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6419cd02690f196b5100003a | What are Luminopsins? | Luminopsins (LMOs) are chimeric proteins consisting of a luciferase fused to an opsin that provides control of neuronal activity. | [
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"text": "Luminopsins (LMOs) are chimeric proteins consisting of a luciferase fused to an opsin that provide control of neuronal activity",
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"text": "Previous work has demonstrated that fusion of a luciferase to an opsin, to create a luminescent opsin or luminopsin",
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"text": "luminopsins, fusion proteins of light-generating luciferase and light-sensing ion channels that could be used to increase neuronal excitability if exposed to a suitable substrate",
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"text": "BL-OG is realized through opsin-luciferase fusion proteins called luminopsins (LMOs)",
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"text": "Luminopsins are fusion proteins of luciferase and opsin that allow interrogation of neuronal circuits at different temporal and spatial resolutions by choosing either extrinsic physical or intrinsic biological light for its activation.",
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"text": "Luminopsins (LMOs) are chimeric proteins consisting of a luciferase fused to an opsin that provide control of neuronal activity, allowing for less cumbersome and less invasive optogenetic manipulation.",
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"text": "This is commonly achieved by utilizing a luminopsin (LMO), a fusion protein of a light-emitting luciferase tethered to a light-sensing opsin.",
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"text": "Previous work has demonstrated that fusion of a luciferase to an opsin, to create a luminescent opsin or luminopsin, provides a genetically encoded means of manipulating neuronal activity via both chemogenetic and optogenetic approaches.",
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"text": "We have bypassed the challenges of external light delivery by directly coupling a bioluminescent light source (a genetically encoded luciferase) to an inhibitory opsin, which we term an inhibitory luminopsin (iLMO).",
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"text": "A non-invasive and highly specific approach to neuronal stimulation is bioluminescent-optogenetics (BL-OG), where genetically expressed light emitting luciferases are tethered to light sensitive channelrhodopsins (luminopsins, LMO); neurons are activated by the addition of the luciferase substrate coelenterazine (CTZ).",
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"text": "We generated a neuronal precursor cell line expressing luminopsin 3 (LMO3), a luciferase-channelrhodopsin fusion protein, which responds to the luciferase substrate coelenterazine (CTZ) with emission of blue light that in turn activates the opsin.",
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"text": "Thus, although preserving the ability to be activated by external light sources, LMOs expand the use of optogenetics by making the same opsins accessible to noninvasive, chemogenetic control, thereby allowing the same probe to manipulate neuronal activity over a range of spatial and temporal scales.",
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"text": "BL-OG is realized through opsin-luciferase fusion proteins called luminopsins (LMOs).",
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"text": "We have previously addressed these challenges by employing bioluminescence and have created a new line of opto-chemogenetic probes termed luminopsins by fusing light-sensing opsins with light-emitting luciferases.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30957296",
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] |
644f0ca257b1c7a315000089 | What are the hallmarks of cancer? | The hallmarks of cancer are a set of characteristics that distinguish cancer cells from normal cells, as proposed by Douglas Hanahan and Robert Weinberg in their seminal paper published in 2000. These hallmarks include: 1) sustained proliferative signaling, which allows cancer cells to continuously divide and grow; 2) evasion of growth suppressors, enabling them to bypass cellular mechanisms that inhibit uncontrolled growth; 3) resistance to cell death, allowing them to avoid apoptosis or programmed cell death; 4) replicative immortality, granting them the ability to maintain telomeres and divide indefinitely; 5) induction of angiogenesis, promoting the formation of new blood vessels for nutrient supply; and 6) activation of invasion and metastasis, enabling the spread of cancer cells to other tissues. In a later update in 2011, two emerging hallmarks were added: 7) reprogramming of energy metabolism, which shifts cellular metabolism towards aerobic glycolysis (Warburg effect); and 8) evading immune destruction by suppressing anti-tumor immune responses. Additionally, two enabling characteristics were identified: genome instability and mutation, leading to genetic alterations that drive cancer progression; and tumor-promoting inflammation, which supports tumor growth and survival. Understanding these hallmarks is crucial for developing targeted therapies against various types of cancers. | [
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"text": "The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction.",
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"text": "We define seven hallmarks of cancer: selective growth and proliferative advantage, altered stress response favoring overall survival, vascularization, invasion and metastasis, metabolic rewiring, an abetting microenvironment, and immune modulation, while highlighting some considerations for the future of the field.",
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"text": "These distinctive and complementary capabilities, defined as the \"hallmarks of cancer,\" include the ability of tumor cells and their microenvironment to sustain proliferative signaling, evade growth suppressors, resist cell death, promote replicative immortality, induce angiogenesis, support invasion and metastasis, reprogram energy metabolism, induce genomic instability and inflammation, and trigger evasion of immune responses.",
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"text": "Human cancers share properties referred to as hallmarks, among which sustained proliferation, escape from apoptosis, and genomic instability are the most pervasive.",
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"text": "Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions.",
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"text": "The hallmarks of cancer described by Hanahan and Weinberg are properties that cancer cells must possess for successful transformation.",
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"text": "They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis.",
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"text": "The integrative concept embodied in the hallmarks of cancer is helping to distill this complexity into an increasingly logical science, and the provisional new dimensions presented in this perspective may add value to that endeavor, to more fully understand mechanisms of cancer development and malignant progression, and apply that knowledge to cancer medicine.",
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"text": "Based on extensive study of the cancer research literature, we propose four novel hallmarks of cancer, namely, the ability of cells to regress from a specific specialized functional state, epigenetic changes that can affect gene expression, the role of microorganisms and neuronal signalling, to be included in the hallmark conceptualization along with evidence of various means to exploit them therapeutically.",
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"text": "The hallmarks of cancer conceptualization is a heuristic tool for distilling the vast complexity of cancer phenotypes and genotypes into a provisional set of underlying principles.",
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"text": "The hallmarks of cancer include six biological processes, including proliferative signaling, evasion of growth suppressors, resistance to cell death, replicative immortality, inducing angiogenesis, and activating invasion and metastasis.",
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"text": "Attention is paid to the emerging hallmarks, deregulation of cellular energy metabolism and evasion of immune destruction, and enabling characteristics, genome instability and mutation and tumour-promoting inflammation.",
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"text": "This progression has been suggested to depend on six essential characteristics identified as the \"hallmarks of cancer,\" which include: self-sufficiency in growth signals, insensitivity to growth-inhibitory signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis.",
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"text": "The six classical hallmarks of cancer (i.e., limitless replication, self-provision of proliferative stimuli, insensitivity to antiproliferative signals, disabled apoptosis, sustained angiogenesis, invasiveness/metastatic potential), as well as other common features of tumors (i.e., avoidance of the immune response, enhanced anabolic metabolism, disabled autophagy) may directly or indirectly implicate deregulated mitochondria.",
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"text": "Hanahan and Weinberg (2000, Cell 100: 57-70) listed \"hallmarks\" of cancer that must be considered in order to understand the underlying determinants of carcinogenesis: (a) self-sufficiency in growth signals; (b) insensitivity to growth-inhibitory (antigrowth) signals; (c) evasion of programmed cell death (apoptosis); (d) limitedless replicative potential; (e) sustained angiogenesis; and (f) tissue invasion and metastasis.",
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"text": "These hallmarks include; unlimited proliferation, evading growth suppressors, resisting cell death, replicative immortality, inducing angiogenesis, initiating invasion and metastasis.",
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"text": "Cancer hallmarks include sustained proliferation, evading growth suppressors, metastasis, replicative immortality, angiogenesis, resisting cell death, altered cellular energetics, and immune evasion.",
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"text": "According to Hanahan and Weinberg, cancer manifests as six essential physiologic hallmarks: (1) self-sufficiency in growth signals, (2) insensitivity to growth-inhibitory signals, (3) evasion of programmed cell death, (4) limitless replicative potential, (5) sustained angiogenesis, and (6) invasion and metastasis.",
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"text": "Tumors arise through waves of genetic alterations and clonal expansion that allow tumor cells to acquire cancer hallmarks, such as genome instability and immune evasion. ",
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"text": "The hallmarks of cancer provide a highly cited and well-used conceptual framework for describing the processes involved in cancer cell development and tumourigenesis.",
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] |
64403a5857b1c7a31500004c | What was the phase of the clinical trial PEACHTREE? | The PEACHTREE trial was a phase III clinical trial. | [
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"text": "Recent results from the PEACHTREE trial (ClinicalTrials.gov Identifier: NCT02595398), a phase III trial with two suprachoroidal injections of CLS-TA at 0 and 12 weeks with follow up lasting 24 weeks, showed the significant improvement in visual acuity and reduction in central subfield thickness, all without increasing the risk of elevated intraocular pressure or accelerated cataract progression.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34322164",
"endSection": "abstract"
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] |
6446838957b1c7a31500006e | Which genes are related to Emery-Dreifuss Muscular Dystrophy (EDMD)? | The following genes are related to Emery-Dreifuss Muscular Dystrophy (EDMD): EMD, LMNA, SYNE1, SYNE2, FHL1, TMEM43, SUN1, SUN2, and TTN. These encode proteins such as emerin, lamin A/C, nesprin-1, nesprin-2, FHL1, LUMA, SUN1, SUN2, and titin, respectively. | [
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"22103509"
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"text": "Emery-Dreifuss muscular dystrophy (EDMD) is an inherited muscular disorder clinically characterized by slowly progressive weakness affecting humero-peroneal muscles, early joint contractures and cardiomyopathy with conduction defects. Autosomal dominant and recessive forms are caused by mutations in lamin A/C gene.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16550925",
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{
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"text": "X-linked recessive form of EDMD is caused by mutation in EMD (or STA) gene ",
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"text": "The LINC components emerin, lamin A/C, SUN1, SUN2, nesprin-1 and nesprin-2 interact with each other at the NE and also with other binding partners including actin filaments and B-type lamins.",
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"text": "Emerin was the first LINC component associated with a human disease, namely EDMD (Emery-Dreifuss muscular dystrophy).",
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"text": "Later on, other components of the LINC complex, such as lamins A/C and small isoforms of nesprin-1 and nesprin-2, were found to be associated with EDMD",
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"text": "Only approximately 46% of the EDMD patients can be linked to genes of LINC and non-LINC components, pointing to further genes involved in the pathology of EDMD",
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"text": " Recently, screening of binding partners of LINC components as candidates identified LUMA (TMEM43), encoding a binding partner of emerin and lamins, as a gene involved in atypical EDMD.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/22103509",
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"text": " EDMD-causing mutations in STA/EMD (encoding emerin",
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"text": "Emery-Dreifuss muscular dystrophy (EDMD) is a rare muscular dystrophy, but is particularly important to diagnose due to frequent life-threatening cardiac complications. EDMD classically presents with muscle weakness, early contractures, cardiac conduction abnormalities and cardiomyopathy, although the presence and severity of these manifestations vary by subtype and individual. Associated genes include EMD, LMNA, SYNE1, SYNE2, FHL1, TMEM43, SUN1, SUN2, and TTN, encoding emerin, lamin A/C, nesprin-1, nesprin-2, FHL1, LUMA, SUN1, SUN2, and titin, respectively.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31840275",
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}
] |
63f02e1bf36125a426000016 | Was AAVS3 developed for hemophilia A? | No. AAVS3 was developed for hemophilia B. | [
"35857660"
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"text": "Phase 1-2 Trial of AAVS3 Gene Therapy in Patients with Hemophilia B.",
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"text": "BACKGROUND: FLT180a (verbrinacogene setparvovec) is a liver-directed adeno-associated virus (AAV) gene therapy that uses a synthetic capsid and a gain-of-function protein to normalize factor IX levels in patients with hemophilia B",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35857660",
"endSection": "abstract"
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] |
642f49db57b1c7a315000014 | List the luciferase substrates | luciferase substrates include coelenterazine (CTZ), Luciferin, ATP, FMNH2, and luciferin analogs like AL3 ((S,E)-2-(6-hydroxy-5-(3-methoxy-3-oxoprop-1-en-1-yl)benzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid), AL4 ((S,E)-2-(5-(2-cyanovinyl)-6-hydroxybenzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid) and AL2 ((S,E)-2-(6-hydroxy-7-(3-methoxy-3-oxoprop-1-en-1-yl)benzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid) as well as long-chain aldehydes--decanal (C10), dodecanal (C12) and tetradecanal (C14)] | [
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"text": "new firefly bioluminescence substrates, and further evaluated their activities in vitro and in vivo. It is worth noting that the maximum biological emission wavelength of novel luciferin analogue AL3 ((S,E)-2-(6-hydroxy-5-(3-methoxy-3-oxoprop-1-en-1-yl)benzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid) is 100 nm red-shifted compared with D-luciferin, ",
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"text": "AL4 ((S,E)-2-(5-(2-cyanovinyl)-6-hydroxybenzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid) ",
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"text": "The new substrate AL2 ((S,E)-2-(6-hydroxy-7-(3-methoxy-3-oxoprop-1-en-1-yl)benzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid) showed better bioluminescence performance in vivo.",
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"text": "The interaction of luciferases from two types of luminous bacteria, Photobacterium leiognathi and Vibrio harveyi, with their substrates [the photorecovered FMNH2 and long-chain aldehydes--decanal (C10), dodecanal (C12) and tetradecanal (C14)] ",
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"text": "Following coadministration of two luciferase substrates, native coelenterazine and luciferin,",
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"endSection": "abstract"
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"text": "Comparisons of experimental data with predictions based upon the three inhibitory models show that product inhibition during luciferase luminescence is noncompetitive with respect to both luciferin and ATP as substrates.",
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"text": "An alternative luciferase (Luc) substrate cyclic luciferin (Cycluc) was recently advanced for BLI applications as providing a stronger, more stable signal at significantly lower doses than the classical substrate D-luciferin (D-Luc) increasing sensitivity of Luc detection 10 to 100 times.",
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"text": "ATP is one of the substrates of luciferase.",
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"text": "D-luciferin, a natural substrate of firefly luciferase, has been reported to have limited brain distribution, possibly due to the efflux transporter, breast cancer resistance protein (Bcrp), at the blood-brain barrier.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34887255",
"endSection": "abstract"
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{
"offsetInBeginSection": 204,
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"text": "4-Methyl-D-luciferin is a substrate of Photinus pyralis luciferase, and it causes light emission in luminometric assays.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2230665",
"endSection": "abstract"
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{
"offsetInBeginSection": 1501,
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"text": "This study examined the pharmacokinetics, brain distribution, and the role of active efflux transporters on the luciferase substrates D-luciferin and CycLuc1.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34887255",
"endSection": "abstract"
},
{
"offsetInBeginSection": 102,
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"text": "Antares, a fusion of the luciferase NanoLuc to the orange fluorescent protein CyOFP, has emerged as a bright bioluminescent reporter with orthogonal substrate specificity to firefly luciferase (FLuc) and its derivatives such as AkaLuc.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32661427",
"endSection": "abstract"
},
{
"offsetInBeginSection": 243,
"offsetInEndSection": 377,
"text": "Here we report cost-effective and efficient syntheses of d-luciferin and 6'-aminoluciferin, two widely used bioluminescent substrates.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25525906",
"endSection": "abstract"
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{
"offsetInBeginSection": 0,
"offsetInEndSection": 87,
"text": "d-Luciferin is a popular bioluminescent substrate of luciferase in the presence of ATP.",
"beginSection": "abstract",
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"endSection": "abstract"
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{
"offsetInBeginSection": 197,
"offsetInEndSection": 347,
"text": "cusing on the tissue distribution of two luciferase substrates, D-luciferin and CycLuc1. D-luciferin, a natural substrate of firefly luciferase, has b",
"beginSection": "abstract",
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"endSection": "abstract"
},
{
"offsetInBeginSection": 699,
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"text": " non-competitive manner with respect to the luciferase substrates D-luciferin and ATP. By contrast, the compound has no effect on Renilla and Gaussia ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22789175",
"endSection": "abstract"
},
{
"offsetInBeginSection": 700,
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"text": "non-competitive manner with respect to the luciferase substrates D-luciferin and ATP. By contrast, the compound has no effect on Renilla and Gaussia l",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22789175",
"endSection": "abstract"
}
] |
645037e557b1c7a31500008c | What are master regulatory genes? | Transcription factors regulating both the identity and patterning of embryonic structures and the development of individual organs are often called master regulatory genes. These genes, as well as other transcription factors, are parts of signaling networks mediating cellular communication, including inductive interactions between nearby tissues. SOX genes are an example of master regulatory genes that control development and are fundamental to the establishment of sex determination in a multitude of organisms. Because a master regulatory gene can regulate the concurrent expression of several genes, its mutation often leads to major diseases. In particular, the master regulatory genes that play a crucial role in the process of organism development may also play a key role in carcinogenesis. | [
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"text": "Transcription factors regulating both the identity and patterning of embryonic structures and the development of individual organs are often called master regulatory genes. These genes, as well as other transcription factors, are parts of signaling networks mediating cellular communication, including inductive interactions between nearby tissues.",
"beginSection": "abstract",
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{
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"text": "The transformation of normal precursors into cancer cells is an intricately regulated, multistep process. The master regulatory genes that play a crucial role in the process of organism development may also play a key role in carcinogenesis.",
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"text": "SOX genesare master regulatory genes controlling development and are fundamental to the establishment of sex determination in a multitude of organisms.",
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"text": "Because a MRG can regulate the concurrent expression of several genes, its mutation often leads to major diseases.",
"beginSection": "abstract",
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"text": "Transcription factors regulating both the identity and patterning of embryonic structures and the development of individual organs are often called master regulatory genes.",
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"text": "Such master regulators are classically seen as acting on the top of a regulatory hierarchy that determines a complete developmental program, and they usually encode transcription factors.",
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{
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"text": "Master genes are known to induce the differentiation of a multipotent cell into a specific cell type.",
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"endSection": "abstract"
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{
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"text": " A poorly understood phenomenon is how developmental master regulators exert functions in different cell- and organ types.",
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"text": " Such master regulators are classically seen as acting on the top of a regulatory hierarchy that determines a complete developmental program, and they usually encode transcription factors.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30043361",
"endSection": "abstract"
}
] |
64402bb057b1c7a315000043 | In what type of clinical trial has RT001 been evaluated against Friedreich's ataxia? | RT001 was evaluatd in a phase I/II double-blind, randomized, comparator-controlled trial in Friedreich's ataxia patients. | [
"29624723"
] | factoid | [
{
"offsetInBeginSection": 0,
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"text": "Randomized, clinical trial of RT001: Early signals of efficacy in Friedreich's ataxia.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/29624723",
"endSection": "title"
},
{
"offsetInBeginSection": 352,
"offsetInEndSection": 500,
"text": "We conducted a phase I/II double-blind, comparator-controlled trial with 2 doses of RT001 in Friedreich's ataxia patients (9 subjects each cohort). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29624723",
"endSection": "abstract"
}
] |
6450bf2557b1c7a31500008d | Which are the known inflammatory myopathies? | The known inflammatory myopathies are polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM), necrotizing myopathy (NM), antisynthetase syndrome (ASS) and overlap myositis (OM). | [
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{
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"text": "Inflammatory myopathies, including polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM), necrotizing myopathy (NM), antisynthetase syndrome (ASS) and overlap myositis (OM), in short myositis, are rare diseases.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35394612",
"endSection": "abstract"
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{
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"text": "This review describes the clinical features, diagnosis and treatment for IIMs, namely polymyositis (PM), dermatomyositis (DM), sporadic inclusion body myositis (sIBM), immune-mediated necrotizing myopathy (IMNM), and myositis associated with antisynthetase syndrome (ASS).",
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{
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"text": "The search strategy from the 2021 Cochrane Physical Activity review in neuromuscular disease was used, and we selected articles that included people with IIM, including Dermatomyositis (DM), Inclusion Body Myositis (IBM), Immune Mediated Necrotising Myopathy (IMNM) [also known as necrotizing autoimmune myopathy (NAM)], and Polymyositis (PM).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35927155",
"endSection": "abstract"
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{
"offsetInBeginSection": 172,
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"text": "We present evidence based on recently emerged clinical, histologic, immunopathologic, demographic and therapeutic observations that these myopathies comprise three major and distinct groups: polymyositis (PM), dermatomyositis (DM), and inclusion-body myositis (IBM).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/1423335",
"endSection": "abstract"
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{
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"text": "The inflammatory myopathies, including dermatomyositis, inclusion body myositis, and polymyositis, are poorly understood autoimmune diseases affecting skeletal muscle.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18351525",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "There are five major types of idiopathic inflammatory myopathies: dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), autoimmune necrotizing myopathy (AINM) and inflammatory myopathies associated with connective tissue diseases (overlap myositis).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19282137",
"endSection": "abstract"
},
{
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"text": "Idiopathic inflammatory myopathy (IIM) is the umbrella term including dermatomyositis (DM), polymyositis (PM), overlap myositis (OM), sporadic inclusion body myositis (IBM) and necrotising autoimmune myopathy (NAM), also known as immune-mediated necrotising myopathy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34155760",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "Idiopathic inflammatory myopathies (IIMs), except for sporadic inclusion body myositis (sIBM), present with subacute symmetrical weakness of the limb girdle muscles, an elevated serum creatine kinase activity, and inflammatory cells in the muscle biopsy (necrotizing autoimmune myopathy being an exception).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24365315",
"endSection": "abstract"
},
{
"offsetInBeginSection": 428,
"offsetInEndSection": 658,
"text": "Five main types of inflammatory myopathies are now widely recognised: dermatomyositis, immune-mediated necrotising myopathy, sporadic inclusion-body myositis, overlap myositis (including antisynthetase syndrome), and polymyositis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30129477",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 140,
"text": "PURPOSE OF REVIEW: The inflammatory myopathies include polymyositis, dermatomyositis, necrotizing autoimmune myopathy (NAM), and inclusion b",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21799409",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 196,
"text": "Idiopathic inflammatory myopathies (IM), including dermatomyositis (DM) and polymyositis (PM), are a group of systemic rheumatologic diseases of unknown etiology characterized by chronic myositis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16769661",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 287,
"text": "Idiopathic inflammatory myopathies are a group of heterogeneous striated muscle acquired autoimmune diseases, characterized by progressive symmetrical muscle weakness, elevated serum levels of muscle enzymes, electromyographic abnormalities and inflammatory infiltrates on muscle biopsy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21794659",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 270,
"text": "Inflammatory myopathies are a group of immune-mediated muscle disorders comprising dermatomyositis; polymyositis; overlap myositis, including antisynthetase syndromes and nonspecific myositis, immune-mediated necrotizing myopathies, and sporadic inclusion body myositis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32703475",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 164,
"text": "The idiopathic inflammatory myopathies are a group of rare disorders including polymyositis (PM), dermatomyositis (DM), and autoimmune necrotizing myopathies (NMs).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23117947",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "OBJECTIVE: The molecular basis of inflammatory myopathies such as dermatomyositis (DM), polymyositis, and inclusion body myositis, which share the characteristics of chronic muscle inflammation and skeletal muscle wasting, are poorly understood",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24757153",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 121,
"text": "The idiopathic inflammatory myopathies include polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22870499",
"endSection": "abstract"
},
{
"offsetInBeginSection": 515,
"offsetInEndSection": 665,
"text": " the common inflammatory myopathies, i.e. dermatomyositis, polymyositis, and sporadic inclusion body myositis, and to describe the specific spectrum o",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33554607",
"endSection": "abstract"
}
] |
63eef8d6f36125a42600000f | L9LS was developed for which disease? | L9LS was developed for malaria. | [
"36260982",
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] | factoid | [
{
"offsetInBeginSection": 165,
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"text": "METHODS: We conducted a phase 1 clinical trial to assess the safety and pharmacokinetics of L9LS, a next-generation antimalarial monoclonal antibody, and its protective efficacy against controlled human malaria infection in healthy adults who had never had malaria or received a vaccine for malaria.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35921449",
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{
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"text": "CONCLUSIONS: In this small trial, L9LS administered intravenously or subcutaneously protected recipients against malaria after controlled infection, without evident safety concerns.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/35921449",
"endSection": "abstract"
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{
"offsetInBeginSection": 0,
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"text": "L9LS, a potent and safe antimalarial monoclonal antibody, demonstrated 88% protective efficacy against infection in a phase 1 trial in healthy adults.1 ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36260982",
"endSection": "abstract"
}
] |
6419d79c690f196b5100003b | Does iron regulate oligodendrocyte maturation? | Yes, iron availability is essential for normal oligodendrocyte maturation as the oligodendrocytes depend on iron for their proper development, differentiation, and myelination. | [
"7768202",
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"34460113",
"11518519",
"25206366",
"31162719",
"28092084",
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] | yesno | [
{
"offsetInBeginSection": 0,
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"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": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31162719",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 96,
"text": "Ontogenetic oligodendrocyte maturation through gestational iron deprivation: The road not taken.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31162719",
"endSection": "title"
},
{
"offsetInBeginSection": 1444,
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"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,
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"text": " the current results provide further evidence of dID impact on myelination, keeping OL away from the maturational path.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31162719",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 118,
"text": "Impaired Postnatal Myelination in a Conditional Knockout Mouse for the Ferritin Heavy Chain in Oligodendroglial Cells.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32868463",
"endSection": "title"
},
{
"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": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32868463",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 104,
"text": "H-ferritin expression in astrocytes is necessary for proper oligodendrocyte development and myelination.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34460113",
"endSection": "title"
},
{
"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": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34460113",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 107,
"text": "Iron modulates the differentiation of a distinct population of glial precursor cells into oligodendrocytes.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11518519",
"endSection": "title"
},
{
"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/25206366",
"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/11518519",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "When disrupted, iron homeostasis negatively impacts oligodendrocyte (OLG) differentiation and impairs myelination.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28092084",
"endSection": "abstract"
},
{
"offsetInBeginSection": 355,
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"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/11518519",
"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/31162719",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"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/25206366",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1479,
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"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/34460113",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1076,
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"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/26398942",
"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.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7768202",
"endSection": "abstract"
}
] |
644ea46d57b1c7a31500007c | What are genome-wide association studies (GWAS)? | Each human has slightly different DNA sequences, called genetic variants, which make each of us unique. Genome-wide association studies (GWAS) provide an important avenue for undertaking an agnostic evaluation of the association between common genetic variants and the risk of disease. Recent advances in our understanding of human genetic variation and the technology to measure such variation have made GWAS feasible. Over the past few years, a multitude of GWAS has identified and replicated many associated variants. These associations could reveal the molecular mechanisms altered in common complex diseases and result in the identification of novel drug targets. | [
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"text": "Each human, when born, has slightly different DNA sequences, which make each of us unique. The variations in DNA sequences are called genetic variants. The primary aim of genome-wide association study (GWAS) is to detect associations between genetic variants and human phenotypes.",
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"text": "Genome-wide association studies (GWAS) have successfully mapped thousands of loci associated with complex traits. These associations could reveal the molecular mechanisms altered in common complex diseases and result in the identification of novel drug targets.",
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"text": "Genome-wide association studies (GWAS) provide an important avenue for undertaking an agnostic evaluation of the association between common genetic variants and risk of disease. Recent advances in our understanding of human genetic variation and the technology to measure such variation have made GWAS feasible. Over the past few years a multitude of GWAS have identified and replicated many associated variants. These findings are enriching our knowledge about the genetic basis of disease and leading some to advocate using GWA study results for genetic testing. For many of the GWA study results, however, the underlying mechanisms remain unclear and the findings explain only a limited amount of heritability.",
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"text": "Genome-wide association study (GWAS) is a powerful study design to identify genetic variants of a trait and, in particular, detect the association between common single-nucleotide polymorphisms (SNPs) and common human diseases such as heart disease, inflammatory bowel disease, type 2 diabetes, and psychiatric disorders.",
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"text": "Genome-wide association studies (GWAS) involve testing genetic variants across the genomes of many individuals to identify genotype-phenotype associations.",
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"text": "Genome-wide association (GWA) studies are best understood as an extension of candidate gene association studies, scaled up to cover hundreds of thousands of markers across the genome in samples usually of several thousand cases and controls.",
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"text": "Genome-wide association studies (GWAS) provide an important avenue for undertaking an agnostic evaluation of the association between common genetic variants and risk of disease.",
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"text": "GWAS are an important discovery tool that require extensive follow-up to map each region, investigate the biological mechanism underpinning the association and eventually test the optimal markers for assessing risk for a disease or its outcome, such as in pharmacogenomics, the study of the effect of genetic variation on pharmacological interventions.",
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"text": "Genome-wide association studies (GWAS) are a powerful tool for investigators to examine the human genome to detect genetic risk factors, reveal the genetic architecture of diseases and open up new opportunities for treatment and prevention.",
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"text": "GWAS have revolutionized the field of complex disease genetics over the past decade, providing numerous compelling associations for human complex traits and diseases.",
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"text": "Genome-wide association studies (GWAS) have developed into a powerful and ubiquitous tool for the investigation of complex traits.",
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"text": "Genome-wide association studies (GWAS) scan the genome to search associations of SNPs with specific traits, like cancer.",
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"text": "Genome-wide association studies (GWAS) evaluate associations between genetic variants and a trait or disease of interest free of prior biological hypotheses.",
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"text": "Genome-Wide Association studies (GWAS) offer an unbiased means to understand the genetic basis of traits by identifying single nucleotide polymorphisms (SNPs) linked to causal variants of complex phenotypes.",
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"text": "Genome-wide association studies (GWAS) have provided valuable insights into the genetic basis of complex traits, discovering >6000 variants associated with >500 quantitative traits and common complex diseases in humans.",
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"text": "Genome-wide association studies (GWAS) provide a hypothesis-free approach to discover genetic variants contributing to the risk of a certain disease or disease-related trait.",
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"text": "Genome-wide association studies (GWAS) are a powerful tool for pathogenetic studies of complex diseases.",
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"text": "Genome-wide association studies (GWAS) have successfully identified many genetic variants associated with complex traits.",
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"text": "Genome-wide association studies (GWAS) and sequencing studies are routinely conducted for the identification of genetic variants that are associated with complex traits.",
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"text": "Genome-wide association studies (GWAS) have been highly informative in discovering disease-associated loci but are not designed to capture all structural variations in the human genome.",
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"text": "Genome-wide association studies (GWAS) detect common genetic variants associated with complex disorders.",
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"text": "Genome-wide association studies (GWASs) have identified abundant genetic susceptibility loci, GWAS of small sample size are far less from meeting the previous expectations due to low statistical power and false positive results.",
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"text": "Genome-wide association studies (GWAS) allow the finding of genetic variants associated with several traits.",
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"text": "Genome-wide association studies (GWAS) play a key role in discovering genetic variations that may contribute towards disease vulnerability.",
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"text": "Genome-wide association studies (GWAS) are a valuable approach to identify single nucleotide polymorphisms (SNPs) associated with a phenotype of interest.",
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"text": "Genome-wide association studies (GWAS) are performed to find associations between genetic variants (i.e. single-nucleotide polymorphisms) and diseases. ",
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"text": "Genome-Wide Association Studies (GWAS) refer to observational studies of a genome-wide set of genetic variants across many individuals to see if any genetic variants are associated with a certain trait.",
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"text": "Genome-wide association studies (GWAS) have identified thousands of susceptibility variants, although most have been associated with small individual risk estimates that offer little predictive value. ",
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"text": "Genome-Wide Association Studies (GWAS) are used to identify statistically significant genetic variants in case-control studies. The main objective is to find single nucleotide polymorphisms (SNPs) that influence a particular phenotype (i.e., disease trait).",
"beginSection": "abstract",
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] |
64121f44201352f04a000037 | What does PROTACs stand for? | PROTACs are proteolysis targeting chimeras. | [
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"text": "Design and synthesis of proteolysis targeting chimeras (PROTACs) as an EGFR degrader based on CO-1686.",
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"text": "The emerging technology proteolysis targeting chimera (PROTAC) could be an alternative strategy to overcome these problems. ",
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6451029f57b1c7a315000094 | What is the incidence of Leigh syndrome? | The incidence of Leigh syndrome ranges from 1:40,000 to 1:77,000 liveborn infants annually. | [
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"text": "Leigh syndrome (LS), or subacute necrotizing encephalomyelopathy, is the most common childhood mitochondrial encephalopathy, accounting for more than 50% of cases in this age group. Its estimated incidence is 1:40,000 - 1:77,000 liveborn infants a year.",
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"text": "Its estimated incidence is 1:40,000 - 1:77,000 liveborn infants a year.",
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"text": "Leigh syndrome occurs with an estimated frequency of 1:77,000-1:34,000 live births.",
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"text": "Leigh syndrome is a neurodegenerative disorder with an incidence of 1 : 40,000 live births.",
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"text": "Leigh syndrome is a progressive neurodegenerative disorder, affecting 1 in 40,000 live births.",
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"text": "It has an incidence of 1 in 77,000 live births worldwide with poor prognosis.",
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64041260201352f04a000013 | What are features of the The Trauma Triad of Death? | The trauma triad of death: hypothermia, acidosis, and coagulopathy. | [
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"text": "It is a serious threat to prehospital patients and especially injured patients, since it can induce a vicious cycle of the synergistic effects of hypothermia, acidosis and coagulopathy; referred to as the trauma triad of death. ",
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"text": "The trauma triad of death: hypothermia, acidosis, and coagulopathy.",
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"text": "The \"new\" golden hour may well be the time in the operating room before the patient reaches the physiologic limit, defined as the onset of the triad: hypothermia, acidosis and coagulopathy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10347389",
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6431f74057b1c7a31500001a | What is a glossectomy? | A glossectomy involves removing part or all of the tongue. | [
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"text": "Surgeons treating advanced carcinoma of the tongue with total glossectomy face many conflicts in view of the morbidity and poor functional and survival outcomes following surgery. I",
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"text": "Ablation of a tongue tumor leaves defects that can be either surgically reconstructed or replaced by a prosthesis to help recreate normalcy and balance in the oral cavity. This clinical report describes a prosthetic design to rehabilitate a patient after a total glossectomy.",
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"text": "Wide variation in negotiated surgical prices was identified. Across-center ratios ranged from 6.2 (partial glossectomy without primary closure) to 22.8 (excision of tongue lesion without closure).",
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"text": "The aim of this study was to test the non-inferiority of the contralateral submental island flap (CSIF) compared with primary closure (PC) regarding local recurrence after partial glossectomy in patients with oral tongue squamous cell carcinoma (OTSCC). T",
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"text": "Locally advanced tongue or tongue base cancer is recommended to be treated by radical resection that is usually detrimental to physiological functions. This study reports the efficacy and treatment outcome of the patients who had received total glossectomy and laryngeal suspension without lip-split mandibulotomy ",
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"text": "To evaluate potential interactions and compensatory mechanisms of subjectively impaired taste function with ortho- and retronasal olfaction after glossectomy.",
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"text": " In this cross-sectional pilot study, chemosensory functions were assessed in 25 patients with tongue carcinomas after glossectomy.",
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"text": "Glossectomy, or tongue reduction, is not commonly performed in Japan even though the proportion of patients with Class III skeletal pattern is higher among Japanese people than among Caucasians.",
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"text": "UNLABELLED: Total glossectomy is the procedure for entire removal of the tongue, practice considered as one of the most mutilating possible done in head and n",
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"text": "UNLABELLED: Total glossectomy is the procedure for entire removal of the tongue, practice considered as one of the most mutilating possible done in head and neck surgery",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12053512",
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644eb55457b1c7a315000081 | What are some examples of epigenetic modifications? | Epigenetic modifications are molecular changes that affect gene expression without altering the underlying DNA sequence. Some major examples of epigenetic modifications include DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA alterations. DNA methylation involves the addition of a methyl group to cytosine bases in the DNA molecule, often leading to gene silencing. Histone modifications encompass various chemical changes to histone proteins, such as methylation and acetylation, which can either activate or repress gene expression depending on the specific modification and its location. Chromatin remodeling refers to structural changes in chromatin that influence the accessibility of DNA to transcription factors and other regulatory proteins. Non-coding RNA alterations involve small RNA molecules like microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) that regulate gene expression post-transcriptionally or through other mechanisms. These epigenetic modifications play crucial roles in various biological processes and have been implicated in the development of numerous diseases, including cardiovascular diseases and cancer. | [
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"text": "Epigenetic modifications may constitute changes in DNA methylation, histone modifications (methylation, acetylation etc), and changes in non-coding RNA, leading to an altered gene expression profile.",
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"text": "Epigenetic modifications viz. DNA methylation, histone modifications, and RNA-based alterations play a crucial role in the development of cardiovascular diseases.",
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"text": "Major epigenetic modifications are DNA methylation, histone modification, chromatin remodeling as well as the noncoding RNAs.",
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"text": "Eukaryotic gene expression is regulated not only by genomic enhancers and promoters, but also by covalent modifications added to both chromatin and RNAs. Whereas cellular gene expression may be either enhanced or inhibited by specific epigenetic modifications deposited on histones (in particular, histone H3), these epigenetic modifications can also repress viral gene expression, potentially functioning as a potent antiviral innate immune response in DNA virus-infected cells.",
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"text": "Examples of epigenetic control are DNA methylation, histone deacetylation and mi-RNA expression.",
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"text": "These modifications are dubbed as \"epigenetic modifications\" and include, among others, histone modifications, DNA methylation, and small RNAs.",
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"text": "Epigenetic changes are defined as inherited modifications that are not present in DNA sequence.",
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"text": "Examples of such modifications include DNA methylation, histone modifications, noncoding RNAs, and chromatin architecture.",
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"text": "DNA methylation and histone modifications, for example, are capable of spatial and temporal regulation of expression-with several studies demonstrating that these epigenetic marks are heritable.",
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"text": "DNA methylation and histone modifications such as methylation, acetylation, and phosphorylation, are two types of epigenetic modifications that alter gene expression.",
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"text": "In the present review we discuss three prominent epigenetic modifications, DNA methylation, histone methylation/acetylation, and the effects of chromatin remodeling complexes.",
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"text": "In the current era of epigenetics research, we have observed many examples of epigenetic modifications, like histone modification and DNA methylation, in various fatal diseases.",
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"text": "Epigenetic modifications, such as DNA methylation and histone modification, result in heritable changes in gene expression without changing the DNA sequence.",
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"text": "DNA methylation has been characterized as the representative example of epigenetic modifications and implicated in numerous biological processes, such as genomic imprinting and X chromosome inactivation.",
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"text": "Methylation and histone acetylation are two of the most well-studied examples of the epigenetic modifications that occur on histone proteins.",
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"text": "One example of epigenetic factors is DNA methylation, which prevents certain genes from being expressed.",
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"text": "DNA methylation is the type of epigenetic modification that alters gene expression without modifying gene sequence.",
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"text": "Epigenetic modifications are chromosome-bound, heritable changes to the genome that do not affect the DNA sequence, and can include DNA methylation, histone modification, and RNA processing.",
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"text": "Epigenetic alterations such as DNA methylation and histone modification are essential for chromatin remodeling and regulation of gene expression including miRNAs.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/23056006",
"endSection": "abstract"
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{
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"text": "This review summarises the main epigenetic modifications in mammals, especially DNA methylation, histone modifications, and ncRNA.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35052371",
"endSection": "abstract"
}
] |
6432f5f257b1c7a31500001c | What does Zanubrutinib inhibit? | Zanubrutinib is a Bruton tyrosine kinase inhibitor. | [
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{
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"text": "In the United States, zanubrutinib, a next-generation BTK inhibitor, has been approved for treating adults with mantle cell lymphoma who have received at least one prior therapy, for adults with Waldenström macroglobulinemia, and for adults with relapsed or refractory marginal zone lymphoma who have received at least one anti-CD20-based therapy. B",
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{
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"text": "To reduce these side effects, zanubrutinib, a next-generation BTK inhibitor, was designed to block BTK more specifically than ibrutinib.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35651781",
"endSection": "abstract"
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] |
6450f02257b1c7a315000091 | Which are the types of Friedreich's Ataxia based on onset age? | The most common type of FRDA is early-onset which has an average age of onset between 10 to 30 years old.
