 |
yesno | Is there an association between presenteeism and depression? | ['yes'] | [
"yes"
]
| ['Yes. Presenteeism is associated with depression. Remission of depression is associated with improvement of presenteeism.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/23439268",
"http://www.ncbi.nlm.nih.gov/pubmed/23244804",
"http://www.ncbi.nlm.nih.gov/pubmed/22856386",
"http://www.ncbi.nlm.nih.gov/pubmed/22532849",
"http://www.ncbi.nlm.nih.gov/pubmed/22261652",
"http://www.ncbi.nlm.nih.gov/pubmed/21880374",
"http://www.ncbi.nlm.nih.gov/pubmed/21669372",
"http://www.ncbi.nlm.nih.gov/pubmed/21525074",
"http://www.ncbi.nlm.nih.gov/pubmed/21220078",
"http://www.ncbi.nlm.nih.gov/pubmed/20953117",
"http://www.ncbi.nlm.nih.gov/pubmed/20726684",
"http://www.ncbi.nlm.nih.gov/pubmed/20715299",
"http://www.ncbi.nlm.nih.gov/pubmed/20073388",
"http://www.ncbi.nlm.nih.gov/pubmed/19339899",
"http://www.ncbi.nlm.nih.gov/pubmed/17156851",
"http://www.ncbi.nlm.nih.gov/pubmed/16989105",
"http://www.ncbi.nlm.nih.gov/pubmed/16282870",
"http://www.ncbi.nlm.nih.gov/pubmed/15951705",
"http://www.ncbi.nlm.nih.gov/pubmed/15804203",
"http://www.ncbi.nlm.nih.gov/pubmed/15572564",
"http://www.ncbi.nlm.nih.gov/pubmed/14665817",
"http://www.ncbi.nlm.nih.gov/pubmed/11329394",
"http://www.ncbi.nlm.nih.gov/pubmed/25539872",
"http://www.ncbi.nlm.nih.gov/pubmed/25435902",
"http://www.ncbi.nlm.nih.gov/pubmed/25211435",
"http://www.ncbi.nlm.nih.gov/pubmed/25173795",
"http://www.ncbi.nlm.nih.gov/pubmed/24854252"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23439268",
"endSection": "abstract",
"offsetInBeginSection": 665,
"offsetInEndSection": 806,
"text": "Presenteeism was positively associated with severity of depression (Health and Work Performance Questionnaire, P < 0.0001; WPAI, P < 0.0001)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23244804",
"endSection": "abstract",
"offsetInBeginSection": 1355,
"offsetInEndSection": 1524,
"text": "Statistically significant correlations (0.32-0.53) were found between presenteeism and increasing disability, fatigue, depression, anxiety, and reduced quality of life. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23244804",
"endSection": "abstract",
"offsetInBeginSection": 1765,
"offsetInEndSection": 1867,
"text": "Presenteeism was associated with increasing fatigue, depression, anxiety, and reduced quality of life."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22856386",
"endSection": "abstract",
"offsetInBeginSection": 655,
"offsetInEndSection": 826,
"text": "Factors with less contribution to presenteeism included physical limitations, depression or anxiety, inadequate job training, and problems with supervisors and coworkers. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22532849",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 191,
"text": "BACKGROUND: Subthreshold depression is highly prevalent in the general population and causes great loss to society especially in the form of reduced productivity while at work (presenteeism)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22261652",
"endSection": "abstract",
"offsetInBeginSection": 212,
"offsetInEndSection": 393,
"text": "Two major causes of worker presenteeism (reduced on-the-job productivity as a result of health problems) are musculoskeletal pain and mental health issues, particularly depression. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22261652",
"endSection": "abstract",
"offsetInBeginSection": 1483,
"offsetInEndSection": 1555,
"text": " Pain and depression were significantly associated with presenteeism. Pr"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21880374",
"endSection": "abstract",
"offsetInBeginSection": 544,
"offsetInEndSection": 734,
"text": "Survey adjusted multivariable logistic regression assessed classification of 12-month, depression-related presenteeism on the basis of socio-demographic, financial, work and health factors. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21669372",
"endSection": "abstract",
"offsetInBeginSection": 842,
"offsetInEndSection": 982,
"text": "RESULTS: The LPT from absenteeism and presenteeism (reduced performance while present at work) was significantly higher among the MDD group."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21525074",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 119,
"text": "BACKGROUND: Depression is reported to be a major cause of illness-related sub-optimal work performance (presenteeism). "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21220078",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 144,
"text": "BACKGROUND: It is amply documented that mood disorders adversely affect job satisfaction, workforce productivity, and absenteeism/presenteeism. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20953117",
"endSection": "abstract",
"offsetInBeginSection": 686,
"offsetInEndSection": 857,
"text": "The difference in productivity loss due to impaired presenteeism was significantly different between the two groups, but the productivity loss due to absenteeism was not. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20726684",
"endSection": "abstract",
"offsetInBeginSection": 1101,
"offsetInEndSection": 1486,
"text": "Disease activity (OR 3.24, 95% CI 1.11-9.48) and depression (OR 3.22, 95% CI 1.22-8.48) were associated with absenteeism, while depression (OR 5.69, 95% CI 1.77-18.27, disease activity (OR 3.97, 95% CI 1.76-8.98), anxiety (OR 3.90, 95% CI 1.83-8.31), self-efficacy (OR 0.71, 95% CI 0.58-0.86), and increasing age (OR 1.04 per year, 95% CI 1.00-1.08) were associated with presenteeism. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20726684",
"endSection": "abstract",
"offsetInBeginSection": 1696,
"offsetInEndSection": 1853,
"text": "Depression, in particular, appears to be associated with employment, absenteeism, and presenteeism, and should therefore be prioritized in clinical practice."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20715299",
"endSection": "abstract",
"offsetInBeginSection": 576,
"offsetInEndSection": 702,
"text": "Depression frequently causes unemployment, absenteeism, and presenteeism, which results in significantly reduced productivity."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20073388",
"endSection": "abstract",
"offsetInBeginSection": 859,
"offsetInEndSection": 1239,
"text": "Presenteeism and absenteeism were significantly worse for the depression group at each time point (p < or = .001). In cross-sectional models, presenteeism was associated with more severe depression symptoms, poorer general physical health, psychologically demanding work, the interaction ofpsychologically demanding work with depression, and less job control (r2 range = .33-.54)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19339899",
