{"id": "converted_1452", "sentence1": "Does dronedarone  affect  T3 and T4 levels?", "sentence2": "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.[SEP]", "label": "no"}
{"id": "converted_34", "sentence1": "Do mutations of AKT1 occur in meningiomas?", "sentence2": "The recent identification of somatic mutations in components of the SHH-GLI1 and AKT1-MTOR signaling pathways indicates the potential for cross talk of these pathways in the development of meningiomas., A mutation in PIK3CA or AKT1 was found in around 9 % of the cases., AKT1E17K mutations cluster with meningothelial and transitional meningiomas and can be detected by SFRP1 immunohistochemistry., AKT1E17K mutations were exclusively seen in meningiomas and occurred in 65 of 958 of these tumors. A strong preponderance was seen in the variant of meningothelial meningioma WHO grade I of basal and spinal localization. In contrast, AKT1E17K mutations were rare in WHO grade II and absent in WHO grade III meningiomas. , We observed strong up-regulation of SFRP1 expression in all meningiomas with AKT1E17K mutation and in HEK293 cells after transfection with mutant AKT1E17K, but not in meningiomas and HEK293 cells lacking this mutation., SMO and AKT1 mutations occur in non-NF2 meningiomas., Recurrent mutations in SMO and AKT1 are mutually exclusive with NF2 loss in meningioma., Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations.,  A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways., Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO., A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways., SMO and AKT1 mutations occur in non-NF2 meningiomas, The recent identification of somatic mutations in components of the SHH-GLI1 and AKT1-MTOR signaling pathways indicates the potential for cross talk of these pathways in the development of meningiomas, A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways, Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO, Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations, Recurrent mutations in SMO and AKT1 are mutually exclusive with NF2 loss in meningioma, A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways. These mutations were present in therapeutically challenging tumors of the skull base and higher grade. , A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways. [SEP]", "label": "yes"}
{"id": "converted_1370", "sentence1": "Are nucleosomes positioned at DNA replication origins?", "sentence2": "yeast origins are characterized by an asymmetric pattern of positioned nucleosomes flanking the ACS. The origin sequences are sufficient to maintain a nucleosome-free origin; however, ORC is required for the precise positioning of nucleosomes flanking the origin., Here, we identify nucleosome occupancy as a likely candidate to set up ORI distribution, we demonstrate that open chromatin domains, characterized by nucleosome depletion, are preferentially permissive for replication, Nucleosome assembly of the template prevented DNA replication. Replication of chromosomes was severely inhibited at more than two-thirds of physiological nucleosome density[SEP]", "label": "no"}
{"id": "converted_2668", "sentence1": "Is the protein pelota a ribosomal rescue factor?", "sentence2": "a novel binding partner of the ribosome recycling protein Pelota, n eukaryotes, Pelota (Dom34 in yeast) and Hbs1 are responsible for solving general problems of ribosomal stall in translation. , In eukaryotes, the protein complex of Pelota (yeast Dom34) and Hbs1 translational GTPase recognizes the stalled ribosome containing the defective mRNA.[SEP]", "label": "yes"}
{"id": "converted_4315", "sentence1": "Is Keutel syndrome a common genetic disorder?", "sentence2": "Keutel syndrome (OMIM 245150) is a very rare syndrome , Keutel syndrome is a rare autosomal-recessive condition characterized by abnormal cartilage calcification., MGP-deficiency in humans leads to Keutel syndrome, a rare genetic disease hallmarked by abnormal soft tissue calcification. [SEP]", "label": "no"}
{"id": "converted_3176", "sentence1": "Can mitochondria pass through membrane nanotubes?", "sentence2": "Membrane nanotubes (MNTs) act as \"highways\" between cells to facilitate the transfer of multiple signals and play an important role in many diseases. Our previous work reported on the transfer of mitochondria via MNTs between cardiomyocytes (CMs) and cardiac myofibroblasts (MFs), Membrane nanotubes play important functional roles in numerous cell activities such as cellular transport and communication.[SEP]", "label": "yes"}
{"id": "converted_3387", "sentence1": "Has ZP-PTH been tested in a phase II clinical trial?", "sentence2": "This system was successfully tested in a Phase 2 clinical trial for the treatment of post-menopausal women with osteoporosis.[SEP]", "label": "yes"}
{"id": "converted_3761", "sentence1": "Do nematodes contain architectural proteins like CTCF?", "sentence2": "A mode of genetic regulation that involves insulators and insulator binding proteins to establish independent transcriptional units is currently not known in nematodes including Caenorhabditis elegans. , the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans., he most highly enriched motif (LM1) corresponds to the X-box motif known from yeast and nematode, uggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans. We , of CTCF from several nematodes is paralleled by a loss of two of its interactors, the polycomb repressive complex subunit SuZ12 and the multifunctional transcription factor TYY1. In contrast to earlier st, SULTS: While orthologs for other insulator proteins were absent in all 35 analysed nematode species, we find orthologs of CTCF in a subset of nematodes. A, Loss of the insulator protein CTCF during nematode evolution, que secondary loss of CTCF from several nematodes is paralleled by a loss of two of its interactors, the polycomb repressive complex subunit SuZ12 and the multifunctional transcription factor TYY1. In con, level. A mode of genetic regulation that involves insulators and insulator binding proteins to establish independent transcriptional units is currently not known in nematodes including Caenorhabditis ,  suggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans. W, Loss of the insulator protein CTCF during nematode evolution.[SEP]", "label": "no"}
{"id": "converted_4475", "sentence1": "Is Acute Necrotizing Encephalopathy (ANE) which typically affects young, healthy children usually triggered by exposure to air pollution?", "sentence2": "Acute necrotizing encephalopathy (ANE) is a recently identified, uncommon encephalopathy affecting children. ANE is characterized by a preceding viral illness followed by seizures and rapid progressive neurologic deterioration. , Acute necrotizing encephalopathy (ANE) is a specific type of encephalopathy usually followed by febrile infection, ANE usually occurs in children under 4 years old after influenza infection, Acute necrotizing encephalopathy of childhood (ANEC) is a disease, characterized by a respiratory or gastrointestinal infection, accompanied with fever, rapid alteration of consciousness, and seizures., Acute necrotizing encephalopathy (ANE) is a rare but distinctive type of acute encephalopathy with global distribution. Occurrence of ANE is usually preceded by a virus-associated febrile illness and ensued by rapid deterioration., Acute necrotizing encephalopathy (ANE) typically affects young, healthy children who develop rapid-onset severe encephalopathy triggered by viral infections., Recurrent acute necrotizing encephalopathy following influenza A in a genetically predisposed family., Background: Among the influenza-associated encephalopathies, acute necrotizing encephalopathy (ANE) has a particularly poor prognosis., Since it was first recognized, neurological complications including acute necrotizing encephalopathy (ANE) have been globally documented in association with this viral infection., Background: Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy seen commonly in children triggered by various prodromal viral infections, most common being influenza virus and Human herpe, Background: Acute necrotizing encephalopathy (ANE), known as influenza-associated encephalitis, typically affects, Acute necrotizing encephalopathy (ANE) is a rapidly progressing neurologic disorder that occurs in children after common viral infections of the respiratory or gastrointestinal systems. , Acute necrotizing encephalopathy (ANE) typically affects young, healthy children who develop rapid-onset severe encephalopathy triggered by viral infections, Background: Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy seen commonly in children triggered by various prodromal viral infections, most common being influenza virus and Human herpes virus-, Acute necrotizing encephalopathy (ANE) presents in children after common viral infections, Acute necrotizing encephalopathy of childhood (ANEC) is a disease characterized by respiratory or gastrointestinal infection and high fever accompanying with rapid alteration of consciousness and seizures, Background: Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy seen commonly in children triggered by various prodromal viral infections, most common being influenza virus and Human herpes virus-6.Objective: We report two rare cases of ANE preceded by Chikungunya infection.Cases: A 13-year old girl presented with a three-day history of headache, fever, se, Acute necrotizing encephalopathy (ANE) is a rapidly progressing neurologic disorder that occurs in children after common viral infections of the respiratory or gastrointestinal systems., Acute necrotizing encephalopathy (ANE) presents in children after common viral infections., Acute necrotizing encephalopathy of childhood associated with influenza type B virus infection in a 3-year-old girl., We report a 12-year-old girl infected with influenza A H1N1 whose clinical course was complicated by rapid progressive neurologic deterioration and striking CT and MRI findings consistent with acute necrotizing encephalopathy (ANE)., We report a 3-year-old previously healthy girl presenting with acute necrotizing encephalopathy of childhood associated with influenza type B virus infection, which resulted in severe neurologic sequelae.[SEP]", "label": "no"}
{"id": "converted_3500", "sentence1": "Does deletion of cohesin change gene expression?", "sentence2": " The conditional deletion of cohesin from noncycling thymocytes preserved enhancer position, H3K27ac, H4K4me1, and enhancer transcription, but weakened interactions between enhancers., Interestingly, ∼ 50% of deregulated genes reside in the vicinity of enhancer elements, suggesting that cohesin regulates gene expression through spatial clustering of enhancer elements., We propose a model for cohesin-dependent gene regulation in which spatial clustering of enhancer elements acts as a unified mechanism for both enhancer-promoter \"connections\" and \"insulation.\"[SEP]", "label": "yes"}
{"id": "converted_95", "sentence1": "Does the CTCF protein co-localize with cohesin?", "sentence2": "To investigate cohesin-non-CTCF (CNC) binding events in vivo we mapped cohesin and CTCF, as well as a collection of tissue-specific and ubiquitous transcriptional regulators using ChIP-seq in primary mouse liver., In contrast to regions of the genome where cohesin and CTCF colocalize, CNC sites coincide with the binding of master regulators and enhancer-markers and are significantly associated with liver-specific expressed genes., Here we report that cohesins colocalize with CTCF at two additional imprinted loci, the Dlk1-Dio3 and the Kcnq1/Kcnq1ot1 loci., By use of human hepatocellular carcinoma cells (HepG2), we found that liver-specific transcription factors colocalize with cohesin independently of CTCF at liver-specific targets that are distinct from those found in breast cancer cells, Because cohesin can colocalize with CTCF, we performed chromatin immunoprecipitation for the cohesin subunit Rad21 and found lineage and stage-specific Rad21 recruitment to CTCF in all Ig loci, Here we show that zebrafish runx1 is directly bound by cohesin and CCCTC binding factor (CTCF) at the P1 and P2 promoters, and within the intron between P1 and P2., The intronic binding sites for cohesin and CTCF coincide with histone modifications that confer enhancer-like properties, and two of the cohesin/CTCF sites behaved as insulators in an in vivo assay, The identified cohesin and CTCF binding sites are likely to be cis-regulatory elements (CREs) for runx1 since they also recruit RNA polymerase II (RNAPII)., We have found that CTCF and cohesin are highly enriched at the convergent and partially overlapping transcripts for the LMP1 and LMP2A genes, but it is not yet known how CTCF and cohesin may coordinately regulate these transcripts, haracterization of constitutive CTCF/cohesin loci: a possible role in establishing topological domains in mammalian genomes, Our analysis revealed: 1) constitutive CTCF loci were located in constitutive open chromatin and often co-localized with constitutive cohesin loci, In brain, a third of CTCF and cohesin binding sites coincide, consistent with the potential for many interactions between cohesin and CTCF but also many instances of independent action, Here, we focus on the emerging roles of CTCF and the cohesin in coordinating long-range interactions between regulatory elements, Chromatin immunoprecipitation for CTCF and the cohesin subunits RAD21 and SMC3 reveals evolutionarily conserved binding sites within unmethylated regions ∼5 kb downstream of the PLAGL1 differentially methylated region and within the PLAGL1 3' untranslated region (UTR), TCF physically links cohesin to chromatin, ohesin and CTCF: cooperating to control chromosome conformation?, Recently, three groups mapped numerous cohesin-binding sites in mammalian chromosomes and found substantial overlap with the CCCTC-binding factor (CTCF), We found that each site contains a conserved CTCF consensus sequence, binds CTCF, and recruits the cohesin subunit Rad21 in vivo, Recent experiments have revealed that cohesin binds to the same sites in mammalian genomes as the zinc finger transcription factor CTCF, Here we review what is known about the roles of cohesin and CTCF in regulating gene expression in mammalian cells, and we discuss how cohesin might mediate the insulator function of CTCF, Previous studies have shown that this major latency control region is occupied by the cellular chromatin boundary factor CTCF and chromosome structural maintenance proteins SMC1, SMC3, and RAD21, which comprise the cohesin complex, Cohesin subunits assembled at the CTCF binding sites and bound CTCF proteins in a cell cycle-dependent manner, We propose that the CTCF-cohesin complex plays a critical role in regulating the cell cycle control of viral gene expression during latency and that failure to maintain cell cycle control of latent transcripts inhibits host cell proliferation and survival, We used chromosome conformation capture to determine long-range interactions among CTCF/cohesin sites over 2 Mb on human chromosome 11 encompassing the beta-globin locus and flanking olfactory receptor genes, These results support a genome-wide role for CTCF/cohesin sites through loop formation that both influences transcription and contributes to cell-type-specific chromatin organization and function, Increased methylation at this promoter triggered the dissociation of the insulator protein CTCF as well as the accompanying cohesin from the BDNF locus, icotinamide adenine dinucleotide (NAD)-regulated DNA methylation alters CCCTC-binding factor (CTCF)/cohesin binding and transcription at the BDNF locus, ecent studies have shown that the protein CTCF, which plays an important role in insulation and in large-scale organization of chromatin within the eukaryotic nucleus, depends for both activities on recruitment of the cohesin complex, We show here that the interaction of CTCF with the cohesin complex involves direct contacts between the cohesin subunit SA2 and specific regions of the C-terminal tail of CTCF, Taken together, our results demonstrate that specific sites on the C terminus of CTCF are essential for cohesin binding and insulator function, The only direct interaction between CTCF and cohesin involves contact with SA2, which is external to the cohesin ring, These numerous CTCF/cohesin sites potentially form the bases of the multiloop rosette structures at the Igh locus that compact during Ig heavy chain rearrangement, We have previously shown that the Kaposi's Sarcoma-Associated Herpesvirus (KSHV) major latency transcripts encoding LANA, vCyclin, vFLIP, v-miRNAs, and Kaposin are regulated, in part, by a chromatin organizing element that binds CTCF and cohesins, Mutation of the CTCF-cohesin binding site reduced or eliminated the chromatin conformation linkages, and deregulated viral transcription and genome copy number control, Our findings indicate that KSHV genomes are organized into chromatin loops mediated by CTCF and cohesin interactions, and that these inter-chromosomal linkages coordinate latent and lytic gene control., We show here that GA disrupts an RNA polymerase II (RNAPII) complex that accumulates at the CTCF-cohesin binding site within the first intron of the latency transcript., GA altered the enrichment of the RNAPII pausing complex, along with pausing factors SPT5 and NELF-A, at the intragenic CTCF-cohesin binding sites., GA treatment also inhibited the transcription of some cellular genes, like c-myc, which contain a similar CTCF-cohesin binding site within the first intron., These findings suggest that RNAPII pauses at intragenic CTCF-cohesin binding sites and that abrogation of this pausing by GA leads to loss of proper mRNA production and defects in sister chromatid cohesion, a process important for both viral and cellular chromosome stability., TCF and cohesin cooperatively mediate the cell-type specific interchromatin interaction between Bcl11b and Arhgap6 loci, Additional experiments verified that the interchromatin interaction between the Bcl11b and Arhgap6 loci was cell-type specific, which was cooperatively mediated by CTCF and cohesin., enome-wide studies of CCCTC-binding factor (CTCF) and cohesin provide insight into chromatin structure and regulation, Recent genome-wide studies mapping the binding sites of CTCF and its interacting partner, cohesin, using chromatin immunoprecipitation coupled with deep sequencing (ChIP-seq) revealded that CTCF globally co-localizes with cohesin, Here, we show by ChIP-Seq that most human subtelomeres contain a CTCF- and cohesin-binding site within ∼1-2 kb of the TTAGGG repeat tract and adjacent to a CpG-islands implicated in TERRA transcription control., These findings indicate that CTCF and cohesin are integral components of most human subtelomeres, and important for the regulation of TERRA transcription and telomere end protection, In addition, we show that this DNA looping requires specific binding of the CTCF/cohesin complex to two symmetrically aligned binding sites in both the transcriptionally active promoters and in one of the enhancers[SEP]", "label": "yes"}
