nirantk/geneticsQA-train huggingface dataset:
Question: Is cadasil syndrome a hereditary disease?

Context:
 CADASIL is the most frequent hereditary small-vessel disease of the brain. The clinical impact of various MR imaging markers has been repeatedly studied in this disorder, but alterations of contrast between gray matter and normal-appearing white matter remain unknown. The aim of this study was to evaluate the contrast alterations between gray matter and normal-appearing white matter on T1-weighted images in patients with CADASIL compared with healthy subjects
 (CADASIL) is the most common form of hereditary cerebral angiopathy
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease, clinically characterized by migraine, recurrent transient ischemic attacks or strokes, psychiatric disorders and cognitive decline. Strokes are typically ischemic, while hemorrhagic events have been only sporadically described
Mutations in the TREX1 and NOTCH3 genes cause retinal vasculopathy with cerebral leukodystrophy (RVCL) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), respectively
We used immunohistochemistry and immunogold electron microscopy (EM) to examine the distribution of GOM and NOTCH3 ectodomain (N3ECD) protein in microvasculature of brain gray matter and white matter in patients with CADASIL, non-CADASIL hereditary small-vessel disease and sporadic age-related degenerative disease, and comparable-age controls

Answer: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease, clinically characterized by migraine, recurrent transient ischemic attacks or strokes, psychiatric disorders and cognitive decline. Strokes are typically ischemic, while hemorrhagic events have been only sporadically described. CADASIL is the most common form of hereditary cerebral angiopathy.
Exact answer: yes
Question: How does Apolipoprotein E4 contribute to the risk of cognitive decline and late onset Alzheimer's disease?

Context:
Apolipoprotein E4 (E4) and type 2 diabetes are major risk factors for cognitive decline and late onset Alzheimer's disease (AD)
Cardiovascular risk factors, especially hypertension, are also major risk factors for Alzheimer's disease (AD).
Clusterin (Apo J) is one of the major risk factors for sporadic form of AD. 
Hypertension is one of the major risk factors for central nervous system (CNS) disorders like stroke and Alzheimer's disease (AD).
Major risk factors for AD are advancing age and diabetes. Lately, obesity has been associated with an increased risk of dementia.

Answer: Apolipoprotein E4 (E4) is a major risk factor for cognitive decline and late onset Alzheimer's disease (AD).
Question: Which is the prognostic impact of hypothyroidism in patients with acute myocardial infarction?

Context:
In-hospital cardiogenic shock (15% vs 3% in the control group; p<0.01) and death (7% vs 1% in the control group; p<0.01) were more frequently observed in the thyroid dysfunction group. 
Thyroid dysfunction, particularly sick euthyroid syndrome, was found to be related to in-hospital and long term mortality in patients with STEMI undergoing primary percutaneous intervention.
A low fT3 level, a common phenomenon in patients with acute myocardial infarctions, is a strong predictor of short-term and long-term poor prognoses in patients with acute myocardial infarctions.
Troponin T and creatine kinase-B with an M-type subunit levels were significantly higher in the nonsurvivors when compared with survivors. Survivors in the AMI group had higher TT3, TT4, and lower FT4 levels, while the nonsurvivors in the AMI group had higher thyrotrophin and lower TT3, FT3 and FT4 levels than controls.
Reverse T3 levels >0.41 nmol/L were associated with an increased risk of 1-year mortality (hazard ratio = 3.0; 95% confidence interval: 1.4 to 6.3; P = 0.005), independent of age, previous myocardial infarction, prior angina, heart failure, serum creatinine level, and peak serum creatine kinase-MB fraction levels.

Answer: Thyroid dysfunction, particularly low T3 syndrome,  is a strong predictor of short-term and long-term poor prognoses in patients with acute myocardial infarctions.
Exact answer: Low T3 Syndrome isassociatedwithpoor prognosis in patients with acute myocardial infarction
Question: What molecule is targeted by suvorexant?