"endSection": "abstract",
"offsetInBeginSection": 671,
"offsetInEndSection": 900,
"text": "Chronic conditions such as depression/anxiety, obesity, arthritis, and back/neck pain are especially important causes of productivity loss. Comorbidities have significant non-additive effects on both absenteeism and presenteeism."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17156851",
"endSection": "abstract",
"offsetInBeginSection": 698,
"offsetInEndSection": 841,
"text": "RESULTS: At baseline, all presenteeism measures were sensitive to differences between those with (N=69) and without (N=363) depression/anxiety."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16989105",
"endSection": "abstract",
"offsetInBeginSection": 1335,
"offsetInEndSection": 1548,
"text": "Depression and anxiety were more consistently associated with \"presenteeism\" (that is, lost productivity while at work) than with absenteeism, whether this was measured by cutback days or by direct questionnaires."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16282870",
"endSection": "abstract",
"offsetInBeginSection": 352,
"offsetInEndSection": 687,
"text": "RESULTS: Substantial research exists about anxiety and depression costs, such as performance and productivity, absenteeism, presenteeism, disability, physical disability exacerbation, mental health treatment, increased medical care costs, exacerbating of physical illness, and studies of mental health care limitations and cost-offset."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15951705",
"endSection": "abstract",
"offsetInBeginSection": 320,
"offsetInEndSection": 507,
"text": "The author discusses the etiology and potential solutions for managing this new component in the productivity equation and in addressing depression, the major contributor to presenteeism."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15804203",
"endSection": "abstract",
"offsetInBeginSection": 1019,
"offsetInEndSection": 1217,
"text": "For employees who are currently depressed, recent research evidence has demonstrated that pharmacotherapy can have a dramatic and positive effect on lost productivity, absenteeism, and presenteeism."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15572564",
"endSection": "abstract",
"offsetInBeginSection": 964,
"offsetInEndSection": 1098,
"text": "Among participants who were still employed, those with depression had significantly more job turnover, presenteeism, and absenteeism. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14665817",
"endSection": "abstract",
"offsetInBeginSection": 791,
"offsetInEndSection": 870,
"text": "Only depression affected both absenteeism-presenteeism and critical incidents. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11329394",
"endSection": "abstract",
"offsetInBeginSection": 1264,
"offsetInEndSection": 1453,
"text": "CONCLUSIONS: Depressive disorders in the workplace persist over time and have a major effect on work performance, most notably on \"presenteeism,\" or reduced effectiveness in the workplace. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25539872",
"endSection": "abstract",
"offsetInBeginSection": 411,
"offsetInEndSection": 596,
"text": "The negative effects of depression include those on patients' occupational functioning, including absenteeism, presenteeism, and reduced opportunities for educational and work success. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25435902",
"endSection": "abstract",
"offsetInBeginSection": 1136,
"offsetInEndSection": 1300,
"text": "The remitted group demonstrated a significant improvement in productivity (particularly presenteeism) when compared with the new visit group (Z = -3.29, p = 0.001)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25211435",
"endSection": "abstract",
"offsetInBeginSection": 652,
"offsetInEndSection": 880,
"text": "Depression in workers leads to significant absenteeism, \"presenteeism\" (diminished capacity due to illness while still present at work), and significantly increased medical expenses in addition to the costs of psychiatric care. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25173795",
"endSection": "abstract",
"offsetInBeginSection": 948,
"offsetInEndSection": 1371,
"text": "Significant predictors of presenteeism and activity impairment at follow-up (controlled for gender, age, spondyloarthritis subgroups and presenteeism at baseline) were presenteeism at baseline, poor quality of life, worse disease activity, decreased physical function, lower self-efficacy pain and symptom, higher scores of anxiety, depression, smoking and low education level, and for activity impairment also female sex. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22261652",
"endSection": "abstract",
"offsetInBeginSection": 1443,
"offsetInEndSection": 1513,
"text": "\" Pain and depression were significantly associated with presenteeism."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17156851",
"endSection": "abstract",
"offsetInBeginSection": 698,
"offsetInEndSection": 841,
"text": "RESULTS: At baseline, all presenteeism measures were sensitive to differences between those with (N=69) and without (N=363) depression/anxiety."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23439268",
"endSection": "abstract",
"offsetInBeginSection": 665,
"offsetInEndSection": 806,
"text": "Presenteeism was positively associated with severity of depression (Health and Work Performance Questionnaire, P < 0.0001; WPAI, P < 0.0001)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23244804",
"endSection": "abstract",
"offsetInBeginSection": 1355,
"offsetInEndSection": 1524,
"text": "Statistically significant correlations (0.32-0.53) were found between presenteeism and increasing disability, fatigue, depression, anxiety, and reduced quality of life. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14665817",
"endSection": "abstract",
"offsetInBeginSection": 791,
"offsetInEndSection": 869,
"text": "Only depression affected both absenteeism-presenteeism and critical incidents."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22856386",
"endSection": "abstract",
"offsetInBeginSection": 655,
"offsetInEndSection": 825,
"text": "Factors with less contribution to presenteeism included physical limitations, depression or anxiety, inadequate job training, and problems with supervisors and coworkers."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15951705",
"endSection": "abstract",
"offsetInBeginSection": 320,
"offsetInEndSection": 507,
"text": "The author discusses the etiology and potential solutions for managing this new component in the productivity equation and in addressing depression, the major contributor to presenteeism."
