nirantk/geneticsQA-train huggingface dataset:
Question: Describe the mechanism of action of drisapersen

Context:
Drisapersen is a 2'-O-methyl-phosphorothioate oligonucleotide designed to skip exon 51 in dystrophin pre-mRNA to restore the reading frame of the mRNA. 
UNLABELLED: Chronic administration of drisapersen, a 2'-OMe phosphorothioate antisense oligonucleotide (AON) to mice and monkeys resulted in renal tubular accumulation, with secondary tubular degeneration.
Currently, the most promising potential drugs are the exon-skipping agents eteplirsen and drisapersen.
Currently, the most promising potential drugs are the exon-skipping agents eteplirsen and drisapersen
Drisapersen is a 2'-O-methyl-phosphorothioate oligonucleotide designed to skip exon 51 in dystrophin pre-mRNA to restore the reading frame of the mRNA
Fast forward 25 years, and two phase 2b/3 trials have been carried out with agents designed to induce de novo dystrophin production in DMD patient's muscle; ataluren (stop codon read through) with 174 patients, and drisapersen (exon skipping) with 186 patients

Answer: Drisapersen is a 2'-O-methyl-phosphorothioate oligonucleotide designed to skip exon 51 in dystrophin pre-mRNA to restore the reading frame of the mRNA. It has potential for treatment of Duchenne muscular dystrophy.
Question: Has Revlimid been approved by the US Food and Drug Administration?

Context:
In the past decade, immunomodulatory drugs have been approved by the US Food and Drug Administration for the treatment of multiple myeloma (MM)-and a number of emerging agents that target the cellular pathways or proteins involved in the pathophysiology of MM are currently in development. Lenalidomide (Revlimid) and pomalidomide induce apoptosis and sensitize MM cells while demonstrating superior efficacy and better tolerability than thalidomide (Thalomid).
In the past decade we have seen four new agents approved by the US Food and Drug Administration for treatment of multiple myeloma: the proteasome inhibitor (PI) bortezomib (Velcade), the immunomodulatory agents lenalidomide (Revlimid) and thalidomide (Thalomid), and liposomal doxorubicin. 
In the past decade we have seen four new agents approved by the US Food and Drug Administration for treatment of multiple myeloma: the proteasome inhibitor (PI) bortezomib (Velcade), the immunomodulatory agents lenalidomide (Revlimid) and thalidomide (Thalomid), and liposomal doxorubicin.
Thalidomide, lenalidomide (Revlimid), and bortezomib (Velcade) are directed not only at MM cells but also at the BM milieu and have moved rapidly from the bench to the bedside and United States Food and Drug Administration approval to treat MM.
Lenalidomide (CC-5013, Revlimid; Celgene Corporation, Summit, NJ), a thalidomide analogue, was granted approval by the U.S. Food and Drug Administration (FDA) on June 29, 2006, for use in combination with dexamethasone in patients with multiple myeloma (MM) who have received at least one prior therapy.
Lenalidomide, an IMiD drug (a novel type of immunomodulating drug) was recently approved by the US Food and Drug Administration for the treatment of transfusion-dependent anemia in patients with myelodysplastic syndromes (MDS) and interstitial deletions of chromosome 5q [del(5q)]
Lenalidomide, a second-generation immunomodulatory drug (IMiD), is approved by the US Food and Drug Administration for treatment of transfusion-dependent anemia in lower-risk MDS patients with deletion 5q chromosomal abnormality
In the past decade we have seen four new agents approved by the US Food and Drug Administration for treatment of multiple myeloma: the proteasome inhibitor (PI) bortezomib (Velcade), the immunomodulatory agents lenalidomide (Revlimid) and thalidomide (Thalomid), and liposomal doxorubicin.
lenalidomide (CC5103 or revlimid) are recently approved for the treatment of multiple myeloma.
 In the past decade, immunomodulatory drugs have been approved by the US Food and Drug Administration for the treatment of multiple myeloma (MM)-and a number of emerging agents that target the cellular pathways or proteins involved in the pathophysiology of MM are currently in development. Lenalidomide (Revlimid) and pomalidomide induce apoptosis and sensitize MM cells while demonstrating superior efficacy and better tolerability than thalidomide (Thalomid).

Answer: Yes, Revlimid has been approved by the US Food and Drug Administration for treatment of multiple myeloma.
Exact answer: yes
Question: How is myotonic dystrophy inherited?