Context:
Suvorexant is the first DORA to be approved and has demonstrated efficacy at decreasing both time to sleep onset and increasing total sleep time compared with placebo. 
Suvorexant: a dual orexin receptor antagonist for the treatment of sleep onset and sleep maintenance insomnia.
CONCLUSION: Suvorexant is the first dual orexin receptor antagonist approved for the treatment of insomnia. 
Crystal structure of the human OX2 orexin receptor bound to the insomnia drug suvorexant.
 The human OX2 receptor (OX2R) belongs to the β branch of the rhodopsin family of GPCRs, and can bind to diverse compounds including the native agonist peptides orexin-A and orexin-B and the potent therapeutic inhibitor suvorexant. 
Orexin receptor antagonism for treatment of insomnia: a randomized clinical trial of suvorexant.
Promotion of sleep by suvorexant-a novel dual orexin receptor antagonist.
The neurotransmitter systems on which the development of these agents were based included serotonin for ondansetron and lorcaserin, dopamine for varenicline, substance P (or neurokinin) for aprepitant, melatonin for ramelteon, and orexin for suvorexant. The indications were chemotherapy-induced nausea and vomiting for ondansetron and aprepitant, smoking cessation for varenicline, weight loss for lorcaserin, and insomnia for suvorexant and ramelteon.
Suvorexant, a dual orexin receptor antagonist for the management of insomnia.
Suvorexant, a dual orexin receptor antagonist for the management of insomnia.
The orexin-1 and orexin-2 receptors are two G protein-coupled receptors that bind the neuropeptides orexin-A and orexin-B. Dual antagonism of the receptors by small molecules is clinically efficacious in the treatment of insomnia, where the most advanced molecule suvorexant has recently been approved.
Suvorexant helps in decreasing wakefulness by counteracting orexin activity.
 The orexin-1 and orexin-2 receptors are two G protein-coupled receptors that bind the neuropeptides orexin-A and orexin-B. Dual antagonism of the receptors by small molecules is clinically efficacious in the treatment of insomnia, where the most advanced molecule suvorexant has recently been approved.
Hypnotic drug development has arguably become more focused in recent years, particularly upon the highly anticipated novel target, the orexin (hypocretin) system. Merck&apos;s suvorexant (MK-4305) is the first compound of the so-called dual orexin receptor antagonist (DORA) class expected to be submitted for FDA approval, with a new drug application anticipated in 2012.

Answer: Suvorexant is a dual orexin receptor antagonist for the treatment of sleep onset and sleep maintenance insomnia.
Exact answer: orexin
Question: How does Twinkle protein impact DNA stability near human mitochondrial DNA deletion breakpoints?

Context:
n this work, we performed a computational analysis of the human mitochondrial genome using the "Pattern Finder" G-quadruplex (G4) predictor algorithm to assess whether G4-forming sequences reside in close proximity (within 20 base pairs) to known mitochondrial DNA deletion breakpoints.
Circular dichroism and UV spectral analysis demonstrated that mitochondrial G-rich sequences near deletion breakpoints prevalent in human disease form G-quadruplex DNA structures.
Direct repeat sequences are not required at the breakpoints of age-associated mitochondrial DNA deletions in rhesus monkeys.
Most of the analyzed deletion breakpoints showed nucleotide repeats flanking the deletions. 
Currently, the multiple types of GQ sequences and their association with human mtDNA stability are unknown.<br><b>RESULTS</b>: Here, we show an association between human mtDNA deletion breakpoint locations (sites where DNA ends rejoin after deletion of a section) and sequences with G-quadruplex forming potential (QFP), and establish the ability of selected sequences to form GQ in vitro.
A biochemical analysis of purified recombinant human Twinkle protein (gene product of c10orf2) showed that the mitochondrial replicative helicase inefficiently unwinds well characterized intermolecular and intramolecular G-quadruplex DNA substrates, as well as a unimolecular G4 substrate derived from a mitochondrial sequence that nests a deletion breakpoint described in human renal cell carcinoma.
DNA sequences proximal to human mitochondrial DNA deletion breakpoints prevalent in human disease form G-quadruplexes, a class of DNA structures inefficiently unwound by the mitochondrial replicative Twinkle helicase.
Association of G-quadruplex forming sequences with human mtDNA deletion breakpoints.