{"id": "converted_1750", "sentence1": "Is synapsin a phosphoprotein?", "sentence2": "Synapsin is an evolutionarily conserved presynaptic phosphoprotein., Synapsins as a family of presynaptic terminal phosphoprotein participates in neuronal development, Synapsin III (SynIII) is a phosphoprotein, The neuronal phosphoprotein synapsin III, Synapsin II is a member of the neuronal phosphoprotein family., phosphoprotein synapsin[SEP]", "label": "yes"}
{"id": "converted_3174", "sentence1": "Was stelara developed by Amgen?", "sentence2": "NICE does not specifically recommend switching from one biologic to another, and only ustekinumab (UST; STELARA®, Janssen Pharmaceuticals, Inc., Horsham, PA, USA) is recommended after anti-tumour necrosis factor failure.[SEP]", "label": "no"}
{"id": "converted_1544", "sentence1": "Could Hyperthermic intraperitoneal chemotherapy (HIPEC) be effective for the treatment of recurrent ovarian cancer?", "sentence2": "The use of HIPEC after aggressive cytoreductive surgery in patients with ovarian cancer with peritoneal dissemination can be performed with acceptable postoperative morbidity rates. Knowledge of the factors associated with the onset of these postoperative adverse events allows better management of the same and offers the patient a safe procedure, These results showed that the association of HIPEC with a complete cytoreduction for recurrent ovarian cancer presents acceptable morbidity and survival, There is level-one evidence suggesting the benefit of postoperative adjuvant intraperitoneal chemotherapy for patients with advanced ovarian cancer after cytoreductive surgery, albeit catheter-related complications resulted after treatment discontinuation. Studies report the use of HIPEC predominantly in the setting of recurrent disease and have demonstrated encouraging results, which merits further investigation in future clinical trials,  The combination of SCR and HIPEC seems to improve survival rate in patients suffering from platinum-sensitive EOC recurrence with respect to no-HIPEC treatments. This result further supports the need of a randomized trial,  Cautious extrapolation of data from standard normothermic, nonintraoperative, intraperitoneal chemotherapy and data from Phase II and nonrandomized comparative studies suggest that HIPEC delivered at the time of surgery for ovarian cancer has definite potential, The available evidence suggests that a potential survival benefit of adding HIPEC may be largest in the settings of secondary CRS for stage III ovarian cancer and salvage CRS for recurrent ovarian cancer, two time-points representing failure of initial standard therapy. There is much less evidence for a potential benefit of HIPEC for less advanced stages (I-II) and for earlier time-points in the treatment of ovarian cancer (upfront, interval and consolidation), Survival benefit of adding Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) at the different time-points of treatment of ovarian cancer, Patients suffering from peritoneal recurrence of ovarian cancer should be considered for radical reoperation with HIPEC in a center with expertise in multimodal therapeutic options. Organ-preserving cytoreductive surgery allows complete cytoreduction with the goal of decreasing morbidity,  In recurrent platinum-sensitive ovarian cancer patients, the use of CRS plus HIPEC represents a safe treatment, able to significantly influence the survival rates compared to chemotherapy alone or surgery plus standard chemotherapy,  The results of our study indicate the feasibility and the potential benefit of a protocol including systemic chemotherapy, surgical cytoreduction and HIPEC in patients with peritoneal carcinomatosis from ovarian cancer. A phase III trial to compare this approach with conventional treatment is needed, In selected patients with heavily pretreated recurrent ovarian cancer, cytoreduction combined with HIPEC may provide a meaningful OS with acceptable morbidity. Optimal results are achieved in patients with a macroscopically complete resection and biologically favorable disease,  HIPEC is a complement to radical surgery/ peritonectomy, which has been shown to be a surgical procedure with high tolerability, low morbimortality, enhanced survival and prolonged disease-free interval in patients with peritoneal carcinomatosis for recurrent ovarian cancer,  Despite the heterogeneity of the studies reviewed, current evidence suggest that complete CRS and HIPEC may be a feasible option with potential benefits that are comparable with the current standard of care. A randomized trial is required to establish the role of HIPEC in ovarian cancer, in the majority of patients with primary and recurrent advanced ovarian cancer, cytoreductive surgery combined with HIPEC can lead to a substantial increase in subsequent rates of disease-free and overall survival,  Peritonectomy procedures combined with HIPEC offer promising long-term survival in patients with diffuse peritoneal ovarian carcinomatosis. They achieve high adequate primary and secondary surgical cytoreduction rates with acceptable morbidity and mortality, Cytoreduction surgery with hyperthermic intraperitoneal chemotherapy in recurrent ovarian cancer improves progression-free survival, especially in BRCA-positive patients- a case-control study., Survival benefit of adding Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) at the different time-points of treatment of ovarian cancer: review of evidence., Some encouraging results have been reported by the treatment of peritoneal carcinomatosis (PC) from ovarian cancer by complete surgical cytoreduction, peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC)., Although standard treatment for advanced epithelial ovarian cancer (EOC) consists of surgical debulking and intravenous platinum- and taxane-based chemotherapy, favorable oncological outcomes have been recently reported with the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)., Trabectedin, Hyperthermic intraperitoneal chemotherapy (HIPEC) and chemo-immunotherapy may be become a promising therapy for the treatment of ovarian cancer., Hyperthermic intraperitoneal chemotherapy (HIPEC) represents a new treatment strategy aimed to improve outcome of patients with advanced ovarian cancer., Favorable oncological outcomes have been reported in several trials with the introduction of Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the treatment of Advanced Epithelial Ovarian Cancer (EOC)., Based on theoretical and experimental basis, HIPEC should stand as an effective treatment for ovarian cancer., Some encouraging results have been reported by the treatment of peritoneal carcinomatosis (PC) from ovarian cancer by complete surgical cytoreduction, peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC), Based on theoretical and experimental basis, HIPEC should stand as an effective treatment for ovarian cancer, Hyperthermic intraperitoneal chemotherapy (HIPEC) represents a new treatment strategy aimed to improve outcome of patients with advanced ovarian cancer, [Importance of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer].[SEP]", "label": "yes"}
{"id": "converted_2626", "sentence1": "Can nanoparticles be used for afterglow imaging?", "sentence2": "Ultralong Phosphorescence of Water-Soluble Organic Nanoparticles for In Vivo Afterglow Imaging, Afterglow or persistent luminescence eliminates the need for light excitation and thus circumvents the issue of autofluorescence, holding promise for molecular imaging. However, current persistent luminescence agents are rare and limited to inorganic nanoparticles. This study reports the design principle, synthesis, and proof-of-concept application of organic semiconducting nanoparticles (OSNs) with ultralong phosphorescence for in vivo afterglow imaging. , This study not only introduces the first category of water-soluble ultralong phosphorescence organic nanoparticles but also reveals a universal design principle to prolong the lifetime of phosphorescent molecules to the level that can be effective for molecular imaging.[SEP]", "label": "yes"}
{"id": "converted_1989", "sentence1": "Does CRISPR inversion of CTCF sites alter genome topology?", "sentence2": "CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function, To test the functional significance of this observation, we combined CRISPR/Cas9-based genomic-DNA-fragment editing with chromosome-conformation-capture experiments to show that the location and relative orientations of CBSs determine the specificity of long-range chromatin looping in mammalian genomes, using protocadherin (Pcdh) and β-globin as model genes. Inversion of CBS elements within the Pcdh enhancer reconfigures the topology of chromatin loops between the distal enhancer and target promoters and alters gene-expression patterns. Thus, although enhancers can function in an orientation-independent manner in reporter assays, in the native chromosome context, the orientation of at least some enhancers carrying CBSs can determine both the architecture of topological chromatin domains and enhancer/promoter specificity. These findings reveal how 3D chromosome architecture can be encoded by linear genome sequences, CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function., CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function.[SEP]", "label": "yes"}
{"id": "converted_3359", "sentence1": "Is the FIP virus thought to be a mutated strain for the Feline enteric Coronavirus?", "sentence2": "Feline infectious peritonitis (FIP) results from mutations in the viral genome during a common feline enteric coronavirus (FECV) infection., It is caused by FIP virus (FIPV), a virulent mutant strain of Feline Enteric Coronavirus (FECV)., Feline infectious peritonitis virus (FIPV) was presumed to arise from mutations in the 3c of a ubiquitous and largely nonpathogenic feline enteric coronavirus (FECV)., Feline enteric coronavirus (FECV) causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP), can arise through mutation of FECV to FIP virus (FIPV)., Feline infectious peritonitis (FIP) is a lethal systemic disease caused by FIP virus (FIPV), a virulent mutant of apathogenic feline enteric coronavirus (FECV)., Feline infectious peritonitis (FIP) is an almost invariably fatal feline coronavirus (FCoV)-induced disease thought to arise from a combination of viral mutations and an overexuberant immune response., BACKGROUND\n\nFeline Infectious Peritonitis (FIP) is a lethal systemic disease, caused by the FIP Virus (FIPV); a virulent mutant of Feline Enteric Coronavirus (FECV)., BACKGROUND Feline Infectious Peritonitis (FIP) is a lethal systemic disease, caused by the FIP Virus (FIPV); a virulent mutant of Feline Enteric Coronavirus (FECV)., This coronavirus is a virulent mutant of the harmless, ubiquitous feline enteric coronavirus (FECV)., Feline infectious peritonitis virus (FIPV) was presumed to arise from mutations in the 3c of a ubiquitous and largely nonpathogenic feline enteric coronavirus (FECV)., Whilst intact in all FECVs, the 3c gene was mutated in the majority (71.4 %) of FIPVs, but not in all, implying that mutation in 3c is not the (single) cause of FIP.[SEP]", "label": "yes"}
{"id": "converted_2517", "sentence1": "Does wheat belongs to the genus Avena, yes or no?", "sentence2": "oat seedlings (Avena sativa), wild green-oat (Avena sativa) ,  Oat (Avena sativa L.), Oat (Avena sativa L.), Avena (Oats), wild oats (Avena fatua L.), oats (genus Avena), Avena sativa L. and A. byzantina C. Koch) ,  oat (Avena sativa L.)., oat (Avena sativa L.) and wheat (Triticum aestivum[SEP]", "label": "no"}
{"id": "converted_4413", "sentence1": "Is there a role for CADM1 in Myelodysplastic syndrome (MDS)?", "sentence2": "Together with the frequent simultaneous deletions of KMT2A, ATM and CBL and mutations of ASXL1, SF3B1 and CBL, we show that CADM1 may be important in the physiopathology of the del(11q) MDS, extending its role as tumor-suppressor gene from solid tumors to hematopoietic malignancies., The CADM1 tumor suppressor gene is a major candidate gene in MDS with deletion of the long arm of chromosome 11.[SEP]", "label": "no"}
{"id": "converted_3344", "sentence1": "Is marimastat effective for small-cell lung cancer?", "sentence2": "The phase III trial in small cell lung cancer was discontinued when the results of study 140 were released in February 2001 showing that marimastat was not significantly more effective than placebo in prolonging the survival of small cell lung cancer patients., CONCLUSION: Treatment with marimastat after induction therapy for SCLC did not result in improved survival and had a negative impact on quality of life., There were no significant differences in survival in a non-small cell lung cancer prinomastat study, and in a small cell lung cancer marimastat trial., There were no significant differences in survival in a non-small cell lung cancer prinomastat study , and in a small cell lung cancer marimastat trial. , The phase III trial in small cell lung cancer was discontinued when the results of study 140 were released in February 2001 showing that marimastat was not significantly more effective than placebo in prolonging the survival of small cell lung cancer patients.[SEP]", "label": "no"}
{"id": "converted_3335", "sentence1": "Does BNN27 promote memory loss?", "sentence2": "The novel dehydroepiandrosterone (DHEA) derivative BNN27 counteracts delay-dependent and scopolamine-induced recognition memory deficits in rats., BNN27 is a novel 17C spiroepoxy-DHEA derivative, which devoid of steroidogenic activity. The neuroprotective effects of BNN27 have been recently reported. The present study was designed to investigate the effects of BNN27 on recognition memory in rats. For this purpose, the novel object task (NOT), a procedure assessing non-spatial recognition memory and the novel location task (NLT), a procedure evaluating spatial recognition memory were used. Intraperitoneal (i.p.) administration of BNN27 (3 and 10mg/kg) antagonized delay-dependent deficits in the NOT in the normal rat, suggesting that this DHEA derivative affected acquisition, storage and retrieval of information. In addition, BNN27 (3 and 10mg/kg, i.p.) counteracted the scopolamine [0.2mg/kg, subcutaneously (s.c.)]-induced non-spatial and spatial recognition memory deficits. These findings suggest that BNN27 may modulate different aspects of recognition memory, potentially interacting with the cholinergic system, relevant to cognition.[SEP]", "label": "no"}