Context:
Myotonic dystrophy type 2 (DM2) is an autosomal dominant, multisystem disorder caused by a CCTG tetranucleotide repeat expansion located in intron 1 of the zinc finger protein 9 gene (ZNF9 gene) on chromosome 3q 21.3.
Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder, caused by an expansion of a CTG triplet repeat in the DMPK gene.
Myotonic dystrophy (DM), the most common form of muscular dystrophy in adults, is a clinically and genetically heterogeneous neuromuscular disorder. DM is characterized by autosomal dominant inheritance, muscular dystrophy, myotonia, and multisystem involvement. Type 1 DM (DM1) is caused by a (CTG)(n) expansion in the 3' untranslated region of DMPK in 19q13.3.
proximal myotonic myopathy (PROMM) and type 2 DM (DM2) but without the DM1 mutation, showed linkage to the 3q21 region and were recently shown to segregate a (CCTG)(n) expansion mutation in intron 1 of ZNF9.
All patients have the DM2 (CCTG)(n) expansion.
Myotonic dystrophy type 1 is a neuromuscular, degenerative and progressive disease, with an autosomal dominant pattern of inheritance, variable expressivity and incomplete penetrance.
The worldwide intergenerational behavior of the DM1 mutation is similar in Costa Rica
Dystrophic myotonia is a sufficiently rare disease inherited mainly by the autosomal dominant type.

Answer: Myotonic dystrophy (DM) is a heterogeneous neuromuscular disease with an autosomal dominant pattern of inheritance.
Exact answer: autosomal dominant
Question: How were plasma levels of thyroid hormones affected by amiodarone and dronedarone treatment in Wistar rats?

Context:
Amiodarone resulted in increased T4, T4/T3 and rT3, whereas dronedarone did not alter the thyroid hormone profile in normal animals.
Fifty-five Wistar rats were randomly allocated to a 2-week oral treatment with either vehicle (n=18), amiodarone (30 mg/kg, n=20), or dronedarone (30 mg/kg, n=17).
Thyroid function was similar in the 3 groups.
Plasma levels of T3, T4, and rT3 were changed after SR 33589 treatment except a decrease in T4 level at the highest dose whilst the T4 T3 ratio and the level of rT3 were dose-dependently increased by amiodarone treatment.

Answer: Amiodarone treatment resulted in increased T4, T4/T3, and rT3 levels in Wistar rats, while dronedarone did not alter the thyroid hormone profile in normal animals.
Question: Where in a protein can a signal sequence be found?

Context:
A transmembrane domain (TMD) at the N-terminus of a membrane protein is a signal sequence that targets the protein to the endoplasmic reticulum (ER) membrane. 
 an N-terminal signal sequence,
soluble AMO possesses an N-terminal signal sequence
n N-terminal "twin arginine" signal sequence suggested 
Proteins destined for the mitochondrial matrix space have leader sequences that are typically present at the most N-terminal end of the nuclear-encoded precursor protein. 
N-terminal signal sequence 
The predicted amino-acid sequence includes an N-terminal signal sequence 
These N-terminal sequences lack a typical signal sequence 
 TAP can be bypassed by targeting peptides directly to the endoplasmic reticulum (ER) using NH2-terminal signal sequences. T
The amino terminal signal sequence, 
An amino-terminal domain containing a signal sequence
A nuclear localization signal (NLS) sequence was previously defined by point mutations in three short adjacent clusters of basic amino acids located in the amino-terminal region of the E1 protein. 
he human homologue also contains a putative N-terminal signal sequence

Answer: Proteins have signal sequences typically resent at the most N-terminal end.
Exact answer: N-terminally
Question: Is Dupilumab used for treatment of atopic dermatitis?

Context:
Dupilumab has demonstrated efficacy in patients with asthma and atopic dermatitis, which are both type 2 helper T-cell-mediated diseases.
Background Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis.
Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis.
Dupilumab is a biologic agent targeted at TH2 cytokines, but indirectly impacts IgE and is an important biologic agent for atopic disease.
Dupilumab for the treatment of atopic dermatitis: A clinical trial review.
Dupilumab is a novel monoclonal antibody that was recently studied in adult patients with moderate-to-severe AD.
Patients treated with dupilumab had marked and rapid improvement in all the evaluated measures of atopic dermatitis disease activity.
The robust effects of dupilumab on skin inflammation and pruritus confirm the pathogenic role of IL-4 and IL-13 signaling in adult AD, and further support the application of Th2 cytokine antagonists in the treatment of this disease.

Answer: Yes, patients treated with dupilumab had marked and rapid improvement in all the evaluated measures of atopic dermatitis disease activity.
Exact answer: yes
Question: Which major signaling pathways are regulated by RIP1?