Then we have mid-life-onset at around 40 years old. And lastly, there’s very-late Onset at over 50 years old. | [
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"text": "Friedreich's ataxia is classically considered a disease with onset in the first or second decade. However, late-onset (age of onset 25-39 years) and very-late-onset (age of onset >40 years) forms do occur rarely.",
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"text": "and Friedreich's ataxia is heterogeneous. Late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia appear to belong to the same clinical and molecular continuum and should be considered togeth",
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"text": " age of 25. Rare variants have been described, such as late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia, occurring after 25 and 40 years, r",
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"text": "spectively. We describe the clinical, functional, and molecular findings from a large series of late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia and compare them with typical-onset Friedreich's ataxia.METHODS: Phenotypic and genotypic comparison of 44 late-onset Friedreich's ataxia, 30 very late-onset Friedreich's ataxia, and 180 typical Friedreich's ataxia was undertaken.RESULTS: Delayed-onset Friedreich's ataxia (late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia) had less frequently dysarthria, abolished tendon reflexes, extensor plantar reflexes, weakness, amyotrophy, ganglionopathy, cerebellar atrophy, scoliosis, and cardiomyopathy than typical-onset Friedreich's ataxia, along with less severe functional disability and shorter GAA expansion on t",
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"text": "Very late-onset Friedreich's ataxia (VLOFA) is characterized by symptomatic onset after 40 years of age and, usually, a benign phenotype.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/16092110",
"endSection": "abstract"
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{
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"text": "ing Scale and EQ-5D. The Friedreich's ataxia cohort was subdivided into three groups: early disease onset (≤14 years), intermediate onset (15-24 years), and late onset (≥25 years), which were compared for clinical characteristics ",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/25566998",
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"text": "he Friedreich's ataxia cohort was subdivided into three groups: early disease onset (≤14 years), intermediate onset (15-24 years), and late onset (≥25 years), which were compared for clinical characteristics and outcome measures. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25566998",
"endSection": "abstract"
}
] |
6402bd7c201352f04a000006 | Which drugs were tested in the FAKTION trial? | The FAKTION trial investigated whether the addition of capivasertib to fulvestrant improved progression-free survival in patients with aromatase inhibitor-resistant advanced breast cancer. | [
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"text": "Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION): overall survival, updated progression-free survival, and expanded biomarker analysis from a randomised, phase 2 trial.",
"beginSection": "title",
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"text": "INTERPRETATION: Updated FAKTION data showed that capivasertib addition to fulvestrant extends the survival of participants with aromatase inhibitor-resistant ER-positive, HER2-negative advanced breast cancer. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35671774",
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"text": "Similarly, there was an overall survival benefit in the FAKTION study with capivasertib. ",
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"text": "Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive breast cancer (FAKTION): a multicentre, randomised, controlled, phase 2 trial.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32035020",
"endSection": "title"
},
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"text": "The FAKTION trial investigated whether the addition of capivasertib to fulvestrant improved progression-free survival in patients with aromatase inhibitor-resistant advanced breast cancer.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32035020",
"endSection": "abstract"
}
] |
64184949690f196b51000039 | Explain gene knock-down. | Gene knock-down refers to the reduction of the expression of a specific gene using various techniques such as RNA interference (RNAi). This method can be used to study gene function, treat genetic diseases and disrupt undesired genetic traits | [
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{
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"text": "Gene knock-down technology using antisense molecules has many applications for studying gene function, disrupting undesirable genetic traits, as well as providing effective therapy for a number of viral diseases. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14961259",
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"text": "The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene.",
"beginSection": "abstract",
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"text": "Short interfering RNAs (siRNAs) have been gaining popularity as the gene knock-down tool of choice by many researchers because of the clean nature of their workings as well as the technical simplicity and cost efficiency in their applications. ",
"beginSection": "abstract",
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"text": "Gene knock down by RNAi is a highly effective approach to silence gene expression in experimental as well as therapeutic settings.",
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"endSection": "abstract"
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"text": "gene silencing, or gene expression down-regulation is the process whereby a double-stranded RNA (dsRNA) induces the homology-dependent degradation of cognate messenger RNA (mRNA).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16509424",
"endSection": "abstract"
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644ea41957b1c7a31500007b | What are the necessary steps for the transition from a precursor mRNA to a mature
mRNA? | The transition from precursor mRNA (pre-mRNA) to mature mRNA involves several critical processing steps. Firstly, the 5'-end of the pre-mRNA undergoes capping, which helps protect the transcript from degradation and facilitates translation initiation. Next, RNA splicing occurs, where introns are removed and exons are joined together to generate a continuous coding sequence. This process can create diverse mature mRNA molecules from a limited number of genes through alternative splicing events that include or exclude specific introns and exons. Finally, the 3'-end of the pre-mRNA undergoes cleavage and polyadenylation, adding a poly(A) tail that enhances stability and promotes nuclear export. Once these processing steps are complete, the mature mRNA is transported from the nucleus to the cytoplasm for translation into proteins by ribosomes. | [
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"text": "RNA splicing is a critical step in the maturation of precursor mRNA (pre-mRNA) by removing introns and exons. The combination of inclusion and exclusion of introns and exons in pre-mRNA can generate vast diversity in mature mRNA from a limited number of genes.",
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"text": "Transport of messenger RNA (mRNA) from the nucleus to the cytoplasm is an essential step of eukaryotic gene expression. In the cell nucleus, a precursor mRNA undergoes a series of processing steps, including capping at the 5' ends, splicing and cleavage/polyadenylation at the 3' ends.",
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"text": "Messenger RNA precursors (pre-mRNAs) are produced as the nascent transcripts of RNA polymerase II (Pol II) in eukaryotes and must undergo extensive maturational processing, including 5'-end capping, splicing, and 3'-end cleavage and polyadenylation.",
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"text": "The cellular transformation of a precursor mRNA (pre-mRNA) into its mature or functional form proceeds by way of a splicing reaction, in which the exons are ligated to form the mature linear RNA and the introns are excised as branched or lariat RNAs.",
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"text": "In eukaryotes, pre-messenger RNA (pre-mRNA) cleavage and polyadenylation is one of the necessary processing steps that produce a mature and functional mRNA.",
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"text": "In the cell nucleus, a precursor mRNA undergoes a series of processing steps, including capping at the 5' ends, splicing and cleavage/polyadenylation at the 3' ends.",
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"text": "The three most prevalent processing steps are the capping reaction at the 5'-end, the removal of intervening sequences by splicing, and the formation of poly (A)-tails at the 3'-end of the message by polyadenylation.",
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"text": "Precursor mRNA (pre-mRNA) splicing is a critical step in gene expression that results in the removal of intronic sequences from immature mRNA, leading to the production of mature mRNA that can be translated into protein.",
"beginSection": "abstract",
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"text": "Spliceosome and 3'-end processing complexes are necessary for the precursor mRNA (pre-mRNA) maturation.",
"beginSection": "abstract",
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"text": "Precursor messenger RNA (pre-mRNA) splicing is a fundamental step in eukaryotic gene expression that systematically removes non-coding regions (introns) and ligates coding regions (exons) into a continuous message (mature mRNA).",
"beginSection": "abstract",
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"text": "RNA splicing is a critical step in the maturation of precursor mRNA (pre-mRNA) by removing introns and exons.",
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"text": "In trypanosomatid parasites, spliced leader (SL) trans splicing is an essential nuclear mRNA maturation step which caps mRNAs posttranscriptionally and, in conjunction with polyadenylation, resolves individual mRNAs from polycistronic precursors.",
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"text": "The process of pre-mRNA cleavage and polyadenylation, and its relationship with RNA splicing and translation, have been extensively studied due to its importance in vivo.",
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"text": "Regulation on pre-mRNA cleavage and polyadenylation affects other processes such as mRNA translocation, stability, and translation.",
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"text": "The 3' ends of most eukaryotic messenger RNAs must undergo a maturation step that includes an endonuc-leolytic cleavage followed by addition of a polyadenylate tail.",
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"text": "mRNA polyadenylation and pre-mRNA splicing are two essential steps for the maturation of most human mRNAs.",
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"text": "Pre-mRNA (precursor mRNA) splicing is a key step in cellular gene expression where introns are excised and exons are ligated together to produce mature mRNA.",
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"text": "The process of removing intronic sequences from a precursor to messenger RNA (pre-mRNA) to yield a mature mRNA transcript via splicing is an integral step in eukaryotic gene expression.",
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"text": "Eukaryotic mRNA synthesis is a complex biochemical process requiring transcription of a DNA template into a precursor RNA by the multi-subunit enzyme RNA polymerase II and co-transcriptional capping and splicing of the precursor RNA to form the mature mRNA.",
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"text": "With this step, a pre-messenger RNA is processed and polyadenylated, giving rise to a mature mRNA bearing the characteristic poly(A) tract.",
"beginSection": "abstract",
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6440420857b1c7a315000050 | What is Apretude used for? | Cabotegravir extended-release (ER) injectable suspension (Apretude™) is the first long-acting injectable option to be approved for HIV-1 pre-exposure prophylaxis (PrEP). | [
"36255686"
] | factoid | [
{
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"text": "Cabotegravir Extended-Release Injectable Suspension: A Review in HIV-1 Pre-Exposure Prophylaxis.",
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"text": "Cabotegravir extended-release (ER) injectable suspension (Apretude™) is the first long-acting injectable option to be approved for HIV-1 pre-exposure prophylaxis (PrEP). ",
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"text": "Cabotegravir ER injectable suspension is indicated in the USA for PrEP to reduce the risk of sexually acquired HIV-1 infection in at-risk adults and adolescents weighing ≥ 35 kg who have a negative HIV-1 test prior to initiation.",
"beginSection": "abstract",
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"text": "With its convenient, less-frequent dosing schedule and its long-acting formulation enabling intramuscular administration, cabotegravir ER injectable suspension represents a novel and efficacious alternative to daily oral PrEP.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36255686",
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}
] |
64463a5057b1c7a315000064 | What are the types of Spinal Muscular Atrophy? | The types of Spinal Muscular Atrophy are: SMA type 1, SMA type 2, SMA type 3, SMA type 4, X-linked SMA and SMA with respiratory distress. | [
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"text": "SMA with a clinical diagnosis of SMA types 1, 2, or 3",
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"text": " In phase 2/3 clinical trials, risdiplam significantly improved motor function in infants with SMA type 1 and in patients aged 2-25 years with SMA types 2 or 3.",
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"text": "Adulthood-onset SMA (SMA type 4) is rare, with few isolated cases reported.",
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"text": "Twenty patients with SMA type 4 were identified in a Brazilian cohort of 227 patients with SMA. ",
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"text": "This study represents the largest cohort of patients with SMA type 4 and provides functional, genetic, radiological and neurophysiological features ",
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"text": "Adolescent and adult patients with SMA types 3 and 4",
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"text": "We found no evidence for the contribution of motor unit and capillary recruitment capacity of the upper arm muscles in adolescent and adult patients with SMA types 3 and 4 as primary limiting factors to premature fatigue during execution of a maximal arm-cycling task.",
"beginSection": "abstract",
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"text": "We report a long-term follow-up in adolescent and adult patients with SMA types 1 and 2.",
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"text": "Nusinersen-treated patients with SMA types 1 and 2 between 2017 and 2022 were retrospectively reviewed. ",
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{
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"text": "Seven patients with SMA (type 1, 1; type 2, 6) with a median age of 23 (range, 12-40)years were treated with nusinersen for 3.55 (1.78-4.53)years.",
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"text": "On October 1st, 666 patients have been enrolled (357 children and 309 adults) by 44 out of 51 open centers of the national network (FILNEMUS) with: 150 type 1 (22%); 278 type 2 (42%), 232 type 3 (35%) and 4 type 4 (1%) respectively.",
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"text": "The identification of the underlying gene defects for familial ALS, spinal muscular atrophy (SMA), and spinal muscular atrophy with respiratory distress (SMARD) has pointed to distinct pathophysiological mechanisms that are responsible for the various forms of the disease. ",
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"text": "Interestingly, UBA1 mutations can also cause infantile-onset X-linked spinal muscular atrophy (XL-SMA).",
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"endSection": "abstract"
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"text": "The mutation identified here and the XL-SMA causative mutations were shown to affect amino acids positioned in the vicinity of UBA1's ATP binding site and to cause structural changes.",
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"text": "The contribution of this same gene to the etiology of XL-SMA is discussed.",
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"text": "Type I spinal muscular atrophy has been subdivided into 3 groups: - type IA, the clinical signs of which set in between birth and 15 days of life with sudden severe motor impairment, sucking-swallowing disorders attesting to bulbar involvement, respiratory distress.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33357591",
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{
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"text": "The childhood form of the spinal muscular atrophy (SMA) is classically subdivided into three groups on the basis of a combination of age of onset, milestones of development and age of survival: acute Werdning-Hoffmann (type I), intermediate Werdnig-Hoffmann (type II) and Kugelberg-Welander disease (type III).",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/1389561",
"endSection": "abstract"
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{
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"text": "Spinal muscular atrophy type 3 (SMA3), also called Kugelberg-Welander SMA, typically presents with muscle fatigue, slowly progressive weakness and atrophy of lower limbs once they have already acquired independent ambulation.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33357593",
"endSection": "abstract"
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{
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"text": "Spinal muscular atrophy, X-linked 2 (SMAX2) is a rare type of spinal muscular atrophy characterized by muscle weakness, hypotonia, areflexia, myopathic face, tongue fibrillations, contractures, bone fractures, and cryptorchidism.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35707597",
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"text": "SMA is classified in three clinical types, SMA I, SMA II, and SMA III, based on the severity of the symptoms and the age of onset.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/16865356",
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{
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"text": "ring seated upper limb tasks in patients with spinal muscular atrophy types 2 and 3.DESIGN: Seventeen persons with spinal muscular atrophy and 15 heal",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/31274514",
"endSection": "abstract"
},
{
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"offsetInEndSection": 283,
"text": "tional ability in children with non-ambulant spinal muscular atrophy types 2 and 3 in a longitudinal multi-center clinical trial. This study assessed ",
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"endSection": "abstract"
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{
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"text": "BACKGROUND & AIMS: Different neuromuscular functional domains in types I and II Spinal Muscular Atrophy (SMAI and SMAII) could lead to differences in body composition (BC) and resting energy expenditure (REE)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27890489",
"endSection": "abstract"
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] |
63eef4f5f36125a42600000b | What disease is treated with Ublituximab? | Ublituximab is being tested for multiple sclerosis. | [
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"text": "Outcomes of Ublituximab compared to Teriflunomide for relapsing multiple sclerosis: A meta-analysis.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35779372",
"endSection": "title"
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"text": "Ublituximab is an anti-CD20 antibody that immunomodulates B-cells for relapsing multiple sclerosis (MS).",
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"text": " In the second part of the review, we summarize medications that have targeted B cells in patients with MS and their current position in the therapeutic armamentarium based on clinical trials and real-world data. Covered therapeutic strategies include the targeting of surface molecules such as CD20 (rituximab, ocrelizumab, ofatumumab, ublituximab) and CD19 (inebilizumab), and molecules necessary for B-cell activation such as B cell activating factor (BAFF) (belimumab) and Bruton's Tyrosine Kinase (BTK) (evobrutinib).",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/35570581",
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"text": "Ublituximab versus Teriflunomide in Relapsing Multiple Sclerosis.",
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"endSection": "title"
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"text": "Ublituximab is being evaluated for the treatment of relapsing multiple sclerosis.",
"beginSection": "abstract",
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"text": "CONCLUSIONS: Among participants with relapsing multiple sclerosis, ublituximab resulted in lower annualized relapse rates and fewer brain lesions on MRI than teriflunomide over a period of 96 weeks but did not result in a significantly lower risk of worsening of disability. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36001711",
"endSection": "abstract"
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"text": "The glycoengineered antibody ublituximab is the next anti-CD20 therapy about to be approved. ",
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"endSection": "abstract"
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"text": "On the other hand, the anti-CD52 monoclonal antibody alemtuzumab and the anti-CD20 monoclonal antibodies rituximab, ocrelizumab, ofatumumab, and ublituximab work via eliminating selected pathogenic cell populations. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35378683",
"endSection": "abstract"
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] |
640c842f201352f04a000025 | What is Palmar Erythema? | Palmar erythema refers to symmetrical, reddish discoloration on the palms of the hands, often accompanied by slight warmth but no scaling or thickening of the skin. It can be caused by various conditions including autoimmune diseases such as Graves' disease. | [
"3830522",
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"text": "Palmar erythema (\"liver palms\") was seen in 32/100 consecutive patients with classical rheumatoid arthritis and in 10/100 patients with various other internal diseases (p less than 0.001",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/3830522",
"endSection": "abstract"
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"text": "Palmar erythema commonly presents as symmetric, blanchable, slightly warm, nonscaling erythema, most frequently involving the thenar and hypothenar eminences of the palmar surface.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22474732",
"endSection": "abstract"
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"text": "Palmar erythema (\"liver palms\") was seen in 32/100 consecutive patients with classical rheumatoid arthritis and in 10/100 patients with various other internal diseases (p less than 0.001).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/3830522",
"endSection": "abstract"
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644efd5157b1c7a315000086 | Are epigenetic changes heritable? | Epigenetics is defined as heritable changes in gene expression that are, unlike mutations, not attributable to alterations in the sequence of DNA. The predominant epigenetic mechanisms are DNA methylation, modifications to chromatin, loss of imprinting, and non-coding RNA. These epigenetic programs may account for a significant fraction of the "missing heritability" problem that is observed in genome-wide association studies. | [
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"text": "Epigenetics is defined as heritable changes in gene expression that are, unlike mutations, not attributable to alterations in the sequence of DNA. The predominant epigenetic mechanisms are DNA methylation, modifications to chromatin, loss of imprinting and non-coding RNA.",
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"text": "Genome-wide association studies of complex physiological traits and diseases consistently found that associated genetic factors, such as allelic polymorphisms or DNA mutations, only explained a minority of the expected heritable fraction. This discrepancy is known as \"missing heritability\", and its underlying factors and molecular mechanisms are not established. Epigenetic programs may account for a significant fraction of the \"missing heritability.\" Epigenetic modifications, such as DNA methylation and chromatin assembly states, reflect the high plasticity of the genome and contribute to stably alter gene expression without modifying genomic DNA sequences.",
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"text": "Epigenetics is defined as heritable changes in gene expression that do not involve a change in DNA sequence.",
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"text": "Epigenetics is defined as mitotically and meiotically heritable changes in gene expression that do not involve a change in the DNA sequence.",
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"text": "Epigenetic changes refer to heritable changes that may modulate gene expression without affecting DNA sequence.",
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"text": "Epigenetic alterations, which, by definition, comprise mitotically and meiotically heritable changes in gene expression that are not caused by changes in the primary DNA sequence, are increasingly being recognized for their roles in carcinogenesis.",
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"text": "Unlike heritable genetic changes, which are always associated with mutations in gene sequence, heritable epigenetic changes can be associated with physical or chemical changes in molecules or only changes in the system.",
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"text": "Epigenetic alterations are defined as heritable changes in gene expression mediated through mechanisms other than alterations in the DNA sequence itself, including DNA promoter methylation and various histone covalent modifications.",
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"text": "Epigenetics refers to heritable phenotypic alterations in the absence of DNA sequence changes, and DNA methylation is one of the extensively studied epigenetic alterations.",
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"text": "Epigenetics is defined as heritable changes that affect gene expression without altering the DNA sequence.",
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"text": "Epigenetics refers to heritable changes in patterns of gene expression that occur without alterations in DNA sequence.",
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"text": "Epigenetic modifications are classified as heritable and reversible chemical modifications of chromatin that do not cause changes in DNA sequence.",
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"text": "Epigenetics is the study of changes in gene activity that can be transmitted through cell divisions but cannot be explained by changes in the DNA sequence.",
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"text": "First, some epigenetic states are transmitted intergenerationally and affect the phenotype of offspring.",
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"text": "One possible but largely unexplored explanation is that exposure to sublethal doses of insecticides may alter epigenetic patterns that are heritable.",
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"text": "DNA methylation is one such heritable epigenetic change, which is causally associated with the transcription regulation of many genes in the mammalian genome.",
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"text": "As a result, heritable epigenetic changes can include any that can alter a wave such as changes in form, midline, frequency, amplitude, or phase.",
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"text": "Epigenetics has been defined as 'a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence' and several epigenetic regulators are recurrently mutated in hematological malignancies.",
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"text": "Epigenetic alterations (epimutations) could thus contribute to heritable variation within populations and be subject to evolutionary processes such as natural selection and drift.",
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"text": "Some of these epigenetic changes appear to be heritable.",
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"text": " First, some epigenetic states are transmitted intergenerationally and affect the phenotype of offspring.",
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"text": " First, stress-induced methylation changes are common and are mostly heritable.",
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"text": "Epigenetic inheritance systems enable the environmentally induced phenotypes to be transmitted between generations.",
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"text": " Epigenetic changes enforced by various environmental and lifestyle factors lead to heritable modifications.",
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"text": " Transient epigenetic changes across the entire genome can influence metabolic outcomes and might or might not be heritable.",
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"text": " More interestingly, epigenetic changes are reversible heritable changes which pass through generations.",
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"text": " However, it is unclear whether the active changes mediated by variations in DNA methyltransferase activity are heritable.",
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"text": "Epigenetic modification refers to heritable changes in the genetic material without any changes in the nucleic acid sequence and results in heritable phenotypic changes.",
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"text": "Epigenetics refers to the heritable, but reversible, regulation of various biological functions mediated principally through changes in DNA methylation and chromatin structure derived from histone modification.",
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"text": "Although epigenetic modifications may contribute substantially to average risk, they will not contribute much to recurrence risk and heritability unless they persist on average for many generations.",
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"text": "Epigenetic processes, defined as heritable changes in gene expression that occur without changes to the DNA sequence, have emerged as a promising area of cardiovascular disease research.",
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"text": "Epigenetic changes can be defined as stable molecular alterations of a cellular phenotype such as the gene expression profile of a cell that are heritable during somatic cell divisions (and sometimes germ line transmissions) but do not involve changes of the DNA sequence itself.",
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"text": "Epigenetic modifications are heritable changes in gene expression not encoded by the DNA sequence.",
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"text": "Epigenetics is defined as the study of changes in gene function that are mitotically or meiotically heritable and do not lead to a change in DNA sequence.",
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"text": "Epigenetic mechanisms are heritable traits that are mediated by changes in a genetic locus that do not involve a modification at the nucleotide level.",
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"text": "ssion, notably during embryonic development. New research indicates that epigenetic factors are heritable, which is why paternal lifestyle may affect ",
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] |
6414c1d0690f196b51000004 | What is the treatment for trichotillomania? | Trichotillomania requires a comprehensive treatment plan and interdisciplinary approach. Behavioral therapy has been used with success in the treatment of trichotillomania, but not all patients are willing or able to comply with this treatment strategy. Pharmacotherapy can be necessary, especially in adolescents and adult patients. Options include tricyclic antidepressants, selective serotonin reuptake inhibitors, and glutamate-modulating agents. Glutamate-modulating agents such as N-acetylcysteine are a good first-line option due to significant benefits and low risk of side effects. | [
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"text": "Trichotillomania requires a comprehensive treatment plan and interdisciplinary approach. ",
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"text": "Behavioral therapy has been used with success in the treatment of trichotillomania, but not all patients are willing or able to comply with this treatment strategy. Pharmacotherapy can be necessary, especially in adolescents and adult patients. Options include tricyclic antidepressants, selective serotonin reuptake inhibitors, and glutamate-modulating agents. Glutamate-modulating agents such as N-acetylcysteine are a good first-line option due to significant benefits and low risk of side effects.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35118122",
"endSection": "abstract"
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64468b0757b1c7a315000070 | What is the cause of Oculopharyngeal Muscular Dystrophy (OPMD)? | The cause of Oculopharyngeal Muscular Dystrophy (OPMD) is an abnormal expansion of the alanine-encoding (GCN)n trinucleotide repeat in the exon 1 of the polyadenosine (poly[A]) binding protein nuclear 1 gene (11-18 repeats in OPMD instead of the normal 10 repeats). | [
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"text": "Oculopharyngeal muscular dystrophy (OPMD) is a late-onset intractable myopathy, characterized by slowly progressive ptosis, dysphagia, and proximal limb weakness. It is caused by the abnormal expansion of the alanine-encoding (GCN)n trinucleotide repeat in the exon 1 of the polyadenosine (poly[A]) binding protein nuclear 1 gene (11-18 repeats in OPMD instead of the normal 10 repeats).",
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"text": "A common cause of OPMD is the short expansion of a GCG or GCA trinucleotide repeat in PABPN1 gene.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/34225694",
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63f0494cf36125a426000028 | Which viral disease can be treated with EDP-938? | Respiratory Syncytial Virus can be treated with EDP-938. | [
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"text": "EDP-938, a Respiratory Syncytial Virus Inhibitor, in a Human Virus Challenge.",
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"text": "EDP-938, a nonfusion replication inhibitor of RSV, acts by modulating the viral nucleoprotein.",
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"text": "EDP-938, a new antiviral with inhibitory activity against the nucleoprotein of the respiratory syncytial virus.",
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"text": "EDP-938 has shown high efficacy against RSV. ",
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"text": "EDP-938, a novel nucleoprotein inhibitor of respiratory syncytial virus, demonstrates potent antiviral activities in vitro and in a non-human primate model.",
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"text": "EDP-938 is a novel non-fusion replication inhibitor of respiratory syncytial virus (RSV). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33720995",
"endSection": "abstract"
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] |
640ddbe9201352f04a000027 | What is the generic name for Imfinzi? | Durvalumab (Imfinzi) is used to treat locally advanced or metastatic cancer. | [
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"text": "durvalumab (Imfinzi™; AstraZeneca) is a fully human monoclonal antibody that blocks programmed cell death ligand-1 binding to its receptors (PD-1 and CD80),",
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"text": "durvalumab (IMFINZI®, Astra-Zeneca",
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"text": "durvalumab (Imfinzi®)",
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"text": "Intravenous durvalumab (Imfinzi™; AstraZeneca) is a fully human monoclonal antibody that blocks programmed cell death ligand-1 binding to its receptors (PD-1 and CD80), resulting in enhanced T-cell responses against cancer cells.",
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"text": "Durvalumab (IMFINZI®), a fully human monoclonal antibody against programmed cell death-ligand 1 (PD-L1), is approved for use in combination with etoposide and either carboplatin or cisplatin for the first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC).",
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"text": "Since 2011, the FDA-approved antibody drugs ipilimumab (Yervoy®), nivolumab (Opdivo®), pembrolizumab (Keytruda®), cemiplimab (Libtayo®), atezolizumab (Tecentriq®), durvalumab (Imfinzi®), and avelumab (Bavencio®), which block the immune checkpoint proteins, have brought about a significant breakthrough in the treatment of a wide range of cancers, as they can induce durable therapeutic responses.",
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"text": "Nevertheless, new therapies have emerged recently, among which PD1 immune checkpoint inhibitors (ICI), such as nivolumab (OPDIVO®, Bristol-Myers Squibb) and pembrolizumab (KEYTRUDA®, Merck & Co), or PD-L1 ICI, such as atezolizumab (TECENTRIQ®, Genentech), durvalumab (IMFINZI®, Astra-Zeneca), and avelumab (BAVENCIO®, EMD Serono).",
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"text": "titumor immunity. This unique mechanism of action in CD103+ DCs may contribute to clinical responses as AZD4635 is being evaluated in clinical trials with IMFINZI (durvalumab, αPD-L1) in patients with solid malignancies.CONCLUSION: We provide evidence implicating suppression of adaptive and innate immunity by adenosine as a mechanism",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32727810",
"endSection": "abstract"
}
] |
644e81fa57b1c7a315000079 | What are negative cell-cycle regulators that can cause cancer when mutated called? | Negative cell-cycle regulators that can cause cancer when mutated are commonly referred to as tumor suppressor genes. These genes play a crucial role in controlling cell division and preventing uncontrolled proliferation, which could lead to the formation of tumors. Tumor suppressor genes function by inhibiting cell cycle progression, promoting DNA repair, and inducing apoptosis in response to cellular stress or damage. Some well-known examples of tumor suppressor genes include TP53 (p53), RB1 (retinoblastoma protein), and CDKN2A (p16INK4a). Mutations or loss of function in these genes can disrupt their ability to regulate the cell cycle, thereby contributing to the development of cancer. In many cases, both copies of a tumor suppressor gene must be inactivated for a complete loss of function, following Knudson's two-hit hypothesis. The identification and study of tumor suppressor genes have significantly advanced our understanding of cancer biology and provided potential targets for therapeutic interventions. | [
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"text": "The cell cycle (or cell-division cycle) is a series of events that take place in a cell, leading to its division and duplication. Cell division requires cell cycle checkpoints (CPs) that are used by the cell to both monitor and regulate the progress of the cell cycle. Tumor-suppressor genes (TSGs) or antioncogenes are genes that protect the cell from a single event or multiple events leading to cancer. When these genes mutate, the cell can progress to a cancerous state.",
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"text": "Deregulation of the cell cycle underlies the aberrant cell proliferation that characterizes cancer and loss of cell cycle checkpoint control promotes genetic instability. During the past two decades, cancer genetics has shown that hyperactivating mutations in growth signalling networks, coupled to loss of function of tumour suppressor proteins, drives oncogenic proliferation.",
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"text": " We now recognize that tumor suppressor genes regulate diverse cellular activities, including cell cycle checkpoint responses, detection and repair of DNA damage, protein ubiquitination and degradation, mitogenic signaling, cell specification, differentiation and migration, and tumor angiogenesis.",
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"text": "p53 is a critical tumor-suppressor protein that guards the human genome against mutations by inducing cell-cycle arrest or apoptosis.",
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"endSection": "abstract"
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"text": "Tumor-suppressor gene p16 is an important negative cell-cycle regulator whose functional loss may significantly contribute to malignant transformation and progression.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/10854145",
"endSection": "abstract"
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{
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"text": "Tumor suppressor genes are negative regulators of cell growth.",
"beginSection": "abstract",
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{
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"text": "Aberrant proteolysis with oncogenic potential is elicited by two major mechanisms: defective degradation of positive cell cycle regulators (i.e., proto-oncoproteins) and enhanced degradation of negative cell cycle regulators (i.e., tumor suppressor proteins).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12665054",
"endSection": "abstract"
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{
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"text": " Genes positively controlling cell cycle checkpoints can be targets for oncogenic activation in cancer, whereas negative regulators, such as tumour suppressor genes, are targeted for inactivation.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11327114",
"endSection": "abstract"
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{
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"text": "The p27(Kip1) protein belongs to a family of cyclin-dependent kinase-inhibitory proteins that are negative regulators of cell cycle progression and have been proposed as candidate tumor suppressor genes.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9815577",
"endSection": "abstract"
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{
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"text": "Retinoblastoma 1 (RB1) is the first discovered tumor suppressor gene and recognized as the simple model system whose encoded defective protein can cause a pediatric cancer retinoblastoma. It functions as a negative regulator of the cell cycle through the interactions with members of the E2F transcription factors family. The protein of the RB1 gene (pRB) is engaged in various cell cycle processes including apoptosis, cell cycle arrest and chromatin remodeling.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/33682629",
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{