}
]
| 5 | BioASQ-training5b | []
| []
| 54f49e56d0d681a040000004 | 97 |
yesno | Is the Paramyxovirus geneome segmented, negative-sense RNA? | ['no'] | [
"no"
]
| ['The paramyxovirus family has a genome consisting of a SINGLE STRAND of negative sense RNA', 'The paramyxovirus family has a genome consisting of a single strand of negative sense RNA.', 'The paramyxovirus family has a genome consisting of a single strand of negative sense RNA'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/10400712",
"http://www.ncbi.nlm.nih.gov/pubmed/19493999",
"http://www.ncbi.nlm.nih.gov/pubmed/28508218",
"http://www.ncbi.nlm.nih.gov/pubmed/9525637",
"http://www.ncbi.nlm.nih.gov/pubmed/25683441",
"http://www.ncbi.nlm.nih.gov/pubmed/24501400",
"http://www.ncbi.nlm.nih.gov/pubmed/16325221",
"http://www.ncbi.nlm.nih.gov/pubmed/10482624",
"http://www.ncbi.nlm.nih.gov/pubmed/9568033",
"http://www.ncbi.nlm.nih.gov/pubmed/25948749",
"http://www.ncbi.nlm.nih.gov/pubmed/22892200",
"http://www.ncbi.nlm.nih.gov/pubmed/29992955",
"http://www.ncbi.nlm.nih.gov/pubmed/23707921",
"http://www.ncbi.nlm.nih.gov/pubmed/25831513",
"http://www.ncbi.nlm.nih.gov/pubmed/28601688"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25683441",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 89,
"text": "The paramyxovirus family has a genome consisting of a single strand of negative sense RNA"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22892200",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 161,
"text": "The avian paramyxovirus type 1 (APMV-1), or Newcastle disease virus (NDV), comprise a diverse group of viruses with a single-stranded, negative-sense RNA genome."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19493999",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 169,
"text": "Members of the Paramyxoviridae such as measles, mumps, and parainfluenza viruses have pleomorphic, enveloped virions that contain negative-sense unsegmented RNA genomes."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24501400",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 231,
"text": "UNLABELLED: Mumps virus (MuV), a paramyxovirus containing a negative-sense nonsegmented RNA genome, is a human pathogen that causes an acute infection with symptoms ranging from parotitis to mild meningitis and severe encephalitis."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25948749",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 95,
"text": "UNLABELLED: Mumps virus (MuV) is a paramyxovirus with a negative-sense nonsegmented RNA genome."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29992955",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 294,
"text": "Paramyxoviridae, a large family of enveloped viruses harboring a nonsegmented negative-sense RNA genome, include important human pathogens as measles, mumps, respiratory syncytial virus (RSV), parainfluenza viruses, and henipaviruses, which cause some of the deadliest emerging zoonoses. There "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25831513",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 223,
"text": "Parainfluenza virus 5 (PIV5) is a member of the Paramyxoviridae family of membrane-enveloped viruses with a negative-sense RNA genome that is packaged and protected by long filamentous nucleocapsid-helix structures (RNPs). "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9525637",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 295,
"text": "The paramyxovirus genome, a nonsegmented, negative-polarity, single-stranded RNA of approximately 15 kb, contains six transcription units flanked at the 3' and 5' ends by a short (approximately 50- to 60-nucleotide) extracistronic sequence, dubbed the positive and negative leader regions. These"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9568033",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 260,
"text": "The replication of nonsegmented minus-strand RNA genomes, like that of Sendai paramyxovirus (SeV), are controlled by the short leader regions present at each end of the linear genomes and antigenomes; the left and right promoters (PL and PR), respectively. Wil"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24501400",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 221,
"text": "UNLABELLED: Mumps virus (MuV), a paramyxovirus containing a negative-sense nonsegmented RNA genome, is a human pathogen that causes an acute infection with symptoms ranging from parotitis to mild meningitis and severe enc"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10482624",
"endSection": "abstract",
"offsetInBeginSection": 189,
"offsetInEndSection": 465,
"text": "s viral glycoprotein cytoplasmic domains may play a role in this coordination, we have investigated the importance of the hemagglutinin-neuraminidase (HN) protein cytoplasmic domain in the assembly of the nonsegmented negative-strand RNA paramyxovirus simian virus 5 (SV5). By"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16325221",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 108,
"text": "Beilong virus, a novel paramyxovirus with the largest genome of non-segmented negative-stranded RNA viruses."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9525637",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 289,
"text": "The paramyxovirus genome, a nonsegmented, negative-polarity, single-stranded RNA of approximately 15 kb, contains six transcription units flanked at the 3' and 5' ends by a short (approximately 50- to 60-nucleotide) extracistronic sequence, dubbed the positive and negative leader regions."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28601688",
"endSection": "abstract",
"offsetInBeginSection": 246,
"offsetInEndSection": 412,
"text": "Paramyxovirus particles are pleomorphic, with a lipid envelope, nonsegmented RNA genomes of negative polarity, and densely packed glycoproteins on the virion surface."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23707921",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 214,
"text": "An alternative method to determine the 5' extremities of non-segmented, negative sense RNA viral genomes using positive replication intermediate 3' tailing: application to two members of the Paramyxoviridae family."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10400712",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 123,
"text": "Simian parainfluenza virus 5 (SV5) is a prototype of the Paramyxoviridae family of nonsegmented negative-sense RNA viruses."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28508218",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 224,
"text": "Human metapneumovirus (HMPV), a single-stranded negative-sense RNA virus belonging to the family Paramyxoviridae, is associated with respiratory tract illness, primarily in young children and persons with underlying disease."