Context:
Major signaling pathways regulated by RIP1 include necroptosis, apoptosis, and pro-survival/inflammation NF-κB activation. 
receptor-interacting protein-1 (RIP1)-mediated necroptosis
TNF-induced apoptotic signaling pathways were assessed by monitoring levels of the anti-apoptotic protein, A20, and cleavage products of the caspase-8 substrate, RIP1.
Receptor-interacting protein (RIP) kinases promote the induction of necrotic cell death pathways. 
Together our results reveal a specific role for the RIP1-RIP3-DRP1 pathway in RNA virus-induced activation of the NLRP3 inflammasome and establish a direct link between inflammation and cell-death signaling pathways.
Necroptosis exhibits a unique signaling pathway that requires the involvement of receptor interaction protein kinases 1 and 3 (RIP1 and RIP3),

Answer: necroptosis
apoptosis  
pro-survival/inflammation NF-κB activation
Exact answer: necroptosis, apoptosis, pro-survival/inflammation NF-κB activation
Question: Is there a role for gamma knife in treatment of Obsessive-Compulsive Disorder?

Context:
OBJECTIVE Functional Gamma Knife radiosurgery (GKRS) procedures have been increasingly used for treating patients with tremor, trigeminal neuralgia (TN), and refractory obsessive-compulsive disorder.
METHODS The authors constructed a linear-quadratic model of BED in functional GKRS with a dose-protraction factor to correct for intrafraction DNA-damage repair and used standard single-fraction doses for trigeminal nerve ablation for TN (85 Gy), thalamotomy for tremor (130 Gy), and capsulotomy for obsessive-compulsive disorder (180 Gy). 
Gamma knife for obsessive compulsive disorder: can it be detrimental?
Gamma knife radiosurgery (GKRS) is also being practised to treat refractory obsessive- compulsive disorder (OCD).
Radio and neurosurgical procedures, including gamma knife radiation and deep brain stimulation, are reserved for severe, treatment-refractory disease that has not responded to multiple treatments, and some patients may benefit from transcranial magnetic stimulation.
 We close with a discussion of gamma knife capsulotomy, a modality with deep historical roots.
Results following gamma knife radiosurgical anterior capsulotomies for obsessive compulsive disorder.
Gamma knife radiosurgery (GKRS) is also being practised to treat refractory obsessive- compulsive disorder (OCD).
Lesion topography and outcome after thermocapsulotomy or gamma knife capsulotomy for obsessive-compulsive disorder: relevance of the right hemisphere.
Neuropsychological outcome of ventral capsular/ventral striatal gamma capsulotomy for refractory obsessive-compulsive disorder: a pilot study
Gamma ventral capsulotomy for treatment of resistant obsessive-compulsive disorder: a structural MRI pilot prospective study
Results following gamma knife radiosurgical anterior capsulotomies for obsessive compulsive disorder
At 28 months, the third patient is living and working independently, and her YBOCS score is 18.CONCLUSION: Within a strict protocol, gamma knife radiosurgery provided improvement of OCD behavior with no adverse effects.
Gamma knife for obsessive compulsive disorder: can it be detrimental?

Answer: Yes. Gamma knife radiosurgery is being increasingly to treat refractory obsessive- compulsive disorder (OCD). It is reserved for severe, treatment-refractory disease that has not responded to multiple treatments.
Exact answer: yes
Question: Which genes are implicated in short QT syndrome?

