nirantk/geneticsQA-train huggingface dataset:
Question: Does TGF-beta play a role in cardiac regeneration after myocardial infarction?

Context:
We then performed a chemical screen and identified several small molecules that increase or reduce cardiomyocyte proliferation during heart development. These compounds act via Hedgehog, Insulin-like growth factor or Transforming growth factor β signaling pathways. 
Here, we report that the balance between the reparative and regenerative processes is achieved through Smad3-dependent TGFβ signaling. 
Thus, TGFβ signaling orchestrates the beneficial interplay between scar-based repair and cardiomyocyte-based regeneration to achieve complete heart regeneration.
As expected, transforming growth factor (TGF)-beta, a profibrotic cytokine, was dramatically upregulated in MI hearts, but its phosphorylated comediator (pSmad) was significantly downregulated in the nuclei of Cx43-deficient hearts post-MI, suggesting that downstream signaling of TGF-beta is diminished substantially in Cx43-deficient hearts. This diminution in profibrotic TGF-beta signaling resulted in the attenuation of adverse structural remodeling as assessed by echocardiography.
Potentially beneficial changes include increases in the HSMP secretory-leucocyte-protease-inhibitor (SLPI) and cytokine transforming growth factor (TGF)-beta(1). Targeting these proteins may mitigate enhanced LV remodeling and dysfunction with aging.
After injury, the presence of macrophages, which secreted high levels of transforming growth factor-beta and vascular endothelial growth factor-A, led to rapid removal of cell debris and replacement by granulation tissue containing inflammatory cells and blood vessels, followed by myofibroblast infiltration and collagen deposition.
Secretion of transforming growth factor-beta and vascular endothelial growth factor-A as well as neovascularization, myofibroblast infiltration, and collagen deposition decreased. 
Repression of proinflammatory cytokine and chemokine synthesis, mediated in part through Transforming Growth Factor (TGF)-beta and Interleukin (IL)-10, is critical for resolution of the inflammatory infiltrate and transition to fibrous tissue deposition.
TGF-beta conducted the myogenic differentiation of CD117+ stem cells by upregulating GATA-4 and NKx-2.5 expression. Therefore, the intramyocardial implantation of TGF-beta-preprogrammed CD117+ cells effectively assisted the myocardial regeneration and induced therapeutic angiogenesis, contributing to functional cardiac regeneration.
These results indicate that TGF-beta/Smad signaling may be involved in the remodeling of the infarct scar after the completion of wound healing per se, via ongoing stimulation of matrix deposition.

Answer: TGFβ signaling orchestrates the beneficial interplay between scar-based repair and cardiomyocyte-based regeneration to achieve complete heart regeneration.
Exact answer: yes
Question: How is CBX1/M31 related to position-effect variegation?

Context:
First, forced expression of full-length SUV39H1 (412 amino acids) redistributes endogenous M31 (HP1beta) and induces abundant associations with inter- and metaphase chromatin
Together, our data reveal a dominant role(s) for the SET domain of SUV39H1 in the distribution of prominent heterochromatic proteins and suggest a possible link between a chromosomal SU(VAR) protein and histone H3
Using this motif, termed chromo box, we have cloned a mouse candidate modifier gene, M31, that also shows considerable sequence homology to Drosophila HP1
Here we report evidence of at least four independently segregating loci in the mouse homologous to the M31 cDNA. One of these loci--Cbx-rs1--maps to the X Chromosome (Chr), 1 cM proximal to Amg and outside the X-inactivation center region
Although there is significant heterochromatic overlap between SUV39H1 and M31 (HP1(beta)) during interphase, mitotic SUV39H1 displays a more restricted spatial and temporal association pattern with metaphase chromosomes than M31 (HP1(beta)), or the related HP1(&agr;) gene product
which complex with the heterochromatin component M31.
In addition, Suv39h1/SUV39H1 proteins associate with M31, currently the only other characterized mammalian SU(VAR) homologue
M31, a murine homolog of Drosophila HP1, is concentrated in the XY body during spermatogenesis
The HP1 class of chromobox genes are thought to encode proteins involved in the packaging of chromosomal DNA into repressive heterochromatin domains, as seen, for example, in position-effect variegation
Study of the distribution of a murine HP1-like chromodomain protein, M31, during spermatogenesis revealed spreading from the tip of the XY body in mid-stage pachytene spermatocytes to include the whole of the XY body in late-pachytene spermatocytes
We also demonstrate that the formation of the XY body during spermatogenic progression in neonatal mice coincides with the expression of a novel nuclear isoform of M31, M31(p21
Furthermore, by overexpressing a mammalian homologue (M31) of Drosophila melanogaster heterochromatin protein 1 (HP1; refs 7,8) in transgenic mouse lines that exhibit PEV, it is possible to modify the proportion of cells that silence the transgene in a dose-dependent manner
Thus, we show M31 overexpression to have two contrasting effects which are dependent on chromosomal context: (i) it enhanced PEV in those lines with centromeric or pericentromeric transgene locations; and (ii) it suppressed PEV when the transgene was non-centromeric