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"text": "The cell cycle is composed of a series of steps which can be negatively or positively regulated by various factors. Chief among the negative regulators is the p53 protein.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2046748",
"endSection": "abstract"
},
{
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"text": "p27Kip1 (p27) is an important negative regulator of the cell cycle and a putative tumor suppressor.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20492666",
"endSection": "abstract"
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{
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"text": "It is now evident that the cell cycle machinery has a variety of elements negatively regulating cell cycle progression. However, among these negative regulators in cell cycle control, only 4 have been shown to be consistently involved in the development of human cancers as tumor suppressors: Rb (Retinoblastoma susceptibility protein), p53, and two recently identified cyclin-dependent kinase inhibitors, p16INK4A/MTS1 and p15INK4B/MTS2.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8652807",
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}
] |
6415c7fb690f196b51000016 | When was Keytruda approved for the treatment of melanoma? | On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA) for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. | [
"28235882"
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"text": "On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28235882",
"endSection": "abstract"
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] |
64468e0d57b1c7a315000071 | What is the incidence of Oculopharyngeal Muscular Dystrophy (OPMD)? | OPMD affects approximately 1 in 80,000 individuals worldwide. However, in some populations, it can affect as much as 1 in 600 individuals due to a strong founder effect. | [
"36401050"
] | factoid | [
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"text": "Oculopharyngeal muscular dystrophy (OPMD) is a late-onset rare muscle disease affecting approximately 1 in 80,000 individuals worldwide. However, it can affect as much as 1:600 individuals in some populations due to a strong founder effect. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36401050",
"endSection": "abstract"
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] |
64041355201352f04a000014 | What are features of the Mackler’s Triad? | The Mackler triad is vomiting, severe chest pain, and subcutaneous cervical emphysema. | [
"34932533"
] | list | [
{
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"text": "Most commonly affecting males between 50 and 70 years of age, Clinically, the Mackler triad is vomiting, severe chest pain, and subcutaneous cervical emphysema.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34932533",
"endSection": "abstract"
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] |
641373fc201352f04a000040 | What is Tastin? | Tastin is a proline-rich cytoplasmic protein that associates with the microtubular cytoskeleton. | [
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"text": "Human tastin, a proline-rich cytoplasmic protein, associates with the microtubular cytoskeleton.",
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"text": "Tastin was originally identified as an accessory protein for trophinin, a cell adhesion molecule that potentially mediates the initial attachment of the human embryo to the uterine epithelium. H",
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"text": "Trophinin, tastin, and bystin have been identified as molecules potentially involved in human embryo implantation",
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"text": "Tastin was previously characterized as an accessory protein for cell adhesion that participates in early embryo implantation",
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"text": "Here, we report that tastin is also required for spindle assembly during mitosis. Tastin protein levels peaked in the G(2)/M phase and abruptly declined after cell division",
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"text": "Tastin was originally identified as an accessory protein for trophinin, a cell adhesion molecule that potentially mediates the initial attachment of the human embryo to the uterine epithelium.",
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"text": "Another, named tastin, is a cytoplasmic protein and is necessary for trophinin to function as a cell adhesion molecule.",
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"endSection": "abstract"
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"text": "Tastin was previously characterized as an accessory protein for cell adhesion that participates in early embryo implantation.",
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"text": "BACKGROUND: Bystin, Trophinin, and Tastin are component proteins of an adhesion molecule complex that plays a crucial role in the initial attachment of the embryo to the uterus.METHODS: Profiling of genes differentially expressed in the perineural invasion (PNI) in vitro model by gene microarray analysis showed overexpression of bystin in prostate cancer cells co-",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16245277",
"endSection": "abstract"
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"text": "Bystin and tastin are cytoplasmic proteins that associate with trophinin by presumably forming an active adhesion machinery.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/11299965",
"endSection": "abstract"
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"text": "Trophinin and tastin, a novel cell adhesion molecule complex with potential involvement in embryo implantation.",
"beginSection": "title",
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"endSection": "title"
},
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"text": "Trophinin and tastin appear to be associated with the cytoskeleton in HT-H and SNG-M cells.",
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"endSection": "abstract"
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"text": "One, named trophinin, is an intrinsic membrane protein and mediates homophilic self-binding.",
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"text": "Tastin and bystin are cytoplasmic proteins required for trophinin to exhibit cell adhesion activity.",
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"endSection": "abstract"
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{
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"text": "BACKGROUND: Trophinin is an intrinsic membrane protein that forms a complex in the cytoplasm with bystin and tastin, linking it microtubule-associated motor dynein (ATPase) in some cell types",
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{
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"text": "Trophinin and tastin form a cell adhesion molecule complex that potentially mediates an initial attachment of the blastocyst to uterine epithelial cells at the time of implantation.",
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"text": "BACKGROUND: Bystin, Trophinin, and Tastin are component proteins of an adhesion molecule complex that plays a crucial role in the initial attachment of the embryo to the uterus",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16245277",
"endSection": "abstract"
}
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644efd2c57b1c7a315000085 | Do epigenetic changes change the DNA sequence? | Epigenetic changes are inheritable modifications that can modify gene expression without changing the DNA sequence. The most common epigenetic alternations consist of DNA methylation and histone modifications. | [
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{
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"text": "Epigenetic modifications, such as DNA methylation and chromatin assembly states, reflect the high plasticity of the genome and contribute to stably alter gene expression without modifying genomic DNA sequences.",
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"endSection": "abstract"
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"text": "Epigenetics is defined as heritable changes in gene expression that are, unlike mutations, not attributable to alterations in the sequence of DNA.",
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"text": "Epigenetic changes are inheritable modifications that can modify the gene expression without changing the DNA sequence. The most common epigenetic alternations consist of DNA methylation and histone modifications.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/33781317",
"endSection": "abstract"
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{
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"text": "Epigenetic changes refer to heritable changes that may modulate gene expression without affecting DNA sequence.",
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"text": "Epigenetic changes are reversible and do not affect the DNA sequence itself but rather control levels of gene expression.",
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"text": "Epigenetic changes, or heritable alterations in gene function that do not affect DNA sequence, are rapidly gaining acceptance as co-conspirators in carcinogenesis.",
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"text": "Environmentally caused changes in chromosomes that do not alter the DNA sequence but cause phenotypic changes by altering gene transcription are summarized as epigenetics.",
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"text": "Epigenetic modifications are heritable changes in gene expression not encoded by the DNA sequence.",
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"text": "Epigenetic regulation is referred to as changes in gene function that do not involve changes in the DNA sequence, it is usually accomplished by DNA methylation, histone modifications (repressive marks such as H3K9me, H3K27me, H2Aub, or active marks such as H3K4me, H3K36me, H3Ac), and chromatin remodeling (nucleosome composition, occupancy, and location).",
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"text": "Epigenetics is the study of changes in gene expression or cellular phenotype that do not change the DNA sequence.",
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"text": "Epigenetic change, which does not involve alteration to the nucleotide sequence, can also cause changes in gene activity by changing the structure of chromatin through DNA methylation or histone modifications.",
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"text": "Epigenetics is defined as mitotically and meiotically heritable changes in gene expression that do not involve a change in the DNA sequence.",
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"text": "These modifications, also known as epigenetic code, do not change the DNA sequence but alter the expression level of specific genes.",
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"endSection": "abstract"
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"text": " Epigenetic regulation refers to heritable factors of genomic modifications that do not involve changes in DNA sequence.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26579435",
"endSection": "abstract"
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{
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"text": "Epigenetics refers to structural modifications to genes that do not change the nucleotide sequence itself but instead control and regulate gene expression.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/20309920",
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"text": "Epigenetics are the heritable changes in gene expression patterns which occur without altering DNA sequence.",
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"text": " Epigenetic changes appear briefly and do not involve permanent changes to the primary DNA sequence.",
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"text": " Epigenetic changes responding to the environmental and intercellular signals can turn on/off specific genes, but do not modify the DNA sequence.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25512705",
"endSection": "abstract"
},
{
"offsetInBeginSection": 116,
"offsetInEndSection": 238,
"text": " Epigenetic changes are reversible and do not affect the DNA sequence itself but rather control levels of gene expression.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35735917",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "Epigenetic regulation refers to heritable changes in gene expression that do not involve any alteration of the DNA sequence.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27730435",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "Epigenetic mechanisms, which include DNA methylation, histone modification, and microRNA (miRNA), can produce heritable phenotypic changes without a change in DNA sequence.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32445090",
"endSection": "abstract"
},
{
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"text": "Epigenetic changes to the genome are biochemical alterations to the DNA that do not change an individual's genome but do change and influence gene expression.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24295192",
"endSection": "abstract"
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{
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"text": "e next, which may alter gene expression but which do not involve changes in the primary DNA sequence. These marks include DNA methylation (methylation",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18847515",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "Epigenetics, the study of functionally relevant chemical modifications to DNA that do not involve a change in the DNA nucleotide sequence, is at the interface between research and clinical medicine.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24298130",
"endSection": "abstract"
},
{
"offsetInBeginSection": 395,
"offsetInEndSection": 564,
"text": "The accessibility of DNA is regulated by epigenetic processes, including methylation of cytosine. In these circumstances the nucleic sequence of the DNA does not change.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31609563",
"endSection": "abstract"
},
{
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"text": "Epigenetics is comprised of the stable and heritable (or potentially heritable) changes in gene expression that do not entail a change in DNA sequence.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15485357",
"endSection": "abstract"
}
] |
6433020c57b1c7a315000023 | What is Ruconest? | Recombinant human C1 esterase inhibitor (rhC1INH) (Ruconest(®), Pharming) is a new drug developed for the relief of symptoms occurring in patients with angioedema due to C1-inhibitor deficiency. the therapeutic efficacy of rhC1INH results from its ability to block the actions of enzymes belonging to the overactivated bradykinin-forming pathway, at multiple locations. Studies have demonstrated the effectiveness of this agent in all localizations of hereditary angioedema attacks. | [
"21426252"
] | summary | [
{
"offsetInBeginSection": 1,
"offsetInEndSection": 108,
"text": "hC1INH: a new drug for the treatment of attacks in hereditary angioedema caused by C1-inhibitor deficiency.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21426252",
"endSection": "title"
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"text": "Recombinant human C1 esterase inhibitor (rhC1INH) (Ruconest(®), Pharming) is a new drug developed for the relief of symptoms occurring in patients with angioedema due to C1-inhibitor deficiency.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21426252",
"endSection": "abstract"
},
{
"offsetInBeginSection": 306,
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"text": "Similar to the purified C1-inhibitor derived from human plasma, the therapeutic efficacy of rhC1INH results from its ability to block the actions of enzymes belonging to the overactivated bradykinin-forming pathway, at multiple locations. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21426252",
"endSection": "abstract"
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{
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"text": "Dose-ranging efficacy studies established 50 U/kg as the recommended dose, and demonstrated the effectiveness of this agent in all localizations of hereditary angioedema attacks.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21426252",
"endSection": "abstract"
}
] |
6446ac0b57b1c7a315000072 | Which are the motor neuron diseases? | Amyotrophic Lateral Sclerosis (ALS), Spinal Bulbar Muscular Atrophy (SBMA), Hereditary Spastic Paraplegia (HSP) and Spinal Muscular Atrophy (SMA) are motor neuron diseases. | [
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"text": "Motor neurons (MNs) are specialized neurons responsible for muscle contraction that specifically degenerate in motor neuron diseases (MNDs), such as amyotrophic lateral sclerosis (ALS), spinal and bulbar muscular atrophy (SBMA), and spinal muscular atrophy (SMA). ",
"beginSection": "abstract",
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"text": "Spinal muscular atrophy (SMA), spinal and bulbar muscular atrophy (SBMA), hereditary spastic paraplegia (HSP), and amyotrophic lateral sclerosis (ALS) are all MNDs",
"beginSection": "abstract",
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"text": "Amyotrophic Lateral Sclerosis (ALS), Spinal Bulbar Muscular Atrophy (SBMA), and Spinal Muscular Atrophy (SMA) are motor neuron diseases (MNDs) characterised by progressive motor neuron degeneration, weakness and muscular atrophy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36143200",
"endSection": "abstract"
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"text": "The most common MND are amyotrophic lateral sclerosis (ALS), proximal spinal muscular atrophy (SMA) and various forms of hereditary and sporadic lower motor neuron syndromes including hereditary motor neuropathies (HMN).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21626001",
"endSection": "abstract"
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{
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"text": "Two motor neuron diseases, amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), are caused by distinct genes involved in RNA metabolism, TDP-43 and FUS/TLS, and SMN, respectively.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23255347",
"endSection": "abstract"
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{
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"text": "Similarly other motor neuron diseases such as the spinal muscular atrophies (SMA) and the motor neuropathies (MN) were grouped following clinical criteria.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12710507",
"endSection": "abstract"
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{
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"text": "There are several types of motor neuron disease: amyotrophic lateral sclerosis (ALS), progressive bulbar palsy (PBP), progressive muscular atrophy (PMA), primary lateral sclerosis (PLS).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32671738",
"endSection": "abstract"
},
{
"offsetInBeginSection": 200,
"offsetInEndSection": 431,
"text": "The umbrella term MND refers to diseases which cause the progressive loss of upper and/or lower motor neurons and a subsequent decrease in motor ability such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31031583",
"endSection": "abstract"
},
{
"offsetInBeginSection": 142,
"offsetInEndSection": 391,
"text": "Degeneration of motor neurons results in progressive muscle weakness, which underlies several debilitating neurological disorders including amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegias (HSP), and spinal muscular atrophy (SMA).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34204831",
"endSection": "abstract"
},
{
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"text": "Motor neuron diseases (MNDs) are a group of neurodegenerative disorders with involvement of upper and/or lower motor neurons, such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), progressive bulbar palsy, and primary lateral sclerosis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15372378",
"endSection": "abstract"
},
{
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"offsetInEndSection": 401,
"text": "Motor neuron diseases may be divided into three categories: those with lower motor neuron involvement--spinal muscular atrophy (SMA) and spinobulbar muscular atrophy (SBMA or Kennedy's disease); those with upper motor neuron involvement--primary lateral sclerosis (PLS) and the spastic paraplegias; and those with combined upper and lower motor neuron involvement--amyotrophic lateral sclerosis (ALS).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14753656",
"endSection": "abstract"
},
{
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"offsetInEndSection": 220,
"text": "Among the motor neuron diseases, three share the clinical features of prominent upper motor neuron signs--amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS) and the hereditary spastic paraplegias (HSP).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16036421",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 211,
"text": "Motor neuron diseases, such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), share several clinical similarities while differing substantially in etiology, disease onset and progression.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33374658",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "Motor neuron diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are neurodegenerative diseases, which cause progressive paralysis and premature death in affected adults and children.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15384941",
"endSection": "abstract"
}
] |
63f04716f36125a426000025 | Donidalorsen was tested for which disease? | Donidalorsen is tested for hereditary angioedema. | [
"36172291",
"35294812"
] | factoid | [
{
"offsetInBeginSection": 0,
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"text": "BACKGROUND: Hereditary angioedema is characterized by recurrent and unpredictable swellings that are disabling and potentially fatal. Selective inhibition of plasma prekallikrein production by antisense oligonucleotide treatment (donidalorsen) may reduce the frequency of attacks and the burden of disease.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35294812",
"endSection": "abstract"
},
{
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"text": "CONCLUSIONS: Among patients with hereditary angioedema, donidalorsen treatment resulted in a significantly lower rate of angioedema attacks than placebo in this small, phase 2 trial.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35294812",
"endSection": "abstract"
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{
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"text": "Investigational therapies, including the activated factor XII inhibitor garadacimab and an antisense oligonucleotide targeting plasma prekallikrein messenger RNA (donidalorsen), have shown promise as long-term prophylaxis. Given the requirement of lifelong management for HAE, further research is needed to determine how best to individualize optimal treatments for each patient.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36172291",
"endSection": "abstract"
}
] |
641dc49b690f196b51000042 | Treatment with plasma exchange (TPE) is used for what diseases | Therapeutic plasma exchange (TPE) is the most common modality employed with the rationale of rapid reduction of a pathogenic substance distributed primarily in the intravascular compartment This includes cancer, infectious diseases like Dengue fever and Covid-19, septic shock and cytokine storm, and others such as Thrombotic thrombocytopenic purpura (TTP), diabetic ketoacidosis concomitant with type IX glycogen storage disease (GSD) and autoimmune disease of the CNS. | [
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"text": "Therapeutic plasma exchange (TPE) is the most common modality employed with the rationale of rapid reduction of a pathogenic substance distributed primarily in the intravascular compartmen",
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"text": "Though therapeutic apheresis modalities are employed frequently in children with kidney disease, most experiences are extrapolated from adult studies. International and national registries need to be established to elucidate the role of apheresis modalities in children with kidney disease.",
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"text": "Rescuing Cancer Immunity by Plasma Exchange in Metastatic Melanoma (ReCIPE-M1)",
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"endSection": "title"
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{
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"text": "Fulminant Hepatic Failure in Dengue Fever Without Plasma Leakage: A Case Report",
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"endSection": "title"
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"text": "Clinical and biochemical endpoints and predictors of response to plasma exchange in septic shock",
"beginSection": "title",
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"endSection": "title"
},
{
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"text": "Recently, a randomized controlled trial (RCT) demonstrated rapid but individually variable hemodynamic improvement with therapeutic plasma exchange (TPE) in patients with septic shock.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35551628",
"endSection": "abstract"
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{
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"text": "Thrombotic thrombocytopenic purpura (TTP) is becoming a curable disease with the introduction of therapeutic plasma exchange (TPE).",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/35689538",
"endSection": "abstract"
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{
"offsetInBeginSection": 0,
"offsetInEndSection": 85,
"text": "Role of Therapeutic Plasmapheresis in SARS-CoV-2 Induced Cytokine Release Syndrome: A",
"beginSection": "title",
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"endSection": "title"
},
{
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"text": "Background: Cytokine release syndrome (CRS) significantly contributes to the pathophysiology and progression of COVID-19. It is speculated that therapeutic plasma exchange (TPE) can dampen CRS via elimination of pathogenic cytokines.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35585996",
"endSection": "abstract"
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{
"offsetInBeginSection": 0,
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"text": "Successful therapeutic plasma exchange in a case with extremely severe hypertriglyceridemia secondary to diabetic ketoacidosis concomitant with type IX glycogen storage diseas",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34690074",
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{
"offsetInBeginSection": 9,
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"text": "Therapeutic plasma exchange (TPE) is a treatment option to reduce thyroid hormones",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35963982",
"endSection": "abstract"
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{
"offsetInBeginSection": 1,
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"text": "herapeutic plasma exchange in hyperthyroidism prior to surgery",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35963982",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 112,
"text": "Therapeutic plasma exchange for optic neuritis attacks in patients with neuromyelitis optica spectrum disorders.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35353437",
"endSection": "title"
},
{
"offsetInBeginSection": 12,
"offsetInEndSection": 116,
"text": "Optic neuritis (ON) causes several sequela. Aggressive treatment with plasma exchange (TPE) is an option",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35353437",
"endSection": "abstract"
},
{
"offsetInBeginSection": 188,
"offsetInEndSection": 295,
"text": " We recruited adults with ON in neuromyelitis optica spectrum disorders (NMOSD) patients treated with TPE. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35353437",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 58,
"text": "Total Plasma Exchange in Neuromuscular Junction Disorders-",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35955999",
"endSection": "title"
},
{
"offsetInBeginSection": 246,
"offsetInEndSection": 300,
"text": "Total plasma exchange (TPE) has proven efficacy in NJD",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35955999",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 102,
"text": "Immunoadsorption and plasma exchange-Efficient treatment options for neurological autoimmune diseases.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34904748",
"endSection": "title"
},
{
"offsetInBeginSection": 12,
"offsetInEndSection": 406,
"text": "Therapeutic plasma exchange (TPE) and immunoadsorption (IA) are first or second line treatment options in patients with neurological autoimmune diseases, including multiple sclerosis, neuromyelitis optica spectrum disorders (NMSOD), chronic inflammatory demyelinating polyneuropathy, acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barré syndrome), and autoimmune encephalitis",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34904748",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 130,
"text": "Therapeutic plasma exchange (TPE) has been used for the treatment of neurologic diseases in which autoimmunity plays a major role.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17224307",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "Therapeutic plasma exchange (TPE) has been used extensively for over 2 decades to treat a variety of autoimmune and congenital diseases and is now widely accepted.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10619926",
"endSection": "abstract"
},
{
"offsetInBeginSection": 106,
"offsetInEndSection": 191,
"text": "TPE is commonly used in neurological disorders where autoimmunity plays a major role.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28194064",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 130,
"text": "Therapeutic plasma exchange (TPE) is commonly used in many neurological disorders where an immune etiology was known or suspected.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18331814",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1730,
"offsetInEndSection": 1837,
"text": "In conclusion; Therapeutic plasma exchange is an effective treatment option in several neurologic diseases.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23619327",
"endSection": "abstract"
},
{
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"text": "INTRODUCTION: Therapeutic plasma exchange (TPE) is commonly used as treatment of certain autoimmune neurological diseases (ANDs), and its main objective is the removal of pathogenic a",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32802495",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 165,
"text": "Therapeutic plasma exchange (TPE) is used in the treatment of neurological, hematological, renal and autoimmune diseases with known or suspected immune pathogenesis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29882008",
"endSection": "abstract"
},
{
"offsetInBeginSection": 132,
"offsetInEndSection": 302,
"text": "TPE has an increasing list of indications in recent years such as neurological, connective tissue, hematological, nephrological, endocrinological and metabolic disorders.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23619327",
"endSection": "abstract"
},
{
"offsetInBeginSection": 303,
"offsetInEndSection": 407,
"text": "We report our multicenter data about therapeutic plasma exchange in patients with neurological diseases.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23619327",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 103,
"text": "Therapeutic plasma exchange in patients with neurological diseases: multicenter retrospective analysis.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23619327",
"endSection": "title"
},
{
"offsetInBeginSection": 1337,
"offsetInEndSection": 1506,
"text": "TPE is an effective treatment in neurologic diseases in which autoimmunity plays an important role in pathogenesis, and it is safe when performed in experienced centers.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17224307",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 95,
"text": "Therapeutic plasma exchange in the treatment of neuroimmunologic disorders: review of 50 cases.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17224307",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 95,
"text": "Therapeutic plasma exchange (TPE) has been mainly used in the treatment of autoimmune diseases.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30924130",
"endSection": "abstract"
},
{
"offsetInBeginSection": 341,
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"text": "TPE is useful in autoimmune haematological, renal, rheumatic and neurological diseases, and is recommended for acute disorders, together with relapsed or worsened chronic diseases that are often unresponsive to conventional treatments.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30924130",
"endSection": "abstract"
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"text": "Therapeutic plasma exchange (TPE) is a treatment administered with the aim of removing a pathogenic material or compound causing morbidity in a variety of neurologic, hematologic, renal, and autoimmune diseases.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33884210",
"endSection": "abstract"
},
{
"offsetInBeginSection": 253,
"offsetInEndSection": 427,
"text": "Diseases that can be treated with TPE are classified into the following categories: (1) endocrinological, (2) neurological, (3) renal/rheumatological, and (4) haematological.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16382247",
"endSection": "abstract"
},
{
"offsetInBeginSection": 571,
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"text": "Moreover, TPE in kidney diseases, for instance: desensitization in renal transplantation(ABO compatible) (living donor)and desensitization in deceased donor, desensitization in renal transplantation(ABO incompatible) (living donor), thrombotic microangiopathy complement Mediated (Factor H autoantibodies), Focal segmental glomerulosclerosis(recurrent in transplanted kidney), ANCA-associated rapidly progressive glomerulonephritis(Dialysis dependence, DAH), Anti-Glomerular basement membrane disease Goodpasture's syndrome)(DAH,Dialysis-independence,) has been utilized as an initial treatment.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31029610",
"endSection": "abstract"
},
{
"offsetInBeginSection": 157,
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"text": " For decades, therapeutic plasma exchange (TPE) is performed for the management of immune-mediated diseases.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34261138",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "Therapeutic plasma-exchange (TPE) is used as primary and adjunctive therapy in treatment of several hematologic diseases.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23619323",
"endSection": "abstract"
},
{
"offsetInBeginSection": 222,
"offsetInEndSection": 329,
"text": " Successful treatment of aHUS with plasma infusions and therapeutic plasma exchange (TPE) is well reported.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24277990",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 86,
"text": "Several neurologic disorders have been treated with therapeutic plasma exchange (TPE).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22277020",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "INTRODUCTION: Therapeutic plasma exchange (TPE) is the first-line treatment for acute thrombotic thrombocytopenic purpura (TTP)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32605805",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1093,
"offsetInEndSection": 1173,
"text": "TPE is effectively and safely carried out in our center in hematologic diseases.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23619323",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 192,
"text": "BACKGROUND: Therapeutic plasma exchange (TPE) is a conventional second-line treatment for patients with multiple sclerosis (MS) or clinically isolated syndrome with steroid-refractory relapses",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35302053",
"endSection": "abstract"
},
{
"offsetInBeginSection": 674,
"offsetInEndSection": 986,
"text": "As a supportive therapy, the plasma exchange was effective in the hyperviscosity syndrome, myasthenia gravis, thrombotic thrombocytopenic syndrome, myasthenia gravis, thrombotic thrombocytopenic purpura (TTP), hypercholesterolaemia, Guillain-Barré Syndrome, haemolytic crisis of a homozygous sickle-cell anaemia.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/1703815",
"endSection": "abstract"
}
] |
644ec7fe57b1c7a315000082 | What are the proteins that are necessary for the use of lactose in E. coli collectively called? | The proteins necessary for the use of lactose in E. coli are collectively called the lac operon. This gene regulatory circuit controls the transcription of genes involved in lactose metabolism and is nearly ubiquitous in E. coli strains, making it a useful phenotype for species identification. The activity of the lac operon is controlled by both cis- and trans-acting regulators, which integrate environmental signals such as glucose and lactose availability to fine-tune gene expression. While most studies of lac operon regulation have focused on a few closely related strains, this system remains an important model for understanding how bacteria adapt their metabolism to changing nutritional conditions. | [
"31719176",
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"34891476",
"34953812",
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] | factoid | [
{
"offsetInBeginSection": 0,
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"text": "The lac operon is one of the best known gene regulatory circuits and constitutes a landmark example of how bacteria tune their metabolism to nutritional conditions. It is nearly ubiquitous in Escherichia coli strains justifying the use of its phenotype, the ability to consume lactose, for species identification.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34367115",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 489,
"text": "Transcription of bacterial genes is controlled by the coordinated action of cis- and trans-acting regulators. The activity and mode of action of these regulators can reflect different requirements for gene products in different environments. A well-studied example is the regulatory function that integrates the environmental availability of glucose and lactose to control the Escherichia colilac operon. Most studies of lac operon regulation have focused on a few closely related strains.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31719176",
"endSection": "abstract"
},
{
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"text": "In the induced state of the lac pathway, the genes comprising the lac operon are transcribed, leading to the production of proteins that import and metabolize lactose.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34953812",
"endSection": "abstract"
}
] |
63fa16d8201352f04a000002 | Alternative microexon splicing is associated with metastasis in which cancer? | Alternative microexon splicing by RBFOX2 and PTBP1 is associated with metastasis in colorectal cancer. | [
"34346508"
] | factoid | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 102,
"text": "Alternative microexon splicing by RBFOX2 and PTBP1 is associated with metastasis in colorectal cancer.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34346508",
"endSection": "title"
},
{
"offsetInBeginSection": 1073,
"offsetInEndSection": 1320,
"text": "Finally, we found that changes in the pattern of microexon splicing were associated with CRC metastasis. Our data thus suggest that altered expression of RBFOX2 and PTBP1 might influence CRC metastasis through the regulation of microexon splicing.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34346508",
"endSection": "abstract"
}
] |
6451034c57b1c7a315000095 | How is Leigh syndrome inherited? | LS is a rare progressive multisystem fatal disorder inherited by autosomal recessive, X-linked and maternal transmission. | [
"24299589"
] | list | [
{
"offsetInBeginSection": 254,
"offsetInEndSection": 376,
"text": "LS is a rare progressive multisystem fatal disorder inherited by autosomal recessive, X-linked and maternal transmission. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24299589",
"endSection": "abstract"
},
{
"offsetInBeginSection": 587,
"offsetInEndSection": 1031,
"text": "LS is due to a deficit of various respiratory chain and Krebs cycle enzymes resulting in insufficient production of adenosine triphosphate (ATP), in particular cytochrome-c-oxidase (COX), pyruvate carboxylase, pyruvate dehydrogenase complex and complex I of the respiratory chain, which share an autosomal recessive and X-linked mode of transmission. Cases with maternal inheritance (MILS) are due to a mitochondrial DNA (mtDNA) point mutation.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/24299589",
"endSection": "abstract"
}
] |
61f901bd882a024a10000047 | List features of the Zinner syndrome. | Zinner syndrome comprises triad of seminal vesicle cyst, unilateral renal agenesis and ipsilateral ejaculatory duct obstruction. | [
"32991910",
"33462046",
"34527910",
"34504629",
"34584848"
] | list | [
{
"offsetInBeginSection": 132,
"offsetInEndSection": 261,
"text": "Zinner syndrome comprises triad of seminal vesicle cyst, unilateral renal agenesis and ipsilateral ejaculatory duct obstruction. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34584848",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 272,
"text": "We present the case of a 51-year-old male with Zinner syndrome, which is a rare disease, resulting from an abnormal evolution of the mesonephric (Wolffian) duct. It consists in cystic dilations of one seminal vesicle and/or ejaculatory duct and ipsilateral renal agenesis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34527910",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "A rare triad of Wolffian duct anomaly known as Zinner syndrome includes unilateral renal agenesis with ipsilateral seminal vesicle cyst and ejaculatory duct obstruction.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34504629",
"endSection": "abstract"
},
{
"offsetInBeginSection": 149,
"offsetInEndSection": 340,
"text": "Zinner syndrome, first described in 1914, refers to a triad of features consisting of seminal vesicle cysts, ejaculatory duct obstruction, and unilateral (mostly ipsilateral) renal agenesis. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32991910",
"endSection": "abstract"
},
{
"offsetInBeginSection": 220,
"offsetInEndSection": 335,
"text": "The triad of SV cysts, ipsilateral renal agenesis and ejaculatory duct obstruction is known as the Zinner syndrome.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33462046",
"endSection": "abstract"
}
] |
644f0a9757b1c7a315000088 | What is a regulon? | Regulons are the basic units of the cellular response system in bacterial cells, and each consists of a set of transcriptionally co-regulated operons. While the term "regulon" is not used in eukaryotes, a group of genes controlled as a unit - usually by the same repressor or activator gene - can be referred to as a regulon. | [
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"32854400",
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] | summary | [
{
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"text": "Regulons, as groups of transcriptionally co-regulated operons, are the basic units of cellular response systems in bacterial cells.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22235300",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "A group of genes controlled as a unit, usually by the same repressor or activator gene, is known as a regulon.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32421805",