Context:
A novel gain-of-function KCNJ2 mutation associated with short-QT syndrome impairs inward rectification of Kir2.1 currents.
In this study, we identified a novel KCNJ2 gain-of-function mutation, M301K, associated with SQTS. 
A mutation in genes related to SQTS was found in 23% of the probands; most of them had a gain of function mutation in HERG (SQTS1).
We present, for the first time, a novel loss-of-function mutation coding for an L-type calcium channel subunit. 
however, a new variant at a heterozygous state was identified in the CACNA2D1 gene (nucleotide c.2264G > C; amino acid p.Ser755Thr), coding for the Ca(v)α(2)δ-1 subunit of the L-type calcium channel.
In the present study, we report the first pathogenic mutation in the CACNA2D1 gene in humans, which causes a new variant of SQTS.
A novel mutation in the KCNH2 gene associated with short QT syndrome.
The altered function of T618I-HERG channels suggests that this mutation in the KCNH2 gene is responsible for the SQTS phenotype in this family. 
Gain of function mutations in three genes encoding K(+) channels have been identified, explaining the abbreviated repolarization seen in this condition: KCNH2 for I(kr) (SQT1), KCNQ1 for I(ks) (SQT2) and KCNJ2 for I(k1) (SQT3). 
To evaluate the possible diagnosis of SQTS, DNA sequencing of genes known to be associated with SQTS was performed and identified a novel mutation in the KCNH2 gene.
The mutation of genes (KCNH2, KCNQ1, and KCNJ2) encoding for cardiac potassium channels plays a central role in SQTS. 
To date, different mutations in genes encoding for cardiac ion channels (KCNH2, KCNQ1, and KCNJ2) have been identified to cause the short QT syndrome. 
Mutations in 3 different genes KCNQ1, KCNH2, and KCNJ2, all encoding cardiac ionic potassium channels have been identified in affected patients. 
Genetic analysis has, to date, identified three distinct forms of the condition, involving gain-of-function mutations to three different cardiac potassium channel genes: KCNH2 (SQT1), KCNQ1 (SQT2) and KCNJ2 (SQT3). 
Three different gain-of-function mutations in genes encoding for cardiac potassium channels (KCNH2, KCNQ1, and KCNJ2) have been identified up to now to cause short QT syndrome. 
To date, three different mutations in genes encoding cardiac ion channels (KCNH2, KCNQ1 and KCNJ2) have been identified as causing short QT syndrome.

Answer: The genes that are implicated in short QT syndrome are KCNJ2, KCNH2, CACNA2D1 and KCNQ1.
Exact answer: KCNJ2, inward rectifier potassium channel gene, HERG, KCNH2, CACNA2D1, KCNQ1, CACNB2b
Question: Which are the different members/isoforms of the Ras oncogenes?

Context:
The major Ras isoforms (K, H, and N) 
Mutations in Ras isoforms such as K-Ras, N-Ras, and H-Ras contribute to roughly 85, 15, and 1% of human cancers, respectively.
the Ras isoforms (H, N and K) 
The mutant forms of KRas, NRas and HRas
 lipidated Ras isoforms (H-Ras and N-Ras)
: H-Ras, K-Ras, and N-Ras regulate cellular growth and survival and are often activated by somatic mutation in human tumors.
Human tumours frequently express Ras proteins (Ha-, Ki-, N-Ras) 
 There are three major ras isoforms: H-, N- and K-Ras. 
All mammalian cells express 3 closely related Ras proteins, termed H-Ras, K-Ras, and N-Ras
hree closely related isoforms, HRAS, KRAS and NRAS, 
H-ras, N-ras, and K-ras are canonical ras gene family members frequently activated by point mutation in human cancers and coding for 4 different, highly related protein isoforms (H-Ras, N-Ras, K-Ras4A, and K-Ras4B).
he 3 Ras isoforms-H-Ras, K-Ras, and N-Ras-
In this study, we compared the leukemogenic potential of activated NRAS, KRAS, and HRAS in the same bone marrow transduction/transplantation model system. 
H-Ras, K-Ras, and N-Ras regulate cellular growth and survival and are often activated by somatic mutation in human tumors.
Ras proteins are small GTPase functioning as molecular switches that, in response to particular extracellular signalling, as growth factors, activate a diverse array of intracellular effector cascades regulating cell proliferation, differentiation and apoptosis. Human tumours frequently express Ras proteins (Ha-, Ki-, N-Ras) activated by point mutations which contribute to malignant phenotype, including invasiveness and angiogenesis.
Ras small GTPases function as transducers of extracellular signals regulating cell survival, growth and differentiation. There are three major ras isoforms: H-, N- and K-Ras. 
All mammalian cells express 3 closely related Ras proteins, termed H-Ras, K-Ras, and N-Ras, that promote oncogenesis when they are mutationally activated at codon 12, 13, or 61.
Ras proteins are proto-oncogenes that are frequently mutated in human cancers. Three closely related isoforms, HRAS, KRAS and NRAS, are expressed in all cells and have overlapping but distinctive functions.
H-ras, N-ras, and K-ras are canonical ras gene family members frequently activated by point mutation in human cancers and coding for 4 different, highly related protein isoforms (H-Ras, N-Ras, K-Ras4A, and K-Ras4B)

Answer: Ras proteins are proto-oncogenes that are frequently mutated in human cancers. Three closely related isoforms, HRAS, KRAS and NRAS, are expressed in all cells and have overlapping but distinctive functions.
H-ras, N-ras, and K-ras are canonical ras gene family members frequently activated by point mutation in human cancers and coding for 4 different, highly related protein isoforms (H-Ras, N-Ras, K-Ras4A, and K-Ras4B)
Exact answer: H-Ras, N-Ras, K-Ras4A, K-Ras4B
Question: What is the role of music therapy in coma patients.