Answer: M31 is a heterochromatin component, that is concentrated in the XY body during spermatogenesis. M31 overexpression has two contrasting effects which are dependent on chromosomal context: (i) it enhanced PEV in those lines with centromeric or pericentromeric transgene locations; and (ii) it suppressed PEV when the transgene was non-centromeric.
Question: Which is the most common editing modification in eukaryotic mRNA?

Context:
One of the most common forms of pre-mRNA editing is A-to-I editing, in which adenosine is deaminated to inosine, which is read as guanosine during translation.
Deamination of adenine by adenosine deaminases that act on RNA (ADARs) leads to the conversion of adenine into inosine (A-I editing) recognized by the splicing and translation systems as guanine.
denosine deaminases editing adenines in transport RNAs (ADATs) convert adenine into inosine in tRNAs of all eukaryotes; as a result, the diversity of tRNA forms in the cell increases.
A-to-I editing events in normal and cancerous human keratinocytes
A-to-I RNA editing can alter codons, substitute amino acids and affect protein sequence, structure, and function.
-to-I RNA editing is a post-transcriptional mechanism frequently used to expand and diversify transcriptome and proteome repertoire in eukaryotic cells
This study describes for the first time A-to-I editing in the coding sequence of a tumor suppressor gene in humans, and suggests that IGFBP7 editing serves as a fine-tuning mechanism to maintain the equilibrium between proliferation and senescence in normal skin.
Adenosine deaminases that act on RNA (ADARs) catalyze the adenosine-to-inosine (A-to-I) conversion, the most common type of RNA editing in higher eukaryotes. 
RNA editing is observed in eukaryotic mRNA, transfer RNA, ribosomal RNA, and non-coding RNAs (ncRNA). The most common RNA editing in the mammalian central nervous system is a base modification, where the adenosine residue is base-modified to inosine (A to I).
It occurs in a wide variety of eukaryotic organisms and in some viruses. One of the most common forms of pre-mRNA editing is A-to-I editing, in which adenosine is deaminated to inosine, which is read as guanosine during translation.
The most common RNA editing in the mammalian central nervous system is a base modification, where the adenosine residue is base-modified to inosine (A to I).
One of the most common forms of pre-mRNA editing is A-to-I editing, in which adenosine is deaminated to inosine, which is read as guanosine during translation.
RNA editing by adenosine deamination (A-to-I) is widespread in humans and can lead to a variety of biological effects depending on the RNA type or the RNA region involved in the editing modification.

Answer: One of the most common forms of pre-mRNA editing is A-to-I editing, in which adenosine is deaminated to inosine, which is read as guanosine during translation.
Exact answer: A-to-I
Question: What is the link between TB (Turbeculosis) infection and TNFa inhibition?

Context:
The use of TNFalpha blockers is associated with reactivation of tuberculosis (TB)
We present two patients with inflammatory bowel disease who, despite negative tuberculosis screening, developed a de novo tuberculosis infection after the start of anti tumor necrosis factor alpha treatment.
To compare the performance of two interferon gamma release assays (IGRAs) and conventional screening tests in patients with inflammatory arthritis undergoing screening for latent tuberculosis infection (LTBI) before treatment with anti-tumour necrosis factor alpha (anti-TNFalpha) compounds.
The occurrence of tuberculosis (TB) in patients treated with immunosuppressive drugs (ISD) is an old problem that has been highlighted by cases occurring in patients using anti-TNFalpha drugs.
TNFalpha plays a pivotal role not only in the inflammatory process but also in the normal response against pathogens and therefore, interfering with this cytokine may increase the risk of infection.

Answer: The occurrence of tuberculosis (TB) in patients treated with immunosuppressive drugs (ISD) is an old problem that has been highlighted by cases occurring in patients using anti-TNFalpha drugs.
Question: Does dasatinib promote or inhibit T-cell proliferation?