}
]
| 11 | BioASQ-training11b | null | null | 5e64f11a1af46fc130000017 | 98 |
yesno | Can tetracyline affect tooth formation? | ['yes'] | [
"yes"
]
| ['Tetracycline is incorporated in the teeth during their formation and leads to their permanent staining. A definite relationship between total dosage and staining and duration of administration and staining was established; the condition occurred with greater frequency (in more than one-third of the children) when the total dosage exceeded 3 g. or the duration of treatment was longer than 10 days.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/3855899",
"http://www.ncbi.nlm.nih.gov/pubmed/6829791",
"http://www.ncbi.nlm.nih.gov/pubmed/737550",
"http://www.ncbi.nlm.nih.gov/pubmed/5447715",
"http://www.ncbi.nlm.nih.gov/pubmed/1410257"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/3855899",
"endSection": "abstract",
"offsetInBeginSection": 149,
"offsetInEndSection": 379,
"text": "he results of that study, reported earlier (Rebich et al., 1983), indicated that over one-fifth of the American Indian children had discoloration of the dentition due to ingestion of tetracycline during the years of tooth formatio"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/6829791",
"endSection": "abstract",
"offsetInBeginSection": 1,
"offsetInEndSection": 184,
"text": "ale Wistar rats prelabeled with tetracycline to mark surfaces of bone and tooth formation-mineralization were placed into orbit for 18.5 days aboard the Soviet COSMOS-1129 Biosatellit"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/737550",
"endSection": "abstract",
"offsetInBeginSection": 195,
"offsetInEndSection": 360,
"text": "It was concluded that the increased tetracycline incorporation reflected a higher rate of mineralization associated with faster tooth formation in the unimpeded toot"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/5447715",
"endSection": "abstract",
"offsetInBeginSection": 1,
"offsetInEndSection": 237,
"text": "n this investigation an attempt has been made to determine the relationship between the staining of permanent teeth by tetracycline administered during the period of tooth formation with the dosage of the drug and the duration of therap"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/5447715",
"endSection": "abstract",
"offsetInBeginSection": 494,
"offsetInEndSection": 787,
"text": " definite relationship between total dosage and staining and duration of administration and staining was established; the condition occurred with greater frequency (in more than one-third of the children) when the total dosage exceeded 3 g. or the duration of treatment was longer than 10 days"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/1410257",
"endSection": "abstract",
"offsetInBeginSection": 120,
"offsetInEndSection": 292,
"text": "This case report suggests the possibility that discoloration from tetracycline may not be limited to tooth development in the child, but may also affect the adult dentition"
}
]
| 3 | Task3BGoldenEnriched | [
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013752",
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013754",
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014070",
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014076",
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014071",
"http://www.biosemantics.org/jochem#4272839",
"http://www.disease-ontology.org/api/metadata/DOID:1091"
]
| []
| 530cf4fe960c95ad0c000009 | 99 |
yesno | Are there web based self management strategies for chronic pain ? | ['yes'] | [
"yes"
]
| ['Yes, there are successful web based self management strategies for chronic pain.', 'Results suggest the potential value of self-management for chronic pain patients and the potential acceptability of web-based delivery of intervention content. ', 'Results suggest the potential value of self-management for chronic pain patients and the potential acceptability of web-based delivery of intervention content. ', 'Results suggest the potential value of self-management for chronic pain patients and the potential acceptability of web-based delivery of intervention content. ', 'Results suggest the potential value of self-management for chronic pain patients and the potential acceptability of web-based delivery of intervention content. ', 'Results suggest the potential value of self-management for chronic pain patients and the potential acceptability of web-based delivery of intervention content. '] | [
"http://www.ncbi.nlm.nih.gov/pubmed/24251273",
"http://www.ncbi.nlm.nih.gov/pubmed/24067267",
"http://www.ncbi.nlm.nih.gov/pubmed/23859438",
"http://www.ncbi.nlm.nih.gov/pubmed/23768119",
"http://www.ncbi.nlm.nih.gov/pubmed/23538392"
]
| [
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24251273",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 69,
"text": "Fibromyalgia Symptom Reduction by Online Behavioral Self-monitoring, "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24251273",
"endSection": "abstract",
"offsetInBeginSection": 368,
"offsetInEndSection": 565,
"text": "This study aimed to evaluate effects of a web-based, self-monitoring and symptom management system (SMARTLog) that analyzes personal self-monitoring data and delivers data-based feedback over time."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24251273",
"endSection": "abstract",
"offsetInBeginSection": 1074,
"offsetInEndSection": 1374,
"text": "Moderate use (3 times weekly x 3 months) increased likelihood of clinically significant improvements in pain, memory, gastrointestinal problems, depression, fatigue, and concentration; heavy use (4.5 times weekly x five months) produced the above plus improvement in stiffness and sleep difficulties."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24067267",
"endSection": "abstract",
"offsetInBeginSection": 2365,
"offsetInEndSection": 2576,
"text": "Results suggest that the tailored online chronic pain management program showed promising effects on pain at 1 and 6 months posttreatment and quality of life at 6 months posttreatment in this naturalistic study."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23859438",
"endSection": "abstract",
"offsetInBeginSection": 1494,
"offsetInEndSection": 1653,
"text": "Results suggest the potential value of self-management for chronic pain patients and the potential acceptability of web-based delivery of intervention content."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23768119",
"endSection": "abstract",
"offsetInBeginSection": 139,
"offsetInEndSection": 499,
"text": "Patient involvement can be fostered by web-based applications combining health information with decision support or behaviour change support. These so-called Interactive Health Communication Applications (IHCAs) can reach great numbers of patients at low financial cost and provide information and support at the time, place and learning speed patients prefer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23538392",
"endSection": "abstract",
"offsetInBeginSection": 129,
"offsetInEndSection": 502,
"text": "Web-based interventions may also be effective in enhancing self-management for individuals with chronic pain, but little is known about long-term effects. Research on Web-based interventions to support self-management following participation in pain management programs is limited. OBJECTIVE: The aim is to examine the long-term effects of a 4-week smartphone-intervention "
}
]
| 5 | BioASQ-training5b | []
| []
| 54fefff26ad7dcbc1200000b | 100 |
yesno | Is ospemifene effective for treatment of dyspareunia? | ['yes'] | [
"yes"
]
| Yes, ospamifene is effective for treatment of dyspareunia. Ospemifene is a selective estrogen receptor modulator, or estrogen receptor agonist/antagonist, that was recently approved by the US Food and Drug Administration for the treatment of dyspareunia associated with vulvar and vaginal atrophy, a chronic condition that affects up to 60% of postmenopausal women. Ospemifene is the first non-estrogen treatment approved for moderate to severe dyspareunia in women with menopause-related vulvar and vaginal atrophy. | [