Context:
[Beneficial effect of preferred music on cognitive functions in minimally conscious state patients].
Several studies have shown that music can boost cognitive functions in normal and brain-damaged subjects. A few studies have suggested a beneficial effect of music in patients with a disorder of consciousness but it is difficult to conclude since they did not use quantified measures and a control condition/group. 
. This new protocol suggests that preferred music has a beneficial effect on the cognitive abilities of MCS patients. 
This review presents an overview of the use of music therapy in neurological early rehabilitation of patients with coma and other disorders of consciousness (DOC) such as unresponsive wakefulness syndrome (UWS) or minimally conscious state (MCS). 
The programs' content consisted of recreation and communication options, which involved activating music, videos, and basic requests, sending and receiving (listening to) text messages, and placing phone calls. 
Active music therapy in the rehabilitation of severe brain injured patients during coma recovery.
Active improvised music therapy may offer an adjuvant from of treatment in the early rehabilitation of severe brain-injured patients.
Our preliminary results show a significant improvement of the collaboration of the severe brain-injured patients and a reduction of undesired behaviours such as inertia (reduced psychomotor initiative) or psychomotor agitation.
Hence, it is possible for music therapy to both establish contact with the seemingly non-responsive patient and re-stimulate the person's fundamental communication competencies and experience at the emotional, social and cognitive levels.
Six studies focused on the provision of multisensory stimulation or music therapy.

Answer: Several studies have shown that music can boost cognitive functions in patients with a disorder of consciousness but it is difficult to conclude since they did not use quantified measures and a control condition/group. Active improvised music therapy may offer an adjuvant form of treatment in the early rehabilitation of severe brain-injured patients.
Question: Does triiodothyronine play a regulatory role in insulin secretion from pancreas?

Context:
Our findings establish that p43 is an important regulator of glucose homeostasis and pancreatic β-cell function and provide evidence for the first time of a physiological role for a mitochondrial endocrine receptor.
The p43(-/-) mice had a major defect in insulin secretion both in vivo and in isolated pancreatic islets and a loss of glucose-stimulated insulin secretion.
We demonstrated that treatment of primary cultures of rat pancreatic islets with T3 results in augmented β-cell vitality with an increase of their functional properties.
Nonetheless, the insulin secretion is sensibly augmented after T3 stimulation.
Plasma glucose concentration of the fetal hypothyroid group during intravenous glucose tolerance test was significantly higher (p=0.003) at 5-20 min as compared to the control group, whereas plasma insulin concentration was significantly lower (p=0.012) at 5-20 min
Although adult offspring born from hypothyroid mothers were euthyroid, their glucose tolerance and glucose stimulated insulin secretion of islets were altered
hyroid hormones modulate the immune system and metabolism, influence insulin secretion
Only T(3) concentrations higher than 250 microM were able to decrease cell viability and proliferation rate, to increase the rate of apoptosis and to reduce glucose-induced insulin secretion.
Islets preincubated with glucose (3.3 mmol/l) and glucagon (1.4 mumol/l) plus theophylline (10 mmol/l), ACTH (0.11 nmol/l), bovine GH (0.46 mumol/l), prolactin (0.2 mumol/l) or tri-iodothyronine (1.0 nmol/l) have significantly lower Ca(2+)-ATPase activity than those preincubated with only 3.3 mmol glucose/l. All these hormones increased the release of insulin significantly.
T3 (0.2 nM) did not affect insulin secretion in the absence or presence of glucose or in the presence of secretagogues (potassium and glyceraldehyde).
In the perfused rat pancreas, the addition of thyroxine (10 micrograms/dL) or 3,5,3'-triiodothyronine (150 ng/dL) to the perfusing medium did not affect insulin secretion.
The administration of thyroxine (40 micrograms/kg, s.c.) in vivo increased the plasma insulin level from 11 +/- 2 microUnits/mL (mean +/- SD) to 30 +/- 7 microUnits/mL
Addition of T3 to the incubation medium, significantly modified the insulin release, but its effect varied according to the glucose concentration in the medium, i.e. it enhanced the insulin release at a glucose concentration between 2 to 8 mmol/l; it has no effect at 12 mmol/glucose, and significantly inhibited the secretion of insulin in the presence of 16.6 mmol/l glucose.
Both T3 and T4 inhibited insulin secretion

Answer: YES
Exact answer: yes