Context:
Dasatinib inhibited antigen-specific proliferation of murine CD4(+) and CD8(+) transgenic T cells in vitro and in vivo
Herein, we show that dasatinib inhibits TCR-mediated signal transduction, cellular proliferation, cytokine production, and in vivo T-cell responses. 
Both dasatinib and staurosporine inhibited T-cell activation, proliferation, cytokine production, and degranulation in a dose-dependent manner. 
Herein, we show that dasatinib inhibits TCR-mediated signal transduction, cellular proliferation, cytokine production, and in vivo T-cell responses
Dasatinib, a small-molecule protein tyrosine kinase inhibitor, inhibits T-cell activation and proliferation
Dasatinib, a small-molecule protein tyrosine kinase inhibitor, inhibits T-cell activation and proliferation.
Dasatinib inhibits the proliferation and function of CD4+CD25+ regulatory T cells.
T-cell functions including proliferation, activation and cytokine production were all uniformly inhibited in the presence of dasatinib. We also demonstrated inhibition of TCR signalling through Src-family kinase LCK, and predicted that inhibition of LCK and other kinases involved in T-cell signalling by dasatinib is responsible for the suppression of T-cell function. 

Answer: Dasatinib inhibits T-cell proliferation
Exact answer: inhibits
Question: What is the effect of enamel matrix derivative on pulp regeneration?

Context:
Among the human studies, two studies reported that EMD is a more efficient DPC procedure compared with calcium hydroxide (Ca(OH)2 ). One study reported Ca(OH)2 to be more efficient for DPC than EMD. One study reported no difference in the efficacies between EMD and Ca(OH)2 for DPC. All animal studies reported EMD to be more effective in reparative dentine formation in comparison with Ca(OH)2 . EMD can provide favourable results in DPC procedures
EMD increased the osteogenic potential of hDPCs
 the expression levels of osteogenesis-related genes, such as ALP, DSPP, BMP, and OPN were also upregulated. In addition, the expression levels of odontogenesis-related transcription factors Osterix and Runx2 were upregulated
EMD could enhance the mineralization of hDPSCs upregulated the expression of markers for odontoblast/osteoblast-like cells. Further studies are required to determine if EMD can improve pulp tissue repair and regeneration
In both the scaffold groups, dentin sialophosphoprotein, dentin matrix protein-1, and osteopontin messenger RNA was up-regulated significantly in EMD-treated hDPCs when compared with the nontreated cells
Proliferated pulp tissue partly filled the space initially occupied by EMDgel and DSP-stained hard tissue was observed alongside exposed dentine surfaces as well as in isolated masses within the proliferated pulp tissue, although the new hard tissue did not cover the pulp exposure
In the EMD-treated teeth, large amounts of newly formed dentin-like hard tissue with associated formative cells outlined the pulpal wound separating the cavity area from the remaining pulp tissue
Inflammatory cells were present in the wound area but not subjacent to the newly formed hard tissue. Morphometric analysis showed that the amount of hard tissue formed in EMD-treated teeth was more than twice that of the calcium-hydroxide-treated control teeth (p < 0.001), suggesting that EMD is capable of promoting reparative processes in the wounded pulp more strongly than is calcium hydroxide

Answer: EMD increased the osteogenic potential of hDPCs. The expression levels of osteogenesis-related genes, such as ALP, DSPP, BMP, and OPN were also upregulated. In addition, the expression levels of odontogenesis-related transcription factors Osterix and Runx2 were upregulated. Proliferated pulp tissue partly filled the space initially occupied by EMDgel and isolated masses within the proliferated pulp tissue.
Exact answer: increase of the osteogenic potential of hDPCs
Question: Which is the target of the drug Denosumab?

Context:
Denosumab is a human monoclonal antibody which specifically blocks receptor activator of nuclear factor κB ligand and is a very potent antiresorptive drug. 
denosumab, a monoclonal antibody against RANKL
Denosumab is a human monoclonal antibody indicated for the treatment of osteoporosis in postmenopausal women with a high risk of fractures. 
Denosumab (Dmab) is a fully human monoclonal antibody against the receptor activator of nuclear factor-κB ligand (RANKL), which, through the prevention of the RANKL/RANK interaction, inhibits osteoclast-mediated bone resorption and significantly reduces the risk of vertebral, nonvertebral, and hip fractures. 