"endSection": "abstract"
},
{
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"text": "Regulons are the basic units of the response system in a bacterial cell, and each consists of a set of transcriptionally co-regulated operons.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26975728",
"endSection": "abstract"
},
{
"offsetInBeginSection": 279,
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"text": "A regulon is conceptually defined as a set of target genes regulated by a transcription factor by physically binding to regulatory motifs to accomplish a specific biological function, such as the CO-FT regulon for flowering timing and fall growth cessation in trees.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32854400",
"endSection": "abstract"
},
{
"offsetInBeginSection": 133,
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"text": "Most bacteria contain dozens of TCSs, each of them responsible for sensing a different range of signals and controlling the expression of a repertoire of target genes (regulon).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32817385",
"endSection": "abstract"
},
{
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"offsetInEndSection": 237,
"text": "A transcriptional regulatory network encompasses sets of genes (regulons) whose expression states are directly altered in response to an activating signal, mediated by trans-acting regulatory proteins and cis-acting regulatory sequences.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15231752",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 122,
"text": "Eukaryotic regulons are regulatory units formed by a set of genes under the control of the same transcription factor (TF).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31825805",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 118,
"text": "Identification of groups of co-regulated genes (regulons) is an important part of studying transcriptional regulation.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16813171",
"endSection": "abstract"
},
{
"offsetInBeginSection": 12,
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"text": "During cancer stage transition, a master regulator (MR) refers to the key gene controlling cancer initiation and progression by orchestrating the associated target genes (termed as its regulon).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30052770",
"endSection": "abstract"
}
] |
6414c5ba690f196b51000007 | Can skin picking phenotype present following methylphenidate treatment? | Newly Developed Skin Picking After Methylphenidate Treatment in Attention Deficit Hyperactivity Disorder. | [
"29298167"
] | yesno | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 126,
"text": "Newly Developed Skin Picking After Methylphenidate Treatment in Attention Deficit Hyperactivity Disorder: Possible Mechanisms.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29298167",
"endSection": "title"
},
{
"offsetInBeginSection": 820,
"offsetInEndSection": 905,
"text": "We describe a case of skin picking developing after methylphenidate therapy for ADHD.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29298167",
"endSection": "abstract"
}
] |
6451060c57b1c7a315000096 | What is the cause of spinal-bulbar muscular atrophy? | Spinal bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion mutation in the androgen receptor (AR) gene. | [
"20689246",
"35996994",
"32773451"
] | factoid | [
{
"offsetInBeginSection": 109,
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"text": "Kennedy's disease is nearly exclusively caused by mutations in the androgen receptor encoding gene (AR).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35996994",
"endSection": "abstract"
},
{
"offsetInBeginSection": 12,
"offsetInEndSection": 193,
"text": "Spinal bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion mutation in the androgen receptor (AR) gene, and mutant AR is presumed to act in motoneurons to cause SBMA.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20689246",
"endSection": "abstract"
},
{
"offsetInBeginSection": 125,
"offsetInEndSection": 286,
"text": "spinal and bulbar muscular atrophy (SBMA), an inherited neuromuscular disorder caused by a CAG trinucleotide repeat expansion in the androgen receptor (AR) gene.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32773451",
"endSection": "abstract"
}
] |
61f7c904882a024a10000027 | Which disease can be treated using Tezepelumab? | Tezepelumab can be used to treat severe asthma. | [
"34572294",
"33368307",
"34572466",
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{
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"text": "SUMMARY: Clinical trials demonstrated that tezepelumab, an anti-TSLP monoclonal antibody, is a promising alternative treatment for asthma that is effective also in nontype 2 asthma.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34608100",
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{
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"text": "Tezepelumab in adults and adolescents with severe, uncontrolled asthma. ",
"beginSection": "abstract",
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"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "In severe, uncontrolled asthma, tezepelumab reduced exacerbations and improved asthma control at 1 y.",
"beginSection": "title",
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"endSection": "title"
},
{
"offsetInBeginSection": 970,
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"text": "Tezepelumab and other anti-alarmins are thus likely to become, in the near future, valuable therapeutic options for the biological treatment of uncontrolled severe asthma.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34572294",
"endSection": "abstract"
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{
"offsetInBeginSection": 1010,
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"text": "Omalizumab, dupilumab, and tezepelumab can directly modulate the ASM in asthma, by specifically blocking the interaction between IgE, IL-4, and TSLP, and their receptors are located on the surface of ASM cells. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34572466",
"endSection": "abstract"
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{
"offsetInBeginSection": 1409,
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"text": "AHR has been suggested as the main treatable trait towards precision medicine in patients suffering from eosinophilic asthma, therefore, well-designed head-to-head trials are needed to compare the efficacy of those mAbs that directly target ASM contractility specifically against the AHR in severe asthma, namely omalizumab, dupilumab, and tezepelumab.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34572466",
"endSection": "abstract"
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{
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"text": "Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial cytokine involved in asthma pathogenesis. In the phase 2b PATHWAY study (ClinicalTrials.gov identifier: NCT02054130), tezepelumab significantly reduced exacerbations in adults with severe, uncontrolled asthma. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33368307",
"endSection": "abstract"
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{
"offsetInBeginSection": 0,
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"text": "Pharmacokinetic and Pharmacodynamic Modeling of Tezepelumab to Guide Phase 3 Dose Selection for Patients With Severe Asthma.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33368307",
"endSection": "title"
},
{
"offsetInBeginSection": 1496,
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"text": "These results support the selection of 210 mg every 4 weeks subcutaneously as the dose for phase 3 studies of tezepelumab in adults and adolescents with severe asthma.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33368307",
"endSection": "abstract"
}
] |
644f0fd257b1c7a31500008a | Do enhancers have to be close to their gene targets? | Enhancers are cis-regulatory elements in the genome that cooperate with promoters to control target gene transcription. Unlike promoters, enhancers are not necessarily adjacent to target genes and can exert their functions regardless of enhancer orientations, positions, and spatial segregations from target genes. | [
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{
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"text": "Enhancers are cis-regulatory elements in the genome that cooperate with promoters to control target gene transcription. Unlike promoters, enhancers are not necessarily adjacent to target genes and can exert their functions regardless of enhancer orientations, positions and spatial segregations from target genes.",
"beginSection": "abstract",
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"text": "Enhancers are often located many tens of kilobases away from the promoter they regulate, sometimes residing closer to the promoter of a neighboring gene.",
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{
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"text": "Many enhancers map quite far from their target genes, on the order of tens or even hundreds of kilobases.",
"beginSection": "abstract",
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"endSection": "abstract"
},
{
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"text": "Enhancers are intergenic DNA elements that regulate the transcription of target genes in response to signaling pathways by interacting with promoters over large genomic distances.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27932455",
"endSection": "abstract"
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{
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"text": "Enhancers have been identified at up to megabase distances from their regulated genes, and/or proximal to or within the introns of unregulated genes.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32038719",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "In metazoans transcriptional enhancers and their more complex relatives, locus control regions, are often located at great linear distances from their target genes.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22183586",
"endSection": "abstract"
},
{
"offsetInBeginSection": 248,
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"text": " Given their distance from the target gene, lack of common motifs, and tissue/cell specificity, enhancer regions are thought to be difficult to predict in DNA sequences.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36071071",
"endSection": "abstract"
},
{
"offsetInBeginSection": 132,
"offsetInEndSection": 339,
"text": " Computational identification of enhancers is difficult because they do not exhibit clear location preference relative to their target gene and also because they lack clearly distinguishing genomic features.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23424115",
"endSection": "abstract"
},
{
"offsetInBeginSection": 68,
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"text": " Enhancers function independently of their distance and orientation to the promoters of target genes.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26373455",
"endSection": "abstract"
},
{
"offsetInBeginSection": 360,
"offsetInEndSection": 516,
"text": " Until recently, identifying each gene's enhancers had been challenging because enhancers do not occupy prescribed locations relative to their target genes.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26100358",
"endSection": "abstract"
},
{
"offsetInBeginSection": 133,
"offsetInEndSection": 339,
"text": "Computational identification of enhancers is difficult because they do not exhibit clear location preference relative to their target gene and also because they lack clearly distinguishing genomic features.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23424115",
"endSection": "abstract"
},
{
"offsetInBeginSection": 125,
"offsetInEndSection": 275,
"text": "cis-regulatory sequences called enhancers. Enhancers can stimulate gene activity at great genomic distances from their targets, raising questions abou",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32197056",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 269,
"text": "Enhancer elements are essential for tissue-specific gene regulation during mammalian development. Although these regulatory elements are often distant from their target genes, they affect gene expression by recruiting transcription factors to specific promoter regions.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23525463",
"endSection": "abstract"
},
{
"offsetInBeginSection": 280,
"offsetInEndSection": 473,
"text": "Epigenetic profiling of different tissues and cell-types has identified a large number of non-coding epigenetic regulatory elements ('enhancers') that can be located far away from coding genes.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30704404",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 271,
"text": "In metazoans, enhancers of gene transcription must often exert their effects over tens of kilobases of DNA. Over the past decade it has become clear that to do this, enhancers come into close proximity with target promoters with the looping away of intervening sequences.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22169023",
"endSection": "abstract"
}
] |
64463f9357b1c7a31500006a | Are there any other types of Spinal Muscular Atrophy except for types 1-4? | Yes, there is an exceptionally rare type of SMA called SMARD1. | [
"8283989",
"34794294",
"2801018"
] | yesno | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 109,
"text": "Spinal muscular atrophy (SMA) with respiratory distress type 1 (SMARD1) is an exceptionally rare type of SMA.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34794294",
"endSection": "abstract"
},
{
"offsetInBeginSection": 902,
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"text": "There are no convincing reports of X-linked SMA hitherto. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/8283989",
"endSection": "abstract"
},
{
"offsetInBeginSection": 146,
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"text": "The total AChE activity was either normal or decreased in the childhood SMA (Type 1), the other SMA groups and disease controls (ALS, X-linked SMA).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2801018",
"endSection": "abstract"
}
] |
63f749cf33942b094c00000a | What is the mechanism of action of Zanidatamab? | Zanidatamab is a humanised, bispecific monoclonal antibody directed against two non-overlapping domains of HER2. | [
"36000541",
"36102999",
"36400106",
"34626563",
"36472472",
"36459075"
] | summary | [
{
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"text": "Zanidatamab and tislelizumab are novel monoclonal antibodies targeting HER2 and PD-1, respectively, and have shown encouraging antitumor activity in early phase studies in multiple cancers, including GEA. ",
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"text": "Population pharmacokinetics of zanidatamab, an anti-HER2 biparatopic antibody, in patients with advanced or metastatic cancer.",
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"text": "Zanidatamab, a novel bispecific antibody, for the treatment of locally advanced or metastatic HER2-expressing or HER2-amplified cancers: a phase 1, dose-escalation and expansion study.",
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"text": "Zanidatamab is a humanised, bispecific monoclonal antibody directed against two non-overlapping domains of HER2. ",
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"text": "Zanidatamab is safe with preliminary efficacy in multiple HER2-expressing and HER2-amplified tumors.",
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"text": "Early phase trials of dabrafenib plus trametinib (BRAF and MEK inhibition) and zanidatamab (a bispecific HER2-antibody) have yielded encouraging response rates.",
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"text": "Of those in late-stage development, marketing application submissions for at least 23 may occur by the end of 2023, of which 5 are bispecific (odronextamab, erfonrilimab, linvoseltamab, zanidatamab, and talquetamab) and 2 are ADCs (datopotamab deruxtecan, and tusamitamab ravtansine).",
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644eae9c57b1c7a315000080 | Describe the function of a transcription factor such as SOX10. | Transcription factors are proteins that bind to DNA sequences to regulate gene transcription. They serve as integration centers of the different signal-transduction pathways affecting a given gene. It is obvious that the regulation of these regulators themselves is of crucial importance for differential gene expression during development and in terminally differentiated cells. In particular, the transcription factor SOX10 plays an important role in vertebrate neural crest development, including the establishment and maintenance of the melanocyte lineage. | [
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"text": "The transcription factor SOX10 plays an important role in vertebrate neural crest development, including the establishment and maintenance of the melanocyte lineage. SOX10 is also highly expressed in melanoma tumors, and SOX10 expression increases with tumor progression.",
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"text": "Transcription factors are proteins that bind to DNA sequences to regulate gene transcription. The transcription factor binding sites are short DNA sequences (5-20 bp long) specifically bound by one or more transcription factors.",
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"text": "Transcription factors serve as integration centres of the different signal-transduction pathways affecting a given gene. It is obvious that the regulation of these regulators themselves is of crucial importance for differential gene expression during development and in terminally differentiated cells.",
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"text": "We propose a role for Sox10 in conferring cell specificity to the function of other transcription factors in developing and mature glia.",
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"text": "SOX10 is a high-mobility-group transcription factor that plays a critical role in the development of neural crest-derived melanocytes.",
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"text": "The high mobility group-domain containing transcription factor Sox10 is an essential regulator of developmental processes and homeostasis in the neural crest, several neural crest-derived lineages and myelinating glia.",
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"text": "Sox10 is a member of the group E Sox transcription factor family and plays key roles in neural crest development and subsequent cellular differentiation.",
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"text": "In most cases, Sox10 exerts its transcriptional effects in concert with other DNA-binding factors, adaptor proteins, and nuclear import proteins.",
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"text": "The SOX10 transcription factor is a characteristic marker for migratory multipotent neural crest (NC) progenitors as well as several of their differentiated derivatives.",
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"text": "The transcription factor Sox10 is an essential regulator of genes that code for structural components of the myelin sheath and for lipid metabolic enzymes in both types of myelinating glia in the central and peripheral nervous systems.",
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"text": "The transcription factor Sox10 is a key regulator of vertebrate neural crest development and serves crucial functions in the differentiation of multiple neural crest lineages.",
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"text": "SOX10 is a well-conserved and widely expressed transcription factor involved in the regulation of embryonic development and in the determination of cell fate.",
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"text": "The transcription factor SOX10 is critical for Schwann cell development and maintenance, and many SOX10 target genes encode proteins required for Schwann cell function.",
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"text": "SOX10 protein is a key transcription factor during neural crest development.",
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{
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"text": " We propose a role for Sox10 in conferring cell specificity to the function of other transcription factors in developing and mature glia.",
"beginSection": "abstract",
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"text": "SOX10 is a transcription factor with well-known functions in neural crest and oligodendrocyte development.",
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"text": "During embryogenesis, the transcription factor, Sox10, drives the survival and differentiation of the melanocyte lineage.",
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"text": "The transcription factor Sox10 functions during multiple consecutive stages of Schwann-cell development in the peripheral nervous system (PNS).",
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"text": "The high-mobility group transcription factor Sox10 exerts many different roles during development of the neural crest and nervous system.",
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"text": "Sox10, a member of the Sry-related HMG-Box gene family, is a critical transcription factor for several important cell lineages, most notably the neural crest stem cells and the derivative peripheral glial cells and melanocytes.",
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"text": "The transcription factor SOX10 is essential for all stages of Schwann cell development including myelination. SOX10 cooperates with other transcription factors to activate the expression of key myelin genes in Schwann cells and is therefore a context-dependent, pro-myelination transcription factor.",
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] |
6450e67457b1c7a31500008e | What is Friedreich's Ataxia? | Friedreich's ataxia (FRDA) is a rare, progressive, and degenerative hereditary disorder caused by a deficiency of frataxin protein. | [
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"text": "Friedreich's ataxia (FA) is a rare, progressive, and degenerative hereditary disorder caused by a deficiency of frataxin protein. This disease is characterised by severe neurological dysfunction and life-threatening cardiomyopathy. ",
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"text": "Friedreich's ataxia (FRDA) is a rare genetic disorder caused by mutations in the gene frataxin, encoding for a mitochondrial protein involved in iron handling and in the biogenesis of iron-sulphur clusters, and leading to progressive nervous system damage.",
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"text": "Friedreich ataxia is an autosomal recessive ataxia with onset usually before puberty whose characteristic clinical features include progressive ataxia of gait and limbs, dysarthria, loss of joint position and vibratory sense, absent knee and ankle jerks, and Babinski signs.",
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"text": "Friedreich ataxia is an autosomal recessive degenerative disease that primarily affects the nervous system and the heart.",
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"text": "Friedreich's ataxia, the most frequent progressive autosomal recessive disorder involving the central and peripheral nervous systems, is mostly associated with unstable expansion of GAA trinucleotide repeats in the first intron of the FXN gene, which encodes the mitochondrial frataxin protein.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/21985033",
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"text": "Friedreich's ataxia, the most common hereditary ataxia, is caused by expansion of a GAA triplet located within the first intron of the frataxin gene on chromosome 9q13.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/12878293",
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"text": "Friedreich's ataxia is a neurodegenerative disorder associated with a GAA trinucleotide repeat expansion in intron 1 of the frataxin (FXN) gene.",
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"text": "BACKGROUND: Friedreich ataxia is an autosomal recessive hereditary spinocerebellar disorder, characterized by progressive limb and gait ataxia due to proprioceptive loss, often complicated by cardiomyopathy, diabetes and skeletal ",
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"text": "Friedreich's ataxia (FRDA) is a neurodegenerative disease caused by reduced expression of the mitochondrial protein frataxin.",
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"text": "BACKGROUND: Friedreich's ataxia is an autosomal recessive mitochondrial disease caused by a triplet repeat expansion in the frataxin gene (FXN), exhibiting cerebellar sensory ataxia, diabetes and car",
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"text": "Friedreich's ataxia is the most common inherited autosomal recessive ataxia and is characterized by progressive degeneration of the peripheral and central nervous systems and cardiomyopathy.",
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"text": "Friedreich's ataxia is an autosomal recessively inherited neurodegenerative disorder caused by expansions of an unstable GAA trinucleotide repeat in the STM7/X25 gene on chromosome 9q.",
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"text": "Friedreich's ataxia is a rare hereditary disease and although the gene defect has already been identified as a deficiency of the mitochondrial protein frataxin, the pathophysiology is still unknown.",
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"text": "Friedreich's ataxia is an autosomal recessive neurogenetic disease that is mainly associated with atrophy of the spinal cord and progressive neurodegeneration in the cerebellum.",
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"text": "Friedreich's ataxia (FRDA) is an autosomal recessive inherited disorder characterized by progressive gait and limb ataxia, dysarthria, areflexia, loss of vibratory and position sense, and a progressive motor weakness of central origin.",
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"text": "Friedreich's ataxia (FA) is a recessive, predominantly neurodegenerative disorder caused in most cases by mutations in the first intron of the frataxin (FXN) gene.",
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"text": "Friedreich's ataxia (FRDA) is a neurodegenerative disease caused by recessive mutations in the frataxin gene that lead to a deficiency of the mitochondrial frataxin (FXN) protein.",
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"text": "Friedreich's ataxia (FRDA) is a rare autosomal recessive spinocerebellar ataxia which in the majority of cases is associated with a GAA-trinucleotide repeat expansion in the first intron of Frataxin gene located on chromosome 9.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28282710",
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"text": "Friedreich ataxia is considered a neurodegenerative disorder involving both the peripheral and central nervous systems.",
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"text": "Friedreich ataxia (FRDA) is a common form of ataxia caused by decreased expression of the mitochondrial protein frataxin.",
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"text": "BACKGROUND: Friedreich's ataxia is an autosomal recessive neurodegenerative disease where impaired mitochondrial function and excessive production of free radicals play a central pathogenetic role",
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"text": "BACKGROUND: Friedreich's ataxia is the most common hereditary ataxia and its clinical spectrum includes cardiac disease, mainly hypertrophic cardiomyopathy",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20073435",
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] |
640418af201352f04a000018 | Is Tilavonemab effective for progressive supranuclear palsy? | No. Tilavonemab is not effective for progressive supranuclear palsy. | [
"33609476"
] | yesno | [
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"text": "INTERPRETATION: A similar safety profile was seen in all treatment groups. No beneficial treatment effects were recorded. Although this study did not provide evidence of efficacy in progressive supranuclear palsy, the findings provide potentially useful information for future investigations of passive immunisation using tau antibodies for progressive supranuclear palsy.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/33609476",
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644e7e4757b1c7a315000077 | What does the term "homeotic transformation" mean? | Homeotic transformation refers to the process of transforming one body part into the likeness of another body part. This process is usually caused by mutations in highly conserved Hox genes, which play a crucial role in embryonic patterning across animal phyla. The study of homeotic-transformation mutants in model organisms such as Drosophila has revolutionized the field of developmental biology | [
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"text": "Homeosis is classically defined as the transformation of one body part into something that resembles another body part.",
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"text": "Homeotic transformation is defined as transformation of one body part into the likeness of something else.",
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"text": "In Drosophila, the misexpression or altered activity of genes from the bithorax complex results in homeotic transformations.",
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"text": "The discovery of the broad conservation of embryonic regulatory genes across animal phyla, launched by the cloning of homeotic genes in the 1980s, was a founding event in the field of evolutionary developmental biology (evo-devo). While it had long been known that fundamental cellular processes, commonly referred to as housekeeping functions, are shared by animals and plants across the planet-processes such as the storage of information in genomic DNA, transcription, translation and the machinery for these processes, universal codon usage, and metabolic enzymes-Hox genes were different: mutations in these genes caused \"bizarre\" homeotic transformations of insect body parts that were certainly interesting but were expected to be idiosyncratic. The isolation of the genes responsible for these bizarre phenotypes turned out to be highly conserved Hox genes that play roles in embryonic patterning throughout Metazoa.",
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"text": "The study of homeotic-transformation mutants in model organisms such as Drosophila revolutionized the field of developmental biology, but how these mutants relate to human developmental defects remains to be elucidated.",
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"text": "Homebox (Hox) genes are involved in this evolutionary mammalian conservation, and homeotic transformation of cervical into thoracic vertebrae (cervical ribs) is a common phenotypic abnormality when Hox gene expression is altered.",
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"text": "A human homeotic transformation resulting from mutations in PLCB4 and GNAI3 causes auriculocondylar syndrome.",
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64463cee57b1c7a315000065 | What is Spinal Muscular Atrophy? | Spinal muscular atrophy (SMA) is a rare autosomal recessive neuromuscular disease which is characterised by muscle atrophy and early death in most patients. It is an autosomal recessive neurodegenerative disorder of alpha motor neurons of spinal cord associated with progressive muscle weakness and hypotonia. | [
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"text": "Spinal muscular atrophy (SMA) is a rare autosomal recessive neuromuscular disease which is characterised by muscle atrophy and early death in most patients. ",
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"text": " Spinal muscular atrophy (SMA), an autosomal recessive neurodegenerative disorder of alpha motor neurons of spinal cord associated with progressive muscle weakness and hypotonia, is the most common genetic cause of infant mortality.",
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"text": "Spinal muscular atrophy (SMA) is an autosomal recessive, lower motor neuron disease.",
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"text": "Spinal muscular atrophy, lower extremity-predominant, is characterized by lower limb muscle weakness and wasting, associated with reduced numbers of lumbar motor neurons and is caused by mutations in DYNC1H1, which encodes a microtubule motor protein in the dynein-dynactin complex and one of its cargo adaptors, BICD2.",
"beginSection": "abstract",
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"text": "Spinal muscular atrophy is an autosomal recessive neurodegenerative disease characterised by degeneration of spinal cord motor neurons, atrophy of skeletal muscles, and generalised weakness.",
"beginSection": "abstract",
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{
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"text": "Spinal muscular atrophy, a hereditary degenerative disorder of lower motor neurons associated with progressive muscle weakness and atrophy, is the most common genetic cause of infant mortality.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22196485",
"endSection": "abstract"
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{
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"text": "Autosomal recessive spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by muscle atrophy combined with motor neuron degeneration.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/13129800",
"endSection": "abstract"
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{
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"text": "Spinal muscular atrophy is an autosomal recessive disease characterized by motor neurone loss, muscle atrophy and weakness.",
"beginSection": "abstract",
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"endSection": "abstract"
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"text": "Spinal muscular atrophy is a group of allelic autosomal recessive disorders characterized by progressive motoneuron loss, symmetric weakness, and skeletal muscle atrophy.",
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"text": "Spinal muscular atrophy (SMA) is a life-threatening autosomal recessive disease that leads to progressive muscle weakness and atrophy, respiratory insufficiency and scoliosis.",
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{
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"text": "Proximal spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder characterized by motor neuron loss and subsequent atrophy of skeletal muscle.",
"beginSection": "abstract",
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"text": "Spinal muscular atrophy is a genetic disorder of the motor neurons that causes profound hypotonia, severe weakness, and often fatal restrictive lung disease.",
"beginSection": "abstract",
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"endSection": "abstract"
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"text": "Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of spinal cord motor neurons and muscular atrophy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18990310",
"endSection": "abstract"
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{
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"text": "Spinal muscular atrophy is an autosomal-recessive neuromuscular disorder, causing progressive proximal weakness and atrophy of the voluntary muscles.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/24334346",
"endSection": "abstract"
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"text": "Spinal muscular atrophy (SMA) is a recessive disorder caused by a mutation in the survival motor neuron 1 gene (SMN1); it affects 1 in 11 000 newborn infants.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30221755",
"endSection": "abstract"
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{
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"text": "Spinal muscular atrophy is a devastating neurodegenerative autosomal recessive disease that results from survival of motor neuron 1 (SMN1) gene mutation or deletion.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31371124",
"endSection": "abstract"
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{
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"text": "Spinal muscular atrophy (SMA) is a debilitating neurological disorder marked by degeneration of spinal motor neurons and muscle atrophy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33979606",
"endSection": "abstract"
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{
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"text": "Spinal muscular atrophy is an autosomal-recessive disorder characterized by degeneration of motor neurons in the spinal cord and caused by mutations in the survival motor neuron 1 gene, SMN1.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26515624",
"endSection": "abstract"
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{
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"text": "Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by loss of lower motor neurons, which leads to proximal muscle weakness and atrophy.",
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"endSection": "abstract"
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"text": "Spinal muscular atrophy (SMA) is an autosomal recessive disorder that is characterized by the degeneration of the motor neurons of the spinal cord leading to muscle atrophy.",
"beginSection": "abstract",
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"text": "Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle weakness and paralysis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22047105",
"endSection": "abstract"
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"text": "Spinal muscular atrophy (SMA) is a rare autosomal recessive disorder characterized by muscle atrophy and weakness resulting from motor neuron degeneration in the spinal cord and brainstem.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28229309",
"endSection": "abstract"
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"text": "Spinal muscular atrophy (SMA) is an autosomal recessive disorder that is the leading genetic cause of infantile death.",
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"endSection": "abstract"
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"text": "Introduction: Spinal muscular atrophy is a rare genetic neurodegenerative disorder affecting the motor neurons of the anterior horn of the spinal cord, which results in muscle atrophy and weakness.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35866733",
"endSection": "abstract"
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{
"offsetInBeginSection": 105,
"offsetInEndSection": 226,
"text": "Spinal muscular atrophy is a human motoneuron disease that is genetically linked to the survival motor neuron gene (SMN).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17761655",
"endSection": "abstract"
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"offsetInEndSection": 144,
"text": "BACKGROUND: Spinal muscular atrophy is a recessively inherited autosomal neuromuscular disorder, with characteristic progressive muscle weakness",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/36376972",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 198,
"text": "Spinal muscular atrophy is a common autosomal recessive neuromuscular disorder caused by mutations in the survival motor neuron gene (SMN), which exists in 2 nearly identical copies (SMN1 and SMN2).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17761649",
"endSection": "abstract"
}
] |
643df77457b1c7a31500003b | What factors are associated with severe COVID-19? | Several factors have been associated with severe COVID-19. Age is a significant risk factor, with older adults being more likely to experience severe symptoms and require hospitalization. Individuals with underlying medical conditions such as obesity, diabetes, hypertension, cardiovascular disease, chronic respiratory disease, and cancer are also at higher risk of developing severe COVID-19. Additionally, male sex has been identified as a risk factor for severe disease. Other factors that may contribute to the severity of COVID-19 include smoking history and immunocompromised status. It is important to note that while these factors have been associated with increased risk of severe disease, anyone can develop severe COVID-19 regardless of age or underlying health conditions. Therefore, it is crucial to continue practicing preventive measures such as wearing masks, social distancing, and frequent hand washing to reduce the spread of the virus and protect vulnerable populations. | [
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"text": " There was low or moderate certainty evidence for a large (≥2-fold) magnitude of association between hospitalisation in people with COVID-19, and: obesity class III, heart failure, diabetes, chronic kidney disease, dementia, age >45 years, male gender, black race/ethnicity (vs non-Hispanic white), homelessness and low income. Age >60 and >70 years may be associated with large increases in mechanical ventilation and severe disease, respectively. For mortality, a large magnitude of association may exist with liver disease, Bangladeshi ethnicity (vs British white), age >45 years, age >80 years (vs 65-69 years) and male gender among 20-64 years (but not older). Associations with hospitalisation and mortality may be very large (≥5-fold) for those aged ≥60 years.",
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"text": "Increasing age (especially >60 years) may be the most important risk factor for severe outcomes.",
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"text": "In multivariable logistic regression analyses, increasing age (adjusted odds ratio [aOR] 1.1, 95% confidence interval [CI] 1.1-1.2, p<0.001), male gender (aOR 1.8, 95% CI 1.2-2.7, p = 0.002), Hispanic ethnicity (aOR 1.9, 95% CI 1.2-3.1, p = 0.01), obesity (3.1, 95% CI 1.9-5.1, p<0.001), asthma history (aOR 2.3, 95% CI 1.3-4.0, p = 0.003), congestive heart failure (aOR 6.0, 95% CI 1.5-25.1, p = 0.01), cerebrovascular disease (aOR 4.9, 95% CI 1.7-14.7, p = 0.004), and diabetes (aOR 3.4, 95% CI 1.9-6.2, p<0.001) were predictive of severe disease diagnoses within 30 days.",
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"text": "The strongest association with risk of severe disease after vaccination was age, which increased among patients aged 50 years or older with an adjusted odds ratio (aOR) of 1.42 (CI, 1.40-1.44) per 5-year increase in age, such that patients aged 80 years or older had an aOR of 16.58 (CI, 13.49-20.37) relative to patients aged 45 to 50 years. Immunocompromising conditions, including receipt of different classes of immunosuppressive medications (eg, leukocyte inhibitor: aOR, 2.80; 95% CI, 2.39-3.28) or cytotoxic chemotherapy (aOR, 2.71; CI, 2.27-3.24) prior to breakthrough infection, or leukemias or lymphomas (aOR, 1.87; CI, 1.61-2.17) and chronic conditions associated with end-organ disease, such as heart failure (aOR, 1.74; CI, 1.61-1.88), dementia (aOR, 2.01; CI, 1.83-2.20), and chronic kidney disease (aOR, 1.59; CI, 1.49-1.69), were also associated with increased risk.",
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"text": "Factors associated with severe COVID-19 were older age [adjusted relative risk (aRR) 1.78, 95% confidence interval (CI) 1.61-1.97; P < 0.0001], diabetes (aRR 2.00, 95% CI 1.20-3.32; P = 0.007), cardiovascular disease (aRR 2.53, 95% CI 1.53-4.17; P < 0.0001), malignancy (aRR 4.57, 95% CI 1.62-12.87; P = 0.004), surgery/trauma (aRR 23.98, 95% CI 10.35-55.57; P < 0.0001) and human immunodeficiency virus infection (aRR 4.24, 95% CI 1.55-11.61; P = 005).",