{"id": "converted_4240", "sentence1": "Is Cabotegravir effective for HIV prevention?", "sentence2": "A new paradigm for antiretroviral delivery: long-acting cabotegravir and rilpivirine for the treatment and prevention of HIV., PURPOSE OF REVIEW: Cabotegravir (CAB) and rilpivirine (RPV) is the first long-acting injectable antiretroviral therapy (ART) option approved for virologically suppressed adults with HIV-1. In addition, long-acting CAB is a promising agent for HIV preexposure prophylaxis (PrEP). , SUMMARY: Clinical trial results support the use of long-acting CAB for HIV PrEP and long-acting CAB and RPV as a switch strategy for adults with HIV-1 who are first virologically suppressed with oral ART. , OBJECTIVE: We had previously shown that long-acting cabotegravir (CAB-LA) injections fully protected macaques from vaginal simian HIV (SHIV) infection., The Potential Impact of Long-Acting Cabotegravir for HIV Prevention in South Africa: A Mathematical Modeling Study.,  Long-acting cabotegravir (CAB LA) is a potential new injectable formulation for human immunodeficiency virus (HIV) PrEP being tested in phase III trials., Design and Testing of a Cabotegravir Implant for HIV Prevention., Cabotegravir and rilpivirine long-acting injectable antiretroviral therapy for the treatment of HIV-1 infection brings promise of a new mode of delivery and potential solutions to some problems of oral therapy, but also new challenges and unanswered questions., Cabotegravir is an investigational integrase inhibitor in development for the treatment and pre-exposure prophylaxis of HIV-1 infection., Bictegravir, cabotegravir, dolutegravir, elvitegravir, and raltegravir are members of the latest class of antiretrovirals available to treat human immunodeficiency virus (HIV) infection, the integrase strand transfer inhibitors., PURPOSE OF REVIEW: Long-acting cabotegravir may provide a novel therapeutic option for both the treatment and prevention of HIV-1 infection that does not necessitate adherence, Long-acting injectable cabotegravir for the prevention of HIV infection, BACKGROUND: The HIV Prevention Trials Network (HPTN) 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was more effective than tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) in preventing human immunodeficiency virus (HIV) in cisgender men and transgender women who have sex with, Areas covered: Here, we review trials of cabotegravir (CAB) as treatment of HIV-1 infection and its potential use as pre-exposure prophylaxis (PrEP) in high risk individuals, including issues around oral lead in and potential resistance emergence. Exper, frequent dosing. This review focuses on the potential benefits and considerations for the study and use of 2 long-acting injectable agents, cabotegravir (GSK1265744LA, CAB LA) and rilpivirine (TMC278LA, RPV LA), for use as chemoprophylaxis for HIV , An evaluation of cabotegravir for HIV treatment and prevention., Cabotegravir long-acting for HIV-1 prevention., Our findings suggest that cabotegravir should be evaluated in clinical trials as a potential option for antiretroviral therapy and preexposure prophylaxis in HIV-2-prevalent settings., Profile of cabotegravir and its potential in the treatment and prevention of HIV-1 infection: evidence to date., Long-Acting Cabotegravir for HIV/AIDS Prophylaxis., Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women., Cabotegravir is a novel human immunodeficiency virus integrase enzyme inhibitor used for prevention and treatment of HIV infection., PURPOSE OF REVIEW: Long-acting cabotegravir may provide a novel therapeutic option for both the treatment and prevention of HIV-1 infection that does not necessitate adherence , Cabotegravir in the treatment and prevention of Human Immunodeficiency Virus-1., Cabotegravir: its potential for antiretroviral therapy and preexposure prophylaxis., Satisfaction and acceptability of cabotegravir long-acting injectable suspension for prevention of HIV: Patient perspectives from the ECLAIR trial.[SEP]", "label": "yes"}
{"id": "converted_820", "sentence1": "Is Lysine-specific demethylase 1 (LSD1) a critical regulator of hematopoiesis?", "sentence2": "Histone lysine-specific demethylase 1 (LSD1) protein is involved in Sal-like protein 4 (SALL4)-mediated transcriptional repression in hematopoietic stem cells, shRNA-mediated knockdown of LSD1 in hematopoietic precursor cells resulted in altered SALL4 downstream gene expression and increased cellular activity, our data revealed that histone demethylase LSD1 may negatively regulate SALL4-mediated transcription, and the dynamic regulation of SALL4-associated epigenetic factors cooperatively modulates early hematopoietic precursor proliferation, Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation,  LSD1 represents a central regulator of hematopoietic stem and progenitor cells,  LSD1-kd led to an extensive expansion of granulomonocytic, erythroid and megakaryocytic progenitors, LSD1-kd was associated with the upregulation of key hematopoietic genes, our findings distinguish LSD1 as a critical regulator of hematopoiesis, A short Gfi-1B isoform controls erythroid differentiation by recruiting the LSD1-CoREST complex through the dimethylation of its SNAG domain, Dynamic interaction between TAL1 oncoprotein and LSD1 regulates TAL1 function in hematopoiesis and leukemogenesis, Here, we reported that protein kinase A (PKA)-mediated phosphorylation regulates TAL1 interaction with the lysine-specific demethylase (LSD1) that removes methyl group from methylated Lys 4 on histone H3 tails. Phosphorylation of serine 172 in TAL1 specifically destabilizes the TAL1-LSD1 interaction leading to promoter H3K4 hypermethylation and activation of target genes that have been suppressed in normal and malignant hematopoiesis, LSD1-mediated epigenetic modification is required for TAL1 function and hematopoiesis, we show that TAL1 is associated with histone demethylase complexes containing lysine-specific demethylase 1 (LSD1), RE1 silencing transcription factor corepressor (CoREST), histone deacetylase 1 (HDAC1), and histone deacetylase 2 in erythroleukemia and T cell leukemia cells, we demonstrate that the TAL1-associated LSD1, HDAC1, and their enzymatic activities are coordinately down-regulated during the early phases of erythroid differentiation, TAL1 recruits LSD1 to the silenced p4.2 promoter in undifferentiated, but not in differentiated, murine erythroleukemia (MEL) cells, the dynamic regulation of TAL1-associated LSD1/HDAC1 complex may determine the onset of erythroid differentiation programs, Epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b is mediated by the cofactors CoREST and LSD1, Inhibition of CoREST and LSD1 perturbs differentiation of erythroid, megakaryocytic, and granulocytic cells as well as primary erythroid progenitors, we show that chromatin regulatory proteins CoREST and LSD1 mediate transcriptional repression by Gfi proteins. Lineage-restricted deployment of these cofactors through interaction with Gfi proteins controls hematopoietic differentiation, Taken together, our findings distinguish LSD1 as a critical regulator of hematopoiesis and point to severe, but reversible, side effects of a LSD1-targeted therapy., LSD1-mediated epigenetic modification is required for TAL1 function and hematopoiesis., Dynamic interaction between TAL1 oncoprotein and LSD1 regulates TAL1 function in hematopoiesis and leukemogenesis., Phosphorylation of serine 172 in TAL1 specifically destabilizes the TAL1-LSD1 interaction leading to promoter H3K4 hypermethylation and activation of target genes that have been suppressed in normal and malignant hematopoiesis., Histone lysine-specific demethylase 1 (LSD1) protein is involved in Sal-like protein 4 (SALL4)-mediated transcriptional repression in hematopoietic stem cells., Taken together, our findings distinguish LSD1 as a critical regulator of hematopoiesis and point to severe, but reversible, side effects of a LSD1-targeted therapy.[SEP]", "label": "yes"}
{"id": "converted_2227", "sentence1": "Is Downs syndrome associated with decreased risk of leukemia?", "sentence2": "The association of Down's syndrome and leukemia has been documented for over 50 years. Multiple studies have established the incidence of leukemia in Down's syndrome patients to be 10- to 20-fold higher than that in the general population., We present a case of congenital acute myeloid leukemia manifesting from the very first day of birth. Diagnosis of acute myeloid leukemia was suspected by the presence of blasts in the peripheral blood smear and was confirmed on bone marrow by flowcytometry. Karyotyping revealed Trisomy 21., Juvenile myelomonocytic leukemia (JMML) and a solitary cases of acute myeloid leukemia (AML) in Downs syndrome. , This was thus confirmed to be a case with transient leukemia with Downs syndrome.[SEP]", "label": "no"}
{"id": "converted_142", "sentence1": "Is amiodarone a class I anti-arrhythmic drug?", "sentence2": "Common class I agents are excluded due to the inherent abnormal cardiac structure and function in the setting of cardiogenic shock. Class III drug options include dofetilide and amiodarone., Amiodarone has been used as an anti-arrhythmic drug since the 1970s and has an established role in the treatment of ventricular tachyarrhythmias. Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile. , Amiodarone, an iodinated benzofuran derivative, introduced in 1960's as an anti-anginal agent, emerged as a potent anti-arrhythmic agent by 1970's and is currently one of the most commonly prescribed drugs in US for ventricular and atrial arrhythmias. Although amiodarone is considered a class III anti-arrhythmic agent, it also has class I, II, IV actions, making it a unique and effective anti-arrhythmic agent., Amiodarone, a representative class III agent, exerts negative dromotropism by suppressing the fast sodium current responsible for conduction in acute administration (class I effects). Chronic amiodarone causes prolongation of ERP (class III effects), which is sometimes associated with negative dromotropism based on the alteration of passive or active membrane properties., Amiodarone, an iodinated benzofuran derivative with predominantly class III anti-arrhythmic effects, is used to treat supraventricular and ventricular arrhythmias., Although amiodarone is considered a class III anti-arrhythmic agent, it also has class I, II, IV actions, making it a unique and effective anti-arrhythmic agent, Amiodarone, a class III antiarrhythmic drug, is one of the most effective drugs used in the treatment of ventricular and paroxysmal supraventricular tachyarrhythmia, Although amiodarone is considered a class III anti-arrhythmic agent, it also has class I, II, IV actions, making it a unique and effective anti-arrhythmic agent, Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile, Amiodarone is a potent class III anti-arrhythmic drug that also possesses beta-blocking properties[SEP]", "label": "no"}
{"id": "converted_47", "sentence1": "Is Weaver syndrome similar to Sotos?", "sentence2": "Overgrowth conditions are a heterogeneous group of disorders characterised by increased growth and variable features, including macrocephaly, distinctive facial appearance and various degrees of learning difficulties and intellectual disability. Among them, Sotos and Weaver syndromes are clinically well defined and due to heterozygous mutations in NSD1 and EZH2, respectively. NSD1 and EZH2 are both histone-modifying enzymes, NSD1 and EZH2 are SET domain-containing histone methyltransferases that play key roles in the regulation of transcription through histone modification and chromatin modeling: NSD1 preferentially methylates lysine residue 36 of histone 3 (H3K36) and is primarily associated with active transcription, while EZH2 shows specificity for lysine residue 27 (H3K27) and is associated with transcriptional repression, Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap, Clinically, Weaver syndrome is closely related to Sotos syndrome, which is frequently caused by mutations in NSD1, Overgrowth syndromes such as Beckwith-Wiedemann syndrome, Sotos syndrome, and Weaver syndrome have an increased risk of neoplasia., Thus, it is not surprising that prenatal overgrowth occurs in several syndromes, including the Sotos and Weaver syndromes., NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes., We conclude therefore that NSD1 mutations account for most cases of Sotos syndrome and a significant number of Weaver syndrome cases in our series., We conclude that intragenic mutations of NSD1 are the major cause of Sotos syndrome and account for some Weaver syndrome cases but rarely occur in other childhood overgrowth phenotypes., Overgrowth syndromes such as Beckwith-Wiedemann syndrome, Sotos syndrome, and Weaver syndrome have an increased risk of neoplasia, NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes, We conclude that intragenic mutations of NSD1 are the major cause of Sotos syndrome and account for some Weaver syndrome cases but rarely occur in other childhood overgrowth phenotypes, Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident. , Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident. The identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes.,  Overgrowth syndromes such as Beckwith-Wiedemann syndrome, Sotos syndrome, and Weaver syndrome have an increased risk of neoplasia. Two previous cases of neuroblastoma have been reported in children with Weaver syndrome., Weaver syndrome is closely related to Sotos syndrome,, Overgrowth syndromes such as Beckwith-Wiedemann syndrome, Sotos syndrome, and Weaver syndrome have an increased risk of neoplasia., Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident., Clinically, Weaver syndrome is closely related to Sotos syndrome, which is frequently caused by mutations in NSD1.[SEP]", "label": "yes"}
{"id": "converted_4717", "sentence1": "Can parasite infections by Schistosoma japonicum prevent or improve asthma?", "sentence2": "Helminths and their products can shape immune responses by modulating immune cells, which are dysfunctional in inflammatory diseases such as asthm, Schistosoma japonicum peptide SJMHE1 suppresses airway inflammation of allergic asthma in mice., Schistosoma japonicum infection downregulates house dust mite-induced allergic airway inflammation in mice., To our knowledge, it is the first study to reveal the impact of S. japonicum infection on house dust mite induced severe asthma. More in depth investigation is need to elucidate the underlying mechanisms, Novel T-cell epitopes on Schistosoma japonicum SjP40 protein and their preventive effect on allergic asthma in mice., hese results reveal a novel form of immune protective mechanism, which may play an important role in the modulating effect of helminth infection on allergic asthmatic reactions., Using a panel of overlapping peptides, we identified T-cell epitopes on SjP40 protein of Schistosoma japonicum, which can induce Th1 cytokine and inhibit the production of Th2 cytokines and airway inflammation in a mouse model of allergic asthma., Helminths and their products can regulate immune response and offer new strategies to control and alleviate inflammation, including asthma., SJMHE1 Peptide from Schistosoma japonicum Inhibits Asthma in Mice by Regulating Th17/Treg Cell Balance via miR-155., We previously found that a peptide named as SJMHE1 from Schistosoma japonicum can suppress asthma in mice, el of overlapping peptides, we identified T-cell epitopes on SjP40 protein of Schistosoma japonicum, which can induce Th1 cytokine and inhibit the production of Th2 cytokines and airway inflammation in a mouse model of allergic asthma. These resul, has been shown that helminth infections including Schistosoma mansoni may modulate atopic diseases including asthma. I, Schistosoma japonicum infection downregulates house dust mite-induced allergic airway inflammation in mice, it is the first study to reveal the impact of S. japonicum infection on house dust mite induced severe asthma. More in depth inv, s study, we investigated the impact of Schistosoma japonicum infection on the allergic airway inflammation induced by repeated intracheal inoculations of house dust mites (HDM), which is a Th17 and neutrophils dominant murine asthma model, mimicking severe asthma. We found, Schistosoma japonicum infection showed protective effects against allergic airway inflammation (AAI)., Therefore, we hypothesize that Schistosoma japonicum egg antigens, a type of native antigen, can induce production of CD4(+) CD25(+) T cells with regulatory activity, modulating airway inflammation and inhibiting asthma development., Schistosoma japonicum infection modulates the development of allergen-induced airway inflammation in mice., It has been shown that helminth infections including Schistosoma mansoni may modulate atopic diseases including asthma., Schistosoma japonicum egg antigens stimulate CD4 CD25 T cells and modulate airway inflammation in a murine model of asthma., Most previous studies focused on understanding the preventive effect of S. japonicum infection on asthma (infection before allergen sensitization), whereas the protective effects of S. japonicum infection (allergen sensitization before infection) on asthma were rarely investigated., In conclusion, our data showed that lung-stage S. japonicum infection could relieve OVA-induced asthma in a mouse model., In this study, we investigated the protective effects of S. japonicum infection on AAI using a mouse model of OVA-induced asthma.,  prior to OVA immunization. These results suggest that both bisexual and male S. japonicum infections may modulate the development of allergic asthma., aponicum, which can induce Th1 cytokine and inhibit the production of Th2 cytokines and airway inflammation in a mouse model of allergic asthma. These, ve found that Schistosoma infection or Schistosoma related products can improve or prevent some immune and inflammatory diseases, such as severe asthm, Our findings indicated that S. japonicum infection was able to effectively inhibit host's allergic airway inflammation, which may be related to the upregulated Treg cells upon infection., These results suggest that both bisexual and male S. japonicum infections may modulate the development of allergic asthma., We found that lung-stage S. japonicum infection significantly ameliorated OVA-induced AAI, whereas post-lung-stage infection did not., In a murine model of asthma, S. japonicum egg antigens decreased the expression of Th2 cytokines, relieved antigen-induced airway inflammation, and inhibited asthma development., We found that S. japonicum infection downregulated airway hyperresponsiveness., However, in recent years, studies have found that Schistosoma infection or Schistosoma related products can improve or prevent some immune and inflammatory diseases, such as severe asthma, inflammatory bowel disease, diabetes and so on., In areas where schistosomiasis is endemic, a negative correlation is observed between atopy and helminth infection, associated with a low prevalence of asthma.[SEP]", "label": "yes"}