"http://www.ncbi.nlm.nih.gov/pubmed/24251418",
"http://www.ncbi.nlm.nih.gov/pubmed/24109197",
"http://www.ncbi.nlm.nih.gov/pubmed/24075094",
"http://www.ncbi.nlm.nih.gov/pubmed/24055829",
"http://www.ncbi.nlm.nih.gov/pubmed/23985562",
"http://www.ncbi.nlm.nih.gov/pubmed/23945733",
"http://www.ncbi.nlm.nih.gov/pubmed/23777900",
"http://www.ncbi.nlm.nih.gov/pubmed/23605694",
"http://www.ncbi.nlm.nih.gov/pubmed/23361170",
"http://www.ncbi.nlm.nih.gov/pubmed/20429673",
"http://www.ncbi.nlm.nih.gov/pubmed/20032798"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24251418",
"endSection": "abstract",
"offsetInBeginSection": 14,
"offsetInEndSection": 175,
"text": "Ospemifene, a novel selective estrogen receptor modulator, has been developed for the treatment of vulvovaginal atrophy and dyspareunia in postmenopausal women. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24251418",
"endSection": "abstract",
"offsetInBeginSection": 1104,
"offsetInEndSection": 1554,
"text": "For the comparison of short-term ospemifene with placebo, parabasal cells (the standardized mean difference [SMD] = -37.5, 95% confidence interval [CI] = -41.83 to -33.17, P < 0.00001), superficial cells (SMD = 9.24, 95% CI = 7.70 to 10.79, P < 0.00001), vaginal PH (SMD = -0.89, 95% CI = -0.98 to -0.80, P = 0.00001), and dyspareunia (SMD = -0.37, 95% CI = -0.43 to -0.30, P = 0.00001) indicated that ospemifene was more effective than the placebo. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24251418",
"endSection": "abstract",
"offsetInBeginSection": 1841,
"offsetInEndSection": 1998,
"text": "This meta-analysis indicates that ospemifene to be an effective and safe treatment for dyspareunia associated with postmenopausal vulvar and vaginal atrophy."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24109197",
"endSection": "abstract",
"offsetInBeginSection": 12,
"offsetInEndSection": 325,
"text": "Ospemifene is a selective estrogen receptor modulator (SERM), or estrogen receptor agonist/antagonist, that was recently approved by the US Food and Drug Administration for the treatment of dyspareunia associated with vulvar and vaginal atrophy, a chronic condition that affects up to 60% of postmenopausal women."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24109197",
"endSection": "abstract",
"offsetInBeginSection": 959,
"offsetInEndSection": 1190,
"text": "In conclusion, ospemifene is a SERM with a unique estrogen agonist/antagonist tissue profile that was recently approved in the US for the treatment of dyspareunia associated with vulvar and vaginal atrophy in postmenopausal women. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24075094",
"endSection": "abstract",
"offsetInBeginSection": 11,
"offsetInEndSection": 334,
"text": "To characterize the pharmacokinetics of the oral, non-estrogen agent ospemifene, an estrogen agonist/antagonist with tissue-selective effects (also called a selective estrogen receptor modulator) that was recently approved for the treatment of dyspareunia associated with vulvar and vaginal atrophy in postmenopausal women."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24055829",
"endSection": "abstract",
"offsetInBeginSection": 401,
"offsetInEndSection": 647,
"text": "Here, we review the estrogen agonist/antagonist profile of ospemifene, a novel triphenylethylene derivative recently approved to treat dyspareunia, a symptom of vulvar and vaginal atrophy (VVA) due to menopause, both preclinically and clinically."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23985562",
"endSection": "abstract",
"offsetInBeginSection": 1257,
"offsetInEndSection": 1348,
"text": " Long-term studies on the endometrial safety of local estrogen and ospemifene are lacking. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23945733",
"endSection": "abstract",
"offsetInBeginSection": 365,
"offsetInEndSection": 590,
"text": "Ospemifene is a tissue-selective estrogen agonist/antagonist (a selective estrogen receptor modulator) recently approved by the US Food and Drug Administration for treatment of dyspareunia, a symptom of VVA, due to menopause."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23777900",
"endSection": "abstract",
"offsetInBeginSection": 1259,
"offsetInEndSection": 1662,
"text": "SERMs with positive vaginal effects (such as improvement in the vaginal maturation index, reduced vaginal pH, and improvement in the signs and symptoms of VVA) on postmenopausal symptomatic women include lasofoxifene (clinical development on hold) and ospemifene, which was recently approved for the treatment of VVA-related dyspareunia, with a class effect warning of potential venous thrombosis risk. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23605694",
"endSection": "abstract",
"offsetInBeginSection": 295,
"offsetInEndSection": 446,
"text": "Ospemifene is the first non-estrogen treatment approved for moderate to severe dyspareunia in women with menopause-related vulvar and vaginal atrophy. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23605694",
"endSection": "abstract",
"offsetInBeginSection": 535,
"offsetInEndSection": 729,
"text": "This article summarizes the milestones in the development of ospemifene leading to this first approval for moderate to severe dyspareunia, a symptom of postmenopausal vulvar and vaginal atrophy."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23361170",
"endSection": "abstract",
"offsetInBeginSection": 11,
"offsetInEndSection": 258,
"text": "The aim of this work was to study the role of ospemifene, a novel selective estrogen receptor modulator, in the treatment of vulvar and vaginal atrophy in postmenopausal women with moderate to severe dyspareunia and physiological vaginal changes. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23361170",
"endSection": "abstract",
"offsetInBeginSection": 1677,
"offsetInEndSection": 1828,
"text": "In this study, once-daily oral ospemifene 60 mg was effective for the treatment of vulvar and vaginal atrophy in postmenopausal women with dyspareunia."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20429673",
"endSection": "abstract",
"offsetInBeginSection": 1152,
"offsetInEndSection": 1367,
"text": "Clinical trials have confirmed that daily doses are well-tolerated and that it is effective in normalizing vaginal maturation index and pH as well as improving the symptoms associated with VVA including dyspareunia."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20032798",
"endSection": "abstract",
"offsetInBeginSection": 1313,
"offsetInEndSection": 1521,
"text": "Ospemifene was shown to be effective and well tolerated for the treatment of the symptoms of vaginal dryness and dyspareunia associated with vulvovaginal atrophy over and above the use of provided lubricants."
}
]
| 5 | BioASQ-training5b | [
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004414",
"http://www.biosemantics.org/jochem#4226329",
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812"
]
| []
| 5335b373d6d3ac6a34000050 | 101 |
yesno | Is lumican a secreted protein? | ['yes'] | [
"yes"
]
| ['Yes, Lumican is a secreted proteoglycan that regulates collagen fibril assembly.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/17050378",
"http://www.ncbi.nlm.nih.gov/pubmed/22814255",
"http://www.ncbi.nlm.nih.gov/pubmed/27126993",
"http://www.ncbi.nlm.nih.gov/pubmed/22266188",
"http://www.ncbi.nlm.nih.gov/pubmed/26351669"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26351669",
"endSection": "abstract",
"offsetInBeginSection": 296,
"offsetInEndSection": 442,
"text": "fibroblasts stimulated with the fibrocyte-secreted inflammatory signal tumor necrosis factor-α secrete the small leucine-rich proteoglycan lumican"
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26351669",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 82,
"text": "TNF-α-stimulated fibroblasts secrete lumican to promote fibrocyte differentiation."