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"text": "Cirrhosis was an independent predictor of severe COVID-19 in patients with AIH (P < 0.001; OR, 17.46; 95% CI, 4.22-72.13).",
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"text": "Data regarding outcome of COVID-19 in patients with autoimmune hepatitis (AIH) are lacking.",
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"text": "Cirrhosis was the strongest predictor for severe COVID-19 in patients with AIH.",
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"text": " Older age, male sex, non-White race, Hispanic ethnicity, obesity, and a higher number of chronic conditions were associated with increased risk of severe infection.",
"beginSection": "abstract",
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"text": "In particular, persons 0 to 44 years of age with cancer, chronic neurologic disorders, hematologic disorders, ischemic heart disease, and other endocrine disorders had a greater than 3-fold increased risk of severe infection compared with persons of the same age without those conditions.",
"beginSection": "abstract",
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"text": "Sleep apnoea is a risk factor for severe COVID-19.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33436406",
"endSection": "title"
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{
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"text": "Various risk factors for a severe course, such as higher age, male gender and pre-existing illnesses are known.",
"beginSection": "abstract",
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"endSection": "abstract"
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{
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"text": "Males could at higher risk of developing severe symptoms of COVID-19 than females.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33050972",
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"text": "COVID-19 severity was associated only with older age and cardiac disease, in a multivariate analysis.",
"beginSection": "abstract",
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{
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"text": "Age, gender, and comorbidities are known to be risk factors for severe COVID-19 but are generally considered independently without accurate knowledge of the magnitude of their effect on risk, potentially resulting in incorrect risk estimation.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33592063",
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{
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"text": "Immune deficiency is a risk factor for severe COVID-19 in people living with HIV.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33368966",
"endSection": "title"
},
{
"offsetInBeginSection": 173,
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"text": " This study aimed to clarify the association between nervous system diseases and severity or mortality in patients with COVID-19.",
"beginSection": "abstract",
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"endSection": "abstract"
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"text": "Health factors such as diabetes, severe obesity and chronic kidney disease are all associated with a more severe outcome following coronavirus disease 2019 (COVID-19) infection.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32878679",
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"text": "BACKGROUND: Lifestyle factors including obesity and smoking are suggested to be correlated with increased risk of COVID-19 severe illness or related death",
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"endSection": "abstract"
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{
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"text": "There is no evidence supporting that NAFLD is a causal risk factor for severe COVID-19. Previous observational associations between NAFLD and COVID-19 are likely attributed to the correlation between NAFLD and obesity.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35124268",
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641791ed690f196b51000032 | Is SARS-CoV-2 transmitted through breast milk? | No, SARS-CoV-2 is not transmitted through breast milk. | [
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"text": "No infectious SARS-CoV-2 in breast milk from a cohort of 110 lactating women.",
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"text": "SARS-CoV-2 RNA can be found infrequently in the breastmilk after recent infection, but we found no evidence that breastmilk contains an infectious virus or that breastfeeding represents a risk factor for transmission of infection to infants.",
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"text": "This article goes beyond prior small studies to provide evidence that infectious SARS-CoV-2 is not present in the milk of lactating women with recent infection, even when SARS-CoV-2 RNA is detected.",
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"text": "Recent SARS-CoV-2 infection or detection of its RNA in human milk is not a contraindication to breastfeeding.",
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"text": "Based on the currently available limited evidence and recognizing the benefits of breastfeeding, it may be concluded that if the health of the mother and her newborn allows, direct breastfeeding or extracted breastmilk should be encouraged by the healthcare providers after a careful discussion of the risks of vertical transmission to the mother and her family",
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"text": "Preventive measures should be taken by COVID-19 mothers to prevent droplet transmission of infection to the infants while breastfeeding.",
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"endSection": "abstract"
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{
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"text": "Currently, there is no evidence of SARS-CoV-2 transmission through breast milk.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/32860259",
"endSection": "abstract"
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{
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"text": "The authors could not find evidence for transmission of SARS-CoV-2 from mother to child through breastmilk in the population studied.",
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"text": "At present, there is limited information on potential transmission of the infection from mother to child, particularly through breast milk and breastfeeding.",
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"endSection": "abstract"
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{
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"text": "However, there is limited published literature related to vertical transmission of any human coronaviruses (including SARS-CoV-2) via human milk and/or breastfeeding.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32472745",
"endSection": "abstract"
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{
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"text": "However, there is limited published literature related to vertical transmission of any human coronavirus (including SARS-CoV-2) via human milk and/or breastfeeding.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32511431",
"endSection": "abstract"
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"text": "and had a benign clinical course. There was no evidence of significant clinical infection during the hospital stay or from outpatient neonatal follow-up data for all the infants included in this study.CONCLUSION: In a small cohort of SARS-CoV-2 positive lactating mothers giving birth at our institution, most of their breast milk samples (95%) contained no detectable virus, and there was no evidence of COVID-19 infection in their breast milk-fed neonates.KEY POINTS: · Breast milk may rarely contain detectable SARS-CoV-2 RNA and was not detected in asymptomatic mothers.. · Breast milk with detectable SARS-CoV-2 RNA from a symptomatic mother had no clinical significance for her infant.. · Breast feeding with appropriate infection control instru",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34182576",
"endSection": "abstract"
},
{
"offsetInBeginSection": 793,
"offsetInEndSection": 886,
"text": "Taken together, our data do not support mother-to-infant transmission of SARS-CoV-2 via milk.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33563823",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1132,
"offsetInEndSection": 1387,
"text": "th SARS-CoV-2 neutralization. Strong correlations between levels of IgA and IgG to SARS-CoV-2 and seasonal coronaviruses were noted.CONCLUSIONS: Our data do not support maternal-to-child transmission of SARS-CoV-2 via milk; however, risk of transmission v",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32995804",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1146,
"offsetInEndSection": 1226,
"text": " Currently, there is no evidence of SARS-CoV-2 transmission through breast milk.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32860259",
"endSection": "abstract"
},
{
"offsetInBeginSection": 42,
"offsetInEndSection": 109,
"text": " Whether SARS-CoV-2 was transmitted through breast milk is unknown.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33344466",
"endSection": "abstract"
},
{
"offsetInBeginSection": 774,
"offsetInEndSection": 938,
"text": "No breast milk samples were positive for SARS-CoV-2 and, to date, there is no evidence on the presence of SARS-CoV-2 in breast milk of pregnant women with COVID-19.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32454808",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1409,
"offsetInEndSection": 1559,
"text": "from 11 women tested negative.INTERPRETATION: Considering the lack of evidence for SARS-CoV-2 transmission through breast milk, breastfeeding counsell",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34013217",
"endSection": "abstract"
}
] |
644ef78f57b1c7a315000084 | Chromatin is tightly packed into what structure inside the nucleus? | Chromatin, a complex of DNA and proteins, is tightly packed into a highly organized structure called the nucleosome inside the nucleus. Nucleosomes are the fundamental repeating units of chromatin and consist of approximately 147 base pairs of DNA wrapped around an octamer of histone proteins, which include two copies each of histone H2A, H2B, H3, and H4. The nucleosomes are connected by linker DNA and further compacted through interactions with additional histone proteins such as histone H1. This organization allows for efficient packaging of the long DNA molecules within the confined space of the nucleus while still permitting access to genetic information for processes like transcription, replication, and repair. The degree of chromatin compaction can vary depending on cellular context and regulatory mechanisms, ultimately influencing gene expression patterns in response to various signals or environmental cues. | [
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"text": "Our genetic information is tightly packaged into a rather ingenious nucleoprotein complex called chromatin in a manner that enables it to be rapidly accessed during genomic processes. Formation of the nucleosome, which is the fundamental unit of chromatin, occurs via a stepwise process that is reversed to enable the disassembly of nucleosomes.",
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"text": "DNA in eukaryotes is packed into chromatin. The basic component of chromatin is the nucleosome consisting of DNA wrapped around a histone octamer. Inside the cell nucleus, chromatin is folded into higher-order structures through various mechanisms, including repositioning of nucleosomes along the DNA, packing of nucleosomes into more condensed 3-dimensional configurations, looping of chromatin fibres, and tethering of chromosomal regions to nuclear structures.",
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"text": "Inside the cell nucleus, chromatin is folded into higher-order structures through various mechanisms, including repositioning of nucleosomes along the DNA, packing of nucleosomes into more condensed 3-dimensional configurations, looping of chromatin fibres, and tethering of chromosomal regions to nuclear structures.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15868422",
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"text": "Chromatin is a tightly packaged structure of DNA and protein within the nucleus of a cell.",
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"text": "The basic unit of chromatin is the nucleosome, which consists of a short piece of DNA wrapped around a core of eight histone proteins.",
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"endSection": "abstract"
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{
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"text": "In addition to their role in packaging DNA, nucleosomes impact the regulation of essential nuclear processes such as replication, transcription, and repair by controlling the accessibility of DNA.",
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"text": "DNA repair in eukaryotic cells takes place in the context of chromatin, where DNA, including damaged DNA, is tightly packed into nucleosomes and higher order chromatin structures.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23109894",
"endSection": "abstract"
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] |
644284a957b1c7a31500005c | Is there any treatment for the Facioscapulohumeral Muscular Dystrophy? | No, currently there are no approved therapies for the Facioscapulohumeral Muscular Dystrophy, only supportive treatment. | [
"31794465",
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] | yesno | [
{
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"text": "The treatment of FSHD is currently supportive only.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31794465",
"endSection": "abstract"
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{
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"text": "Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive muscular dystrophy without approved therapies.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35428982",
"endSection": "abstract"
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] |
644e7e5257b1c7a315000078 | What is the role of enhancers in cancer? | Enhancers are regulatory elements that control gene expression by binding to transcription factors and promoting the recruitment of RNA polymerase II to the promoter region. In cancer, enhancers can play a critical role in driving oncogenic transcriptional programs by activating genes involved in cell proliferation, survival, and invasion. Enhancer activation can occur through various mechanisms, including genetic alterations such as amplifications or translocations, epigenetic modifications such as histone acetylation or DNA methylation, and aberrant signaling pathways. Recent studies have shown that enhancer hijacking is a common mechanism of oncogene activation in cancer, where non-coding mutations can create de novo enhancers or redirect existing ones to drive oncogenic gene expression. Targeting enhancer-driven transcriptional programs has emerged as a promising therapeutic strategy for cancer treatment, with several ongoing clinical trials testing small molecule inhibitors of key transcriptional regulators or chromatin modifiers involved in enhancer regulation. | [
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"text": "Recent advances in genome-wide analyses have revealed that the deregulation of distal gene regulatory elements, such as enhancers, appears in several pathophysiological conditions, including cancer. Beyond the conventional function of enhancers in recruiting transcription factors to gene promoters, enhancer elements are also transcribed into noncoding RNAs known as enhancer RNAs (eRNA). Accumulating evidence suggests that uncontrolled enhancer activity with aberrant eRNA expression promotes oncogenesis. Interestingly, tissue-specific, transcribed eRNAs from active enhancers can serve as potential therapeutic targets or biomarkers in several cancer types.",
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"text": "Enhancers are cis-regulatory sequences that fine-tune expression of their target genes in a spatiotemporal manner. They are recognized by sequence-specific transcription factors, which in turn recruit transcriptional coactivators that facilitate transcription by promoting assembly and activation of the basal transcriptional machinery. Their functional importance is underscored by the fact that they are often the target of genetic and nongenetic events in human disease that disrupt their sequence, interactome, activation potential, and/or chromatin environment. Dysregulation of transcription and addiction to transcriptional effectors that interact with and modulate enhancer activity are common features of cancer cells and are amenable to therapeutic intervention.",
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"text": "Enhancer is one kind of cis-elements regulating gene transcription, whose activity is tightly controlled by epigenetic enzymes and histone modifications. Active enhancers are classified into typical enhancers, super-enhancers and over-active enhancers, according to the enrichment and location of histone modifications.",
"beginSection": "abstract",
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"text": "Recent studies have revealed enhancer dysregulation as one of the important features for cancer. Variations in enhancer regions and mutations of enhancer regulatory genes are frequently observed in cancer cells, and altering the activity of onco-enhancers is able to repress oncogene expression, and suppress tumorigenesis and metastasis.",
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"text": "The disruption of enhancer activity, through genetic or epigenetic alterations, can impact cell-type-specific functions, resulting in a wide range of pathologies. In cancer, these alterations can promote a 'cell identity crisis', in which enhancers associated with oncogenes and multipotentiality are activated, while those promoting cell fate commitment are inactivated. Overall, these alterations favor an undifferentiated cellular phenotype.",
"beginSection": "abstract",
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"text": "Enhancers are selectively utilized to orchestrate gene expression programs that first govern pluripotency and then proceed to highly specialized programs required for the process of cellular differentiation.",
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"endSection": "abstract"
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"text": "Enhancer elements function as the logic gates of the genetic regulatory circuitry. One of their most important functions is the integration of extracellular signals with intracellular cell fate information to generate cell type-specific transcriptional responses. Mutations occurring in cancer often misregulate enhancers that normally control the signal-dependent expression of growth-related genes. This misregulation can result from trans-acting mechanisms, such as activation of the transcription factors or epigenetic regulators that control enhancer activity, or can be caused in cis by direct mutations that alter the activity of the enhancer or its target gene specificity. These processes can generate tumour type-specific super-enhancers and establish a 'locked' gene regulatory state that drives the uncontrolled proliferation of cancer cells.",
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"endSection": "abstract"
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{
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"text": "Transcription factors, cofactors, chromatin regulators, and transcription apparatuses interact with transcriptional regulatory elements, including promoters, enhancers, and super-enhancers (SEs), to coordinately regulate the transcription of target genes and thereby control cell behaviors. Among these transcriptional regulatory components and related elements, SEs often play a central role in determining cell identity and tumor initiation and progression. Therefore, oncogenic SEs, which are generated within cancer cells in oncogenes and other genes important in tumor pathogenesis, have emerged as attractive targets for novel cancer therapeutic strategies in recent years.",
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"endSection": "abstract"
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{
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"text": "Transcriptional dysregulation of these pathways is commonly associated with tumorigenesis and the development of cancer. Genetic and epigenetic alterations may mediate dysregulated transcriptional activity. One of the most important epigenetic alternations is the non-coding regulatory element, which includes both enhancers and super-enhancers (SEs). SEs, characterized as large clusters of enhancers with aberrant high levels of transcription factor binding, have been considered as key drivers of gene expression in controlling and maintaining cancer cell identity. In cancer cells, oncogenes acquire SEs and the cancer phenotype relies on these abnormal transcription programs driven by SEs, which leads to cancer cells often becoming addicted to the SEs-related transcription programs, including prostate cancer.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33299103",
"endSection": "abstract"
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{
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"text": "In fact, many human cancers and diseases are associated with the malfunction of enhancers.",
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{
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"text": "We discuss how enhancer dysregulation is a common theme in SWI/SNF mutant cancers and describe how resultant alterations in enhancer and super-enhancer activity conspire to block development and differentiation while promoting stemness and self-renewal.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35911061",
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{
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"text": "Mutations occurring in cancer often misregulate enhancers that normally control the signal-dependent expression of growth-related genes.",
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"endSection": "abstract"
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{
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"text": "Many human cancers were found to associate with enhancer malfunction, due to genetic and epigenetic alterations, which in some cases directly drive tumour growth.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31916476",
"endSection": "abstract"
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{
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"text": "These processes can generate tumour type-specific super-enhancers and establish a 'locked' gene regulatory state that drives the uncontrolled proliferation of cancer cells.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/27364481",
"endSection": "abstract"
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{
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"text": "In cancer, super-enhancers have multifaceted roles by activating various oncogenes and other cancer-related genes and shaping characteristic gene expression patterns in cancer cells.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/35967935",
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{
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"text": "In this review we discuss different mechanisms through which enhancers are exploited in malignant B cells, from the well-studied translocations juxtaposing oncogenes to immunoglobulin loci, through enhancer dysregulation by sequence variants and mutations, to enhancer hijacking by viruses.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34210001",
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{
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"text": "In cancer, these alterations can promote a 'cell identity crisis', in which enhancers associated with oncogenes and multipotentiality are activated, while those promoting cell fate commitment are inactivated.",
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{
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"text": "Super-enhancers, characterized as large clusters of enhancers in close proximity, have been identified as essential oncogenic drivers required for the maintenance of cancer cell identity.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30885876",
"endSection": "abstract"
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] |
6441371857b1c7a315000057 | What are the currently used non-pharmacological measures for the management of procedural pain in neonates? | Breastfeeding or breast milk can be an effective measure for managing procedural pain in neonates, along with other non-pharmacological measures like holding, swaddling, and skin-to-skin contact. | [
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"text": " Non-pharmacological comfort measures such as breastfeeding, swaddling and sweet solutions are inconsistently implemented and are not always practical or effective in reducing the transmission of noxious input to the brain. ",
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"text": "In this comparative effectiveness research 195 neonates >36 weeks' gestation were randomised to three groups, receiving during heel stick: (i) breastfeeding, (ii) sucrose 24% liquid with non-nutritive sucking and (iii) sucrose 24% gel with non-nutritive sucking. ",
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"text": "All the methods analysed has shown to be effective in reducing pain",
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"text": "There was an increase in odds of pain following liquid sucrose compared to breastfeeding (OR = 1.60; 95% CI: 0.82-3.3; p = 0.17).",
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"text": "Sucrose 24% gel with non-nutritive sucking seems to be a valid alternative when breastfeeding is not possible. Further research is needed.",
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{
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"text": "Oral sucrose is commonly given to children to reduce procedural pain.",
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{
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"text": "he present systematic review and meta-analyses demonstrate that glucose reduces pain scores and crying during single heel lances and venipunctures. Results indicate that 20% to 30% glucose solutions have analgesic effects and can be recommended as an alternative to sucrose for procedural pain reduction in healthy term and preterm neonates.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23748256",
"endSection": "abstract"
}
] |
644e642a57b1c7a315000075 | Do all proteins start with methionine? | All proteins do not necessarily start with methionine, but it is common for eukaryotic and archaeal proteins to begin with this amino acid. During the initiation of translation, the first codon in the mRNA sequence is typically an AUG codon, which codes for methionine. This process is facilitated by the initiator tRNA (tRNAi^Met) that carries methionine and recognizes the start codon. However, there are exceptions to this rule. In some cases, alternative start codons such as CUG, GUG, or UUG can be used to initiate translation in both prokaryotes and eukaryotes. These alternative start codons usually code for amino acids like leucine or valine instead of methionine. Additionally, post-translational modifications can occur after protein synthesis, leading to the removal of the initial methionine or its modification into another amino acid like acetylated methionine or formylmethionine (fMet), which is commonly found in bacterial proteins. Therefore, while many proteins do initially start with methionine due to the canonical AUG start codon, there are exceptions where alternative initiation events or post-translational modifications result in proteins that do not begin with this amino acid. | [
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"text": "The use of several translation initiation codons in a single mRNA, by expressing several proteins from a single gene, contributes to the generation of protein diversity. A small, yet growing, number of mammalian mRNAs initiate translation from a non-AUG codon, in addition to initiating at a downstream in-frame AUG codon. Translation initiation on such mRNAs results in the synthesis of proteins harbouring different amino terminal domains potentially conferring on these isoforms distinct functions.",
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"text": "In eukaryotes, it is generally assumed that translation initiation occurs at the AUG codon closest to the messenger RNA 5' cap. However, in certain cases, initiation can occur at codons differing from AUG by a single nucleotide, especially the codons CUG, UUG, GUG, ACG, AUA and AUU. While non-AUG initiation has been experimentally verified for a handful of human genes, the full extent to which this phenomenon is utilized--both for increased coding capacity and potentially also for novel regulatory mechanisms--remains unclear.",
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"text": "The removal of N-terminal translation initiator Met by methionine aminopeptidase (MetAP) is often crucial for the function and stability of proteins.",
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"text": "Protein synthesis is initiated by methionine in eukaryotes and by formylmethionine in prokaryotes. N-terminal methionine can be co-translationally cleaved by the enzyme methionine aminopeptidase (MAP).",
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"text": "Our understanding of translation underpins our capacity to engineer living systems. The canonical start codon (AUG) and a few near-cognates (GUG, UUG) are considered as the 'start codons' for translation initiation in Escherichia coli.",
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"text": "Translation from non-canonical start codons ranged from 0.007 to 3% relative to translation from AUG.",
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"text": "Protein synthesis is initiated universally with the amino acid methionine. In Escherichia coli, studies with anticodon sequence mutants of the initiator methionine tRNA have shown that protein synthesis can be initiated with several other amino acids. In eukaryotic systems, however, a yeast initiator tRNA aminoacylated with isoleucine was found to be inactive in initiation in mammalian cell extracts.",
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"text": "Our results show that in the presence of the corresponding mutant initiator tRNAs, AGG and GUC can initiate protein synthesis in COS1 cells with methionine and valine, respectively. CAG initiates protein synthesis with glutamine but extremely poorly, whereas UAG could not be used to initiate protein synthesis with glutamine.",
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"text": "Methionine is the universal translation start but the first methionine is removed from most mature proteins.",
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"text": "Protein synthesis generally starts with a methionine that is removed during translation.",
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"text": "Most mature proteins do not retain their initial N-terminal amino acid (methionine in the cytosol and N-formyl methionine in the organelles).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11738381",
"endSection": "abstract"
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6442810c57b1c7a31500005a | Which are the types of Facioscapulohumeral Muscular Dystrophy? | There are two types of Facioscapulohumeral Muscular Dystrophy: FSHD1 and FSHD2. | [
"21496633"
] | list | [
{
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"text": " The molecular genetics of FSHD are complex, with current understanding focusing on epigenetic effects related to contraction-dependent (FSHD1) and contraction-independent (FSHD2) effects of a hypomethylated repeat sequence (D4Z4), in the presence of a specific 4qA161 phenotype. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21496633",
"endSection": "abstract"
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] |
644f057357b1c7a315000087 | Which transcription factors are essential for the melanocyte lineage? | Microphthalmia-associated transcription factor (MITF) is the master regulator of the melanocyte lineage. It governs multiple steps in the development of melanocytes, including specification from the neural crest, growth, survival, and terminal differentiation. However, MITF does not act alone. ChIP-seq studies have indicated that the transcription factors SOX10, YY1, and TFAP2A co-occupy subsets of regulatory elements bound by MITF in melanocytes. Analyses at single loci also support roles for LEF1, RB1, IRF4, and PAX3 acting in combination with MITF, while sequence motif analyses suggest that additional transcription factors co-localize with MITF at many melanocyte-specific regulatory elements. Nonetheless, the precise biochemical functions of each of these MITF collaborators and their contributions to gene expression remain to be elucidated. | [
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"text": "Microphthalmia-associated transcription factor (MITF) is the master regulator of the melanocyte lineage.",
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"text": "MITF and SOX10 actively recruit BRG1 to a set of MITF-associated regulatory elements (MAREs) at active enhancers. Combinations of MITF, SOX10, TFAP2A, and YY1 bind between two BRG1-occupied nucleosomes thus defining both a signature of transcription factors essential for the melanocyte lineage and a specific chromatin organisation of the regulatory elements they occupy.",
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"text": "MITF governs multiple steps in the development of melanocytes, including specification from neural crest, growth, survival, and terminal differentiation.",
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"text": "However, MITF does not act alone.",
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"text": "ChIP-seq studies have indicated that the transcription factors SOX10, YY1, and TFAP2A co-occupy subsets of regulatory elements bound by MITF in melanocytes. Analyses at single loci also support roles for LEF1, RB1, IRF4, and PAX3 acting in combination with MITF, while sequence motif analyses suggest that additional transcription factors colocalize with MITF at many melanocyte-specific regulatory elements. However, the precise biochemical functions of each of these MITF collaborators and their contributions to gene expression remain to be elucidated.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28649789",
"endSection": "abstract"
},
{
"offsetInBeginSection": 682,
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"text": "Combinations of MITF, SOX10, TFAP2A, and YY1 bind between two BRG1-occupied nucleosomes thus defining both a signature of transcription factors essential for the melanocyte lineage and a specific chromatin organisation of the regulatory elements they occupy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25803486",
"endSection": "abstract"
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{
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"text": "The microphthalmia-associated transcription factor (Mitf) is essential for melanocytic lineage development and for expression of melanogenic enzymes, such as tyrosinase.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11830592",
"endSection": "abstract"
},
{
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"text": "Mitf encodes a basic helix-loop-helix transcription factor that plays an essential role in the differentiation of the retinal pigmented epithelium (RPE) and neural crest-derived melanocytes.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15277526",
"endSection": "abstract"
},
{
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"text": "Commitment to the melanocyte lineage is characterized by the onset of expression of the microphthalmia-associated transcription factor (Mitf).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17000761",
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{
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"text": "The microphthalamia-associated transcription factor (MITF) is an integral transcriptional regulator in melanocyte, the lineage from which melanoma cells originate.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12789278",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 135,
"text": "Commitment to the melanocyte lineage is characterized by the onset of microphthalmia-associated transcription factor (Mitf) expression.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/10770922",
"endSection": "abstract"
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{
"offsetInBeginSection": 462,
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"text": "BRG1 is essential for melanoma cell proliferation in vitro and for normal melanocyte development in vivo.",
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"endSection": "abstract"
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{
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"text": "Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells.",
"beginSection": "title",
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"endSection": "title"
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{
"offsetInBeginSection": 1001,
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"text": "MITF-BRG1 interplay thus plays an essential role in transcription regulation in melanoma.",
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"endSection": "abstract"
},
{
"offsetInBeginSection": 105,
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"text": "The basic helix-loop-helix microphthalmia transcription factor (MITF) is the master regulator determining the identity and properties of the melanocyte lineage, and is regarded as a lineage-specific 'oncogene' that has a critical role in the pathogenesis of melanoma.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21258399",
"endSection": "abstract"
},
{
"offsetInBeginSection": 273,
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"text": "MITF regulates expression of numerous pigmentation genes to promote melanocyte differentiation, as well as fundamental genes for maintaining cell homeostasis, including genes encoding proteins involved in apoptosis (eg, BCL2) and the cell cycle (eg, CDK2).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28263292",
"endSection": "abstract"
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{
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"text": "During embryogenesis, the transcription factor, Sox10, drives the survival and differentiation of the melanocyte lineage.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23935512",
"endSection": "abstract"
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{
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"text": "MITF encodes a transcription factor that is essential for normal melanocyte development and appears to regulate expression of several pigmentation genes.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/12819038",
"endSection": "abstract"
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{
"offsetInBeginSection": 324,
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"text": "Mitf is a basic helix-loop-helix-leucine zipper transcription factor whose M isoform is restricted to neural crest derived melanocytes and is essential for the development of these cells in vertebrates from mammals to fish.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/14660543",
"endSection": "abstract"
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{
"offsetInBeginSection": 826,
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"text": " In melanocytes, studies have so far focused on the Sox10 protein which functions both during melanocyte specification and at later times in the melanocyte lineage.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15760336",
"endSection": "abstract"
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{
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"text": " However, the molecular mechanisms by which SOX10 guides the appropriate gene expression programs necessary to promote the melanocyte lineage are not fully understood.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26206884",
"endSection": "abstract"
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{
"offsetInBeginSection": 475,
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"text": " SMARCA4 is also required for development of multipotent neural crest precursors into melanoblasts, which differentiate into pigment-producing melanocytes.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36112085",
"endSection": "abstract"
},
{
"offsetInBeginSection": 990,
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"text": " During specification, Sox10 activates the Mitf gene as the key regulator of melanocyte development.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15760336",
"endSection": "abstract"
},
{
"offsetInBeginSection": 953,
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"text": " MITF directs the terminal differentiation of melanocytes, and PAX3 helps to establish the properties of the melanocyte stem cells.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22999738",
"endSection": "abstract"
},
{
"offsetInBeginSection": 473,
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"text": " Functionally, Tfap2b is required for only a few late-stage embryonic melanocytes, and is essential for McSC-dependent melanocyte regeneration.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/35021087",
"endSection": "abstract"
},
{
"offsetInBeginSection": 105,
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"text": "Here, by screening a pool of candidate transcription factors, we identify that a combination of the three factors, MITF, SOX10 and PAX3, directly converts mouse and human fibroblasts to functional melanocytes.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25510211",
"endSection": "abstract"
}
] |
644298cc57b1c7a315000062 | What is the cause of Facioscapulohumeral Muscular Dystrophy type 2 (FSHD2)? | FSHD2 is caused by mutations in the protein regulating the methylation status of chromatin - SMCHD1. | [
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{
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"text": "Facial-scapular-humeral myodystrophy Landouzy-Dejerine (FSHD) is an autosomal dominant disease, the basis of its pathogenesis is ectopic expression of the transcription factor DUX4 in skeletal muscle.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30871534",
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"text": "FSHD2 is caused by the mutations in the protein regulating the methylation status of chromatin - SMCHD1.",
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"text": "Given the previous report of SMCHD1 mutations in FSHD2 and the clinical presentations consistent with the FSHD phenotype, we conclude that the SMCHD1 mutation is the likely cause of the disease in this family.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/24128691",
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"text": "Exome sequencing identifies a novel SMCHD1 mutation in facioscapulohumeral muscular dystrophy 2.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/24128691",
"endSection": "title"
},
{
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"text": "Recently, mutations in SMCHD1 combined with a permissive 4q35 allele were reported to cause FSHD2.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/24128691",
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{