Answer: Denosumab (Dmab) is a fully human monoclonal antibody against the receptor activator of nuclear factor-κB ligand (RANKL).
Exact answer: receptor activator of nuclear factor-κB ligand, RANKL
Question: What is the mechanism of action of Osimertinib?

Context:
In addition, mutations leading to resistance to first-line EGFR and ALK TKIs can now be successfully inhibited by soon to be approved third-generation EGFR TKIs (osimertinib, rociletinib) and second-generation ALK TKIs (ceritinib, alectinib). 
Gefitinib, erlotinib, and afatinib are the EGFR tyrosine kinase inhibitors that are presently in clinical use. Understanding resistance mechanisms has led to the identification of a secondary mutational target, T790M, in more than half of patients, for which osimertinib has been approved. 
Third-generation EGFR TKIs against the T790M mutation have been in active clinical development. These agents include osimertinib, rociletinib, HM61713, ASP8273, EGF816, and PF-06747775. 
PURPOSE: Osimertinib (AZD9291) 80 mg once daily is approved by the US FDA for the treatment of patients with metastatic EGFR T790M-positive NSCLC whose disease has previously progressed on EGFR-TKI therapy. Osimertinib PK was evaluated to define the dose and dosing interval, whether a fixed-dosing approach can be used globally, and the impact of formulation and food on exposure.
RECENT FINDINGS: Third-generation TKIs in clinical development include osimertinib, rociletinib, and HM61713.
In this study, we investigated the interaction between ABCB1 and osimertinib, a novel selective, irreversible third-generation EGFR TKI that has recently been approved by the U.S. Food and Drug Administration. 
Considering that osimertinib is a clinically approved third-generation EGFR TKI, our findings suggest that a combination therapy with osimertinib and conventional anticancer drugs may be beneficial to patients with MDR tumors.
In our study, we investigated whether osimertinib (AZD9291), a third-generation irreversible tyrosine kinase inhibitor of both activating EGFR mutations and resistance-associated T790M point mutation, could reverse MDR induced by ABCB1 and ABCG2 in vitro, in vivo, and ex vivo Our results showed that osimertinib significantly increased the sensitivity of ABCB1- and ABCG2-overexpressing cells to their substrate chemotherapeutic agents in vitro and in the model of ABCB1-overexpressing KBv200 cell xenograft in nude mice. 
The potency of 1st (erlotinib), 2nd (afatinib) and 3rd (osimertinib and rociletinib) generation EGFR-TKIs was compared in vitro for human lung cancer cell lines and Ba/F3 cells, which exogenously express mutated or wild type EGFR
Osimertinib (AZD9291, Tagrisso™), an oral, third-generation EGFR TKI, has been designed to target the EGFR T790M mutation, while sparing wild-type EGFR.
Early phase clinical data suggest the third generation EGFR TKIs such as osimertinib, rociletinib, and HM61713 are highly efficacious and well tolerated.
We review the rapid clinical development and approval of the third-generation EGFR TKI osimertinib for treatment of NSCLCs with EGFR-T790M.

Answer: Osimertinib is a third-generation irreversible tyrosine kinase inhibitor of both activating EGFR mutations and resistance-associated T790M point mutation.
Question: What is adhesive capsulitis

Context:
Adhesive capsulitis (frozen shoulder) is a common cause of shoulder pain and disability
Adhesive capsulitis is characterized by painful, gradual loss of active and passive shoulder motion resulting from fibrosis and contracture of the joint capsule.
Painful stiffening of the shoulder, 'frozen shoulder' is a common cause of shoulder pain and disability.
Current adhesive capsulitis was defined as restriction of external rotation and one or more additional directional restrictions with history of shoulder pain.
Adhesive capsulitis is a clinical syndrome of pain and severely decreased joint motion ("frozen shoulder") caused by thickening and contraction of the joint capsule and synovium.
Adhesive capsulitis is, in most cases, a self-limiting condition of poorly understood etiology that results in shoulder pain and large mobility deficits. 
Adhesive capsulitis of the shoulder is a condition of unknown etiology that results in the development of restriction of active and passive glenohumeral motion.
Adhesive capsulitis of the shoulder is an idiopathic condition characterized clinically by pain and limitation of movement

Answer: Adhesive capsulitis also known as "frozen shoulder" is characterized by painful, gradual loss of active and passive shoulder motion resulting from fibrosis and contracture of the joint capsule.
Question: Is microRNA(miRNA) 30 involved in post-ischemic cardiac remodeling?