Answer: The Twinkle protein impacts DNA stability near human mitochondrial DNA deletion breakpoints by inefficiently unwinding G-quadruplex DNA structures formed by sequences proximal to the deletion breakpoints. This inefficient unwinding is observed for intermolecular, intramolecular, and unimolecular G4 substrates derived from mitochondrial sequences near deletion breakpoints.
Question: How many different mutations have been associated with Muenke syndrome?

Context:
Muenke syndrome is an autosomal dominant craniosynostosis syndrome resulting from a defining point mutation in the Fibroblast Growth Factor Receptor3 (FGFR3) gene. 
The associated of FGFR3 mutations with craniosynostosis has been restricted to three mutations, the common p.Pro250Arg in Muenke syndrome, p.Ala391Glu in Crouzon syndrome with acanthosis nigricans, and p.Pro250Leu identified in a family with isolated craniosynostosis. 
The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes. 
 Fibroblasts from 10 individuals each with Apert syndrome (FGFR2 substitution S252W), Muenke syndrome (FGFR3 substitution P250R), Saethre-Chotzen syndrome (various mutations in TWIST1) and non-syndromic sagittal synostosis (no mutation detected) were cultured. 
The identification of the P250R mutation allowed the confirmation of the Muenke Syndrome in 9 out of the 52 cases referred. 
Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3). 

Answer: Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3).
Exact answer: One
Question: Has whole exome sequencing been performed in Alzheimer patients?

Context:
Pilot whole-exome sequencing of a German early-onset Alzheimer's disease cohort reveals a substantial frequency of PSEN2 variants.
We performed whole-exome sequencing in early-onset Alzheimer disease (EOAD) and late-onset Alzheimer disease (LOAD) families followed by functional studies of select variants.
Whole-exome sequencing revealed a nonsense mutation in PRNP (NM_000311, c.C478T; p.Q160*; rs80356711) associated with homozygosity for the V allele at position 129 of the protein, further highlighting how very similar genotypes in PRNP result in strikingly different phenotypes.
In the search for new genes in Alzheimer's disease, classic linkage-based and candidate-gene-based association studies have been supplanted by exome sequencing, genome-wide sequencing (for mendelian forms of Alzheimer's disease), and genome-wide association studies (for non-mendelian forms). 
We performed whole exome sequencing in a Turkish patient clinically diagnosed with Alzheimer's disease from a consanguineous family 
Performing exome sequencing in 14 autosomal dominant early-onset Alzheimer disease (ADEOAD) index cases without mutation on known genes (amyloid precursor protein (APP), presenilin1 (PSEN1) and presenilin2 (PSEN2)), we found that in five patients, the SORL1 gene harbored unknown nonsense (n=1) or missense (n=4) mutations

Answer: Yes, numerous whole exome sequencing studies of ALzheimer patients have been conducted.
Exact answer: yes
Question: How many clinical trials for off-label drugs in neonates are cited in the literature.

Context:
Of the 17 Paediatric Investigation Plans submitted, 14 have resulted in an EMA Decision, 3 were withdrawn by the applicants, 8 were granted a full waiver from development, and 1 resulted in a negative opinion. Decisions as issued included 15 clinical trials, with at least 1,282 children to be recruited into studies across five different products. Neonates were included in four of the products. CONCLUSIONS: The small number of submissions indicates a lack of new drugs being developed for the management of pain. Ethical concerns that too many vulnerable children will be recruited into clinical trials must be balanced against limiting the number of off-label prescribing and obtaining age-appropriate information on paediatric use.
Paediatric Investigations Plans (PIPs) submitted with a Decision (outcome) reached between September 2007 and March 2010 were included in the analysis.