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"text": "Facioscapulohumeral muscular dystrophy type 2 (FSHD2) accounts for approximately 5% of all cases of FSHD and describes patients without a D4Z4 repeat contraction on chromosome 4.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/34711481",
"endSection": "abstract"
},
{
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"text": "Type 1 facioscapulohumeral muscular dystrophy (FSHD) is caused by contraction of D4Z4 repeats on 4q35, whereas type 2 FSHD is associated with mutations of the SMCHD1 or DNMT3B gene in the presence of a disease-permissive 4qA haplotype.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30923442",
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{
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"text": "Facioscapulohumeral muscular dystrophy (FSHD) 2 is caused by a combination of heterozygous structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHD1) mutation plus DNA hypomethylation on D4Z4.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30327220",
"endSection": "abstract"
},
{
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"text": "The less common form of the disease, FSHD2, results from haploinsufficiency of the SMCHD1 gene in individuals carrying a permissive 4qA allele, also leading to the derepression of DUX4, further supporting a central role for DUX4.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28915324",
"endSection": "abstract"
},
{
"offsetInBeginSection": 463,
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"text": "iduals and 1-10 repeats in patients), and FSHD2 is caused by mutations in SMCHD1 or DNMT3B. Here, we present clinical features and results of genetic ",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/29402602",
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{
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"text": "OBJECTIVE: To determine whether congenital arhinia/Bosma arhinia microphthalmia syndrome (BAMS) and facioscapulohumeral muscular dystrophy type 2 (FSHD2), 2 seemingly unrelated disorders both caused by heterozygous pathogenic missense variants in the SMCHD1 gene, might represent different ends of a broad single phenotypic spectrum associated with SMCHD1 dysfunction",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29980640",
"endSection": "abstract"
}
] |
6446c89e57b1c7a315000073 | What is Spinal-bulbar muscular atrophy (SBMA)? | Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease (KD), is a recessive X-linked and adult-onset neurodegenerative disorder caused by the expansion of trinucleotide cytosine-adenine-guanine (CAG) repeats in exon 1, which encodes a polyglutamine tract in the androgen receptor (AR) gene. | [
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"text": "Spinal and bulbar muscular atrophy (SBMA) is an X-linked and adult-onset neurodegenerative disorder caused by the expansion of trinucleotide cytosine-adenine-guanine repeats, which encodes a polyglutamine tract in the androgen receptor gene.",
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"text": "Kennedy's disease (KD), also known as spinal and bulbar muscular atrophy (SBMA), is a rare, adult-onset, X-linked recessive neuromuscular disease caused by CAG expansions in exon 1 of the androgen receptor gene (AR).",
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"text": "Spinal and bulbar muscular atrophy (SBMA) is an X-linked adult motor neuron disorder caused by an abnormal CAG-repeat expansion in the first exon of the androgen receptor gene. ",
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"text": "Spinal and bulbar muscular atrophy (SBMA) is a late-onset motor neuron disease characterized by proximal muscle atrophy, weakness, contraction fasciculations, and bulbar involvement.",
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"text": "Spinal and bulbar muscular atrophy (SBMA) is an adult-onset degenerative disorder of the neuromuscular system resulting in slowly progressive weakness and atrophy of the proximal limb and bulbar muscles.",
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"text": "Spinal and bulbar muscular atrophy (SBMA) is an X-linked, adult-onset motor neuronopathy that is caused by expansion of a trinucleotide (CAG) repeat in the androgen-receptor gene.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/8545913",
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"text": "Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is an adult-onset, X-linked motor neuron disease characterized by muscle atrophy, weakness, contraction fasciculations, and bulbar involvement.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22476656",
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"text": "Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disorder of lower motor neurons characterized by proximal limb muscular atrophy, bulbar involvement, marked fasciculation, hand tremor and gynaecomastia.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/24785145",
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"text": "Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motor neuron disease, caused by the expansion of a trinucleotide repeat (TNR) in exon 1 of the androgen receptor (AR) gene.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/12189162",
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"text": "Spinal and bulbar muscular atrophy (SBMA) is an adult-onset neurodegenerative disease characterized by slowly progressive muscle weakness and atrophy.",
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"text": "Spinal and bulbar muscular atrophy (SBMA), or Kennedy disease, is an adult-onset lower motor neuron disease characterized by slowly progressive muscle weakness and atrophy.",
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"text": "Spinal and bulbar muscular atrophy (SBMA) is a hereditary neurodegenerative disease characterized by slowly progressive muscle weakness and atrophy of bulbar, facial, and limb muscles.",
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"text": "Spinal and bulbar muscular atrophy (SBMA) is a rare, X-linked neuromuscular disease characterised by lower motor neurons degeneration, slowly progressive myopathy and multisystem involvement.",
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"text": "Spinal and bulbar muscular atrophy: a trinucleotide-repeat expansion neurodegenerative disease.",
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"text": "X-linked spinal and bulbar muscular atrophy (SBMA; Kennedy's disease) is a polyglutamine (polyQ) disease in which the affected males suffer progressive motor neuron degeneration accompanied by signs of androgen insensitivity, such as gynecomastia and reduced fertility.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/16772330",
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"text": "SBMA (spinal and bulbar muscular atrophy), also called Kennedy disease, is an X-chromosomal recessive adult-onset neurodegenerative disorder caused by death of the spinal and bulbar motor neurones and dorsal root ganglia.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/11436124",
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{
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"text": "Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's Disease, is a late-onset X-linked progressive neuromuscular disease, which predominantly affects males.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32152060",
"endSection": "abstract"
},
{
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"text": "Spinal and Bulbar Muscular Atrophy (SBMA) is an X-linked adult-onset progressive neuromuscular disease that affects the spinal and bulbar motor neurons and skeletal muscles.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/35726299",
"endSection": "abstract"
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{
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"text": "SBMA, also known as Kennedy's disease, is a neurodegenerative disease caused by an expansion of a repeat of the trinucleotide CAG encoding glutamine in the gene encoding androgen receptor (AR).",
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{
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"text": "Spinal bulbar muscular atrophy (SBMA) is a classic CAG-repeat neurodegenerative disease.",
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{
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"text": "Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a rare, X-linked hereditary lower motor neuron disease, characterized by progressive muscular weakness.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/30006721",
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{
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"text": "Spinal and bulbar muscular atrophy (SBMA) is an adult-onset, X-linked motor neuron disease characterized by muscle atrophy, weakness, and bulbar involvement.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/21952871",
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{
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"text": "Spinal and bulbar muscular atrophy (SBMA) or Kennedy's disease is a motor neurone disease characterized by muscle atrophy, weakness, contraction fasciculations and bulbar involvement.",
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{
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"text": "Kennedy's disease, or spinal and bulbar muscular atrophy (SBMA), is a rare X-linked motoneuron disorder with variable signs of androgen insensitivity.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/8749704",
"endSection": "abstract"
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{
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"text": " Moderate meiotic instability has been demonstrated in X-linked spinal and bulbar muscular atrophy (SBMA, Kennedy's disease).",
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"text": "Spinal and bulbar muscular atrophy (SBMA) is a hereditary neuromuscular disease affecting only males characterized by progressive muscular atrophy and weakness in bulbar and limb muscles.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/31669728",
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{
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"text": "Spinal and bulbar muscular atrophy (SBMA) is an adult form of X-linked motor neuron disease caused by an expansion of a CAG repeat sequence in the first exon of the androgen receptor (AR) gene.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/17854832",
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{
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"text": "Spinal and bulbar muscular atrophy (SBMA) is an X-linked, late-onset neuroendocrine disorder resulting from an expansion of a CAG repeat in the androgen receptor gene.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/15851746",
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{
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"text": "Spinal and bulbar muscular atrophy (SBMA) is an X-linked adult motor neuron disorder caused by an abnormal CAG-repeat expansion in the first exon of the androgen receptor gene.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/17852020",
"endSection": "abstract"
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{
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"text": "Spinal and bulbar muscular atrophy (SBMA) is a rare X-linked motor neuron disease with significant phenotypic viability.",
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"text": "Spinal and bulbar muscular atrophy (SBMA) is an adult-onset hereditary neurodegenerative disease caused by the expansions of CAG repeats in the androgen receptor (AR) gene.",
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"text": "INTRODUCTION: Spinal and bulbar muscular atrophy (SBMA) is an X-linked, late-onset neuro-endocrine disorder resulting from an expansion of a CAG repeat in the androgen receptor gene",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/15924079",
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{
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"text": "Spinal and bulbar muscular atrophy (SBMA) is a hereditary motor neuron disease caused by the expansion of a polyglutamine tract in the androgen receptor (AR).",
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{
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"text": "Spinal and bulbar muscular atrophy (SBMA) is an X-linked recessive motor neuron disease characterized by slowly progressive weakness and atrophy of proximal limbs and bulbar muscles.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/25811990",
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"text": "Spinal and bulbar muscular atrophy (SBMA, or Kennedy's disease) is an X-linked, late-onset neuro-endocrine disorder characterized by degeneration of motor neurons in the spinal cord and brainstem and partial androgen insensitivity.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/19078709",
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6417921b690f196b51000033 | What are common symptoms in female carriers of DMD? | Female carriers of Duchenne Muscular Dystrophy (DMD) may experience muscle weakness and cardiomyopathy. Common symptoms include pseudohypertrophy of calf muscles, muscular weakness, compensatory movements, and longer timed performance on functional tasks. Some female carriers may also present with asymmetrical muscle weakness. | [
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"text": "8% of female DMD carriers have muscle weakness and cardiomyopathy. ",
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"text": "Pseudohypertrophy of calf muscles, muscular weakness, compensatory movements and longer timed performance on functional tasks were observed in most of the cases. ",
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"text": "Clinical manifestation of asymmetrical muscle weakness and compensatory movements, or both can be found in female carriers of DMD mutations, which can adversely affect posture and functional performance of these patients.",
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"text": "BACKGROUND: Female carriers of Duchenne muscular dystrophy (DMD), although usually asymptomatic, develop muscle weakness up to 17% of the time, and a third present cardiac abnormalities or cognitive",
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"text": "The symptomatic females shared mild but progressive muscular weakness and increased serum creatin kinase (CK) levels.",
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"text": "Approximately 8% of female Duchenne muscular dystrophy (DMD) carriers are manifesting carriers and have muscle weakness to some extent.",
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"text": "Two to 20% of female heterozygotes with a P/LP variant develop symptoms of dystrophinopathy ranging from mild muscle weakness to significant disability similar to Becker muscular dystrophy.",
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"text": "Female carriers of Duchenne muscular dystrophy (DMD) presenting with DMD symptomology similar to males with DMD, such as skeletal muscle weakness and cardiomyopathy, are termed manifesting carriers.",
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"text": "ales. Female DMD/BMD carriers (DMDc/BMDc) are mostly free of skeletal muscle symptoms, but they are also prone to cardiomyo",
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"text": "Female carriers of mutations in the dystrophin gene (DMD-carriers) may manifest clinically in the skeletal muscle, the heart, or both.",
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"text": "Cardiomyopathy is sometimes the only clinical symptom in female carriers of DMD.",
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"text": " Cardiomyopathy is common and often prevalent at similar frequency in female DMD carriers irrespective of whether they manifest skeletal muscle disease.",
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"text": "Female carriers of DMD gene mutations may be symptomatic and show variable skeletal as well as cardiac muscle symptoms.",
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"text": " Cardiomyopathy is sometimes the only clinical symptom in female carriers of DMD.",
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"text": " Our findings show abnormal muscle energy metabolism in DMD/BMD female carriers.",
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"text": " DMD/BMD female carriers are usually asymptomatic, although about 8 % may exhibit muscle or cardiac symptoms.",
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"text": " mutations were found. 28 (22%) women had symptoms. 22 (17%) had muscle weakness, varying from mild to moderately severe. Muscle weakness was found in",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/10382696",
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6446caac57b1c7a315000074 | Which are the types of Charcot-Marie-Tooth Disease (CMT)? | CMT1, or hypertrophic form in which mutations or a duplication were found on chromosome 17 is the most frequent (CMT1A), CMT2 is the neuronal form, CMT3 is termed the Dejerine-Sottas disease, CMT4 recessive forms, CMT5 a form with associated pyramidal features, and CMTX. | [
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"text": "There are four types: CMT1, CMT2, CMT3 and CMT4, depending upon the involvement of specific gene deficit, inheritance pattern, age of onset and whether the primary defect results in an abnormality of the myelin or axon of the nerve.",
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"text": "Clinically, CMT can be divided into two main types: a demyelinating type (CMT1, CMT3, CMT4 and CMTX1) and an axonal type (CMT2)",
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"text": " CMT1, or hypertrophic form in which mutations or a duplication were found on chromosome 17 is the most frequent (CMT1A), CMT2 is the neuronal form, CMT3 is termed the Dejerine-Sottas disease, CMT4 recessive forms, CMT5 a form with associated pyramidal features, and CMTX. ",
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"text": "Charcot-Marie-Tooth (CMT) is a group of inherited diseases clinically and genetically heterogenous, characterised by length dependent degeneration of axons of the peripheral nervous system. A missense mutation (p.R158H) in the pyruvate dehydrogenase kinase 3 gene (PDK3) has been identified as the genetic cause for an X-linked form of CMT (CMTX6) in two unrelated families. ",
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"text": "The subdivision into demyelinating CMT1 and axonal CMT2 types was a milestone and is still valid for the majority of patients.",
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"text": "Intermediate conduction velocities are often found in males with X-linked CMT (CMTX), and different intermediate CMT types have been identified",
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"text": "The association of neuropathy and optic atrophy (also known as CMT type 6) has been described with autosomaldominant, recessive and X-linked modes of inheritance.",
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"text": "Mutations in Mitofusin 2 have been found to cause dominant forms of CMT6.",
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"text": "Mutations of the gene encoding mitofusin 2 (MFN2) have recently been identified as the cause of approximately one-third of dominantly inherited cases of the axonal degenerative forms of Charcot-Marie-Tooth disease (CMT type 2A) and of rarer variants.",
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"text": "The latter include a severe, early-onset axonal neuropathy, which may occur in autosomal dominant or recessive forms, as well as some instances associated with pyramidal tract involvement (CMT type 5),",
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"text": "with optic atrophy (CMT type 6),",
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"text": "Two principal forms of Charcot-Marie-Tooth (CMT) disease have been distinguished: CMT 1, corresponding to a demyelinating type, and CMT 2, corresponding to an axonal type.",
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"text": "Charcot-Marie-Tooth disease (CMT), the most common inherited peripheral neuropathy, is a progressive sensorimotor neuropathy divided into types 1 and 2 based upon electrophysiologic and neuropathologic differences.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/1549221",
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{
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"text": "Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common form, exhibiting autosomal dominant inheritance and linkage to chromosome 17p11.2p12.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/8128981",
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{
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"text": "Recent work has identified the gene products corresponding to CMT1A, CMT1B and CMTX as peripheral myelin protein-22(PMP22), Po and connexin 32, respectively.",
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"text": "A systematic computer-based literature search was conducted on PubMed, using the following MeSH: (1) intermediate Charcot-Marie-Tooth; (2) X-linked intermediate Charcot-Marie-Tooth; and (3) X-linked Charcot-Marie-Tooth and electrophysiology.",
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"text": "Charcot-Marie-Tooth disease (CMT) has been classified into two types, CMT1 and CMT2, demyelinating and axonal forms, respectively.",
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"text": "Two major types can be distinguished based on electrophysiologic phenotypes: CMT type 1 (CMT1) displays uniformly decreased nerve conduction velocity associated with a demyelinating hypertrophic neuropathy, and CMT type 2 (CMT2) displays normal or near-normal nerve conduction velocity associated with a neuronal defect.",
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"text": "Clinically, CMT can be divided into two main types: a demyelinating type (CMT1, CMT3, CMT4 and CMTX1) and an axonal type (CMT2).",
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"text": "Common clinical manifestations of CMTX, as in other forms of Charcot-Marie-Tooth disease (CMT), are distal muscle wasting and weakness, hyporeflexia, distal sensory disturbance, and foot deformities.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/12185164",
"endSection": "abstract"
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"text": "Charcot-Marie-Tooth disease (CMT) has been classified into two types: demyelinating forms (CMT1) and axonal forms (CMT2).",
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"text": "y known to affect 1 in 2500 individuals. There are four types: CMT1, CMT2, CMT3 and CMT4, depending upon the involvement of specific gene deficit, inh",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34540429",
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] |
6442933f57b1c7a315000060 | What is the cause of Facioscapulohumeral Muscular Dystrophy type 1 (FSHD1)? | Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is caused by contraction of the D4Z4 repeat array. | [
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"text": "There are two types of the disease: FSHD1 (MIM:158900) and FSHD2 (MIM: 158901), which have different genetic causes but are phenotypically indistinguishable. In FSHD1, partial deletion of the D4Z4 repeats on the 4th chromosome affects the expression of DUX4",
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"text": "Facial-scapular-humeral myodystrophy Landouzy-Dejerine (FSHD) is an autosomal dominant disease, the basis of its pathogenesis is ectopic expression of the transcription factor DUX4 in skeletal muscle.",
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"text": "FSHD2 is a rare form of facioscapulohumeral muscular dystrophy (FSHD) characterized by the absence of a contraction in the D4Z4 macrosatellite repeat region on chromosome 4q35 that is the hallmark of FSHD1.",
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"text": "The myopathy facioscapulohumeral muscular dystrophy type 1 (FSHD1) is caused by copy number variation of the D4Z4 macrosatellite repeat on chromosome 4.",
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"text": "The autosomal dominant myopathy facioscapulohumeral muscular dystrophy (FSHD1, OMIM 158900) is caused by contraction of the D4Z4 repeat array on 4qter.",
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"text": "Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is caused by contraction of the D4Z4 repeat array on chromosome 4 to a size of 1-10 units.",
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"text": "Facioscapulohumeral muscular dystrophy 1 (FSHD1) is caused by a contraction in the number of D4Z4 repeats on chromosome 4, resulting in relaxation of D4Z4 chromatin causing inappropriate expression of DUX4 in skeletal muscle.",
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"text": "Facioscapulohumeral dystrophy type 1 (FSHD1) is caused by contraction of the D4Z4 repeat array on chromosome 4q resulting in sporadic misexpression of the transcription factor DUX4 in skeletal muscle tissue.",
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"text": "Autosomal dominant FSHD1 (95% of patients) is characterized by chromatin relaxation induced by pathogenic contraction of a macrosatellite repeat called D4Z4 located on the 4q subtelomere (FSHD1 patients harbor 1 to 10 D4Z4 repeated units).",
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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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"text": "tal muscle. The genetic cause of FSHD1 is contraction of the D4Z4 macrosatellite array on chromosome 4 alleles associated with a permissive haplotype causing infrequent sporadic expression of th",
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"text": "Sporadic DUX4 expression in FSHD myocytes is associated with incomplete repression by the PRC2 complex and gain of H3K9 acetylation on the contracted D4Z4 allele.",
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"text": "Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is caused by contraction of the D4Z4 repeat array.",
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"text": " dystrophy type 1 (FSHD1) is caused by copy number variation of the D4Z4 macrosatellite repeat on chromosome 4. In unaffected individuals the number o",
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"text": "Facioscapulohumeral muscular dystrophy (FSHD) is caused by the loss of repression at the D4Z4 locus leading to aberrant double homeobox 4 (DUX4) expression in skeletal muscle.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/32576599",
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] |
6450f1b457b1c7a315000092 | What is Kearns-Sayre syndrome (KSS)? | Kearns-Sayre Syndrome (KSS) is a rare mitochondrial disease characterized by a primary dysfunction of the mitochondrial respiratory chain. It is a rare mitochondrial disorder with a triad of features, including progressive external ophthalmoplegia, pigmentary retinopathy, and an alteration of cardiac conduction. KSS is a rare, multisystem mitochondrial encephalomyopathy. | [
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"text": "Kearns Sayre Syndrome (KSS) is a rare mitochondrial disease characterized by a primary dysfunction of the mitochondrial respiratory chain. ",
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"text": "Kearns-Sayre syndrome is a rare mitochondrial disorder. It had a triad of features, including progressive external ophthalmoplegia, pigmentary retinopathy, and an alteration of cardiac conduction.",
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"text": "Kearns-Sayre syndrome (KSS) is a rare, multisystem mitochondrial encephalomyopathy.",
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"text": "Kearns-Sayre syndrome (KSS), first described in 1958, is a multisystem disease defined by a characteristic triad of progressive external ophthalmoplegia, pigmentary retinopathy and atrioventricular block.",
"beginSection": "abstract",
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"text": "KSS is a mitochondrial disorder that occurs rarely; the actual incidence is unknown.",
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"text": "The Kearns-Sayre syndrome (KSS) is a distinctive type of progressive external ophthalmoplegia, characterized by pigmentary degeneration of the retina, heart block, elevated concentration of cerebrospinal fluid protein, and abnormal muscle mitochondria.",
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"text": "Kearns-Sayre syndrome (KSS) is a form of mitochondrial myopathy in which specific clinical features, namely progressive external ophthalmoplegia, pigmentary retinal degeneration and cardiac conduction defects, occur.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/1424198",
"endSection": "abstract"
},
{
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"text": "UNLABELLED: Kearns-Sayre syndrome (KSS) is a rare mitochondrial DNA deletion syndrome defined as the presence of ophthalmoplegia, pigmentary retinopathy, onset less than age 20 years, and one of the following: cardiac conduction defects, cerebellar syndrome, or cerebrospinal fluid protein abov",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22875312",
"endSection": "abstract"
},
{
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"text": "Kearns-Sayre Syndrome is form of rare mitochondrial cytopathy, first described by Thomas P. Kearns and George Pomeroy Sayre in 1958 and is characterized by progressive external opthalmoplegia, cardiac conduction block, pigmentary retinal degeneration, variable number of red ragged fibers on muscle biopsy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22231766",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "Kearns-Sayre syndrome (KSS) is a mitochondrial encephalomyopathy characterized by progressive external ophthalmoplegia (PEO), pigmentary retinopathy and onset before the age of 20 years.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16735000",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "Kearns Sayre syndrome (KSS) is a mitochondrial disorder characterized by the emergence before age 20 of progressive external ophthalmoplegia, pigmentary retinopathy, together with other heterogeneous clinical manifestations, including cardiac conduction defects, muscle abnormalities and endocrinopathies.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16735969",
"endSection": "abstract"
},
{
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"text": "Kearns-Sayre syndrome (KSS) is a mitochondrial disorder.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9677732",
"endSection": "abstract"
},
{
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"text": "Kearns-Sayre syndrome (KSS) is a sporadic multisystem disorder due to a defect of oxidative phosphorylation and associated with clonally-expanded rearrangements of mitochondrial DNA (mtDNA) deletions (Delta-mtDNAs) and/or duplications (dup-mtDNAs).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11018246",
"endSection": "abstract"
},
{
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"text": "INTRODUCTION: Kearns-Sayre syndrome (KSS) is a mitochondrial disorder characterized by progressive external ophthalmoplegia, pigmentary retinopathy, onset before 20 years, and ragged-red fibers on ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16977556",
"endSection": "abstract"
},
{
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"text": "Kearns-Sayre syndrome (KSS) is a progressive neuromuscular disease characterized by ophthalmoplegia, cardiac conduction block, and pigmentary retinopathy associated with abnormal mitochondrial structure and function.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9832255",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 291,
"text": "Kearns-Sayre syndrome (KSS) is a rare syndrome characterized by the triad of progressive external ophthalmoplegia, pigmentary retinopathy and cardiac conduction system disturbances; it is a mitochondrial encephalomyopathy with which usually presents before the patient reaches the age of 20.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23102393",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 96,
"text": "Kearns-Sayre Syndrome (KSS) is a subtype of chronic progressive external ophthalmoplegia (CPEO).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35477912",
"endSection": "abstract"
},
{
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"text": "Kearns-Sayre syndrome (KSS) was first described in 1958 as 'a rare neuromuscular disorder defined by a characteristic triad of progressive external ophthalmoplegia, pigmentary retinopathy, atrioventricular block and cerebellar ataxia'.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26949540",
"endSection": "abstract"
},
{
"offsetInBeginSection": 66,
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"text": "scribed. Kearns-Sayre syndrome (KSS) is a mitochondrial disorder characterized by retinitis pigmentosa, external ophthalmoplegia, and hea",
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"endSection": "abstract"
},
{
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"text": "Kearns-Sayre syndrome (KSS) is a multisystem mitochondrial disorder characterized by the invariant triad: onset before 20, progressive external ophthalmoplegia and pigmentary retinal degeneration, plus at least one of the following: complete (or not) heart block, cereberal dysfunction and CSF protein above 100 mg/dl.",
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"endSection": "abstract"
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{
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"text": " This has lead to increasing interest in the contribution which mtDNA deletions make to Kearns-Sayre Syndrome (KSS) and other disorders.",
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"endSection": "abstract"
},
{
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"text": "Kearns-Sayre syndrome (KSS) is the most commonly diagnosed mitochondrial myopathy and it produces severe neuromuscular symptoms.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9509412",
"endSection": "abstract"
},
{
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"text": "Kearns-Sayre syndrome (KSS) is a disease with severe clinical symptoms that often arises from a mitochondrial DNA deletion of 4977 bp.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7946321",
"endSection": "abstract"
},
{
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"offsetInEndSection": 83,
"text": "Kearns-Sayre syndrome (KSS) is a disorder caused by mutations in mitochondrial DNA.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27709644",
"endSection": "abstract"
},
{
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"text": "Kearns-Sayre syndrome (KSS) is a rare genetic abnormality.",
"beginSection": "abstract",
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"endSection": "abstract"
},
{
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"offsetInEndSection": 106,
"text": "Kearns-Sayre syndrome (KSS) is a rare mitochondrial myopathy that usually develops before 20 years of age.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25368789",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 339,
"text": "Kearns-Sayre syndrome (KSS) is a rare mitochondrial DNA (mtDNA) deletion syndrome that typically presents before 20 years of age and is characterized by chronic progressive external ophthalmoplegia, pigmentary retinopathy, and a combination of cardiac conduction defects, cerebellar ataxia, and elevated cerebrospinal fluid protein levels.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31158487",
"endSection": "abstract"
},
{
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"offsetInEndSection": 199,
"text": "Kearns-Sayre syndrome (KSS), a rare form of mitochondrial myopathy, is a triad of chronic progressive external ophthalmoplegia, bilateral pigmentary retinopathy, and cardiac conduction abnormalities.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29416473",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 114,
"text": "Kearns-Sayre syndrome (KSS) is a sporadic multisystem disorder due to rearrangements in mitochondrial DNA (mtDNA).",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/10465502",
"endSection": "abstract"
},
{
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"offsetInEndSection": 138,
"text": "Kearns Sayre Syndrome (KSS) is a rare mitochondrial disease characterized by a primary dysfunction of the mitochondrial respiratory chain.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35795638",
"endSection": "abstract"
},
{
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"offsetInEndSection": 194,
"text": "UNLABELLED: Kearns Sayre syndrome (KSS) is a multisystem disorder with a confounding variety of clinical manifestations, including ocular myopathy, pigmentary retinopathy, heart block and ataxia",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9727847",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 305,
"text": "UNLABELLED: Kearns-Sayre syndrome (KSS) is a rare mitochondrial DNA deletion syndrome defined as the presence of ophthalmoplegia, pigmentary retinopathy, onset less than age 20 years, and one of the following: cardiac conduction defects, cerebellar syndrome, or cerebrospinal fluid protein above 100 mg/dl",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22875312",
"endSection": "abstract"
},
{
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"offsetInEndSection": 254,
"text": "BACKGROUND: Kearns-Sayre syndrome (KSS) is a rare multisystem mitochondrial disorder characterized by onset before 20 years of age and a typical clinical triad: progressive external ophthalmoplegia, pigmentary retinopathy and cardiac conduction anomalies",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36181358",
"endSection": "abstract"
}
] |
64178f76690f196b51000026 | What is golodirsen's mechanism of action? | Golodirsen is a phosphorodiamidate morpholino oligomer (PMO) designed to induce exon 53 skipping in pre-mRNA processing. This exon skipping restores the reading frame of the primary transcript of DMD, resulting in the production of truncated but partially functional dystrophin, which can potentially slow down the progression of the disease. | [
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"text": "Golodirsen (Vyondys 53™), an antisense oligonucleotide of the phophorodiamidate morpholino oligomer (PMO) subclass designed to induce exon 53 skipping",
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"text": "Antisense oligonucleotides, e.g., phosphorodiamidate morpholino oligomers (PMOs), can induce therapeutic exon skipping during pre-mRNA processing to restore the reading frame of the primary transcript of DMD. As a result, truncated but partially functional dystrophin is produced, potentially slowing down the disease progression.",
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"text": "Golodirsen is a provisionally approved PMO-based drug for approx. 8% of all DMD patients amenable to exon 53 skipping.",
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"text": "Golodirsen (Vyondys 53™), an antisense oligonucleotide of the phophorodiamidate morpholino oligomer (PMO) subclass designed to induce exon 53 skipping, has been developed by Sarepta Therapeutics for the treatment of Duchenne muscular dystrophy (DMD).",
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"text": "In December 2019, intravenous golodirsen received its first global approval in the USA for the treatment of DMD in patients with a confirmed mutation of the DMD gene that is amenable to exon 53 skipping, based on positive results from a phase I/II clinical trial.",
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"text": "Several exon skipping antisense oligonucleotides (eteplirsen, golodirsen, viltolarsen, and casimersen) have been approved for the treatment of Duchenne muscular dystrophy, but many more are in development targeting an array of different DMD exons.",
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"text": "Two exon 53 skipping PMOs, golodirsen and viltolarsen, have received conditional approval for treating patients due to their ability to restore dystrophin protein expression.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36401027",
"endSection": "abstract"
}
] |
64467df857b1c7a31500006c | What is Emery-Dreifuss Muscular Dystrophy (EDMD)? | Emery-Dreifuss Muscular Dystrophy (EDMD) is an inherited disorder characterized by joint contractures, muscle weakness, and heart problems. It is caused by mutations in the EMD gene and can affect both males and females. | [
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"text": " Emery-Dreifuss Muscular Dystrophy (EDMD) is an early-onset, slowly-progressive group of myopathies, presenting with joint contractures, muscle weakness and cardiac abnormalities.",
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"text": "Emery-Dreifuss muscular dystrophy (EDMD) is an uncommon, gradually progressive X-linked myopathy, and it could result in rigid spinal deformity. ",
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"text": "X-Linked Emery-Dreifuss muscular dystrophy is caused by mutations in the gene encoding emerin.",
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"text": "Emery-Dreifuss muscular dystrophy (EDMD) is a progressive muscle-wasting disorder defined by early contractures of the Achilles tendon, spine, and elbows.",
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"text": "Emery-Dreifuss muscular dystrophy (EDMD) is an inherited muscular disorder characterized by the triad of progressive weakness in humero-peroneal muscles, early onset contractures and cardiomyopathy with conduction block that shows a high risk of sudden death.",
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"text": "Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked recessive disorder characterized by slowly progressing contractures, wasting of skeletal muscle and cardiomyopathy.",
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"text": "Emery-Dreifuss muscular dystrophy (EDMD) is a rare muscular dystrophy, but is particularly important to diagnose due to frequent life-threatening cardiac complications.",
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"text": "Emery-Dreifuss muscular dystrophy (EDMD) is the third most common X-linked muscular dystrophy.",
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"text": "Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked humeroperoneal dystrophy associated with cardiomyopathy that is distinct from the Duchenne and Becker forms of X-linked muscular dystrophy.",
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"text": "Emery-Dreifuss muscular dystrophy (EDMD) is an inherited muscular disorder clinically characterized by slowly progressive weakness affecting humero-peroneal muscles, early joint contractures and cardiomyopathy with conduction defects.",
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"text": "Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early contractures of elbows and Achilles tendons, slowly progressive muscle wasting and weakness, and a cardiomyopathy with conduction blocks which is life-threatening.",
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"text": "Emery-Dreifuss muscular dystrophy (EDMD) is characterised by early contractures, slowly progressive muscle wasting and weakness with a distinctive humero-peroneal distribution and cardiac conduction defects leading to dilated cardiomyopathy.",
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"text": "Emery-Dreifuss muscular dystrophy (EDMD), a rare inherited disease, is characterized clinically by humero-peroneal muscle atrophy and weakness, multijoint contractures, spine rigidity and cardiac insufficiency with conduction defects.",
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"text": "Emery-Dreifuss muscular dystrophy (EDMD) was delineated as a separate form of muscular dystrophy nearly 40 years ago, based on the distinctive clinical features of early contractures and humero-peroneal weakness, and cardiac conduction defects.",