{"id": "converted_4025", "sentence1": "Is Lanabecestat effective for Alzheimer's disease?", "sentence2": "INTRODUCTION: The APECS and AMARANTH trials showed that beta-secretase (BACE) inhibitors verubecestat and lanabecestat failed to slow cognitive and functional decline in individuals with prodromal or early Alzheimer's disease. , Conclusions and Relevance: Treatment with lanabecestat was well tolerated and did not slow cognitive or functional decline., INTRODUCTION: The APECS and AMARANTH trials showed that beta-secretase (BACE) inhibitors verubecestat and lanabecestat failed to slow cognitive and functional decline in individuals with prodromal or early Alzheimer's disease., INTRODUCTION: The APECS and AMARANTH trials showed that beta-secretase (BACE) inhibitors verubecestat and lanabecestat failed to slow cognitive and functional decline in individuals with prodromal or early Alzheime, INTRODUCTION: The APECS and AMARANTH trials showed that beta-secretase (BACE) inhibitors verubecestat and lanabecestat failed to slow cognitive and functional decline in individuals with prodromal or early Alzhei[SEP]", "label": "no"}
{"id": "converted_1589", "sentence1": "Has proteomics been used in the study of the dry eye syndrome?", "sentence2": "Tear proteomic analysis of patients with type 2 diabetes and dry eye syndrome by two-dimensional nano-liquid chromatography coupled with tandem mass spectrometry., Dry eye syndrome in diabetic patients is associated with aberrant expression of tear proteins, and the findings could lead to identification of novel pathways for therapeutic targeting and new diagnostic markers.,  2D electrophoresis (2DE) and Differential gel electrophoresis (DIGE) was done to identify differentially expressed proteins. , Two dimensional electrophoretic analysis of human tears: collection method in dry eye syndrome., Identification of tear fluid biomarkers in dry eye syndrome using iTRAQ quantitative proteomics., This study demonstrated that iTRAQ technology combined with 2D-nanoLC-nanoESI-MS/MS quantitative proteomics is a powerful tool for biomarker discovery.[SEP]", "label": "yes"}
{"id": "converted_941", "sentence1": "Do selenoproteins and selenium play a role in prostate cancer prevention?", "sentence2": "The selenoprotein-deficient mice exhibited accelerated development of lesions associated with prostate cancer progression, implicating selenoproteins in cancer risk and development and raising the possibility that selenium prevents cancer by modulating the levels of these selenoproteins, Notably and in contrast to previous studies, RWPE-1 cells were significantly more sensitive to selenite than either of the prostate cancer cell lines. These results demonstrate that selenoproteins and selenium metabolism are regulated at multiple levels in prostate cells, In a low-selenium population, SOD2-Ala16+ men homozygous for SEPP1-Ala234 are at an increased risk of prostate cancer/aggressive prostate cancer especially if ever-smokers, because they are likely to produce more mitochondrial H(2)O(2) that they cannot remove, thereby promoting prostate tumor cell proliferation and migration., Our results support a role of selenium and polymorphisms in selenoenzymes in prostate cancer etiology, which warrants confirmation in future studies., This study provides evidence that SEP15 genetic variation may influence PCa mortality. Additionally, the association of selenium with PCa mortality was modified by a variant, suggesting the possibility that some men with PCa may benefit more from selenium than others, depending on their genotype., We conclude that decreased SEPP concentration in serum might represent an additional valuable marker for prostate cancer diagnostics., The recently completed Selenium and Vitamin E Cancer Prevention Trial (SELECT) was one of the largest human cancer prevention trials ever undertaken. Its purpose was to assess the role of selenium and vitamin E in prostate cancer prevention, but SELECT found no decline in prostate cancer., We studied Se levels in whole blood, plasma and prostate of 32 PC and 40 benign prostate hyperplasia (BPH) patients and in the control group composed of 39 healthy subjects. The selenoenzyme glutathione peroxidase (GSH-Px) was also measured in the patients' red cells, plasma and prostate tissue. Se concentration in whole blood and plasma in both groups of patients was lower as compared with controls, while in prostate gland it was significantly higher in PC than in BPH patients and controls. Red cell GSH-Px activity was the same in PC patients and controls but significantly lower in BPH patients., Of particular interest was the positive correlation between tissue GPx activity and Gleason score, with this relationship achieving statistical significance among African-Americans (r = 0.67, P = 0.02)[SEP]", "label": "no"}
{"id": "converted_1430", "sentence1": "Is the UGT1A1*28 polymorphism associated with irinotecan response in Caucasians?", "sentence2": "These variants are associated with greater risk of serious toxicity., Homozygous carriers of UGT1A1*28 as well as those with additional UGT1A variants can suffer from severe irinotecan toxicity[SEP]", "label": "yes"}
{"id": "converted_3539", "sentence1": "Are gut microbiota profiles altered by irradiation?", "sentence2": "Specific Members of the Gut Microbiota are Reliable Biomarkers of Irradiation Intensity and Lethality in Large Animal Models of Human Health., Irradiation profoundly impacted gut microbiota profiles in both animals., Our findings suggest that gut symbiont-based probiotics can be used as agents for reversing radiation-induced ecological fitness decrease.[SEP]", "label": "yes"}
{"id": "converted_2973", "sentence1": "Have yeast prions become important models for the study of the basic mechanisms underlying human amyloid diseases?", "sentence2": "Endogenous yeast amyloids that control heritable traits and are frequently used as models for human amyloid diseases are termed yeast prions, Fibrous cross-β aggregates (amyloids) and their transmissible forms (prions) cause diseases in mammals (including humans) and control heritable traits in yeast. , These infectious yeast amyloidoses are outstanding models for the many common human amyloid-based diseases that are increasingly found to have some infectious characteristics., Yeast prions (infectious proteins) were discovered by their outré genetic properties and have become important models for an array of human prion and amyloid diseases., Yeast prions are models for both rare mammalian prion diseases and for several very common amyloidoses such as Alzheimer's disease, type 2 diabetes, and Parkinson's disease. , Yeast prions are important models for human amyloid diseases in general, particularly because new evidence is showing infectious aspects of several human amyloidoses not previously classified as prions. , Mechanism of amyloid formation is critical for a complete understanding of the yeast prion phenomenon and human amyloid-related diseases. , Yeast prions are important models for human amyloid diseases in general, particularly because new evidence is showing infectious aspects of several human amyloidoses not previously classified as prions., Endogenous yeast amyloids that control heritable traits and are frequently used as models for human amyloid diseases are termed yeast prions., Mechanism of amyloid formation is critical for a complete understanding of the yeast prion phenomenon and human amyloid-related diseases., Here we summarize the results of studies of prions of the yeast Saccharomyces cerevisiae and of the use of yeast model for investigation of some human amyloidoses, such as prion diseases, Alzheimer's, Parkinson's, and Huntington's diseases., Yeast prions increasingly are serving as models for the understanding and treatment of many mammalian amyloidoses., Yeast prions, based on self-seeded highly ordered fibrous aggregates (amyloids), serve as a model for human amyloid diseases., These infectious yeast amyloidoses are outstanding models for the many common human amyloid-based diseases that are increasingly found to have some infectious characteristics.<br>, The yeast system has provided considerable insight into the biology of amyloid and prions., Yeast prions are important models for human amyloid diseases in general, particularly because new evidence is showing infectious aspects of several human amyloidoses not previously classified as prions., We also review studies of the roles of chaperones, aggregate-collecting proteins, and other cellular components using yeast that have led the way in improving the understanding of similar processes that must be operating in many human amyloidoses.[SEP]", "label": "yes"}
{"id": "converted_2877", "sentence1": "Can enasidenib be used for the treatment of acute myeloid leukemia?", "sentence2": "In August 2017, the United States Federal Drug Administration (FDA) approved enasidenib (Idhifa, Celgene/Agios) for adults with relapsed and refractory acute myelogenous leukemia (AML) with an IDH2 mutation. [SEP]", "label": "yes"}
{"id": "converted_3269", "sentence1": "Is Li–Fraumeni syndrome a rare, autosomal recessive, hereditary disorder that predisposes carriers to cancer development?", "sentence2": "Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome inherited in an autosomal dominant fashion that involves a germline mutation of tumor protein 53 (TP53). , Li-Fraumeni syndrome (LFS), a multiorgan cancer predisposition caused by germline TP53 mutations, confers significant cancer risks for young people (15-39 years). Yet evidence of how individuals experience this condition and the psychosocial implications are lacking. Therefore, this systematic review assessed the psychosocial implications of living with, or at risk of, an autosomal dominant condition as a young person, to, Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disorder caused by a mutation in the p53 gene., Li-Fraumeni syndrome (LFS) is an autosomal dominant disorder occurring at a young age that predisposes individuals to multiple forms of cancer and to a heterogeneous spectrum of malignancies., Li-Fraumeni syndrome (LFS) is a rare hereditary autosomal dominant cancer disorder., Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer disorder., Li-Fraumeni syndrome (LFS) is a rare, autosomal dominant, hereditary cancer predisposition disorder., Li-Fraumeni syndrome is a rare autosomal dominant cancer predisposition syndrome., Li-Fraumeni syndrome is an autosomal dominant disorder that is characterized by various types of cancer in childhood and adult cases., Li-Fraumeni syndrome (LFS) is a rare hereditary cancer syndrome associated with an autosomal dominant mutation inheritance in the TP53 tumor suppressor gene and a wide spectrum of cancer diagnoses., The Li-Fraumeni syndrome is an autosomal dominant disorder characterized by a high risk of developing osteosarcoma and has been found in up to 3% of children with osteosarcoma., Li-Fraumeni syndrome (LFS) is a rare, autosomal dominant, hereditary cancer predisposition disorder., Li-Fraumeni syndrome (LFS) is an inherited, autosomal-dominant condition that predisposes individuals to a wide-spectrum of tumors at an early age., The Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary disorder associated with different tumor types in childhood and young adults.[SEP]", "label": "no"}
{"id": "converted_1965", "sentence1": "Is butterfly rash a symptom of Systemic lupus erythematosus?", "sentence2": "Diagnosing SLE can be challenging because of the myriad of clinical features and substantial variability between patients. Cutaneous involvement is present in about 60% of cases and typically manifests as a malar or butterfly rash., The prevalence of systemic lupus erythematosus (SLE) is 28 per 100,000. , We report a 12 years old female patient with an overlap syndrome involving autoimmune hepatitis (AIH) and systemic lupus erythematosus (SLE). The patient presented with jaundice, hepatosplenomegaly, malaise, polyarthralgia, arthritis and butterfly rash on the face., Some of the clinical characteristics of SLE patients observed were nephritis (53.7%), fever (53.26%), neuropsychological disorder (36.18%), malar/butterfly rash (27.6%), pulmonary disorder (22.6%), photosensitivity (21.6%), cardiac involvement (21.1%) and oral ulcers (19.09%). , Systemic lupus erythematosus and infections: a retrospective study in Saudis., The prevalence of the following manifestations was significantly higher for pediatric than for adult-onset disease including: lupus nephritis (43% pediatric vs 26.4% for adult-onset), hematological disorders (57% vs 36.4%), photosensitivity (20% vs 9%), butterfly rash (61% vs 35.5%) and mucosal ulceration (11.4% vs 4%). , Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease with highest prevalence among women of childbearing age. , We described a unique case of a 25-year-old Arab young woman who was diagnosed with SLE, depending on clinical, laboratory investigations and after she had fulfilled the diagnostic criteria for SLE and had presented the following findings: constitutional findings (fatigue, fever, and arthralgia); dermatologic finding (photosensitivity and butterfly rash); chronic renal failure (proteinuria up to 400 mg in 24 hours); hematologic and antinuclear antibodies (positivity for antinuclear factor (ANF), anti-double-stranded DNA antibodies, direct Coombs, ANA and anti-DNA, low C4 and C3, aCL by IgG and IgM). , Grade 1 and 2-3 inflammatory process occurred in 53 (63%) and 31 (37%) patients respectively. Symptom complexes \"systemic inflammation\", \"butterfly rash\", \"wrist petechiae\", \"enanthema of the oral mucous membrane\", and other lesions were regarded as the markers of SLE activity. , Systemic lupus erythematosus (SLE) remains a challenging medical problem. , Rembrandt's Maria Bockenolle has a butterfly rash and digital deformities: overlapping syndrome of rheumatoid arthritis and systemic lupus erythematosus., A butterfly rash on the patient's face suggested a diagnosis of systemic lupus erythematosus (SLE)., A butterfly rash on the patients face suggested a diagnosis of systemic lupus erythematosus (SLE), The diagnosis of SLE could be excluded and the butterfly rash attributed to a laminar hemorrhage, an ecchymosis due to the autoimmune thrombocytopenia., We describe a case of KD who developed a typical butterfly rash, reminiscent of SLE. , The diagnosis of SLE was made 22 years ago based on Raynaud's phenomenon, butterfly rash, hair loss, photosensitivity and positive antinuclear antibody. , Symptom complexes \"systemic inflammation\", \"butterfly rash\", \"wrist petechiae\", \"enanthema of the oral mucous membrane\", and other lesions were regarded as the markers of SLE activity., Rembrandt's Maria Bockenolle has a butterfly rash and digital deformities: overlapping syndrome of rheumatoid arthritis and systemic lupus erythematosus., To investigate, various unspecific, but otherwise typical clinical symptoms of skin and mucous membranes that arise in SLE patients other than those defined as SLE criteria such as butterfly rash, chronic cutaneous lupus erythematosus, oral ulcers, and increased photosensitivity.[SEP]", "label": "yes"}