},
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22266188",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 90,
"text": "Secreted 70kDa lumican stimulates growth and inhibits invasion of human pancreatic cancer."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22814255",
"endSection": "abstract",
"offsetInBeginSection": 1185,
"offsetInEndSection": 1359,
"text": "the elevated level of lumican secretion to extracellular space leads to actin cytoskeletal remodeling followed by an increase in migration capacity of human colon LS180 cells"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27126993",
"endSection": "abstract",
"offsetInBeginSection": 375,
"offsetInEndSection": 450,
"text": "Lumican is a secreted proteoglycan that regulates collagen fibril assembly."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17050378",
"endSection": "abstract",
"offsetInBeginSection": 1071,
"offsetInEndSection": 1180,
"text": "This is the first time that the synthesis and secretion of lumican in human melanoma cell lines is reported. "
}
]
| 11 | BioASQ-training11b | null | null | 5ad255210340b9f058000018 | 102 |
yesno | Does molindone affect body weight? | ['yes'] | [
"yes"
]
| Yes, molindone has a tendency to cause weight loss or limited weight gain. | [
"http://www.ncbi.nlm.nih.gov/pubmed/22372512",
"http://www.ncbi.nlm.nih.gov/pubmed/20502331",
"http://www.ncbi.nlm.nih.gov/pubmed/20494268",
"http://www.ncbi.nlm.nih.gov/pubmed/18794207",
"http://www.ncbi.nlm.nih.gov/pubmed/17253473",
"http://www.ncbi.nlm.nih.gov/pubmed/12518268",
"http://www.ncbi.nlm.nih.gov/pubmed/11488257",
"http://www.ncbi.nlm.nih.gov/pubmed/10796464",
"http://www.ncbi.nlm.nih.gov/pubmed/10553730",
"http://www.ncbi.nlm.nih.gov/pubmed/10548138",
"http://www.ncbi.nlm.nih.gov/pubmed/8800628",
"http://www.ncbi.nlm.nih.gov/pubmed/7481576",
"http://www.ncbi.nlm.nih.gov/pubmed/8290673",
"http://www.ncbi.nlm.nih.gov/pubmed/2671060",
"http://www.ncbi.nlm.nih.gov/pubmed/3780420",
"http://www.ncbi.nlm.nih.gov/pubmed/842709"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22372512",
"endSection": "abstract",
"offsetInBeginSection": 1464,
"offsetInEndSection": 1540,
"text": "Mean weight increased by 0.54 kg, and mean body mass index by 0.24 kg/m(2). "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20502331",
"endSection": "abstract",
"offsetInBeginSection": 479,
"offsetInEndSection": 712,
"text": "A large-scale trial comparing a first-generation antipsychotic (molindone) with newer agents did not find significant differences in treatment response, although the newer antipsychotics were associated with more severe weight gain. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20494268",
"endSection": "abstract",
"offsetInBeginSection": 1495,
"offsetInEndSection": 1602,
"text": "No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20494268",
"endSection": "abstract",
"offsetInBeginSection": 902,
"offsetInEndSection": 1349,
"text": "The three treatment arms did not significantly differ in symptom decrease or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18794207",
"endSection": "abstract",
"offsetInBeginSection": 1400,
"offsetInEndSection": 1698,
"text": "Olanzapine and risperidone were associated with significantly greater weight gain. Olanzapine showed the greatest risk of weight gain and significant increases in fasting cholesterol, low density lipoprotein, insulin, and liver transaminase levels. Molindone led to more self-reports of akathisia. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17253473",
"endSection": "abstract",
"offsetInBeginSection": 2130,
"offsetInEndSection": 2320,
"text": "Molindone is no more or less likely than typical drugs to cause movement disorders, but it does cause significantly more weight loss (2RCTs n=60 RR 2.78, CI 1.10 to 6.99, NNH 5 CI 2 to 77). "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17253473",
"endSection": "abstract",
"offsetInBeginSection": 2490,
"offsetInEndSection": 2670,
"text": "Molindone may be an effective antipsychotic but its adverse effect profile does not differ significantly from that of typical antipsychotics (apart from the event of weight loss). "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12518268",
"endSection": "abstract",
"offsetInBeginSection": 113,
"offsetInEndSection": 459,
"text": "Convergent evidence suggests a hierarchy in the magnitude of BWG that may be induced by diverse agents, being very high for clozapine and olanzapine; high for quetiapine, zotepin, chlorpromazine, and thioridazine; moderate for risperidone and sertindole; and low for ziprazidone, amisulpiride, haloperidol, fluphenazine, pimozide, and molindone. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11488257",
"endSection": "abstract",
"offsetInBeginSection": 943,
"offsetInEndSection": 1037,
"text": "Loxapine and molindone induce weight decreases, and these exceptions are difficult to explain."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10796464",
"endSection": "abstract",
"offsetInBeginSection": 2837,
"offsetInEndSection": 2983,
"text": "It is no more or less likely than typical drugs to cause movement disorders, but causes significantly more weight loss (RR 2.78, CI 1.10 to 6.99)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10796464",
"endSection": "abstract",
"offsetInBeginSection": 3154,
"offsetInEndSection": 3339,
"text": "Molindone may be an effective antipsychotic; however, its adverse effect profile does not differ significantly from that of typical antipsychotics, apart from the event of weight loss. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10553730",
"endSection": "abstract",
"offsetInBeginSection": 704,
"offsetInEndSection": 844,
"text": "Among conventional agents, mean weight change ranged from a reduction of 0.39 kg with molindone to an increase of 3.19 kg with thioridazine."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10548138",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 110,
"text": "Weight gain has been reported with nearly every antipsychotic drug on the market (molindone is an exception). "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8800628",
"endSection": "abstract",
"offsetInBeginSection": 2144,
"offsetInEndSection": 2260,
"text": "Although almost all antipsychotics induce bodyweight gain, molindone and loxapine appear to induce bodyweight loss. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7481576",
"endSection": "abstract",
"offsetInBeginSection": 242,
"offsetInEndSection": 385,
"text": "Clozapine and low-potency phenothiazines are associated with the largest gains and molindone with weight loss, but the mechanism is not known. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8290673",
"endSection": "abstract",
"offsetInBeginSection": 717,
"offsetInEndSection": 840,
"text": "On average, molindone patients lost 5 pounds over the 6 weeks of treatment, whereas thioridazine patients gained 6 pounds. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2671060",
"endSection": "abstract",
"offsetInBeginSection": 714,
"offsetInEndSection": 856,
"text": "Clinically, molindone has a tendency to cause weight loss and may have less effect on seizure threshold than conventional antipsychotic agents"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/3780420",
"endSection": "abstract",
"offsetInBeginSection": 81,
"offsetInEndSection": 407,
"text": " Monthly weights and neuroleptic dosages during the first three months of psychiatric hospitalization were compared between matched groups of patients receiving molindone, a combination of molindone and other neuroleptics, or other neuroleptic drugs. We found no significant differences in weight gain among the three groups. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/842709",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 267,
"text": "The weight-reducing property of molindone, a recently introduced antipsychotic drug, was tested in 9 hospitalized chronic schizophrenic patients. There was an average weight loss of 7.6 kg after 3 months on molindone; most of the loss occurred during the first month."