Context:
The myocardium of the failing heart undergoes a number of structural alterations, most notably hypertrophy of cardiac myocytes and an increase in extracellular matrix proteins, often seen as primary fibrosi
Connective tissue growth factor (CTGF) is a key molecule in the process of fibrosis and therefore seems an attractive therapeutic target
CTGF is importantly regulated by 2 major cardiac microRNAs (miRNAs), miR-133 and miR-30.
the expression of both miRNAs was inversely related to the amount of CTGF in 2 rodent models of heart disease and in human pathological left ventricular hypertrophy. Second, in cultured cardiomyocytes and fibroblasts, knockdown of these miRNAs increased CTGF levels. Third, overexpression of miR-133 or miR-30c decreased CTGF levels, which was accompanied by decreased production of collagens.
miR-30 importantly limit the production of CTGF
miR-30 directly downregulate CTGF, a key profibrotic protein, and thereby establish an important role for these miRNAs in the control of structural changes in the extracellular matrix of the myocardium.

Answer: Myocardial remodeling after an ischemic insult involves extracellular matrix proteins with increased fibrosis
Initial experimental data indicate that miRNA 30 decreases CTGF a key molecule in the process of fibrosis, by directly downregulating the production of CTGF
Exact answer: yes
Question: Is vemurafenib effective for hairy-cell leukemia?

Context:
CONCLUSIONS: A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia.
Our results strongly support and inform the clinical use of BRAF and MEK inhibitors in HCL.
The therapeutic approach of vemurafenib in treatment-refractory hairy cell leukemia is promising and offers an additional treatment option. 
Successful re-treatment of a relapsed V600E mutated HCL patient with low-dose vemurafenib.
Recent identification of the recurrent V600E BRAF mutation in a majority of HCL patients has led some teams to evaluate the clinical potential of vemurafenib, a BRAF V600 specific inhibitor in a limited number of refractory HCL patients. Recently, we published the case of an HCL patient successfully treated with a low dose of vemurafenib.
We present here the successful retreatment of this patient with a second line of vemurafenib. Our data suggest for the first time that vemurafenib at the dose of 240 mg once a day could be sufficient to maintain a complete hematological remission after an initial induction treatment with low-dose vemurafenib (2 × 240 mg) daily without inducing major toxicity.
The discovery of the BRAF mutation has created a therapeutic target exploited by oral inhibitors like vemurafenib and dabrafenib.
[Successful use of vemurafenib in a patient with resistant hairy cell leukemia].
The frequent persistence of phosphorylated ERK-positive leukemic cells in bone marrow at the end of treatment suggests bypass reactivation of MEK and ERK as a resistance mechanism.CONCLUSIONS: A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia. 
A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia.
A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia.
The therapeutic approach of vemurafenib in treatment-refractory hairy cell leukemia is promising and offers an additional treatment option.

Answer: Yes, vemurafenib is highly effective in patients with relapsed or refractory hairy-cell leukemia.
Exact answer: yes
Question: List viral vectors used in gene therapy.

Context:
Not only can some genetically engineered adenoviral vectors achieve remarkably efficient and specific gene delivery to target cells, but they also may act as anticancer agents by selectively replicating within cancer cells
. Using these criteria, we then evaluate approaches made to model PD using viral vectors to date, including both adeno-associated viruses and lentiviruses
Recombinant AAV (rAAV) vectors are a suitable vector for gene therapy studies because of desired characteristics such as low immunogenicity, transfection of non-dividing and dividing cells, and long-term expression of the transgene.
Over the last five years, the number of clinical trials involving AAV (adeno-associated virus) and lentiviral vectors continue to increase by about 150 trials each year. For continued success, AAV and lentiviral expression cassettes need to be designed to meet each disease's specific needs. 
describes commonly used gene therapeutics (herpes simplex viral vector (HSV) and adeno-associated viral vector (AAV))
This study examined the efficacy of gene therapy of lung adenocarcinoma using specifically controlled type I herpes simplex virus recombinant vector expressing Gibbon ape leukemia virus membrane fusion glycoprotein gene (GALV.fus)

Answer: adeno-associated viruses
lentiviruses
herpes simplex viral vector
Exact answer: adeno-associated viruses, lentiviruses, herpes simplex viral vector