{"id": "converted_3033", "sentence1": "Is there a link between BCL11B haploinsufficiency and syndromic neurodevelopmental delay?", "sentence2": "BCL11B mutations in patients affected by a neurodevelopmental disorder with reduced type 2 innate lymphoid cells., Using massively parallel sequencing we identified 13 patients bearing heterozygous germline alterations in BCL11B. Notably, all of them are affected by global developmental delay with speech impairment and intellectual disability; however, none displayed overt clinical signs of immune deficiency. Six frameshift mutations, two nonsense mutations, one missense mutation, and two chromosomal rearrangements resulting in diminished BCL11B expression, arose de novo. A further frameshift mutation was transmitted from a similarly affected mother. Interestingly, the most severely affected patient harbours a missense mutation within a zinc-finger domain of BCL11B, probably affecting the DNA-binding structural interface, similar to the recently published patient. Furthermore, the most C-terminally located premature termination codon mutation fails to rescue the progenitor cell proliferation defect in hippocampal slice cultures from Bcl11b-deficient mice. Concerning the role of BCL11B in the immune system, extensive immune phenotyping of our patients revealed alterations in the T cell compartment and lack of peripheral type 2 innate lymphoid cells (ILC2s), consistent with the findings described in Bcl11b-deficient mice. Unsupervised analysis of 102 T lymphocyte subpopulations showed that the patients clearly cluster apart from healthy children, further supporting the common aetiology of the disorder. Taken together, we show here that mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodevelopmental delay. In addition, we suggest that missense mutations affecting specific sites within zinc-finger domains might result in distinct and more severe clinical outcomes., Taken together, we show here that mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodevelopmental delay. , Taken together, we show here that mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodevelopmental delay.[SEP]", "label": "no"}
{"id": "converted_2451", "sentence1": "Can multiple myeloma patients develop hyperviscosity syndrome?", "sentence2": "Multiple myeloma (MM) is an immedicable malignancy of the human plasma cells producing abnormal antibodies (also referred to as paraproteins) leading to kidney problems and hyperviscosity syndrome. , This skin condition may be observed in patients with the following condtions, such as primary polycythemic hyperviscosity (polycythemia, thrombocytemia) treated with hydroxyurea, primary plasma hyperviscosity (multiple myeloma, cryoglobulinemia, cryofibrinogenemia, dysfibrinogenemia, and connective tissue diseases), primary sclerocythemic hyperviscosity (hereditary spherocytosis, thalassemia, and sickle cell disease). ,  A 73-year-old woman with known MM who received little treatment for several years, presented secondary to dysarthria and at first was thought to have hyperviscosity syndrome. ,  After a comprehensive evaluation ruled out common causes of acute renal failure, the patient underwent testing with a bone survey, urine protein electrophoresis (UPEP), serum protein electrophoresis (SPEP), and immunoelectrophoresis for suspected plasma cell dyscrasia and received plasmapheresis for hyperviscosity syndrome and nephrotoxicity, which resulted in improved renal function. Lab results showed monoclonal gammopathy, elevated serum free light chains, and Bence Jones protein in the urine with a follow-up bone marrow biopsy indicating plasma cell dyscrasia. The patient received a diagnosis of multiple myeloma (MM) and was started on chemotherapy and immunosuppression. , Plasmapheresis (PE) is recommended for patients with hyperviscosity syndrome or cast nephropathy presented with AKI, which may help to increase the dialysis-independency., Multiple myeloma is a neoplastic plasma-cell disorder resulting from malignant plasma cells in the bone marrow. It can cause a hyperviscosity syndrome secondary to the paraproteinaemia associated with the disease. The increased hyperviscosity can lead to retinal vein occlusions and other ocular problems that may challenge clinicians. , Etiologies are various but symptomatic hyperviscosity is more common in Waldenström's macroglobulinemia and multiple myeloma. , Double filtration plasmapheresis in a dog with multiple myeloma and hyperviscosity syndrome., A 12 year old, 38 kg, mix-breed, intact male dog presented with a 20 day history of clinical signs consistent with hyperviscosity syndrome secondary to multiple myeloma. , The present study reported for the first time the use of double filtration plasmapheresis to reduce clinical signs of hyperviscosity syndrome in a dog with multiple myeloma., An otherwise healthy young man presents with bilateral CRVO as the first sign of hyperviscosity syndrome in the setting of new multiple myeloma.,  In haematology the most common indication for plasmapheresis is the supportive treatment of multiple myeloma. The procedure is performed in patients with high protein levels endangered with hyperviscosity syndrome., Five to 10 percent of patients with multiple myeloma are suffered from the hyperviscosity syndrome because of increased serum viscosity due to the presence of myeloma protein., Plasmapheresis is known as an efficient method for rapid improvement of the hyperviscosity syndrome, and double filtration plasmapheresis is most commonly used for plasma exchange of multiple myeloma patients in our country., PE is the most effective method in the treatment of hyperviscosity syndrome often seen with multiple myeloma and Waldenström's macroglobulinemia, and it is therapy of choice for this complication., Patients with multiple myeloma who have complications secondary to hyperviscosity are treated by chemotherapy and/or plasmapheresis.[SEP]", "label": "yes"}
{"id": "converted_2868", "sentence1": "Is pazopanib an effective treatment of glioblastoma?", "sentence2": "RESULTS: The six-month progression-free survival (PFS) rates in phase II (n = 41) were 0% and 15% in the PTEN/EGFRvIII-positive and PTEN/EGFRvIII-negative cohorts, respectively, leading to early termination. , Single-agent pazopanib did not prolong PFS in this patient population but showed in situ biological activity as demonstrated by radiographic responses.[SEP]", "label": "no"}
{"id": "converted_2", "sentence1": "Is the protein Papilin secreted?", "sentence2": "Using expression analysis, we identify three genes that are transcriptionally regulated by HLH-2: the protocadherin cdh-3, and two genes encoding secreted extracellular matrix proteins, mig-6/papilin and him-4/hemicentin. , We found that mig-6 encodes long (MIG-6L) and short (MIG-6S) isoforms of the extracellular matrix protein papilin, each required for distinct aspects of DTC migration. Both MIG-6 isoforms have a predicted N-terminal papilin cassette, apilins are homologous, secreted extracellular matrix proteins which share a common order of protein domains. , The TSR superfamily is a diverse family of extracellular matrix and transmembrane proteins, many of which have functions related to regulating matrix organization, cell-cell interactions and cell guidance. This review samples some of the contemporary literature regarding TSR superfamily members (e.g. F-spondin, UNC-5, ADAMTS, papilin, and TRAP) where specific functions are assigned to the TSR domains., Papilins are extracellular matrix proteins , Papilin is an extracellular matrix glycoprotein ,  Collagen IV, laminin, glutactin, papilin, and other extracellular matrix proteins were made primarily by hemocytes and were secreted into the medium. , A sulfated glycoprotein was isolated from the culture media of Drosophila Kc cells and named papilin.[SEP]", "label": "yes"}
{"id": "converted_2664", "sentence1": "Is recursive splicing more common in short introns?", "sentence2": "Recent work in human and fruitfly tissues revealed that long introns are extensively processed cotranscriptionally and in a stepwise manner, before their two flanking exons are spliced together, Cutting a Long Intron Short: Recursive Splicing and Its Implications.,  Furthermore, we uncover the potential to investigate the multi-step nature of splicing, assessing various types of recursive splicing events, Recursive splicing is a process in which large introns are removed in multiple steps by re-splicing at ratchet points--5' splice sites recreated after splicing., Together, these results indicate that recursive splicing is commonly used in Drosophila, occurs in humans, and provides insight into the mechanisms by which some large introns are removed., Recursive splicing in long vertebrate genes., Moreover, the RS-sites are found in some of the longest introns across vertebrates. , The peculiarities of large intron splicing in animals., These \"large introns\" must be spliced out of the pre-mRNA in a timely fashion, which involves bringing together distant 5' and 3' acceptor and donor splice sites., Using a computational analysis of the genomic sequences, we show that vertebrates lack the proper enrichment of RP-sites in their large introns, and, therefore, require some other method to aid splicing, Subdivision of large introns in Drosophila by recursive splicing at nonexonic elements., Recursive splice sites predicted with highly stringent criteria are found at much higher frequency than expected in the sense strands of introns>20 kb, but they are found only at the expected frequency on the antisense strands, and they are underrepresented within introns<10 kb., These transcripts arise by use of two alternative transcription sites and complex alternative splicing mechanisms and encode proteins with long or short N-terminal domains, complete or incomplete GGL domains, 7 distinct C-terminal domains and a common internal domain where the RGS domain is found., These patterns of enrichment and conservation indicate that recursive splice sites are advantageous in the context of long introns., Many genes with important roles in development and disease contain exceptionally long introns, but special mechanisms for their expression have not been investigated., However, some long Drosophila melanogaster introns contain a cryptic site, known as a recursive splice site (RS-site), that enables a multi-step process of intron removal termed recursive splicing., The effect of splice site strength was context-dependent and much more significant for the 3' splice site of the longer alternative intron than for the 3' splice site of the shorter alternative intron and the common 5' splice sites; it was also more significant in the rat minigene than in the mouse minigene., Cutting a Long Intron Short: Recursive Splicing and Its Implications., Recursive splicing in long vertebrate genes.[SEP]", "label": "no"}
{"id": "converted_3370", "sentence1": "Is Nivolumab (Opdivo) a PD-L1 inhibitor?", "sentence2": "Fatal Myocarditis Following Treatment with the PD-1 Inhibitor Nivolumab,  PD-1 inhibitor nivolumab (Opdivo), programmed cell death protein 1 (PD-1)-blocking antibodies nivolumab or pembrolizumab , An improvement in the understanding of the role of the immune system in tumor immunosurveillance has led to the development of the programmed death-1 ( PD-1 ) immune checkpoint inhibitor nivolumab ( Opdivo) . , Nivolumab (Opdivo(®); Nivolumab BMS™) was the first programmed death (PD)-1 immune checkpoint inhibitor to be approved for use in advanced, squamous non-small cell lung cancer (NSCLC) following prior chemotherapy.[SEP]", "label": "no"}
{"id": "converted_4040", "sentence1": "Is there an upper limit on the functional fraction of the human genome?", "sentence2": "Mutational load considerations lead to the conclusion that the functional fraction within the human genome cannot exceed 25%, and is probably considerably lower.[SEP]", "label": "yes"}
{"id": "converted_4512", "sentence1": "Does p85α homodimerize?", "sentence2": "homodimerized p85α, p110α-free p85α homodimerizes, homodimeric but not monomeric p85α[SEP]", "label": "yes"}
{"id": "converted_1854", "sentence1": "Is vortioxetine effective for treatment of depression?", "sentence2": "Vortioxetine is the most recently approved medication for the treatment of major depressive disorder (MDD). , [Vortioxetine: a new antidepressant to treat depressive episodes]., Vortioxetine is a new antidepressant, which mechanism of action is multimodal, targeting the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT3, 5-HT7 receptors and the serotonin transporter (5-HTT). , In short-term studies (8 weeks), vortioxetine is more efficacious than placebo in decreasing depressive symptoms as measured by the MADRS total score, response rate (vortioxetine: 53.2% vs placebo: 35.2%) and remission rate (vortioxetine: 29.2% vs placebo: 19.3%). In a long-term study (52 weeks), vortioxetine is also superior to placebo in preventing relapses and recurrences. Moreover, in second line treatment, after failure of a first line selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrin reuptake inhibitor (SNRI), vortioxetine is superior to agomelatine in improving depressive symptoms and achieving response and remission. , Against this background, we feature the novel antidepressants vortioxetine, vilazodone and milnacipran/levomilnacipran with regard to their serotonin receptor targets such as the 5-HT1A, 5-HT3 and 5-HT7 which may account for their specific effects on certain symptoms of depression (e.g. cognition and anxiety) as well as a characteristic side-effect profile., CONCLUSION: Vortioxetine dominated venlafaxine XR in South Korea and is a relevant treatment option for MDD patients initiating or switching therapy., Vortioxetine: a New Treatment for Major Depressive Disorder., INTRODUCTION: Vortioxetine is a structurally novel medication that has recently been approved for treatment of major depressive disorder (MDD)., EXPERT OPINION: Results of placebo-controlled trials suggest efficacy and an overall safety profile comparable to existing first-line antidepressants. , The authors suggest that vortioxetine is currently a good second-line antidepressant option and shows promise, pending additional long-term data, to become a first-line antidepressant option., Clinical studies indicate that vortioxetine is effective in the treatment of major depression, though there is no suggestion of superiority over active comparators., Vortioxetine has been effective in various animal models of depression and anxiety and clinical studies have shown the antidepressant and antianxiety properties of vortioxetine in a dose range of 5-20 mg/day., Vortioxetine was significantly more effective than was placebo, with a standardized mean difference (SMD) of -0.118 (95% CIs, -0.203 to -0.033, P = 0.007)., Vortioxetine for the treatment of depression., Vortioxetine for the treatment of major depression., Vortioxetine (Lu-AA-21004; 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine hydrobromide) is a novel orally active molecule that is being investigated by Lundbeck and Takeda for the treatment of major depression and generalized anxiety disorders., Vortioxetine (Lu AA21004) is a multi-modal antidepressant in clinical development for the treatment of major depressive disorder (MDD)., A randomized, double-blind, fixed-dose study comparing the efficacy and tolerability of vortioxetine 2.5 and 10 mg in acute treatment of adults with generalized anxiety disorder., Vortioxetine has been effective in various animal models of depression and anxiety and clinical studies have shown the antidepressant and antianxiety properties of vortioxetine in a dose range of 5-20 mg/day., Secondary endpoints included response and remission rates, anxiety symptoms(Hamilton Anxiety Rating Scale), Clinical Global Impression, overall functioning (Sheehan Disability Scale), health-related quality of life(EuroQol 5 Dimensions), productivity (work limitation questionnaire) and family functioning (Depression and Family Functioning Scale).RESULTS: Primary endpoint noninferiority was established and vortioxetine (n = 252) was superior to agomelatine (n = 241) by 2.2 MADRS points (p<0.01)., Vortioxetine (Lu AA21004) is an antidepressant with a mechanism of action thought to be related to a combination of 2 pharmacologic actions: direct modulation of several receptors and inhibition of the serotonin transporter.To evaluate the efficacy of vortioxetine 10 and 20 mg once daily in outpatients with major depressive disorder.This 8-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study was conducted from July 2010 to January 2012 among adults with a primary diagnosis of recurrent major depressive disorder (DSM-IV-TR).Eligible subjects were randomized in 1:1:1 ratio to 1 of 3 treatment arms: vortioxetine 10 mg, vortioxetine 20 mg, or placebo once daily for 8 weeks., Vortioxetine (Lu AA21004) is a new antidepressant that combines a number of neurotransmitter reuptake and receptor effects that have been thought to predict efficacy as a treatment for depressive and anxiety disorders.This review summarizes the pharmacology and neurobiology of vortioxetine, In the study of elderly patients, vortioxetine 5 mg (n = 136) improved 12-item Health Status Questionnaire scores significantly more than placebo (n = 148) for the domains of health perception (10.4, P &lt; 0.0001, SES of 0.54), mental health (7.9, P &lt; 0.001, SES of 0.44), and energy (6.4, P &lt; 0.05, SES of 0.28) (FAS, mixed model for repeated measures).Vortioxetine yielded significant, meaningful HRQoL improvements in 6 MDD studies of 6 to 8 weeks duration., All references included were published between 1999 and 2014.All studies that included humans and were published in English, with data describing vortioxetine for the treatment of MDD, were reviewed.Vortioxetine is a novel multimodal antidepressant agent, which inhibits the 5-HT transporter protein, acts as a 5-HT3 antagonist, 5-HT1A receptor agonist, 5-HT7 receptor antagonist, and a partial agonist of the 5-HT1B receptor, Vortioxetine has been effective in various animal models of depression and anxiety and clinical studies have shown the antidepressant and antianxiety properties of vortioxetine in a dose range of 5-20 mg/day, Vortioxetine is an antidepressant with multimodal activity which has shown efficacy in major depressive disorder (MDD) patients in six of ten short-term, randomized, placebo-controlled trials (completed end 2012).We performed meta-regression analyses to indirectly compare vortioxetine to seven marketed antidepressants with different mechanisms of action, Data were available from 51 human trials involving vortioxetine, and included a total of 7,666 healthy volunteers and patients with a diagnosis of major depressive disorder (MDD) or generalized anxiety disorder who were exposed to at least 1 dose of vortioxetine for a total of 2,743 patient-years.Vortioxetine was effective in treating MDD in the United States at a dose of 20 mg/d, Vortioxetine is a recently approved multimodal antidepressant with anxiolytic properties in preclinical studies.This double-blind, placebo-controlled study assessed the efficacy and tolerability of vortioxetine in subjects with a primary diagnosis of generalized anxiety disorder.Subjects (n = 457) were randomized 1:1:1 to treatment with placebo or vortioxetine 2.5 or 10 mg once daily, There was a significant difference for nausea between the two groups (OR=3.01, 95 % CI=2.22-4.09, Z=7.08, P=0.00001), but no significant differences were observed for the other four adverse effects.CONCLUSIONS: For the treatment of major depressive disorder, our results show that a dose of 5 mg/day vortioxetine was more effective, but more easily induced nausea, compared to placebo., The efficacy and safety of 5 mg/d Vortioxetine compared to placebo for major depressive disorder: A meta-analysis., Vortioxetine: a meta-analysis of 12 short-term, randomized, placebo-controlled clinical trials for the treatment of major depressive disorder., Vortioxetine in the treatment of adult patients with major depressive disorder: a meta-analysis of randomized double-blind controlled trials., Vortioxetine has been effective in various animal models of depression and anxiety and clinical studies have shown the antidepressant and antianxiety properties of vortioxetine in a dose range of 5-20 mg/day. , Clinical studies indicate that vortioxetine is effective in the treatment of major depression, though there is no suggestion of superiority over active comparators., The incidence of treatment-emergent adverse events was significantly higher in the duloxetine group than in the vortioxetine group.Duloxetine was more effective but less well-tolerated than vortioxetine in MDD., There was no significant difference in discontinuation rates between vortioxetine and comparators owing to inefficacy (OR 0.983, 95% CI 0.585 to 1.650), whereas discontinuation owing to AEs was significantly less common in the vortioxetine than in the comparator group (OR 0.728, 95% CI 0.554 to 0.957).Studies examining the role of vortioxetine in the treatment of MDD are limited.Although our results suggest that vortioxetine may be an effective treatment option for MDD, they should be interpreted and translated into clinical practice with caution, as the meta-analysis was based on a l, We performed a meta-analysis to increase the statistical power of these studies and enhance our current understanding of the role of vortioxetine in the treatment of MDD.We performed an extensive search of databases and the clinical trial registry., BACKGROUND: Vortioxetine is a recently approved multimodal antidepressant with anxiolytic properties in preclinical studies.OBJECTIVE: This double-blind, placebo-controlled study assessed the efficacy and tolerability of vortioxetine in subjects with a primary diagnosis of generalized anxiety disorder.METHODS: Subjects (n = 457) were randomized 1:1:1 to treatment with placebo or vortioxetine 2.5 or 10 mg once daily., Vortioxetine significantly improved objective and subjective measures of cognitive function in adults with recurrent MDD and these effects were largely independent of its effect on improving depressive symptoms., Furthermore, a statistically significant number of patients with MDD who were on vortioxetine have achieved a greater than or equal to 50% reduction in depression symptoms from baseline., BACKGROUND: Vortioxetine is a novel multimodal compound that has recently been approved by the FDA for the treatment of major depressive disorder (MDD)., Although our results suggest that vortioxetine may be an effective treatment option for MDD, they should be interpreted and translated into clinical practice with caution, as the meta-analysis was based on a limited number of heterogeneous RCTs.., Vortioxetine is an effective agent for the treatment of MDD, but it does not have any clear advantages over other available treatment options.., Vortioxetine was significantly more effective than placebo for acute treatment of major depressive disorder (MDD)., Duloxetine was more effective but less well-tolerated than vortioxetine in MDD., Vortioxetine is an orally administered small molecule developed by Lundbeck A/S for the once-daily treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD). Vortioxetine received its first global approval for MDD in the USA in September 2013 and regulatory approval for its use in this indication in the EU (where it has received a positive opinion) and Canada is awaited. , This article summarizes the milestones in the development of vortioxetine leading to this first approval for MDD., Vortioxetine was efficacious and well tolerated in the treatment of patients with major depressive disorder., On the primary efficacy endpoint, both vortioxetine doses were statistically significantly superior to placebo, with a mean difference to placebo (n=158) of -5.5 (vortioxetine 15 mg, P<0.0001, n=149) and -7.1 MADRS points (vortioxetine 20 mg, P<0.0001, n=151)., The change in the severity of depressive and anxiety symptoms was maintained throughout the study as reflected by a 24-item Hamilton Depression Scale total score of 8.2 at week 52 (from 17.6 at open-label baseline) in the observed case data set., Vortioxetine is a multi-modal antidepressant that functions as a human 5-HT3A and 5-HT7 receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist, and inhibitor of the serotonin transporter. , Approval for the treatment of MDD was based on a clinical development programme that included six positive 6-8 week studies, including one study in elderly people, and one positive maintenance study in adults., Vortioxetine represents another option for the treatment of MDD. , The multimodal compounds vortioxetine and vilazodone are examples of this approach with diverse mechanisms, and their different clinical effects will provide valuable insights into serotonergic modulation of glutamate transmission for the potential treatment of depression and associated cognitive dysfunction., Two new antidepressant drugs, vilazodone (marketed in the USA) and vortioxetine (in development) incorporate partial 5-HT1A-R agonist properties with SERT blockade., Novel drugs in development include those that combine multiple simultaneous pharmacologic mechanisms in addition to SERT inhibition within the same molecule, such as vilazodone (combining 5HT1A partial agonism with SERT inhibition), triple reuptake inhibitors (combining norepinephrine and dopamine reuptake inhibition with SERT inhibition), and vortioxetine, a multimodal antidepressant combining actions at the G protein receptor mode (5HT1A and 5HT1B partial agonism and 5HT7 antagonism), at the ion channel mode (5HT3 antagonism) as well as the neurotransmitter transporter mode (SERT inhibition). , In this study of adults with MDD treated for 8 weeks with vortioxetine 2.5 mg or 5 mg per day, reductions in depression symptoms were not statistically significant compared with placebo. , However, on the basis of these findings, vortioxetine (2.5, 5, 10 mg/day) demonstrated a favourable safety and tolerability profile and maintained effectiveness over 12 months of treatment. , In this study of adults with MDD, 5 mg vortioxetine did not differ significantly from placebo in reducing depression symptoms after 6 wk of treatment., After 8 weeks of treatment with Lu AA21004 10 mg, there was a significant reduction in HDRS-24 total score compared with placebo in adults with MDD., In conclusion, Lu AA21004 was efficacious and well tolerated in the treatment of elderly patients with recurrent major depressive disorder., Thus, Lu AA21004 was effective in preventing relapse of MDD and was well tolerated as maintenance treatment.,  Findings on secondary outcome measures, using MMRM instead of LOCF, were supportive of likely efficacy for Lu AA21004 5mg and 10mg and duloxetine. , In this study, treatment with 5 mg and 10 mg Lu AA21004 for 6 wk was efficacious and well tolerated in patients with MDD., Results from phase II clinical trials have reported improvement in depression and anxiety symptoms after 6 weeks of treatment. [SEP]", "label": "yes"}
{"id": "converted_4", "sentence1": "Is RANKL secreted from the cells?", "sentence2": "Osteoprotegerin (OPG) is a soluble secreted factor that acts as a decoy receptor for receptor activator of NF-κB ligand (RANKL) , Osteoprotegerin (OPG) is a secreted glycoprotein and a member of the tumor necrosis factor receptor superfamily. It usually functions in bone remodeling, by inhibiting osteoclastogenesis through interaction with a receptor activator of the nuclear factor κB (RANKL)., e RANKL/OPG ratio secreted by osteoblasts increased and RANK expression by osteoclasts increased, leading to increased osteoclastogenesis, Osteoprotegerin (OPG) is an essential secreted protein in bone turnover due to its role as a decoy receptor for the Receptor Activator of Nuclear Factor-kB ligand (RANKL) in the osteoclasts, thus inhibiting their differentiation, We identify a TNFSF11 transcript variant that extends the originally identified transcript encoding secreted RANKL., Activated human T cells express alternative mRNA transcripts encoding a secreted form of RANKL., OPG, on the other hand, is secreted by osteoblast as a decoy receptor for RANKL, prevents RANKL from binding to RANK and thus prevents bone resorption, Receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) are cytokines predominantly secreted by osteoblasts and play a central role in differentiation and functional activation of osteoclasts, Although B. abortus-activated T cells actively secreted the pro-osteoclastogenic cytokines RANKL and IL-17, osteoclastogenesis depended on IL-17, because osteoclast generation induced by Brucella-activated T cells was completely abrogated when these cells were cultured with BMMs from IL-17 receptor knockout mice. ,  osteoclastogenesis and bone destruction in autoimmune arthritis. We isolated human fibroblasts from RA, pyrophosphate arthropathy (PPA) and osteoarthritis (OA) patients and analyzed their RANKL/OPG expression profile and the capacity of their secreted factors to induce osteoclastogenesis., Osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) are cytokines predominantly secreted by osteoblasts and play critical roles in the differentiation and function of osteoclasts. [SEP]", "label": "yes"}
{"id": "converted_3791", "sentence1": "Do nematodes contain a CTCF gene?", "sentence2": "Our findings show that CTCF and possibly chromatin insulation are present in basal nematodes. We suggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans., The most highly enriched motif (LM1) corresponds to the X-box motif known from yeast and nematode. ,  show that three ZF proteins from three basal nematodes cluster together with known CTCF proteins whereas no zinc finger protein of C. elegans and other derived nematodes does so.CO, SULTS: While orthologs for other insulator proteins were absent in all 35 analysed nematode species, we find orthologs of CTCF in a subset of nematodes. A, of CTCF from several nematodes is paralleled by a loss of two of its interactors, the polycomb repressive complex subunit SuZ12 and the multifunctional transcription factor TYY1. In contrast to earlier st, LUSION: Our findings show that CTCF and possibly chromatin insulation are present in basal nematodes. We , uggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans. We , ESULTS: While orthologs for other insulator proteins were absent in all 35 analysed nematode species, we find orthologs of CTCF in a subset of nematodes. ,  suggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans. W, e show that three ZF proteins from three basal nematodes cluster together with known CTCF proteins whereas no zinc finger protein of C. elegans and other derived nematodes does so.CO, o investigate the pattern of CTCF occurrence in nematodes, we performed phylogenetic analysis with the ZF protein sets of completely sequenced nematodes. , r findings show that CTCF and possibly chromatin insulation are present in basal nematodes. W,  propose a switch in the regulation of gene expression during nematode evolution, from the common vertebrate and insect type involving distantly acting regulatory elements and chromatin insulation to a so far poorly characterised mode present in more derived nematodes. H, We therefore searched in nematodes for orthologs of proteins that are involved in chromatin insulation.R, The unique secondary loss of CTCF from several nematodes is paralleled by a loss of two of its interactors, the polycomb repressive complex subunit SuZ12 and the multifunctional transcription factor TYY1.[SEP]", "label": "yes"}
{"id": "converted_1507", "sentence1": "Do thyroid hormone receptors change after brain injury?", "sentence2": "For example, the T3 receptor alpha was predominantly expressed in stroke-tissue, indicating that regeneration of nerves in stroke tissue may be facilitated by increased T3 receptor alpha expression., TRα expression was also increased in human infants with IVH. , Thus, in infants with IVH the combined elevation in deiodinase-3 and reduction in deiodinase-2 decreases TH signaling that can be worsened by an increase in unliganded TRα. , A rapid increase of the total number of binding sites for T3 appeared within 30 min of ischemia and reached over 40% by 3 h. During the same 3-h period, the relative binding affinity was reduced by 25%. Upon recirculation after 30 min or 3 h of ischemia, a rapid reversal of measured T3 binding sites occurred, which progressed to 20-30% below the control value by the recirculation period of 3 h. [SEP]", "label": "yes"}