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"text": "Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked inherited disease characterized by early contracture of the elbows, Achilles tendons and post-cervical muscles, slow progressive muscle wasting and weakness and cardiomyopathy presenting with arrhythmia and atrial paralysis: heart block can eventually lead to sudden death.",
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"text": "Emery-Dreifuss muscular dystrophy (EDMD) is a rare X-linked recessive disease characterized by the clinical triad of early childhood joint contractures, progressive weakness in muscles and cardiac involvement and can result in sudden death.",
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"text": "Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked recessive or autosomal dominant progressive muscular dystrophy characterized by progressive muscle wasting and weakness with scapulo-humero-peroneal distribution, early contracture and cardiomyopathy with conduction block.",
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"text": "The most frequent and best known form is Emery-Dreifuss muscular dystrophy (EDMD), a skeletal myopathy characterized by progressive muscular weakness, joint contractures, and cardiac disease.",
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"text": "X-linked recessive Emery-Dreifuss muscular dystrophy (EDMD) is an inherited muscle disorder characterized by the clinical triad of progressive wasting of humero-peroneal muscles, early contractures of the elbows, Achilles tendons and postcervical muscles, and cardiac conduction block with a high risk of sudden death.",
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"text": "INTRODUCTION: Emery-Dreifuss muscular dystrophy (EDMD) is a disease characterized by skeletal muscle wasting, major tendon contractures, and cardiac condu",
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"text": "Emery-Dreifuss muscular dystrophy (EDMD) is an inherited disorder characterized by the clinical triad of life-threatening progressive cardiomyopathy with conduction defect, early onset joint contractures and slow progressive muscle weakness in scapulo-humero-peroneal distribution.",
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"text": "Emery-Dreifuss Muscular Dystrophy (EMD or EDMD) is a rare X-linked recessive disorder, characterized by progressive muscle wasting and weakness, contractures, and cardiomyopathy, manifesting as heart block.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/11385714",
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"text": "Emery-Dreifuss muscular dystrophy (EDMD) is a distinctive form of muscular dystrophy which is often associated with cardiac abnormalities.",
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"text": "Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked muscular dystrophy in which cardiac involvement can be serious.",
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{
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"text": "Emery Dreifuss Muscular Dystrophy (EDMD) is an inherited disorder which leads to progressive worsening of muscular function.",
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"endSection": "abstract"
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"text": "Emery-Dreifuss muscular dystrophy (EDMD) is a rare X-linked muscular dystrophy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2311208",
"endSection": "abstract"
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"text": "Emery-Dreifuss muscular dystrophy (EDMD) is a rare and genetically heterogeneous disorder.",
"beginSection": "abstract",
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"endSection": "abstract"
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"text": "Emery-Dreifuss muscular dystrophy is a rare form of muscular dystrophy associated with cardiac implications such as cardiomyopathy and arrhythmias leading to sudden death.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12075650",
"endSection": "abstract"
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"text": "Emery Dreifuss muscular dystrophy (EDMD) is a hereditary muscular disorder, characterized by contractures, progressive muscular wasting and cardiac involvement.",
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"text": "Emery Dreifuss muscular dystrophy (EDMD) is an uncommon hereditary myopathy characterized by 3 symptoms: slow progressive muscular atrophy, muscular contractures and cardiac disease which affect prognosis.",
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"document": "http://www.ncbi.nlm.nih.gov/pubmed/17042210",
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"text": "Emery-Dreifuss muscular dystrophy (EDMD), clinically characterized by scapulo-humero-peroneal muscle atrophy and weakness, multi-joint contractures with spine rigidity and cardiomyopathy with conduction defects, is associated with structural/functional defect of genes that encode the proteins of nuclear envelope, including lamin A and several lamin-interacting proteins.",
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6402c910201352f04a00000c | Can losartan reduce brain atrophy in Alzheimer's disease? | No. 12 months of treatment with losartan was well tolerated but was not effective in reducing the rate of brain atrophy in individuals with clinically diagnosed mild-to-moderate Alzheimer's disease. | [
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"text": "INTERPRETATION: 12 months of treatment with losartan was well tolerated but was not effective in reducing the rate of brain atrophy in individuals with clinically diagnosed mild-to-moderate Alzheimer's disease.",
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640f857d201352f04a00002b | What is CHARMS with respect to medical review of predictive modeling? | CHARMS stands for CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS). | [
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"text": "The CHARMS (critical appraisal and data extraction for systematic reviews of prediction modelling studies) checklist was created to provide methodological appraisals of predictive models, based on the best available scientific evidence and through systematic reviews.",
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"text": "However, these models should be developed appropriately (CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modeling Studies [CHARMS] and Prediction model Risk Of Bias ASsessment Tool [PROBAST] statements).",
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"text": "tudies with model updating. Data was extracted following the Checklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS) checklist.PRIMARY AND SECONDARY OUTCOME MEA",
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"text": "methods in oncology. We used the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement, Prediction model Risk Of Bias ASsessment Tool (PROBAST) and CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS) to assess the methodological conduct of i",
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"text": "inclusion criteria). We followed the CHARMS recommendations (Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies), extracting the information from its 11 domains (Source of data",
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"text": "ion making. Systematic reviews of prognostic model studies can help identify prognostic models that need to further be validated or are ready to be implemented in healthcare.OBJECTIVES: To provide a step-by-step guidance on how to conduct and read a systematic review of prognostic model studies and to provide an overview of methodology and guidance available for every step of the review progress.SOURCES: Published, peer-reviewed guidance articles.CONTENT: We describe the following steps for conducting a systematic review of prognosis studies: 1) Developing the review question using the Population, Index model, Comparator model, Outcome(s), Timing, Setting format, 2) Searching and selection of articles, 3) Data extraction using the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist, 4) Quality and risk of bias assessment using the Prediction model Risk Of Bias ASsessment (PROBAST) tool, 5) Analysing data and undertaking quantitative meta-analysis, and 6) Presenting summary of findings, inte",
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"text": "The authors did not put any restrictions on the models included in their study regarding the model setting, prediction horizon or outcomes.Data extraction and synthesis Checklists of critical appraisal and data extraction for systematic reviews of prediction modelling studies (CHARMS) and prediction model risk of bias assessment tool (PROBAST) were used to guide developing of a standardised data extraction form.",
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"text": "acted the data. We used the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies (CHARMS) checklist for the risk of ",
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"text": "ical appraisal and data extraction for systematic reviews of prediction modeling studies (CHARMS) and the prediction model risk of bias assessment tool (PROBAST) were used for the data extraction process and critical appraisal.RESULTS: From the 29",
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6410eb95201352f04a00002e | Which splicing factors have been associated with alternative splicing in PLN R14del hearts? | Bioinformatical analysis pointed to the tissue-specific splicing factors Srrm4 and Nova1 as likely upstream regulators of the observed splicing changes in the PLN-R14del cardiomyocytes. | [
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"text": "Our work suggests that an intricate interplay of programs controlling gene expression levels and AS is fundamental to organ development, especially for the brain and heart.",
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"text": "Bioinformatical analysis pointed to the tissue-specific splicing factors Srrm4 and Nova1 as likely upstream regulators of the observed splicing changes in the PLN-R14del cardiomyocytes. ",
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64162fb0690f196b5100001a | What are the most common mutation types in Duchenne muscular Dystrophy? | The most common mutation types in Duchenne muscular Dystrophy are deletions, point mutations, and duplications. | [
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"text": " 64% deletions, 18% duplications and 18% point mutations. ",
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"text": "Of these, 406 (70.5%) were exonic deletions, 64 (11.1%) were exonic duplications, and one was a deletion/duplication complex rearrangement (0.2%). Small mutations were identified in 105 cases (18.2%), most being nonsense/frameshift types (75.2%). Mutations in splice sites, however, were relatively frequent (20%). ",
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"text": "gene deletion rate was 54.3% (391/720), and gene duplication rate was 10.6% (76/720)",
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"text": "The rate of deletion mutant occurred in Exon 45-54 was 71.9% (281/391) in all gene deletion patients; meanwhile, the rate of gene duplication occurred in Exon 1-40 was 82.9% (63/76) in all gene duplication ones.",
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"text": "In all the patients with gene deletion and duplication, the rate of DMD and IMD was 90.6% (423/467), and BMD, 9.4% (44/467).",
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"text": "The Duchenne Muscular dystrophy (DMD) is the most frequent muscle disorder in childhood caused by mutations in the Xlinked dystrophin gene (about 65% deletions, about 7% duplications, about 26% point mutations and about 2% unknown mutations). ",
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"text": "The Duchenne Muscular dystrophy (DMD) is the most frequent muscle disorder in childhood caused by mutations in the Xlinked dystrophin gene (about 65% deletions, about 7% duplications, about 26% point mutations and about 2% unknown mutations).",
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"text": "While in earlier studies equal mutation rates in males and females had been reported, a breakdown by mutation types can better explain the sex ratio of mutations: Point mutations and duplications arise preferentially during spermatogenesis whereas deletions mostly arise in oogenesis.",
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"text": "l spectrum. This information is extremely beneficial for basic scientific research, genetic diagnosis, trial planning, clinical care, and gene therapy.METHODS: We collected data from 1400 patients (1042 patients with confirmed unrelated Duchenne muscular dystrophy [DMD] or Becker muscular dystrophy [BMD]) registered in the Chinese Genetic Disease Registry from March 2012 to August 2017 and analyzed the genetic mutational characteristics of these patients.RESULTS: Large deletions were the most frequent type of mutation (72.2%), followed by nonsense mutations (11.9%), exon duplications (8.8%), small deletions (3.0%), splice-site mutations (2.1%), small insertions (1.3%), missense mutations (0.6%), and a combination mutation of a dele",
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"text": "Deletions were the most common mutation type (256, 79%), followed by point mutations (45, 13.9%) and duplications (23, 7.1%).",
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63eef3ebf36125a42600000a | What is the target of Litifilimab? | Litifilimab is a humanized monoclonal antibody against BDCA2 that is being developed for treatment of cutaneous lupus erythematosus. | [
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"text": "Trial of Anti-BDCA2 Antibody Litifilimab for Cutaneous Lupus Erythematosus.",
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"text": "Whether treatment with litifilimab, a humanized monoclonal antibody against BDCA2, would be efficacious in reducing disease activity in patients with cutaneous lupus erythematosus has not been extensively studied.",
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"text": "Trial of Anti-BDCA2 Antibody Litifilimab for Systemic Lupus Erythematosus.",
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"text": " The safety and efficacy of subcutaneous litifilimab, a humanized monoclonal antibody that binds to BDCA2, in patients with SLE have not been extensively studied.",
"beginSection": "abstract",
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64136fbf201352f04a00003d | What is AUROC in context of predictive modeling? | . The area under the receiver operator characteristics curve (AUROC) | [
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"text": "Our models predict GDM with high accuracy even at pregnancy initiation (area under the receiver operating curve (auROC) = 0.85), substantially outperforming a baseline risk score (auROC = 0.68).",
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"text": " prediction of pancreatic cancer. Two popular models were evaluated: logistic regression and a recurrent neural network.RESULTS: For logistic regression, using UMLS delivered the optimal area under the receiver operating characteristics (AUROC) results in both dengue hemorrhagic fever (81",
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"text": "Area under the receiver operating characteristics (AUROC) curve is often used to evaluate risk models.",
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"text": "stic tests. Rather, researchers use the area under the receiver operating characteristic (AUROC) as the key metric to gauge and report predictive performa",
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"text": "Area under a receiver-operating-characteristic (AUROC) curve is widely used in medicine to summarize the ability of a continuous predictive marker to predict a binary outcome.",
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"text": "The c statistic, or area under the receiver operating characteristic (ROC) curve, achieved popularity in diagnostic testing, in which the test characteristics of sensitivity and specificity are relevant to discriminating diseased versus nondiseased patients.",
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"text": "-day mortality, respectively. When using only baseline variables to predict mortality, all algorithms except SVM (area under the receiver operator characteristic curve [AUROC], 0.83 [95% confidence interval {CI}, 0.69-0.97]) had AUROC >0.9: GBM (AUROC, 0.96 [0.94-1.0]), RF (AUROC, 0.96 [0.92-1.0]), CNN (AUROC, 0.96 [0.92-0.99]), and logistic regress",
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"text": "We assessed model performance using two metrics, the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC), to illustrate the differences in information they convey in the setting of class imbalance.",
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"text": "The two approaches were explored and validated within the context of mRNA expression level prediction and have the area under the ROC curve (auROC) values ranging from 0.75 to 0.94.",
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"text": ".4%) and validation (47.4%) cohorts. The FibroGENE-DT yielded the area under the receiver operating characteristic curve (AUROCs) of 0.87, 0.85 and 0.804 for the prediction of fast fibrosis progression, cirrhosis and significant fibrosis risk, respectively, with compara",
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{
"offsetInBeginSection": 1711,
"offsetInEndSection": 1952,
"text": "ement (oral or IV) was 41.1%. Independent predictors using history alone were female sex, decreasing age, surgical history, and non-Caucasian ethnicity (model area under the receiver operating characteristic curve [AUROC], 0.59 [95% confiden",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31094792",
"endSection": "abstract"
},
{
"offsetInBeginSection": 808,
"offsetInEndSection": 1084,
"text": " reduction of at least I° MR. One-year mortality was 28.2%.In Kaplan-Meier analysis, one- year mortality was significantly higher in RVD-pts (34.8% vs 2.8%, p = 0.009).Area under the Receiver Operating Characteristic (AUROC) for SHFM and MAGGIC were comparable for both scores",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33088899",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1371,
"offsetInEndSection": 1584,
"text": "Using a standard multivariate approach to combine predictors, the PPIN model achieved an AUROC (area under the receiver operating characteristic curve) of 0.81 with a sensitivity of 48% given a specificity of 90%.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23620757",
"endSection": "abstract"
},
{
"offsetInBeginSection": 360,
"offsetInEndSection": 510,
"text": "cognitive impairment was evaluated using area under the receiver operating characteristic curve (AUROC), and multivariate logistic regression was appl",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35879562",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1005,
"offsetInEndSection": 1155,
"text": "ssion, using UMLS delivered the optimal area under the receiver operating characteristics (AUROC) results in both dengue hemorrhagic fever (81.15%) an",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32930711",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1325,
"offsetInEndSection": 1475,
"text": "s). Sensitivity, specificity, predictive values and area under receiving operating curves (AUROC) of RBUS for VCUG abnormalities were determined.RESUL",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25958031",
"endSection": "abstract"
},
{
"offsetInBeginSection": 598,
"offsetInEndSection": 748,
"text": "ys). Model performance was assessed using area under the receiver operator characteristic curve (AUROC). Pre-N8-GP prophylaxis models learned from dat",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34865209",
"endSection": "abstract"
},
{
"offsetInBeginSection": 536,
"offsetInEndSection": 686,
"text": "agnostic threshold were evaluated using area under the receiver operating characteristic curve (AUROC). Stratification analysis by age and MP-IgM tite",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34154565",
"endSection": "abstract"
},
{
"offsetInBeginSection": 543,
"offsetInEndSection": 693,
"text": " learning algorithms was assessed by the area under the receiver operating characteristic curve (AUROC). The conventional scoring models had various p",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35505048",
"endSection": "abstract"
},
{
"offsetInBeginSection": 471,
"offsetInEndSection": 621,
"text": "sing PubMed, MEDLINE, and Scopus databases. Papers with area under the receiver operating curve (AUROC) scores reported were included in the analysis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33203588",
"endSection": "abstract"
},
{
"offsetInBeginSection": 837,
"offsetInEndSection": 987,
"text": "nstruct the prediction model. Finally, the area under the receiver operating characteristic (AUROC) curve was used to compare the model performance.RE",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36329470",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1029,
"offsetInEndSection": 1179,
"text": "cy for tasks such as predicting: in-hospital mortality (area under the receiver operator curve [AUROC] across sites 0.93-0.94), 30-day unplanned readm",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31304302",
"endSection": "abstract"
},
{
"offsetInBeginSection": 112,
"offsetInEndSection": 262,
"text": "rognostic tests. Rather, researchers use the area under the receiver operating characteristic (AUROC) as the key metric to gauge and report predictive",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31093546",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1005,
"offsetInEndSection": 1216,
"text": "ssion, using UMLS delivered the optimal area under the receiver operating characteristics (AUROC) results in both dengue hemorrhagic fever (81.15%) and pancreatic cancer (80.53%) tasks. For recurrent neural netw",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32930711",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1325,
"offsetInEndSection": 1466,
"text": "s). Sensitivity, specificity, predictive values and area under receiving operating curves (AUROC) of RBUS for VCUG abnormalities were determi",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25958031",
"endSection": "abstract"
},
{
"offsetInBeginSection": 471,
"offsetInEndSection": 577,
"text": "sing PubMed, MEDLINE, and Scopus databases. Papers with area under the receiver operating curve (AUROC) sc",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33203588",
"endSection": "abstract"
},
{
"offsetInBeginSection": 837,
"offsetInEndSection": 955,
"text": "nstruct the prediction model. Finally, the area under the receiver operating characteristic (AUROC) curve was used to ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36329470",
"endSection": "abstract"
},
{
"offsetInBeginSection": 112,
"offsetInEndSection": 266,
"text": "rognostic tests. Rather, researchers use the area under the receiver operating characteristic (AUROC) as the key metric to gauge and report predictive per",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31093546",
"endSection": "abstract"
},
{
"offsetInBeginSection": 360,
"offsetInEndSection": 706,
"text": "cognitive impairment was evaluated using area under the receiver operating characteristic curve (AUROC), and multivariate logistic regression was applied to evaluate predictive accuracy of biomarkers on cognitive impairment; 178 subjects (41 PD, 31 VaD and 106 normal controls) were included. In multiple linear regression analysis of PD patients",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35879562",
"endSection": "abstract"
},
{
"offsetInBeginSection": 652,
"offsetInEndSection": 945,
"text": "of outcome (AC), sensitivity (SN), specificity (SP), and area under receiver-operating curve (AUROC) were compared between 3 models: KCC (INR, creatinine, coma grade, pH), CART analysis using only KCC variables (KCC-CART) and a CART model using new variables (NEW-CART).RESULTS: Traditional KC",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25885260",
"endSection": "abstract"
},
{
"offsetInBeginSection": 652,
"offsetInEndSection": 941,
"text": "models of the EGFR mutation status (Model 1: area under the receiver operating characteristic curve [AUROC] = 0.910, 95% CI 0.861-0.945; Model 2: AUROC = 0.859, 95% CI 0.803-0.904; Model 3: AUROC = 0.711, 95% CI 0.643-0.773). A testing set (n = 50) and temporal validation data set (n = 70",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31807867",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1029,
"offsetInEndSection": 1371,
"text": "cy for tasks such as predicting: in-hospital mortality (area under the receiver operator curve [AUROC] across sites 0.93-0.94), 30-day unplanned readmission (AUROC 0.75-0.76), prolonged length of stay (AUROC 0.85-0.86), and all of a patient's final discharge diagnoses (frequency-weighted AUROC 0.90). These models outperformed traditional, c",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31304302",
"endSection": "abstract"
},
{
"offsetInBeginSection": 838,
"offsetInEndSection": 1056,
"text": " matrix, accuracy, precision, recall, F1 score, and Area under the Receiver Operating Characteristics (AUROC) were used to evaluate the performance of predictive models.RESULTS: Ability of prediction was between 68.6% ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35509018",
"endSection": "abstract"
},
{
"offsetInBeginSection": 846,
"offsetInEndSection": 1064,
"text": " accuracy, precision, recall, F1 score, and Area under the Receiver Operating Characteristics (AUROC) were used to evaluate the performance of predictive models.RESULTS: Ability of prediction was between 68.6% and 61.5",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35509018",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1023,
"offsetInEndSection": 1173,
"text": "s), positive predictive values (PPVs), and area under the receiver operating characteristic curve (AUROC), of machine learning models when predicting ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31509205",
"endSection": "abstract"
},
{
"offsetInBeginSection": 645,
"offsetInEndSection": 838,
"text": "ance of prediction, accuracy of discrimination (area under the receiver operating characteristic curve [AUROC]), calibration, and validity of the two predictive models were investigated. The co",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28323524",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 734,
"text": "The area under the receiver operating characteristic (ROC) curve (AUC) is commonly used for assessing the discriminative ability of prediction models even though the measure is criticized for being clinically irrelevant and lacking an intuitive interpretation. Every tutorial explains how the coordinates of the ROC curve are obtained from the risk distributions of diseased and non-diseased individuals, but it has not become common sense that therewith the ROC plot is just another way of presenting these risk distributions. We show how the ROC curve is an alternative way to present risk distributions of diseased and non-diseased individuals and how the shape of the ROC curve informs about the overlap of the risk distributions.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31967640",
"endSection": "abstract"
}
] |
63fa13da201352f04a000001 | Is PRP-40 regulation of microexons a conserved phenomenon? | Yes, PRP-40 regulation of neuronal microexons is a widely conserved phenomenon. | [
"34348142"
] | yesno | [
{
"offsetInBeginSection": 1011,
"offsetInEndSection": 1095,
"text": "PRP-40 regulation of neuronal microexons is therefore a widely conserved phenomenon.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34348142",
"endSection": "abstract"
}
] |
64178e15690f196b51000020 | Is casimersen effective for the treatment of Duchenne muscular dystrophy? | Yes, casimersen is effective for the treatment of Duchenne muscular dystrophy. | [
"33861387"
] | yesno | [
{
"offsetInBeginSection": 568,
"offsetInEndSection": 761,
"text": "Casimersen received its first approval on 25 February 2021, in the USA, for the treatment of DMD in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33861387",
"endSection": "abstract"
},
{
"offsetInBeginSection": 762,
"offsetInEndSection": 943,
"text": "he approval, granted under the US FDA Accelerated Approval Program, was based on an observed increase in dystrophin production in skeletal muscle in patients treated with casimersen",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33861387",
"endSection": "abstract"
}
] |
63f02ceaf36125a426000015 | Which are the targets of Tirzepatide? | Tirzepatide is a dual incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist in the form of a synthetic linear peptide. | [
"35658024",
"35593668",
"35651477"
] | summary | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 110,
"text": "Designing a Dual GLP-1R/GIPR Agonist from Tirzepatide: Comparing Residues Between Tirzepatide, GLP-1, and GIP.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35651477",
"endSection": "title"
},
{
"offsetInBeginSection": 102,
"offsetInEndSection": 277,
"text": "he efficacy and safety of tirzepatide, a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, in people with obesity are not known.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35658024",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 144,
"text": "Tirzepatide - a dual GIP/GLP-1 receptor agonist - a new antidiabetic drug with potential metabolic activity in the treatment of type 2 diabetes.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35593668",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 400,
"text": "The incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are responsible for up to 65% of postprandial insulin secretion. Tirzepatide, developed by Eli Lilly, is a dual GIP/GLP-1 receptor agonist in the form of a synthetic linear peptide; its acylation technology allows it to bind to albumin, thus making it possible to dose the drug once a week. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35593668",
"endSection": "abstract"
}
] |
640e2616201352f04a00002a | Is medical hydrology the same as Spa therapy? | No, medical hydrology and spa therapy are related but not the same. Medical hydrology involves the therapeutic use of water in a medical setting, while spa therapy uses water treatments in a relaxation and wellness setting. | [
"35779167",
"32568298",
"32875343"
] | yesno | [
{
"offsetInBeginSection": 187,
"offsetInEndSection": 315,
"text": "hydrotherapy,\" \"balneotherapy,\" \"spa therapy,\" \"spa treatment,\" \"creno-balneotherapy,\" \"water treatments,\" and \"aqua therapy,\" o",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35779167",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 554,
"text": "Spa therapy is an integral part of the treatment of burn scars. The objective of this systematic review is to provide an overview of the spa therapy used in the treatment of burn scars and analyze its effects reported in clinical studies. We used the PRISMA checklist and queried 8 scientific databases from August 2019 to July 2020 for articles referenced with the specific key words: (burn) AND ((spa) OR (crenotherap*) OR (sulfur bath) OR (balneo*) OR (hydrotherap*) OR (mineral water) OR (thermal water) OR (spring water) OR (health resort medicine))",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32875343",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 249,
"text": "Soon after qualification, Fortescue Fox (1858-1940) began practice in a Scottish spa where he acquired a lifelong interest in chronic disorders, especially arthritis. He worked to improve the status of spa medicine, recasting it as medical hydrology",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32568298",
"endSection": "abstract"
},
{
"offsetInBeginSection": 167,
"offsetInEndSection": 250,
"text": "He worked to improve the status of spa medicine, recasting it as medical hydrology.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32568298",
"endSection": "abstract"
},
{
"offsetInBeginSection": 166,
"offsetInEndSection": 250,
"text": " He worked to improve the status of spa medicine, recasting it as medical hydrology.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32568298",
"endSection": "abstract"
}
] |
6410fa66201352f04a000034 | How does CYP1A2 relate to coffee consumption and apetite? | CYP1A2 rs762551 polymorphism modifies the association of habitual coffee consumption with BMI, in part by influencing appetite, energy intake and circulating levels of the orexigenic hormone asprosin. In specific, high coffee consumption was more prevalent in rapid compared to slow metabolizers (P = 0.008 after adjustment for age, sex, and BMI) and was associated with lower appetite perception and lower BMI only in rapid metabolizers (P for interaction of rs762551 genotype*coffee consumption = 0.002 and 0.048, respectively) | [
"34564706"
] | summary | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 204,
"text": "CYP1A2 polymorphisms modify the association of habitual coffee consumption with appetite, macronutrient intake, and body mass index: results from an observational cohort and a cross-over randomized study.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34564706",
"endSection": "title"
},
{
"offsetInBeginSection": 1340,
"offsetInEndSection": 1952,
"text": "High coffee consumption was more prevalent in rapid compared to slow metabolizers (P = 0.008 after adjustment for age, sex, and BMI) and was associated with lower appetite perception and lower BMI only in rapid metabolizers (P for interaction of rs762551 genotype*coffee consumption = 0.002 and 0.048, respectively). This differential association of rs762551 genotype and coffee consumption with BMI was more evident in individuals at higher genetic risk of obesity (mean adjusted difference in BMI = -5.82 kg/m2 for rapid versus slow/intermediate metabolizers who consumed more than 14 cups of coffee per week).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34564706",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1965,
"offsetInEndSection": 2256,
"text": "CYP1A2 rs762551 polymorphism modifies the association of habitual coffee consumption with BMI, in part by influencing appetite, energy intake and circulating levels of the orexigenic hormone asprosin. This association is more evident in subjects with high genetic predisposition to obesity. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34564706",
"endSection": "abstract"
}
] |
64178e73690f196b51000023 | Is eteplirsen effective for the treatment of Duchenne muscular dystrophy? | Yes, eteplirsen is effective for the treatment of Duchenne muscular dystrophy. | [
"34797383",
"33523015",
"34420980"
] | yesno | [
{
"offsetInBeginSection": 1347,
"offsetInEndSection": 1641,
"text": "Eteplirsen-treated patients experienced a statistically significant longer median time to LOA by 2.09 years (5.09 vs. 3.00 years, p < 0.01) and significantly attenuated rates of pulmonary decline vs. natural history patients (FVC%p change: -3.3 vs. -6.0 percentage points annually, p < 0.0001).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34420980",
"endSection": "abstract"
},
{
"offsetInBeginSection": 967,
"offsetInEndSection": 1200,
"text": "At Years 3 and 4, eteplirsen-treated patients demonstrated markedly greater mean 6MWT than controls (difference in change from baseline of 132 m [95%CI (29, 235), p = 0.015] at Year 3 and 159 m [95%CI (66, 253), p = 0.002] at Year 4)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33523015",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1202,
"offsetInEndSection": 1341,
"text": "At Year 4, a significantly greater proportion of eteplirsen-treated patients were still ambulant versus controls (10/12 vs 3/11; p = 0.020)",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33523015",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1606,
"offsetInEndSection": 1803,
"text": " In this retrospective matched control study, eteplirsen treatment resulted in attenuation of ambulatory decline over a 4-year observation period, supporting long-term benefit in patients with DMD.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33523015",
"endSection": "abstract"
}
] |
63f03939f36125a42600001b | What is the use of darolutamide? | Darolutamide is an approved treatment of non-metastatic, castration-resistant prostate cancer (also called nmCRPC). | [
"34308608",
"33830214",
"35656777"
] | summary | [
{
"offsetInBeginSection": 1482,
"offsetInEndSection": 1648,
"text": "CONCLUSIONS: All three ARAT agents are efficacious options for the treatment of nmCRPC, whereas darolutamide appears to have the most favorable tolerability profile. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34308608",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 335,
"text": "BACKGROUND: For nonmetastatic castration-resistant prostate cancer (nmCRPC), 3 drugs under patent protection-apalutamide, enzalutamide, and darolutamide-were approved based on randomized, placebo-controlled trials; 1 drug with generic availability, abiraterone acetate, showed efficacy in a single-arm trial and is commonly prescribed.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33830214",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1701,
"offsetInEndSection": 1920,
"text": "CONCLUSIONS: For nmCRPC, darolutamide offered optimal efficacy and safety among approved drugs, and abiraterone acetate may offer comparable metastasis-free survival benefit with cost savings from generic availability. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33830214",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 160,
"text": "Darolutamide and survival in metastatic, hormone-sensitive prostate cancer: a patient and caregiver perspective and plain language summary of the ARASENS trial.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35656777",
"endSection": "title"
},
{
"offsetInBeginSection": 687,
"offsetInEndSection": 846,
"text": "Darolutamide is an approved treatment for a different type of prostate cancer called non-metastatic, castration-resistant prostate cancer (also called nmCRPC).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35656777",
"endSection": "abstract"
}
] |
64136664201352f04a00003b | What are the main clinical features of small-fiber neuropathy (SFN)? | The main clinical features of small-fiber neuropathy (SFN) include pain, sensory disturbances, and autonomic dysfunction. | [
"32654574",
"36430572",
"30247738",
"23982054",
"34698404",
"29029847",
"18524793",
"17948213",
"30125923",
"35130356",
"30569495",
"36005471"
] | list | [
{
"offsetInBeginSection": 155,
"offsetInEndSection": 272,
"text": " Selective SFN (without large fiber affection) manifests with pain, sensory disturbances, or autonomic dysfunction. T",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35130356",
"endSection": "abstract"
},
{
"offsetInBeginSection": 14,
"offsetInEndSection": 236,
"text": "Neuropathic pain (NP) is a main feature of Fabry disease (FD) as consequence of small fiber neuropathy. Restless legs syndrome (RLS) in FD was not described, but it is an important feature in other small fiber neuropathies",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17948213",
"endSection": "abstract"
},
{
"offsetInBeginSection": 13,
"offsetInEndSection": 184,
"text": "mall fiber neuropathy (SFN) can be associated with autoantibodies, including those of IgM class with specificity for the trisulfated heparan disaccharide (TS-HDS) antigen.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34698404",
"endSection": "abstract"
},
{
"offsetInBeginSection": 12,
"offsetInEndSection": 234,
"text": "Up to 50% of small fiber neuropathy (SFN) cases are idiopathic, but novel antibodies to Trisulfated Heparin Disaccharide (TS-HDS) and fibroblast growth factor receptor 3 (FGFR-3) have been implicated in half of these cases",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36005471",
"endSection": "abstract"
},
{
"offsetInBeginSection": 683,
"offsetInEndSection": 961,
"text": "an the patients without SFN. Restless leg syndrome was also more frequently observed in patients with SFN, who had pain aggravated at rest that improved by moving.CONCLUSIONS: These findings are in favor of the sensitization of relatively spared large Aβ-fibers and second-order",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30247738",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 218,
"text": "Small fiber neuropathies (SFN) comprise a clinical syndrome typically associated with acral burning pain, where the pathophysiological processes affect the thinly myelinated A-delta and the unmyelinated C nerve fibers.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30125923",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 210,
"text": "Small fibre neuropathy (SFN), a condition dominated by neuropathic pain, is frequently encountered in clinical practise either as prevalent manifestation of more diffuse neuropathy or distinct nosologic entity.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18524793",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "Neuropathic pain is a characteristic feature of small fiber neuropathy (SFN), which in 18% of the cases is caused by genetic variants in voltage-gated sodium ion channels.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36430572",
"endSection": "abstract"
},
{
"offsetInBeginSection": 240,
"offsetInEndSection": 466,
"text": "SFN was defined by the presence of suggestive sensory painful symptoms with normal nerve conduction studies and abnormal neurophysiologic tests for small nerve fibers or a low intraepidermal nerve fiber density at skin biopsy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23982054",
"endSection": "abstract"
},
{
"offsetInBeginSection": 94,
"offsetInEndSection": 222,
"text": "SFN is clinically dominated by neuropathic pain and autonomic complaints, leading to a significant reduction in quality of life.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30569495",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "Small-fiber neuropathy (SFN) is a disorder of thinly myelinated Aδ and unmyelinated C fibers. SFN is clinically dominated by neuropathic pain and autonomic complaints, leading to a significant reduction in quality of life.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30569495",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 336,
"text": "INTRODUCTION: Small fiber neuropathy (SFN) is a heterogeneous group of disorders affecting thin myelinated Aδ and unmyelinated C fibers. Common symptoms include neuropathic pain and autonomic disturbances, and the typical clinical presentation is that of a length-dependent polyneuropathy, although other distributions could be present.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32654574",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 452,
"text": "Small fiber neuropathy (SFN) is a peripheral nervous system disease due to affection of A-delta or C-fibers in a proximal, distal, or diffuse distribution. Selective SFN (without large fiber affection) manifests with pain, sensory disturbances, or autonomic dysfunction. Though uniform diagnostic criteria are unavailable, most of them request typical clinical features and reduced intra-epidermal nerve fiber density on proximal or distal skin biopsy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35130356",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 480,
"text": "Small fibre neuropathies are a heterogeneous group of disorders affecting thinly myelinated Aδ-fibres and unmyelinated C-fibres. Although multiple causes of small nerve fibre degeneration have been reported, including via genetic mutations, the cause of small fibre neuropathy remains unknown in up to 50% of cases. The typical clinical presentation of small fibre neuropathy is that of a symmetrical, length-dependent polyneuropathy associated with sensory or autonomic symptoms.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29029847",
"endSection": "abstract"
}
] |
6415c53e690f196b51000012 | When was Keytruda approved by the FDA for the treatment of metastatic non-small cell lung cancer? | On October 24, 2016, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda) for treatment of metastatic non-small cell lung cancer. | [
"28835513"
] | factoid | [
{
"offsetInBeginSection": 0,