Answer: There are no reports on clinical trials of off-label drugs in neonates. An analysis of Pediatric Investigation Plans submitted between 2007 and 2010 shows that neonates were included in the study of 4 products, but it is unknown if the trial drugs are off-label and if the trials are being conducted at all.
Exact answer: none, 0, zero
Question: Is CD56 useful in Ewing sarcoma prognosis?

Context:
Excellent prognosis in a subset of patients with Ewing sarcoma identified at diagnosis by CD56 using flow cytometry
There was a highly significant correlation between CD56 expression and progression-free survival (PFS; 69% in low/negative expression versus 30% in high expression groups, P = 0.024)
In patients with localized nonpelvic disease, those expressing low/negative CD56 had 100% PFS versus 40% in the high expressing group (P = 0.02)
CD56 was found to be an independent prognostic marker with an 11-fold increased risk for relapse in patients with localized disease (P = 0.006)
CD56 expression could be used to reveal ES patients with excellent prognosis or patients predisposed to relapse, thus improving treatment stratification and implementation of personalized therapy
Excellent prognosis in a subset of patients with Ewing sarcoma identified at diagnosis by CD56 using flow cytometry.
Three years after diagnosis the patient presented with severe respiratory difficulty and following resection, the final pathology revealed multiple tumors with foci of high grade sarcoma compatible with primitive neuroectodermal tumor/extraskeletal Ewing sarcoma based on morphology and immunohistochemistry (CD99, CD56).
CD56 expression could be used to reveal ES patients with excellent prognosis or patients predisposed to relapse, thus improving treatment stratification and implementation of personalized therapy.
Identification of CD56 and CD57 by flow cytometry in Ewing's sarcoma or primitive neuroectodermal tumor.
CD56 expression could be used to reveal ES patients with excellent prognosis or patients predisposed to relapse, thus improving treatment stratification and implementation of personalized therapy.

Answer: Excellent prognosis in a subset of patients with Ewing sarcoma identified at diagnosis by CD56 using flow cytometryIn patients with localized nonpelvic disease, those expressing low/negative CD56 had 100% PFS versus 40% in the high expressing group (P = 0.02)
CD56 expression could be used to reveal Ewing sarcoma patients with excellent prognosis or patients predisposed to relapse, thus improving treatment stratification and implementation of personalized therapy.
Exact answer: yes
Question: Gene silencing can be achieved by RNA interference (RNAi) in eukaryotic organisms. What is the name of the analogous process in prokaryotic organisms?

Context:
he CRISPR-Cas (clustered regularly interspaced short palindromic repeats, CRISPR-associated genes) is an adaptive immunity system in bacteria and archaea that functions via a distinct self-non-self recognition mechanism that is partially analogous to the mechanism of eukaryotic RNA interference (RNAi).
RNA-guided RNA cleavage by a CRISPR RNA-Cas protein complex.
Compelling evidence indicates that the CRISPR-Cas system protects prokaryotes from viruses and other potential genome invaders.
RNA in defense: CRISPRs protect prokaryotes against mobile genetic elements.
n this article, we discuss our current understanding of this fascinating adaptive and heritable defense system, and describe functional similarities and differences with RNAi in eukaryotes.
Bacteria have developed several defense mechanisms against bacteriophages over evolutionary time, but the concept of prokaryotic RNA interference mediated defense mechanism against phages and other invading genetic elements has emerged only recently. Clustered regularly interspaced short palindromic repeats (CRISPR) together with closely associated genes (cas genes) constitute the CASS system that is believed to provide a RNAi-like defense mechanism against bacteriophages within the host bacterium.
In many prokaryotes, noncoding RNAs that arise from the clustered regularly interspaced short palindromic repeat (CRISPR) loci are now thought to mediate defense against viruses and other molecular invaders by an RNAi-like pathway.

Answer: Bacteria have developed several defense mechanisms against bacteriophages over evolutionary time, but the concept of prokaryotic RNA interference mediated defense mechanism against phages and other invading genetic elements has emerged only recently. Clustered regularly interspaced short palindromic repeats (CRISPR) together with closely associated genes (cas genes) constitute the CASS system that is believed to provide a RNAi-like defense mechanism against bacteriophages within the host bacterium.
Exact answer: CRISPR-Cas
Question: What are the pyknons?