{"id": "converted_3962", "sentence1": "Is MIS-C or Multisystem  Inflammatory syndrome in children a complication of Covid-19?", "sentence2": "Much remains unknown about the risk factors, pathogenesis, prognosis, and specific therapy for this emerging manifestation of COVID-19 known as Multisystem Inflammatory Syndrome in Children (MIS-C)., Multisystem Inflammatory Syndrome in Children During the Coronavirus 2019 Pandemic: A Case Series, COVID-19 and Multisystem Inflammatory Syndrome in Latin American Children,  This study aims to assess COVID-19 and Multisystem Inflammatory Syndrome (MIS-C) in Latin American children,, A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation., We apply systems-level analyses of blood immune cells, cytokines, and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2, and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage., OBJECTIVE: Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease (COVID-19) is a rare and challenging diagnosis requiring early treatment., This syndrome is now known as either \"Pediatric Inflammatory Multisystem Syndrome temporally related with COVID-19\" (PIMS-TS) (1), or Multisystem Inflammatory Syndrome in Children (MIS-C) (2) and is currently considered a rare post-COVID-19 complication which, in a minority of cases, can lead to death., Multisystem Inflammatory Syndrome in Children (MIS-C) associated with Coronavirus Disease 2019 (COVID-19) is a newly recognized condition in which children with recent SARS-CoV-2 infection present with a constellation of symptoms including hypotension, multiorgan involvement, and elevated inflammatory markers. Thes, Background: Kawasaki-like syndrome occurring in children during the COVID-19 pandemic has been labelled multisystem inflammatory syndrome in children (MIS-C) by the CDC and paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS) by , em inflammatory syndrome in children (MIS-C), a possible complication of COVID-19, has been described as a hyperinflammatory condition with multiorgan involvement similar to that in Kawasaki disease or toxic shock syndrome in children with evidence of SARS-CoV-2 infection. This revie, BACKGROUND: A small subset of pediatric patients develop a rare syndrome associated with Coronavirus Disease 2019 (COVID-19) infection called multisystem inflammatory syndrome in childr,  adults. However, the newly described multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been associated with cardiac complicat, BACKGROUND: Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection i, OBJECTIVE: Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease (COVID-19) is a rare and challenging diagnosis requiring early tr, Background: Multisystem inflammatory syndrome in children (MIS-C), also known as pediatric inflammatory multisystem syndrome, is a new dangerous childhood disease that is temporally associated with coronavirus disease 2019 (, Recent COVID-19 publications describe a variety of clinical presentations including an asymptomatic state, pneumonia, a hemophagocytic lymphohistiocytosis like syndrome, Multisystem Inflammatory Syndrome in Children (MIS-C) but, also called Pediatric Inflammatory Multisystem Syndrome-Toxic Shock (PIMS-TS), Kawasaki Disease, and myocarditis., We analyzed peripheral blood immune responses in hospitalized SARS-CoV-2 infected pediatric patients (pediatric COVID-19) and patients with MIS-C. MIS-C patients had patterns of T cell-biased lymphopenia and T cell activation similar to severely ill adults, and all patients with MIS-C had SARS-CoV-2 spike-specific antibodies at admission., Multisystem inflammatory syndrome in children (MIS-C), a possible complication of COVID-19, has been described as a hyperinflammatory condition with multiorgan involvement similar to that in Kawasaki disease or toxic shock syndrome in children with evidence of SARS-CoV-2 infection., It includes a discussion of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, as well as other aspects of the COVID-19 pandemic that are affecting children and families, such as poisonings, childhood immunizations, mental health, nonaccidental trauma, and neglect., Importance: To date, no study has characterized the mucocutaneous features seen in hospitalized children with multisystem inflammatory syndrome in children (MIS-C) or the temporal association of these findings with the onset of systemic symptoms.Objective: To describe the mucocutaneous findings seen in children with MIS-C during the height of the coronavirus disease 2019 (COVID-19) pandemic in New York City in 2020.Design, Setting, and Participants: A retrospective case series was conducted of 35 children admitted to 2 hospitals in New York City between April 1 and July 14, 2020, who met Centers for Disease Control and Prevention and/or epidemiologic criteria for MIS-C.Main Outcomes and Measures: Laboratory and clinical characteristics, with emphasis on mucocutaneous findings, of children who met criteria for MIS-C., This condition, since defined as the multisystem inflammatory syndrome in children (MIS-C), is assumed to be a delayed immune response to coronavirus disease 2019 (COVID-19), and there are frequently cardiac manifestations of ventricular dysfunction and/or coronary artery dilation.Methods: We surveyed the inpatient MIS-C management approaches of the members of the International Kawasaki Disease Registry across 38 institutions and 11 countries.Results: Among the respondents, 56% reported using immunomodulatory treatment for all MIS-C patients, regardless of presentation., DESIGN: Children ages 0-22 years with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presenting to urgent care clinics or being hospitalized for confirmed/suspected SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) at Massachusetts General Hospital were offered enrollment in the Massachusetts General Hospital Pediatric COVID-19 Biorepository., We recently discovered a superantigen-like motif, similar to Staphylococcal enterotoxin B (SEB), near the S1/S2 cleavage site of SARS-CoV-2 Spike protein, which might explain the multisystem-inflammatory syndrome (MIS-C) observed in children and cytokine storm in severe COVID-19 patients., METHODS: An extensive search strategy was conducted by combining the terms multisystem inflammatory syndrome in children and coronavirus infection or using the term multisystem inflammatory syndrome in children in bibliographic electronic databases (PubMed, EMBASE, and CINAHL) and in preprint servers (BioRxiv.org and MedRxiv.org) following the Preferred Reporting Items for Systematic Reviews and Metaanalyses guidelines to retrieve all articles published from January 1, 2020, to July 31, 2020., Here, we show that pediatric patients with multisystem inflammatory syndrome in children (MIS-C) possess higher SARS-CoV-2 spike IgG titers compared to those with severe coronavirus disease 2019 (COVID-19), likely reflecting a longer time since onset of infection in MIS-C patients., Here, we show that pediatric patients with multisystem inflammatory syndrome in children (MIS-C) possess higher SARS-CoV-2 spike IgG titers compared to those with severe coronavirus disease 2019 (COVID-19), likely reflecting a longer time since onset of infection in MIS-C patients., Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV2 infection in otherwise healthy children., Data on multisystem inflammatory syndrome in children (MIS-C) related to coronavirus disease-19 (COVID-19) is increasing in the current COVID-19 pandemic., Introduction Multisystem inflammatory syndrome in children (MIS-C) is a unique clinical complication of SARS-CoV-2 infection observed in pediatric patients., New onset diabetes with diabetic ketoacidosis in a child with multisystem inflammatory syndrome due to COVID-19., Case presentation An eight-year-old female presented with hyperglycemia, ketosis and metabolic acidosis consistent with diabetic ketoacidosis (DKA) in the setting of fever, rash, respiratory distress, hemodynamic instability, reduced systolic function with dilation of the left anterior descending artery, and positive SARS-CoV-2 antibodies suggestive of MIS-C., However, the newly described multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been associated with cardiac complications.M, Toxic shock-like syndrome and COVID-19: Multisystem inflammatory syndrome in children (MIS-C)., Many of these cases feature a toxic shock-like syndrome or Kawasaki-like syndrome in the setting of SARS-CoV-2 positive diagnostic testing and the CDC has termed this presentation Multisystem Inflammatory Syndrome (MIS-C)., We describe a case of MIS-C in a child who presented to our Emergency Department (ED) twice and on the second visit was found to have signs of distributive shock, multi-organ injury and systemic inflammation associated with COVID-19., PURPOSE OF REVIEW: Here we summarize current knowledge about multisystem inflammatory syndrome in children (MIS-C), a presumed postinfectious inflammatory condition that has emerged as an important COVID-19-associated complication, to help clinicians identify and manage cases.RECENT FINDINGS: Clinical presentation of MIS-C is do, MIS-C is a rare yet severe and highly critical complication of COVID-19 infection in pediatrics, leading to serious and life-threatening illnesses., BACKGROUND: A multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C) has recently been described.OBJECTIVE: To evaluate imaging findings of MIS-C associated with COVID-19.SUBJECTS AND METHODS: Imaging studies and medical records of sixteen patients (0-20 years) admit, BACKGROUND: Recently, cases of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 have been reporte, Recent reports have described a secondary Multisystem Inflammatory Syndrome in Children (MIS-C) after a prior COVID-19 infection that often has features of Kawasaki disease (KD).,  discharged home (length of hospital stay 3-20 days). There were no mortalities.CONCLUSION: MIS-C associated with COVID-19 is characterized predominantly by cardiovascular abnormalities, though also solid visceral organ, gallbladder, and bowel abnormalities as well as ascites, reflecting a multisystemic inflammatory process.CLINICAL IMPACT: The constellation of imaging findings in the setting of COVID-19 may alert pediatr, Multisystem Inflammatory Syndrome in Children Temporally Related to COVID-19: A Case Report From Saudi Arabia., BACKGROUND: Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection , ric patients. An association between COVID-19 and a Kawasaki-like inflammatory syndrome has recently presented in pediatric patients.CASE REPORT: We report a unique case of multisystem inflammatory syndrome in children presenting with characteristic findings in a child who later developed cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation.CONCLUSION: Recognition of these early signs and symptoms facilitates screening and risk stratification of pediatric COVID-19 cas, Severe cardiac dysfunction in a patient with multisystem inflammatory syndrome in children associated with COVID-19: Retrospective diagnosis of a puzzling presentation. A case report.[SEP]", "label": "yes"}
{"id": "converted_1739", "sentence1": "Is there a relationship between thyroid hormone altered metabolism and coronary artery disease?", "sentence2": "The results showed that higher levels of TSH within the reference range were independently associated with the presence of CAD only among subjects less than or equal to 65 years old, suggesting age might influence the relationship., FT3 levels within the normal range were inversely correlated with the presence and severity of CAD. Moreover, lower FT3 concentrations were correlated with the Gensini score and independently predicted the presence and severity of CAD., High TSH within the reference range was associated with increased risk of coronary death in women (P(trend) 0·005), but not in men. The risk of coronary death was also increased among women with subclinical hypothyroidism or subclinical hyperthyroidism, compared to women with TSH of 0·50-1·4 mU/l. ,  Prevalence of CHD was more common in hypothyroid and moderate SCH patients., The angiographic results were as follows: significant coronary disease (SH 28.1% vs. non-SH 43.8%; p=0.087); three-vessel disease (9.4% vs. 9.9%; p=0.919); two-vessel disease (12.5% vs. 13.4%; p=0.892); single-vessel disease (6.3% vs. 29.5%; p=0.051); minimal lesions (9.4% vs. 10.9%; p=0.794); and no coronary disease (62.4% vs, 45.3%; p=0.064)., Lower fT3 levels were predictive of both single-vessel (p = 0.012) and multivessel (p = 0.009) CAD. Through a multivariate logistic regression analysis, fT3 was still linked to the presence of CAD (hazard ratio [HR]: 0.48, 95% confidence interval [CI]: 0.34-0.68, p < 0.001)., Our study showed that FT(4) levels were associated with the presence and the severity of CAD. Also, this study suggests that elevated serum FT(4) levels even within normal range could be a risk factor for CAD. , The present meta-analysis indicates that sub-clinical hypothyroidism is associated with both, a significant risk of CHD at baseline and at follow-up., The incidence of multi-vessel disease was higher in patients with high TSH level (p=0.026). TSH level showed a significant correlation with age (r=0.109, p=0.044) and Gensini's score (r=0.117, p=0.045). The multivariate analysis revealed that age (OR 2.39, p=0.001), diabetes (OR 3.74, p=0.001), creatinine (OR 2.06, p=0.008), and smoking (OR 1.85, p=0.045) were independent predictors for significant coronary artery disease, but TSH level did not predict coronary artery stenosis., These data in patients referred for coronary angiography suggest that variation of thyroid function within the statistical normal range may influence the presence and severity of coronary atherosclerosis.[SEP]", "label": "yes"}
{"id": "converted_1548", "sentence1": "Is the gene SLC6A2 associated with orthostatic intolerance?", "sentence2": "Orthostatic intolerance is a debilitating syndrome characterized by tachycardia on assumption of upright posture. The norepinephrine (NE) transporter (NET) has been implicated in a genetic form of the disorder. , Thus attenuated baroreflex function and reduced sympathetic outflow may contribute to the orthostatic intolerance of severe NET deficiency., A mutation in the human norepinephrine transporter gene (SLC6A2) associated with orthostatic intolerance disrupts surface expression of mutant and wild-type transporters.,  Recently, our laboratory reported a polymorphism in the human NET (hNET) gene A457P in an individual with the autonomic disorder orthostatic intolerance (OI). , Nonsynonymous single nucleotide polymorphisms (SNPs) in the human NET (hNET) gene that influence transporter function can contribute to disease, such as the nonfunctional transporter, A457P, identified in orthostatic intolerance. , Orthostatic intolerance is not necessarily related to a specific mutation (Ala457Pro) in the human norepinephrine transporter gene., We propose that chromatin-modifying events associated with SLC6A2 gene suppression may constitute a mechanism of POTS., The goal of the present study was to further characterize the role and regulation of the SLC6A2 gene in POTS., In the absence of altered SLC6A2 gene sequence or promoter methylation, this reduced expression was directly correlated with chromatin modifications.  We propose that chromatin-modifying events associated with SLC6A2 gene suppression may constitute a mechanism of POTS., A coding mutation in the norepinephrine transporter gene (SLC6A2) sequence has been reported in 1 family kindred only. The goal of the present study was to further characterize the role and regulation of the SLC6A2 gene in POTS.[SEP]", "label": "yes"}
{"id": "converted_309", "sentence1": "Is TREM2 associated with Alzheimer's disease in humans?", "sentence2": "Genetic deficits and loss of function for the triggering receptor expressed in myeloid cells 2 (TREM2; encoded at chr6p21.1), a transmembrane spanning stimulatory receptor of the immunoglobulin/lectin-like gene superfamily, have been associated with deficiencies in phagocytosis and the innate immune system in Alzheimer's disease., Recent works have demonstrated a rare functional variant (R47H) in triggering receptor expressed on myeloid cells (TREM) 2 gene, encoding TREM2 protein, increase susceptibility to late-onset Alzheimer's disease (AD),, possible involvement of TREM2 in AD pathogenesis., TREM2 is associated with the risk of Alzheimer's disease in Spanish population., Two recent studies have reported the association of rs75932628-T in the TREM2 gene with the risk for Alzheimer's disease (AD)., we report the first positive replication study in a Spanish population and confirm that TREM2 rs75932628-T is associated with the risk for AD., (TREM2) has recently been identified as a rare risk factor for late-onset Alzheimer's disease (AD)., In this study we examined the association between TREM2 exon 2 variants and early-onset AD in a sample of Caucasian subjects of French origin including 726 patients with age of onset ≤65 years and 783 controls., We found significantly more variants in exon 2 of TREM2 in patients with Alzheimer's disease than in controls in the discovery set, The most commonly associated variant, rs75932628 (encoding R47H), showed highly significant association with Alzheimer's disease (P<0.001)., Our findings strongly implicate variant TREM2 in the pathogenesis of Alzheimer's disease. Given the reported antiinflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer's disease, Recent works have demonstrated a rare functional variant (R47H) in triggering receptor expressed on myeloid cells (TREM) 2 gene, encoding TREM2 protein, increase susceptibility to late-onset Alzheimer's disease (AD), with an odds ratio similar to that of the apolipoprotein E ε4 allele., The rs75932628-T variant of the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) has recently been identified as a rare risk factor for late-onset Alzheimer's disease (AD)., BACKGROUND: Homozygous loss-of-function mutations in TREM2, encoding the triggering receptor expressed on myeloid cells 2 protein, have previously been associated with an autosomal recessive form of early-onset dementia., CONCLUSIONS: Heterozygous rare variants in TREM2 are associated with a significant increase in the risk of Alzheimer's disease., RESULTS: A rare missense mutation (rs75932628-T) in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2), which was predicted to result in an R47H substitution, was found to confer a significant risk of Alzheimer's disease in Iceland (odds ratio, 2.92; 95% confidence interval [CI], 2.09 to 4.09; P=3.42×10(-10)).[SEP]", "label": "yes"}