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"text": "On October 24, 2016, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda; Merck & Co., Inc., https://www.merck.com) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose tumors express programmed death-ligand 1 (PD-L1) as determined by an FDA-approved test, as follows: (a) first-line treatment of patients with mNSCLC whose tumors have high PD-L1 expression (tumor proportion score [TPS] ≥50%), with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations, and (b) treatment of patients with mNSCLC whose tumors express PD-L1 (TPS ≥1%), with disease progression on or after platinum-containing chemotherapy. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28835513",
"endSection": "abstract"
}
] |
6417949d690f196b51000035 | Which gene therapies are under investigation for Duchenne muscular dystrophy? | Gene therapies under investigation for Duchenne muscular dystrophy include exon skipping, stop codon read-through, gene editing, and gene replacement. | [
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{
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"text": " In relation to clinical trials, in the last ten years, has experienced great advances in the field of therapeutic options, divided into two major therapeutic targets: 1) the area of gene therapies and 2) trying to reverse or block the pathophysiological processes of the disease, such as inflammation, fibrosis, muscle regeneration, etc. ",
"beginSection": "abstract",
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{
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"text": "Several promising gene therapies are currently under investigation. These include gene replacement, exon skipping, suppression of stop codons.",
"beginSection": "abstract",
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"endSection": "abstract"
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{
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"text": "More recently, a promising gene editing tool referred to as CRISPR/Cas9 offers exciting perspectives for restoring dystrophin expression in patients with DMD.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29351004",
"endSection": "abstract"
},
{
"offsetInBeginSection": 271,
"offsetInEndSection": 561,
"text": "Adeno-associated virus-vectorized gene therapies to restore dystrophin protein expression using gene replacement or antisense oligonucleotide-mediated pre-mRNA splicing modulation have emerged, making great strides in uncovering barriers to gene therapies for DMD and other genetic diseases",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34175043",
"endSection": "abstract"
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{
"offsetInBeginSection": 522,
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"text": "We recently showed that antisense oligoribonucleotide-mediated skipping of exon 46 efficiently induced dystrophin synthesis in cultured muscle cells from Duchenne muscular dystrophy patients carrying an exon 45 deletion.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12206800",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1125,
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"text": "The success of induced exon skipping has spawned a number of \"fusion therapies\", including vector-mediated dystrophin exon skipping and ex vivo viral delivery of splice-switching antisense molecules into myogenic stem cells, followed by implantation, which may address long term oligomer delivery issues.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20041827",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "Several clinical trials have recently demonstrated that oligonucleotide-based drugs induced targeted exon skipping in dystrophin pre-mRNA in Duchenne muscular dystrophy patients, resulting in novel expression of a truncated but functional isoform of the dystrophin protein.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22846203",
"endSection": "abstract"
},
{
"offsetInBeginSection": 516,
"offsetInEndSection": 715,
"text": "These strategies include gene replacement with adeno-associated virus, exon skipping with antisense oligonucleotides, and mutation suppression with compounds that \"read through\" stop codon mutations.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23328943",
"endSection": "abstract"
},
{
"offsetInBeginSection": 150,
"offsetInEndSection": 398,
"text": "There are several promising genetic approaches, including viral delivery of the missing dystrophin gene, read-through of translation stop codons, exon skipping to restore the reading frame and increased expression of the compensatory utrophin gene.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23609411",
"endSection": "abstract"
},
{
"offsetInBeginSection": 133,
"offsetInEndSection": 418,
"text": "So far, there is no effective treatment but new gene-based therapies are currently being developed with particular noted advances in using conventional gene replacement strategies, RNA-based approaches, or cell-based gene therapy with a main focus on Duchenne muscular dystrophy (DMD).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19527108",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "Myodys, a full-length dystrophin plasmid vector for Duchenne and Becker muscular dystrophy gene therapy.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18228186",
"endSection": "title"
},
{
"offsetInBeginSection": 450,
"offsetInEndSection": 762,
"text": "The first viral-mediated gene transfer for any muscle disease was carried out at Columbus Children's Research Institute and Ohio State University for limb girdle muscular dystrophy type 2D, and the first viral-mediated trial of gene transfer for Duchenne muscular dystrophy is under way at the same institutions.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17846262",
"endSection": "abstract"
},
{
"offsetInBeginSection": 271,
"offsetInEndSection": 562,
"text": "Adeno-associated virus-vectorized gene therapies to restore dystrophin protein expression using gene replacement or antisense oligonucleotide-mediated pre-mRNA splicing modulation have emerged, making great strides in uncovering barriers to gene therapies for DMD and other genetic diseases.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34175043",
"endSection": "abstract"
},
{
"offsetInBeginSection": 742,
"offsetInEndSection": 1174,
"text": "Of all novel molecular interventions currently being investigated for Duchenne muscular dystrophy, perhaps the most promising method aiming to restore dystrophin expression to diseased cells is known as 'exon skipping' or splice-modulation, whereby antisense oligonucleotides eliminate the deleterious effects of DMD mutations by modulating dystrophin pre-messenger RNA splicing, such that functional dystrophin protein is produced.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20150322",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 94,
"text": "Targeted exon skipping as a potential gene correction therapy for Duchenne muscular dystrophy.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12206800",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 114,
"text": "Several new approaches to gene therapy for the muscular dystrophies involve oligonucleotides as targeting vectors.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12206797",
"endSection": "abstract"
},
{
"offsetInBeginSection": 146,
"offsetInEndSection": 448,
"text": "gene therapy, an approach that demonstrates promise for treating Duchenne muscular dystrophy. Gene therapy is not limited to replacement of defective genes but also includes strategies using surrogate genes with alternative but effective means of improving cellular function or repairing gene mutations",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17846262",
"endSection": "abstract"
},
{
"offsetInBeginSection": 107,
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"text": "rophy gene which abort dystrophin synthesis. We have explored a gene correction therapy aimed at restoration of the reading frame in Duchenne muscular",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12206800",
"endSection": "abstract"
},
{
"offsetInBeginSection": 359,
"offsetInEndSection": 579,
"text": "on gene replacement and gene/expression repair, including exon-skipping, vector-mediated gene therapy and cell therapy. Therapeutic strategies for different forms of muscular dystrophy are discussed, with an emphasis on ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/23387802",
"endSection": "abstract"
}
] |
63f02a82f36125a426000013 | Does CIDEB mutation protect from liver disease? | Yes. CIDEB mutation protects from liver disease. | [
"35939579"
] | yesno | [
{
"offsetInBeginSection": 0,
"offsetInEndSection": 65,
"text": "Germline Mutations in CIDEB and Protection against Liver Disease.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35939579",
"endSection": "title"
},
{
"offsetInBeginSection": 897,
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"text": "We also found that variants in CIDEB, which encodes a structural protein found in hepatic lipid droplets, had a protective effect. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35939579",
"endSection": "abstract"
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{
"offsetInBeginSection": 2119,
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"text": "CONCLUSIONS: Rare germline mutations in CIDEB conferred substantial protection from liver disease.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35939579",
"endSection": "abstract"
}
] |
64089b21201352f04a000021 | Can you summarize the function of CDK9? | CDK9 (cyclin-dependent kinase 9) is a serine/threonine-specific protein kinase that is involved in the regulation of transcription. It is a component of the positive transcription elongation factor b (P-TEFb) complex, which is essential for the phosphorylation of the C-terminal domain of RNA polymerase II and the subsequent transcriptional elongation. | [
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"text": "Cdk9 is a member of the Cdc2-like family of kinases. Its cyclin partners are members of the family of cyclin T (T1, T2a and T2b) and cyclin K. The Cdk9/cyclin T complexes appear to be involved in regulating several physiological processes",
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{
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"text": "We previously cloned a cdc2-related kinase, cdk9/PITALRE, that is able to phosphorylate the retinoblastoma protein i",
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{
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"text": "hese results suggest that, among other roles, cdk9/PITALRE plays a role not unlike cdk5 in the differentiation of certain cell types.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9766517",
"endSection": "abstract"
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{
"offsetInBeginSection": 10,
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"text": " CDK9/Cyclin T1 kinase is a protein kinase, indirectly involved in the cell cycle progression in the form of transcription elongation",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31603123",
"endSection": "abstract"
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{
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"text": "Among various clinically validated kinases, the cyclin-dependent kinases (CDK) are one of the extensively studied drug targets for clinical developmen",
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},
{
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"text": "Cyclin-dependent kinases (CDKs) are a broad family of proteins involved in the cell cycle and transcriptional regulation. In this article, we explore the antitumoral activity of a novel proteolysis-targeting chimera (PROTAC) compound against CDK9",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35628286",
"endSection": "abstract"
},
{
"offsetInBeginSection": 240,
"offsetInEndSection": 427,
"text": "Cdk9/cyclin T1 belongs to the P-TEFb complex, and is responsible for the phosphorylation of the carboxyl-terminal domain (CTD) of the RNA Polymerase II, thus promoting general elongation.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12432243",
"endSection": "abstract"
},
{
"offsetInBeginSection": 93,
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"text": "Cdk9 function depends on its kinase activity and also on its regulatory units: the T-family cyclins and cyclin K. Recently, several studies confirmed the role of cdk9 in different cellular processes such as signal transduction, basal transcription, HIV-Tat- and MyoD-mediated transcription and differentiation.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/11532614",
"endSection": "abstract"
},
{
"offsetInBeginSection": 930,
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"text": "This data suggests the involvement of Cdk9 in several physiological processes in the cell, the deregulation of which may be related to the genesis of transforming events, that may in turn lead to the onset of cancer.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12432243",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "CDK9 is a prominent member of the transcriptional CDKs subfamily, a group of kinases whose function is to control the primary steps of mRNA synthesis and processing by eukaryotic RNA polymerase II.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27833949",
"endSection": "abstract"
},
{
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"offsetInEndSection": 293,
"text": "Cyclin-dependent kinase 9 (CDK9), with its cyclin T regulatory subunit, is a component of the positive transcription elongation factor b (P-TEFb) complex, which stimulates transcription elongation and also functions in co-transcriptional histone modification, mRNA processing, and mRNA export.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21200140",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 481,
"text": "Cyclin Dependent Kinase 9 (CDK9) is one of the most important transcription regulatory members of the CDK family. In conjunction with its main cyclin partner-Cyclin T1, it forms the Positive Transcription Elongation Factor b (P-TEFb) whose primary function in eukaryotic cells is to mediate the positive transcription elongation of nascent mRNA strands, by phosphorylating the S2 residues of the YSPTSPS tandem repeats at the C-terminus domain (CTD) of RNA Polymerase II (RNAP II).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34062779",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 367,
"text": "CDK9 is a prominent member of the transcriptional CDKs subfamily, a group of kinases whose function is to control the primary steps of mRNA synthesis and processing by eukaryotic RNA polymerase II. As a cyclin-dependent kinase, CDK9 activation in vivo depends upon its association with T-type cyclins to assemble the positive transcription elongation factor (P-TEFb).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/27833949",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "Cyclin-dependent kinase 9 (CDK9), the kinase component of positive transcription elongation factor b (P-TEFb), is essential for transcription of most protein-coding genes by RNA polymerase II (RNAPII).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34146121",
"endSection": "abstract"
}
] |
6410eead201352f04a000030 | How does RBM24 control QT interval? | RBM24 controls cardiac QT interval through CaMKIIδ splicing. | [
"36454480"
] | summary | [
{
"offsetInBeginSection": 1178,
"offsetInEndSection": 1350,
"text": "Thus, our data suggest that RBM24 is a critical regulator of CaMKIIδ to control the cardiac QT interval, highlighting the key role of splicing regulation in cardiac rhythm.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36454480",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 60,
"text": "RBM24 controls cardiac QT interval through CaMKIIδ splicing.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36454480",
"endSection": "title"
}
] |
64105502201352f04a00002d | Is North Star Ambulatory Assessment score a reliable clinical outcome for disease progression assessment in Duchenne Muscular Dystrophy? | Yes, North Star Ambulatory Assessment score is a reliable clinical outcome and widely used for disease progression assessment in Duchenne Muscular Dystrophy. | [
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] | yesno | [
{
"offsetInBeginSection": 1854,
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"text": "The results showed a significant difference in the NSAA score between the deletion and nonsense groups at the age of 3 years (P = 0.04).",
"beginSection": "abstract",
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{
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"text": "The boys were evaluated with standardized assessments at the screening and baseline visits at 32 sites in 5 countries (US, UK, Canada, Italy, Germany). Assessments included timed rise from floor, timed 10 m walk/run, six-minute walk distance, North Star Ambulatory Assessment (NSAA) and forced vital capacity (FVC). Mean age at baseline was 5.9 years (range 4.1-8.1 years). Test-retest reliability was high for functional assessments, regardless of time lag between assessments (up to 90 days) and for the majority of age groups. Correlations were strong among the functional measures and timed tests, less so with FVC.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35618576",
"endSection": "abstract"
},
{
"offsetInBeginSection": 11,
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"text": "The North Star Ambulatory Assessment (NSAA) is a validated 17-item functional rating scale and widely used to assess motor function in boys with Duchenne muscular dystrophy (DMD).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35626905",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1319,
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"text": "hese exploratory analyses reveal additional approaches to interpreting the NSAA data beyond just change in NSAA total score. These observations also highlight the importance of reporting items as \"not obtainable\" for a patient with a temporary/transient physical disability that impacts their ability to perform the NSAA test.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35998119",
"endSection": "abstract"
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{
"offsetInBeginSection": 836,
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"text": "measurement. All analyses were performed using the Rasch Unidimensional Measurement Model.RESULTS: Overall, Rasch analysis supported the NSAA as being a reliable (high Person Separation Index of 0.91) and valid (good targeting, little misfit, no reversed thresholds) measure of ambul",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21410696",
"endSection": "abstract"
},
{
"offsetInBeginSection": 144,
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"text": "We hypothesised that boys with DMD could be clustered into groups sharing similar trajectories of ambulatory function over time, as measured by the North Star Ambulatory Assessment (NSAA) total score.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31479456",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "INTRODUCTION: The North Star Ambulatory Assessment (NSAA) tool is a key instrument for measuring clinical outcomes in patients with Duchenne muscular dy",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35998119",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 145,
"text": "The North Star Ambulatory Assessment is a functional scale specifically designed for ambulant boys affected by Duchenne muscular dystrophy (DMD).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20634072",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1416,
"offsetInEndSection": 1581,
"text": " North Star Ambulatory Assessment in Brazilian Portuguese is a reliable and valid instrument to measure functional capacity in boys with Duchenne muscular dystrophy.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28648683",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 344,
"text": "Functional variability among boys with Duchenne muscular dystrophy (DMD) is well recognised and complicates interpretation of clinical studies. We hypothesised that boys with DMD could be clustered into groups sharing similar trajectories of ambulatory function over time, as measured by the North Star Ambulatory Assessment (NSAA) total score.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31479456",
"endSection": "abstract"
}
] |
63f032caf36125a42600001a | What is the mechanism of action of rilzabrutinib? | Rilzabrutinib is oral Bruton tyrosine kinase (BTK) inhibitor. | [
"35302767",
"36182620",
"35301810"
] | summary | [
{
"offsetInBeginSection": 0,
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"text": "This study aimed to define the clinically relevant supratherapeutic dose of rilzabrutinib, an oral Bruton tyrosine kinase (BTK) inhibitor, and evaluate potential effects of therapeutic and supratherapeutic exposures on cardiac repolarization in healthy subjects.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35301810",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 104,
"text": "Discovery of Reversible Covalent Bruton's Tyrosine Kinase Inhibitors PRN473 and PRN1008 (Rilzabrutinib).",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35302767",
"endSection": "title"
},
{
"offsetInBeginSection": 303,
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"text": "Herein, we describe the design of covalent reversible BTK inhibitors and the discoveries of PRN473 (11) and rilzabrutinib (PRN1008, 12). ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35302767",
"endSection": "abstract"
},
{
"offsetInBeginSection": 813,
"offsetInEndSection": 1016,
"text": "Ongoing trials include new B-cell/plasma-cell targeting agents such as the Bruton tyrosine kinase inhibitors ibrutinib and rilzabrutinib, and the anti-CD38 MoAbs daratumumab and its analogue isatuximab. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36182620",
"endSection": "abstract"
}
] |
641368ee201352f04a00003c | What are the types/categories of adult diffuse gliomas. | The four main types/categories of adult diffuse gliomas are:
1. Astrocytomas
2. Oligodendrogliomas
3. Mixed Gliomas
4. Ependymomas | [
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{
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"text": " Adult-type diffuse gliomas are genetically defined and include astrocytoma, isocitrate dehydrogenase (IDH)-mutant, oligodendroglioma, IDH-mutant and 1p/19q codeleted, and glioblastoma, IDH-wildtype",
"beginSection": "abstract",
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"text": " According to the 2021 World Health Organization classification, the three risk types included (1) low-risk, expecting oligodendroglioma, isocitrate dehydrogenase (IDH)-mutant, and 1p/19q-codeleted; (2) intermediate-risk, expecting astrocytoma, IDH-mutant; and (3) high-risk, expecting glioblastoma, IDH-wildtype.",
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"text": "Adult-type diffuse gliomas are genetically defined and include astrocytoma, isocitrate dehydrogenase (IDH)-mutant, oligodendroglioma, IDH-mutant and 1p/19q codeleted, and glioblastoma, IDH-wildtype.",
"beginSection": "abstract",
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"text": "A review of adult-type diffuse gliomas in the WHO CNS5 classification with special reference to Astrocytoma, IDH-mutant and Oligodendroglioma, IDH-mutant and 1p/19q codeleted.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35562130",
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"text": "thogenesis and prognosis. Furthermore, the previous broad category of adult-type diffuse gliomas has been consolidated into 3 types: astrocytoma, isocitrate dehydrogenase (IDH) mutant; oligodendroglioma, IDH mutant and 1p/19q codeleted; and gl",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36006639",
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{
"offsetInBeginSection": 437,
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"text": "This review briefly discusses two tumor types: astrocytoma, IDH-mutant, and oligodendroglioma, IDH-mutant and 1p/19q codeleted, with emphasis on relevant changes in their classification and defining molecular genetic alterations.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35562130",
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"text": "Since brainstem biopsies are rarely performed, these tumours are commonly classified according to their MR imaging characteristics into 4 subgroups: (a) diffuse intrinsic low-grade gliomas, (b) enhancing malignant gliomas, (c) focal tectal gliomas and (d) exophytic gliomas/other subtypes.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/25641008",
"endSection": "abstract"
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{
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"text": "C > 0.5, k > 0.6, p < 0.001). IBGS type-I, type-II, and type-III gliomas had good specificity in identifying IDHmut 1p19q-codel oligodendroglioma (training - 97%, validation - 85%); IDHmut 1p19q non-codel astrocytoma (training - 80%, validation - 85.9%); and IDHwt glioblastoma (training - 76.5%, validation- 87.3%) respectively (p-value < 0.01).CONCLUSIONS: Imaging-based stratification of adult diffuse gliomas predicted patient survival and correlate",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35876874",
"endSection": "abstract"
},
{
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"text": "In the new WHO classification 2021, adult-type diffuse astrocytic gliomas subdivide into isocitrate dehydrogenase (IDH)-mutant astrocytoma, IDH-mutant and 1p/19q-codeleted oligodendroglioma, and IDH-wildtype glioblastoma.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36299937",
"endSection": "abstract"
},
{
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"text": "Recent genetic studies have revealed that the major categories of gliomas, such as circumscribe astrocytomas, infiltrating astrocytomas/oligodendrogliomas, and glioblastoma, roughly correspond to major genetic alterations, including isocitrate dehydrogenases (IDHs) 1/2 mutations, TP53 mutations, co-deletion of chromosome arms 1p/19q, and BRAF mutation/fusion.",
"beginSection": "abstract",
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"endSection": "abstract"
},
{
"offsetInBeginSection": 151,
"offsetInEndSection": 590,
"text": "This improves diagnostic accuracy and prognostication: oligo-astrocytoma no longer exists as a clinical entity; isocitrate dehydrogenase (IDH) mutant and 1p/19q co-deleted oligodendroglioma is a smaller category with better prognosis; IDH wild-type 'low-grade' glioma has a much poorer prognosis; and glioblastoma is divided into IDH mutant (with an better prognosis than pre-2016 glioblastoma) and IDH wild type (with a poorer prognosis).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31175262",
"endSection": "abstract"
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{
"offsetInBeginSection": 203,
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"text": "A four-tiered WHO grading scheme has been successfully applied to a spectrum of diffusely infiltrative astrocytomas, but it is not fully applicable to other gliomas, including oligodendrogliomas and ependymomas.",
"beginSection": "abstract",
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"endSection": "abstract"
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"text": "This has resulted in a major revision of the WHO classification, which is now for adult diffuse glioma centered around isocitrate dehydrogenase (IDH) and 1p/19q diagnostics.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/28339700",
"endSection": "abstract"
},
{
"offsetInBeginSection": 247,
"offsetInEndSection": 370,
"text": "The major representatives in this subgroup are the diffuse astrocytic, oligodendroglial, and mixed oligo-astrocytic tumors.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16700618",
"endSection": "abstract"
},
{
"offsetInBeginSection": 246,
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"text": " The major representatives in this subgroup are the diffuse astrocytic, oligodendroglial, and mixed oligo-astrocytic tumors.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16700618",
"endSection": "abstract"
},
{
"offsetInBeginSection": 609,
"offsetInEndSection": 759,
"text": "ssion, and 1p/19q co-deletion detection in adult diffuse gliomas (Grade II, III, and IV) and to correlate them with clinicopathological and histopatho",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34729052",
"endSection": "abstract"
},
{
"offsetInBeginSection": 198,
"offsetInEndSection": 348,
"text": "vide into isocitrate dehydrogenase (IDH)-mutant astrocytoma, IDH-mutant and 1p/19q-codeleted oligodendroglioma, and IDH-wildtype glioblastoma. The T2-",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36299937",
"endSection": "abstract"
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{
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"text": "include astrocytoma, isocitrate dehydrogenase (IDH)-mutant, oligodendroglioma, IDH-mutant and 1p/19q codeleted, and glioblastoma, IDH-wildtype. This r",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35562130",
"endSection": "abstract"
},
{
"offsetInBeginSection": 494,
"offsetInEndSection": 644,
"text": "hese changes has been the division of adult astrocytomas into IDH-wildtype and IDH-mutant categories in addition to histologic grade as part of the ma",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32640746",
"endSection": "abstract"
},
{
"offsetInBeginSection": 148,
"offsetInEndSection": 363,
"text": "O classification, five main molecular subgroups of adult diffuse gliomas can be distinguished based on the 1p/19q codeletion, isocitrate dehydrogenase (IDH), and histone H3.3 mutation status. In the future, this cla",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/30148717",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "Adult gliomas are most often infiltrative. The World Health Organization (WHO) has classed them into three major groups according to the presomptive cell of origin: astrocytoma, oligodendroglioma and mixed oligoastrocytoma. Depending on the presence or absence of a small number of signs of anaplasia (mitosis, nuclear atypia, cell density, microvascular proliferation and necrosis) the WHO distinguishes grade II (LGG), III (anaplastic), and IV (glioblastomas, GBM).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/21889777",
"endSection": "abstract"
}
] |
6415ca99690f196b51000019 | Have chimeric antigen receptor (CAR)-T cell therapies been approved for the treatment of B cell malignancies? | Yes, four chimeric antigen receptor (CAR)-T cell therapies now approved for the treatment of B cell malignancies. | [
"33833444"
] | yesno | [
{
"offsetInBeginSection": 345,
"offsetInEndSection": 592,
"text": "Engineered T cells have achieved success in the treatment of blood cancers, with four chimeric antigen receptor (CAR)-T cell therapies now approved for the treatment of B cell malignancies based on their unprecedented efficacy in clinical trials. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33833444",
"endSection": "abstract"
}
] |
64178e4b690f196b51000022 | Is golodirsen effective for the treatment of Duchenne muscular dystrophy? | Yes, golodirsen can be considered effective for the treatment of Duchenne muscular dystrophy. | [
"36401026",
"34788571",
"32026421",
"33025945"
] | yesno | [
{
"offsetInBeginSection": 783,
"offsetInEndSection": 902,
"text": "Golodirsen is a provisionally approved PMO-based drug for approx. 8% of all DMD patients amenable to exon 53 skipping. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/33025945",
"endSection": "abstract"
},
{
"offsetInBeginSection": 599,
"offsetInEndSection": 710,
"text": "This article summarizes the milestones in the development of golodirsen leading to this first approval for DMD.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32026421",
"endSection": "abstract"
},
{
"offsetInBeginSection": 252,
"offsetInEndSection": 513,
"text": "n December 2019, intravenous golodirsen received its first global approval in the USA for the treatment of DMD in patients with a confirmed mutation of the DMD gene that is amenable to exon 53 skipping, based on positive results from a phase I/II clinical trial",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32026421",
"endSection": "abstract"
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{
"offsetInBeginSection": 334,
"offsetInEndSection": 486,
"text": "To date, four PMOs, including eteplirsen, casimersen, viltolarsen, and golodirsen, have been conditionally approved by the FDA for the treatment of DMD.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/36401026",
"endSection": "abstract"
},
{
"offsetInBeginSection": 965,
"offsetInEndSection": 1069,
"text": "Golodirsen increased dystrophin protein (16.0-fold; P < 0.001) and exon skipping (28.9-fold; P < 0.001).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34788571",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1381,
"offsetInEndSection": 1552,
"text": "This study provides evidence for golodirsen biologic activity and long-term safety in a declining DMD population and suggests functional benefit versus external controls. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/34788571",
"endSection": "abstract"
}
] |
63f043e4f36125a426000023 | Is Baricitinib effective for Alopecia Areata? | Yes. In two phase 3 trials involving patients with severe alopecia areata, oral baricitinib was superior to placebo with respect to hair regrowth at 36 weeks. | [
"35334197",
"35330989"
] | yesno | [
{
"offsetInBeginSection": 345,
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"text": "Thus far, it has been approved for the treatment of rheumatoid arthritis (RA); however, an increasing number of studies have suggested that baricitinib can be used to treat dermatological diseases, such as atopic dermatitis (AD), psoriasis, vitiligo, and alopecia areata. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35330989",
"endSection": "abstract"
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{
"offsetInBeginSection": 744,
"offsetInEndSection": 979,
"text": "We reviewed the application, efficacy, side effects, precautions, limitations and prospect of baricitinib in atopic dermatitis, psoriasis, vitiligo and alopecia areata (AA) in recent 5 years including clinical trials and case reports. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35330989",
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{
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"text": "Two Phase 3 Trials of Baricitinib for Alopecia Areata.",
"beginSection": "title",
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"endSection": "title"
},
{
"offsetInBeginSection": 1870,
"offsetInEndSection": 2037,
"text": "CONCLUSIONS: In two phase 3 trials involving patients with severe alopecia areata, oral baricitinib was superior to placebo with respect to hair regrowth at 36 weeks. ",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/35334197",
"endSection": "abstract"
}
] |
64137616201352f04a000041 | Anemia is not associated with chronic kidney failure | No, anemia is a common complication of chronic kidney failure. | [
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"text": "This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure",
"beginSection": "abstract",
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"text": "Anaemia is a common manifestation ofa chronic kidney failure. ",
"beginSection": "abstract",
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{
"offsetInBeginSection": 0,
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"text": "The hormone deficiency that underlies anemia in chronic kidney failure can now be corrected",
"beginSection": "abstract",
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"endSection": "abstract"
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{
"offsetInBeginSection": 919,
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"text": "We call this interrelationship between congestive heart failure, chronic kidney insufficiency, and anemia the Cardio-Renal Anemia syndrome.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15467179",
"endSection": "abstract"
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{
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"text": "Anemia is a major problem in patients with chronic kidney insufficiency.",
"beginSection": "abstract",
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{
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"text": "Correction of the anemia with erythropoietin and intravenous iron led to a marked improvement in patients' functional status and their cardiac function, and to a marked fall in the need for hospitalization and for high-dose diuretics; renal function usually improved or at least stabilized.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15467179",
"endSection": "abstract"
},
{
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"text": "The anemia is very often associated with chronic kidney disease (CKD).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18670732",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 114,
"text": "The role of anemia in congestive heart failure and chronic kidney insufficiency: the cardio renal anemia syndrome.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/15467179",
"endSection": "title"
},
{
"offsetInBeginSection": 116,
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"text": "While iron deficiency is often stated as a cause of anemia in chronic renal failure prior to end-stage renal disease, its relative contribution is debated.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9375826",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 115,
"text": "Anemia in chronic renal failure is predominantly caused by diminished erythropoietin synthesis by diseased kidneys.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9375826",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1828,
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"text": "We infer that impaired utilization of iron may be a significant factor in the anemia of chronic renal failure.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9375826",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "BACKGROUND: Kidney failure causes anemia and is associated with a very high risk of coronary heart di",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16442920",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 113,
"text": "BACKGROUND: Kidney failure is known to cause anemia, which is associated with a higher risk of cardiac failure an",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/12076240",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 156,
"text": "The correction of anemia in patients with the combination of chronic kidney disease and congestive heart failure may prevent progression of both conditions.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18670732",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 120,
"text": "BACKGROUND: Anemia, a common complication of chronic kidney disease, usually develops as a consequence of erythropoietin",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17108343",
"endSection": "abstract"
},
{
"offsetInBeginSection": 101,
"offsetInEndSection": 215,
"text": "In patients with CKD, anemia is often caused by decreased erythropoietin production relative to hemoglobin levels.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22536082",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1467,
"offsetInEndSection": 1551,
"text": "Clearly more work is needed to clarify the relationship between anemia, CKD and CHF.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/18670732",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 76,
"text": "Use of EPOGEN for treatment of anemia associated with chronic renal failure.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/2357306",
"endSection": "title"
},
{
"offsetInBeginSection": 200,
"offsetInEndSection": 270,
"text": " Heart failure, anemia and chronic renal failure are mutually related.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/16623112",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 90,
"text": "Uremic Toxins Affect Erythropoiesis during the Course of Chronic Kidney Disease: A Review.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/32899941",
"endSection": "title"
},
{
"offsetInBeginSection": 817,
"offsetInEndSection": 924,
"text": " Partial, but not complete, correction of anemia is associated with improved outcomes in patients with CKD.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/19833421",
"endSection": "abstract"
},
{
"offsetInBeginSection": 433,
"offsetInEndSection": 558,
"text": " The high prevalence of anemia in chronic kidney disease is explained by a combination of erythropoietin and iron deficiency.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22454095",
"endSection": "abstract"
},
{
"offsetInBeginSection": 91,
"offsetInEndSection": 181,
"text": " Many advanced chronic kidney disease patients have both anemia and chronic heart failure.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/22680636",
"endSection": "abstract"
},
{
"offsetInBeginSection": 1669,
"offsetInEndSection": 1821,
"text": " In conclusion, anemia is associated with a rapid decrease in kidney function in patients with heart failure, particularly in those with underlying CKD.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17437743",
"endSection": "abstract"
},
{
"offsetInBeginSection": 151,
"offsetInEndSection": 284,
"text": " This analysis was conducted to evaluate whether anemia is a risk factor for kidney function decrease in patients with heart failure.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17437743",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 86,
"text": "Anemia as a risk factor for kidney function decline in individuals with heart failure.",
"beginSection": "title",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/17437743",
"endSection": "title"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 204,
"text": "End stage renal disease (ESRD) invariably leads to anemia which has been mainly attributed to compromised release of erythropoietin from the defective kidneys with subsequent impairment of erythropoiesis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/29151105",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "Chronic kidney disease (CKD) is a widespread health problem in the world and anaemia of renal origin is a common problem.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/20443766",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
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"text": "Anemia is the most common hematologic complication in end-stage renal disease (ESRD). It is ascribed to decreased erythropoietin production, shortened red blood cell (RBC) lifespan, and inflammation.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/26948278",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 440,
"text": "Anemia is one of the most characteristic and visable manifestations of chronic renal failure. Investigators in the past decade have provided a better understanding of this anemia. The etiology of the anemia of chronic renal failure has three facets: first is reduced erythropoietin production by damaged kidneys; second is the presence of inhibitors to red blood cell (RBC) production in uremic serum; and third is red blood cell hemolysis.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/7034633",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 378,
"text": "Cardiovascular disease remains the major cause of mortality in patients with end stage renal disease (ESRD). The pathophysiology of cardiac dysfunction in ESRD is complex and not fully understood. However, it appears that the two major determinants of left ventricular (LV) hypertrophy and dysfunction are anemia and hypertension, both of which are very common in ESRD patients.",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/9241712",
"endSection": "abstract"
},
{
"offsetInBeginSection": 0,
"offsetInEndSection": 376,
"text": "NGAL, also known as lipocalin 2, is a stress protein located on the cell surface that is known for its involvement in iron transport. This study is aimed to evaluate the correlation between the iron profile and NGAL concentration in serum among chronic kidney disease patients under dialysis in order to find its diagnostic value with regards to iron deficiency anaemia (IDA).",
"beginSection": "abstract",
"document": "http://www.ncbi.nlm.nih.gov/pubmed/31994917",
"endSection": "abstract"
}
] |
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