}
]
| 5 | BioASQ-training5b | [
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015430",
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019440",
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001837",
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001836",
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008972",
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001835",
"http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015431",
"http://www.biosemantics.org/jochem#4249624"
]
| []
| 52cae04c03868f1b06000024 | 103 |
yesno | Is Loss of function one of the cardinal signs of inflammation? | ['yes'] | [
"yes"
]
| ['Functio Laesa also known as loss of function is considered to be the 5th cardinal sign of inflammation.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/12776909",
"http://www.ncbi.nlm.nih.gov/pubmed/28282278",
"http://www.ncbi.nlm.nih.gov/pubmed/29135930",
"http://www.ncbi.nlm.nih.gov/pubmed/12799851"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12776909",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 215,
"text": "The concept of the four cardinal signs of acute inflammation comes from antiquity as rubor et tumor cum calore et dolore, (redness and swelling with heat and pain) extended later by functio laesa (loss of function)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29135930",
"endSection": "abstract",
"offsetInBeginSection": 60,
"offsetInEndSection": 255,
"text": "As early as 2000 years ago, the Roman encyclopaedist Aulus Cornelius Celsus recognised four cardinal signs of this response-redness, heat, swelling and pain; a fifth sign is loss of function.[..."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12799851",
"endSection": "abstract",
"offsetInBeginSection": 1008,
"offsetInEndSection": 1195,
"text": "It was Galen who added the disturbance of function (functio laesa) as the fifth cardinal sign of inflammation to the four well-known cardinal signs of Celsus (rubor, calor, tumor, dolor)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28282278",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 245,
"text": "Tumor, calor, rubor, and dolor describe four cardinal signs of inflammation. The fifth-functio laesa, or loss of function-was promulgated by Rudolf Virchow, who, in the 19th century, also noted an intricate link between inflammation and cancer. "
}
]
| 11 | BioASQ-training11b | null | null | 5a7a44b4faa1ab7d2e000010 | 104 |
yesno | Are there lncRNAs that control the extent of neuronal outgrowth? | ['yes'] | [
"yes"
]
| ['Yes. there are lncRNAs which regulate the extent of neuronal outgrowth.', 'Yes. LncRNAs are involved in a variety of biological processes, including the epigenetic control of gene expression, post-transcriptional regulation of mRNA, and neuronal outgrowth.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/30401432"
]
| [
{
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30401432",
"endSection": "title",
"offsetInBeginSection": 0,
"offsetInEndSection": 55,
"text": "Regulation of Neuroregeneration by Long Noncoding RNAs."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30401432",
"endSection": "abstract",
"offsetInBeginSection": 308,
"offsetInEndSection": 774,
"text": "Here, we profiled gene expression following sciatic nerve crush in mice and identified long noncoding RNAs (lncRNAs) that act in the regenerating neurons and which are typically not expressed in other contexts. We show that two of these lncRNAs regulate the extent of neuronal outgrowth. We then focus on one of these, Silc1, and show that it regulates neuroregeneration in cultured cells and in vivo, through cis-acting activation of the transcription factor Sox11."
}
]
| 11 | BioASQ-training11b | null | null | 5e447f2448dab47f26000013 | 105 |
yesno | Is protein Fbw7 a SCF type of E3 ubiquitin ligase? | ['yes'] | [
"yes"
]
| ['The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase. SCF(Fbw7) facilitates polyubiquitination and subsequent degradation of various proteins such as Notch, cyclin E, c-Myc and c-Jun.', 'Fbxw7 (also known as Fbw7, SEL-10, hCdc4, or hAgo) is the F-box protein subunit of an Skp1-Cul1-F-box protein (SCF)-type ubiquitin ligase complex that plays a central role in the degradation of Notch family members.The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase. SCF(Fbw7) facilitates polyubiquitination and subsequent degradation of various proteins such as Notch, cyclin E, c-Myc and c-Jun.', 'Fbxw7 (also known as Fbw7, SEL-10, hCdc4, or hAgo) is the F-box protein subunit of an Skp1-Cul1-F-box protein (SCF)-type ubiquitin ligase complex that plays a central role in the degradation of Notch family members.The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase. SCF(Fbw7) facilitates polyubiquitination and subsequent degradation of various proteins such as Notch, cyclin E, c-Myc and c-Jun.'] | [
"http://www.ncbi.nlm.nih.gov/pubmed/18094723",
"http://www.ncbi.nlm.nih.gov/pubmed/23820376",
"http://www.ncbi.nlm.nih.gov/pubmed/23776410",
"http://www.ncbi.nlm.nih.gov/pubmed/23507969",
"http://www.ncbi.nlm.nih.gov/pubmed/22665065",
"http://www.ncbi.nlm.nih.gov/pubmed/22608923",
"http://www.ncbi.nlm.nih.gov/pubmed/22124735",
"http://www.ncbi.nlm.nih.gov/pubmed/21827743",
"http://www.ncbi.nlm.nih.gov/pubmed/21349854",
"http://www.ncbi.nlm.nih.gov/pubmed/21282377",
"http://www.ncbi.nlm.nih.gov/pubmed/20935640",
"http://www.ncbi.nlm.nih.gov/pubmed/19679664",
"http://www.ncbi.nlm.nih.gov/pubmed/20826802",
"http://www.ncbi.nlm.nih.gov/pubmed/14672936"
]
| [
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18094723",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 183,
"text": "FBW7 (F-box and WD repeat domain-containing 7) is the substrate recognition component of an evolutionary conserved SCF (complex of SKP1, CUL1 and F-box protein)-type ubiquitin ligase."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23820376",
"endSection": "abstract",
"offsetInBeginSection": 359,
"offsetInEndSection": 700,
"text": "However, very few E3 ubiquitin ligases are known to target G-CSFR for ubiquitin-proteasome pathway. Here we identified F-box and WD repeat domain-containing 7 (Fbw7), a substrate recognizing component of Skp-Cullin-F box (SCF) E3 ubiquitin Ligase physically associates with G-CSFR and promotes its ubiquitin-mediated proteasomal degradation."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23776410",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 132,
"text": "FBW7 is a crucial component of an SCF-type E3 ubiquitin ligase, which mediates degradation of an array of different target proteins."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23507969",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 225,
"text": "F-box and WD repeat domain-containing 7 (FBW7), the substrate-binding subunit of E3 ubiquitin ligase SCF(FBW7) (a complex of SKP1, cullin-1 and FBW7), plays important roles in various physiological and pathological processes."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22665065",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 232,