Context:
Using an unsupervised pattern-discovery method, we processed the human intergenic and intronic regions and catalogued all variable-length patterns with identically conserved copies and multiplicities above what is expected by chance. Among the millions of discovered patterns, we found a subset of 127,998 patterns, termed pyknons, which have additional nonoverlapping instances in the untranslated and protein-coding regions of 30,675 transcripts from 20,059 human genes
In a recent paper in PNAS, Rigoutsos et al. (2006) describe a nonrandom pattern of repeated elements, called pyknons, which are found more frequently in the 3' untranslated regions of genes than in other regions of the human genome
Discovery of pyknons, the most frequent, variable-length DNA sequence motifs in the human genomes, suggests extensive sequence-based connectivity between non-coding and protein-coding components of human genomes
Short blocks from the noncoding parts of the human genome have instances within nearly all known genes and relate to biological processes.
Pyknons are non-random sequence patterns significantly repeated throughout non-coding genomic DNA that also appear at least once among coding genes. They are interesting because they portend an unforeseen connection between coding and non-coding DNA. Pyknons have only been discovered in the human genome, so it is unknown whether pyknons have wider biological relevance or are simply a phenomenon of the human genome
these data reveal that pyknons represent a biologically important link between coding and non-coding DNA
Pyknons are non-random sequence patterns significantly repeated throughout non-coding genomic DNA that also appear at least once among coding genes.
Pyknons are non-random sequence patterns significantly repeated throughout non-coding genomic DNA that also appear at least once among coding genes
The pyknons arrange combinatorially in the untranslated and coding regions of numerous human genes where they form mosaics

Answer: Using an unsupervised pattern-discovery method, the human intergenic and intronic regions were processed and all variable-length patterns with identically conserved copies and multiplicities above what is expected by chance were catalogued. Among the millions of discovered patterns, a subset of 127,998 patterns was found, termed pyknons, which have additional nonoverlapping instances in the untranslated and protein-coding regions of 30,675 transcripts from 20,059 human genes. The pyknons arrange combinatorially in the untranslated and coding regions of numerous human genes where they form mosaics. Pyknons might represent a biologically important link between coding and non-coding DNA.
Question: Which genes have been found mutated in Gray platelet syndrome patients?

Context:
We detected a nonsense mutation in the gene encoding the transcription factor GFI1B (growth factor independent 1B) that causes autosomal dominant gray platelet syndrome. 
The genetic defect responsible for gray platelet syndrome was recently identified in biallelic mutations in the NBEAL2 gene.
Here we show that mutations in NBEAL2 (neurobeachin-like 2), which encodes a BEACH/ARM/WD40 domain protein, cause GPS and that megakaryocytes and platelets from individuals with GPS express a unique combination of NBEAL2 transcripts. 
Linkage analysis revealed a 63 cM region on the X chromosome between markers G10578 and DXS6797, which segregated with the platelet phenotype and included the GATA1 gene. Sequencing of GATA1 revealed a G-to-A mutation at position 759 corresponding to amino acid change Arg216Gln. 
We identified a family with gray platelet syndrome (GPS) segregating as a sex-linked trait. 
X-linked gray platelet syndrome due to a GATA1 Arg216Gln mutation

Answer: The genetic defects responsible for gray platelet syndrome are mutations in the genes NBEAL2, GATA1 and GFI1B.
The genetic defect responsible for gray platelet syndrome was recently identified in biallelic mutations in the NBEAL2 gene.
A nonsense mutation in the gene encoding the transcription factor GFI1B (growth factor independent 1B) that causes autosomal dominant gray platelet syndrome.
X-linked gray platelet syndrome due to a GATA1 Arg216Gln mutation.
Exact answer: neurobeachin-like 2, NBEAL2, GATA1, GFI1B