"text": "The tumor suppressor Fbxw7 (also known as Sel-10, hCdc4, hAgo, or Fbw7) is an F-box protein that functions as the substrate-recognition subunit of an SCF ubiquitin ligase complex and targets a group of oncoproteins for degradation. "
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22608923",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 191,
"text": "Fbw7 is the substrate recognition component of the Skp1-Cullin-F-box (SCF)-type E3 ligase complex and a well-characterized tumor suppressor that targets numerous oncoproteins for destruction."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22124735",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 136,
"text": "Fbw7 is a member of F-box family proteins, which constitute one subunit of Skp1, Cul1, and F-box protein (SCF) ubiquitin ligase complex."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21827743",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 274,
"text": "The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase. SCF(Fbw7) facilitates polyubiquitination and subsequent degradation of various proteins such as Notch, cyclin E, c-Myc and c-Jun."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21349854",
"endSection": "abstract",
"offsetInBeginSection": 270,
"offsetInEndSection": 485,
"text": "Fbxw7 (also known as Fbw7, SEL-10, hCdc4, or hAgo) is the F-box protein subunit of an Skp1-Cul1-F-box protein (SCF)-type ubiquitin ligase complex that plays a central role in the degradation of Notch family members."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21282377",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 314,
"text": "The Fbxw7 (F-box/WD repeat-containing protein 7; also called CDC4, Sel10, Ago, and Fbw7) component of the SCF (Skp1/Cullin/F-box protein) E3 ubiquitin ligase complex acts as a tumor suppressor in several tissues and targets multiple transcriptional activators and protooncogenes for ubiquitin-mediated degradation."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21827743",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 144,
"text": "The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20935640",
"endSection": "abstract",
"offsetInBeginSection": 227,
"offsetInEndSection": 475,
"text": "We demonstrate here that Fbw7 (F-box and WD repeat domain containing-7), the substrate recognition component of an SCF (complex of SKP1, CUL1 and F-box protein)-type E3 ubiquitin ligase, is a key regulator of NSC/NPC viability and differentiation."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21282377",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 314,
"text": "The Fbxw7 (F-box/WD repeat-containing protein 7; also called CDC4, Sel10, Ago, and Fbw7) component of the SCF (Skp1/Cullin/F-box protein) E3 ubiquitin ligase complex acts as a tumor suppressor in several tissues and targets multiple transcriptional activators and protooncogenes for ubiquitin-mediated degradation."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19679664",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 177,
"text": "The SCF(Fbw7) ubiquitin ligase complex plays important roles in cell growth, survival, and differentiation via the ubiquitin-proteasome-mediated regulation of protein stability."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20935640",
"endSection": "abstract",
"offsetInBeginSection": 227,
"offsetInEndSection": 475,
"text": "We demonstrate here that Fbw7 (F-box and WD repeat domain containing-7), the substrate recognition component of an SCF (complex of SKP1, CUL1 and F-box protein)-type E3 ubiquitin ligase, is a key regulator of NSC/NPC viability and differentiation."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20826802",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 271,
"text": "F-box and WD-40 domain protein 7 (Fbw7) provides substrate specificity for the Skp1-Cullin1-F-box protein (SCF) ubiquitin ligase complex that targets multiple oncoproteins for degradation, including cyclin E, c-Myc, c-Jun, Notch, and mammalian target of rapamycin (mTOR)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21827743",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 144,
"text": "The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20826802",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 271,
"text": "F-box and WD-40 domain protein 7 (Fbw7) provides substrate specificity for the Skp1-Cullin1-F-box protein (SCF) ubiquitin ligase complex that targets multiple oncoproteins for degradation, including cyclin E, c-Myc, c-Jun, Notch, and mammalian target of rapamycin (mTOR)."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21827743",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 144,
"text": "The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14672936",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 236,
"text": "Mammalian Fbw7 (also known as Sel-10, hCdc4, or hAgo) is the F-box protein component of an SCF (Skp1-Cul1-F-box protein-Rbx1)-type ubiquitin ligase, and the mouse Fbw7 is expressed prominently in the endothelial cell lineage of embryos."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21827743",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 144,
"text": "The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase."
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21827743",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 143,
"text": "The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21827743",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 143,
"text": "The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20935640",
"endSection": "abstract",
"offsetInBeginSection": 230,
"offsetInEndSection": 476,
"text": "We demonstrate here that Fbw7 (F-box and WD repeat domain containing-7), the substrate recognition component of an SCF (complex of SKP1, CUL1 and F-box protein)-type E3 ubiquitin ligase, is a key regulator of NSC/NPC viability and differentiation"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23820376",
"endSection": "abstract",
"offsetInBeginSection": 459,
"offsetInEndSection": 699,
"text": "Here we identified F-box and WD repeat domain-containing 7 (Fbw7), a substrate recognizing component of Skp-Cullin-F box (SCF) E3 ubiquitin Ligase physically associates with G-CSFR and promotes its ubiquitin-mediated proteasomal degradation"
},
{
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23776410",
"endSection": "abstract",
"offsetInBeginSection": 0,
"offsetInEndSection": 131,
"text": "FBW7 is a crucial component of an SCF-type E3 ubiquitin ligase, which mediates degradation of an array of different target proteins"
}
]
| 5 | BioASQ-training5b | [
"http://www.uniprot.org/uniprot/SKP1_ASPFN",
"http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D044843",
"http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D044767"
]
| []
| 550ae16bc2af5d5b70000009 | 106 |
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