{"id": "converted_529", "sentence1": "Is TALEN being used on stem cells?", "sentence2": "Precise correction of the dystrophin gene in duchenne muscular dystrophy patient induced pluripotent stem cells by TALEN and CRISPR-Cas9., Genetic correction of patient-derived induced pluripotent stem cells (iPSCs) by TALENs or CRISPR-Cas9 holds promise for DMD gene therapy; however, the safety of such nuclease treatment must be determined., We generated helper-dependent, capsid-modified adenovirus (HD-Ad5/35) vectors for zinc-finger nuclease (ZFN)- or transcription activator-like effector nuclease (TALEN)-mediated genome editing in human CD34+ hematopoietic stem cells (HSCs) from mobilized adult donors. , We used transcription activator-like effector nuclease (TALEN)-mediated gene editing in mouse embryonic stem cells (mESCs) to produce mice with targeted gene disruptions and insertions in two Y-linked genes--Sry and Uty., Transcription activator-like effector nuclease (TALEN)-mediated gene correction in integration-free β-thalassemia induced pluripotent stem cells., A TALEN genome-editing system for generating human stem cell-based disease models., Low incidence of off-target mutations in individual CRISPR-Cas9 and TALEN targeted human stem cell clones detected by whole-genome sequencing., Using CRISPR-Cas9 and TALEN targeted human pluripotent stem cell clones, we performed whole-genome sequencing at high coverage in order to assess the degree of mutagenesis across the entire genome., A modified TALEN-based system for robust generation of knock-out human pluripotent stem cell lines and disease models., In this study, we utilized a cell-penetrating peptide-based system for ZFN and TALEN delivery., At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location., We report here the use of TALENs to rapidly and efficiently generate mutant alleles of 15 genes in cultured somatic cells or human pluripotent stem cells, the latter for which we differentiated both the targeted lines and isogenic control lines into various metabolic cell types., Zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) have been successfully used to knock out endogenous genes in stem cell research., Here we report different methods to efficiently perform TALEN-mediated gene integration and inactivation in different mammalian cell systems including induced pluripotent stem cells and delineate experimental examples associated with these approaches, Together, our results demonstrate that TALE-based transcriptional repressor and TALENs are two promising approaches for loss-of-function studies of microRNA clusters in somatic cells and pluripotent stem cells, We report here the use of TALENs to rapidly and efficiently generate mutant alleles of 15 genes in cultured somatic cells or human pluripotent stem cells, the latter for which we differentiated both the targeted lines and isogenic control lines into various metabolic cell types, TALEN-mediated generation and genetic correction of disease-specific human induced pluripotent stem cells., Baculoviral transduction facilitates TALEN-mediated targeted transgene integration and Cre/LoxP cassette exchange in human-induced pluripotent stem cells., We used transcription activator-like effector nuclease (TALEN)-mediated gene editing in mouse embryonic stem cells (mESCs) to produce mice with targeted gene disruptions and insertions in two Y-linked genes--Sry and Uty. , Using CRISPR-Cas9 and TALEN targeted human pluripotent stem cell clones, we performed whole-genome sequencing at high coverage in order to assess the degree of mutagenesis across the entire genome. , A 5% modification rate was observed in human induced pluripotent stem cells (hiPSCs) treated with TAT-TALEN as measured by the Surveyor assay.  TAT-TALEN protein-mediated gene disruption was applicable in hiPSCs and represents a promising technique for gene knockout in stem cells., Here we engineered transcription activator-like effector nucleases (TALENs) for five distinct genomic loci. At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location., Seamless correction of the sickle cell disease mutation of the HBB gene in human induced pluripotent stem cells using TALENs., At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location. Our data suggest that TALENs employing the specific architectures described here mediate site-specific genome modification in human pluripotent cells with similar efficiency and precision as do zinc-finger nucleases (ZFNs).[SEP]", "label": "yes"}
{"id": "converted_1383", "sentence1": "Is there an association between c-reactive protein concentrations and outcomes of subarachnoid hemorrhage patients? ", "sentence2": "Besides the baseline characteristics, daily interleukin-6 (IL-6), procalcitonin, C-reactive protein levels, and leukocyte counts were prospectively measured until day 14 after subarachnoid hemorrhage. Occurrence of infectious complications and application of therapeutic hypothermia were assessed as confounding factors. The primary end point was outcome after 3 months, assessed by Glasgow Outcome Scale; the secondary end point was the occurrence of DINDs. RESULTS: : During a 3-year period, a total of 138 patients were included. All inflammatory parameters measured were higher in patients with unfavorable outcome (Glasgow Outcome Scale score, 1-3)., Twenty-three and 28 patients showed poor outcome and symptomatic vasospasm after SAH, respectively. Both preoperative and postoperative CRP levels were significantly higher in patients with a poor outcome compared with patients with a good outcome (P<0.05)., e area under the receiver operating characteristic curve of CRP measured on postoperative day 1 or 2 (CRP POD1-2) for predicting a poor clinical outcome was 0.870, and its cutoff point of 4 mg/dL had a sensitivity of 0.826 and a specificity of 0.843., A high CRP level after aneurysm treatment was associated with severe neurological deterioration on admission, cerebral infarction, intracerebral hemorrhage, and surgical decompression (P<0.05)., CRP POD1-2, and not the preoperative CRP, was an independent factor in predicting symptomatic vasospasm (P<0.05). In patients with symptomatic vasospasm, an increase in the postoperative CRP was associated with the time profile of developing symptomatic vasospasm., Postoperative CRP, especially CRP POD1-2, can be a useful prognostic factor for both poor outcome and symptomatic vasospasm in patients with aneurysmal SAH., Serum CRP levels were related to severity of aSAH. Patients with lower GCS scores and higher Hunt and Hess and Fisher grades presented statistically significant higher serum CRP levels. Patients with higher serum CRP levels had a less favorable prognosis., Increased serum CRP levels were strongly associated with worse clinical prognosis in this study., After SAH, the value of C-reactive protein (CRP)--an acute phase sensitive inflammatory marker--as a prognostic factor has been poorly studied, with conflicting results., Admission (18.0 ± 35.7 vs 8.5 ± 8.4 mg/l) and postoperative (41.0 ± 40.2 vs 21.1 ± 24.1 mg/l) CRP levels were higher (p < 0.001) in those with a poor outcome than in those with a favourable outcome, but CRP values did not predict delayed cerebral ischaemia or cerebral infarction., Higher increase in CRP level between admission and postoperative morning, however, independently predicted poor outcome (p = 0.004)., CRP levels correlate with outcome but do not seem to predict delayed cerebral ischaemia or infarction after SAH., Systemic oxygen consumption is associated with hsCRP levels in the first 14 days after SAH and is an independent predictor of DCI., Intracranial hypertension was associated with an inflammatory response, indicating activation of the inflammatory cascade in the brain (ECF) and systemic circulation with high IL-6 and C-reactive protein (CRP) plasma levels after SAH, the latter associated with unfavourable outcome., Patients with angiographic vasospasm had higher CRP measurements in serum and CSF, in a statistically significant fashion (p < 0.0001). Additionally, patients with higher CRP levels in serum and CSF had less favorable outcome in this cohort., Furthermore, patients developing angiographically proven vasospasm demonstrated significantly elevated CRP levels in serum and CSF, and increased CRP measurements were strongly associated with poor clinical outcome in this cohort., Finally, serum concentrations of ICAM-1, VCAM-1, and hsCRP during the early (P = .0055, P = .0266, and P = .0266) and late (P = .0423, P = .0041, and P = .0004) period were significantly higher in patients with DIND than in patients without DIND. CONCLUSIONS: Serum levels of ICAM-1, VCAM-1 and hsCRP during the early and late period following SAH correlate with DIND, CRP levels on days 5, 6, 7, and 8 were statistically significantly higher in the group of patients developing a DIND (P < 0.025, P < 0.016, P < 0.011, P < 0.0002)., Overall CRP values were higher with increasing severity of the initial ictus according to the Hunt and Hess Scale and to the outcome according to the Glasgow Outcome Scale from day 3 on., The presented data do not prove that WBCs and CRP values have a direct contribution to the pathogenesis of ischemic complications following SAH, but it supports the assertion that inflammation may present a common pathogenic pathway in the development of such complications., The CRP and TGF-beta1 levels in CSF are strongly concerned with communicating hydrocephalus after SAH.[SEP]", "label": "yes"}
{"id": "converted_3608", "sentence1": "Is amantadine ER the first approved treatment for akinesia?", "sentence2": "Extended-release amantadine (amantadine ER) is the first approved medication for the treatment of dyskinesia.[SEP]", "label": "no"}
{"id": "converted_3396", "sentence1": "Autophagy is the process where a virus obtains nutrients from it's host, yes or no?", "sentence2": "In this study, we demonstrate that autophagy is a critical mediator of the viral degradation pathway and that this pathway is not HIV-1 specific., Autophagy is important in cellular homeostasis for the cell survival mechanism., Autophagy is a cellular survival pathway that is necessary for the degradation of cellular constituents such as long-lived proteins and damaged organelles., Autophagy-related genes (ATGs) regulate the autophagy and also control the crosstalk with autophagy-associated cell death and apoptosis in some condition. , Autophagy is an evolutionarily conserved cellular process in which intracellular components are eliminated via lysosomal degradation to supply nutrients for organelle biogenesis and metabolic homeostasis., Autophagy is a lysosome-associated, degradative process that catabolizes cytosolic components to recycle nutrients for further use and maintain cell homeostasis., Autophagy is a self-eating process, in which the damaged or excessed cell organelles and misfolded protein aggregates are removed from the cellular microenvironment., Autophagy is a lysosome-associated, degradative process that catabolizes cytosolic components to recycle nutrients for further use and maintain cell homeostasis., Autophagy is an evolutionarily conserved cellular process in which intracellular components are eliminated via lysosomal degradation to supply nutrients for organelle biogenesis and metabolic homeostasis., Autophagy is a homeostatic process involved in the turnover or elimination of cytoplasmic components, damaged organelles, and protein aggregates via a lysosomal degradation mechanism., Autophagy is known as a catabolic process for the recycling of the cytoplasmic macromolecules.[SEP]", "label": "no"}
{"id": "converted_1391", "sentence1": "Can RNASeq be used for the analysis of nascent transcripts?", "sentence2": "Here, we utilize nascent RNA sequencing to document dosage compensation during transcriptional elongation., Here we show that RNA-seq can also be used for studying nascent RNAs undergoing transcription, Conversely, the nuclear fraction shows an enrichment of unprocessed RNA compared with total RNA-seq, making it suitable for analysis of nascent transcripts and RNA processing dynamics.[SEP]", "label": "yes"}
{"id": "converted_3552", "sentence1": "Is the BAGEL algorithm used for arrayed CRISPR screens?", "sentence2": "BAGEL: a computational framework for identifying essential genes from pooled library screens., The adaptation of the CRISPR-Cas9 system to pooled library gene knockout screens in mammalian cells represents a major technological leap over RNA interference, the prior state of the art. New methods for analyzing the data and evaluating results are needed.RESULTS: We offer BAGEL (Bayesian Analysis of Gene EssentiaLity), a supervised learning method for analyzing gene knockout screens. Coupled with gold-standard reference sets of essential and nonessential genes, BAGEL offers significantly greater sensitivity than current methods, while computational optimizations reduce runtime by an order of magnitude.CONCLUSIONS: Using BAGEL, we identify ~2000 fitness genes in pooled library knockout screens in human cell lines at 5 % FDR, a major advance over competing platforms. BAGEL shows high sensitivity and specificity even across screens performed by different labs using different libraries and reagents., CONCLUSIONS\n\nUsing BAGEL, we identify ~2000 fitness genes in pooled library knockout screens in human cell lines at 5 % FDR, a major advance over competing platforms., BAGEL: a computational framework for identifying essential genes from pooled library screens, CONCLUSIONS\nUsing BAGEL, we identify ~2000 fitness genes in pooled library knockout screens in human cell lines at 5 % FDR, a major advance over competing platforms., CONCLUSIONS: Using BAGEL, we identify ~2000 fitness genes in pooled library knockout screens in human cell lines at 5 % FDR, a major advance over competing platforms., Conclusions Using BAGEL, we identify ~2000 fitness genes in pooled library knockout screens in human cell lines at 5 % FDR, a major advance over competing platforms.[SEP]", "label": "no"}
{"id": "converted_764", "sentence1": "Is insulin-like growth factor-I (IGF-I) able to affect tendon protein synthesis in classic Ehlers-Danlos syndrome patients?", "sentence2": "Tendon protein synthesis rate in classic Ehlers-Danlos patients can be stimulated with insulin-like growth factor-I, IGF-I injections significantly increased FSR values in cEDS patients but not in controls, In conclusion, baseline protein synthesis rates in connective tissue appeared normal in cEDS patients, and the patients responded with an increased tendon protein synthesis rate to IGF-I injections, In conclusion, baseline protein synthesis rates in connective tissue appeared normal in cEDS patients, and the patients responded with an increased tendon protein synthesis rate to IGF-I injections, IGF-I injections significantly increased FSR values in cEDS patients but not in controls (delta values: cEDS 0[SEP]", "label": "yes"}
{"id": "converted_4409", "sentence1": "Does addition of valproic acid improve survival of patients with diffuse intrinsic pontine glioma?", "sentence2": "Median event-free survival (EFS) and overall survival (OS) for DIPG were 7.8 (95% CI 5.6-8.2) and 10.3 (7.4-13.4) months, and estimated one-year EFS was 12% (2%-31%). Median EFS and OS for HGG were 9.1 (6.4-11) and 12.1 (10-22.1) months, and estimated one-year EFS was 24% (7%-45%). , CONCLUSION: Addition of VPA and bevacizumab to radiation was well tolerated but did not appear to improve EFS or OS in children with DIPG or HGG., Event-free survival and overall survival of patients not treated with valproic acid were 6.5 and 7.8 months. Accelerated failure time model (a parametric multivariate regression test for time-to-failure data) showed a statistically significant superiority of the median event-free survival of treated patients (6.5 vs. 9.5 months in treated patients; HR 0.54-95 % CI 0.33-0.87; p < 0.05) and also of overall survival (7.8 vs. 13.4 months in treated patients; HR 0.60-95 % CI 0.37-0.98; p = 0.05).[SEP]", "label": "no"}
{"id": "converted_384", "sentence1": "Is nintedanib effective for Idiopathic Pulmonary Fibrosis?", "sentence2": "In this review, we present the positive results of recently published clinical trials regarding therapy for IPF, with emphasis on pirfenidone and nintedanib., Nintedanib: evidence for its therapeutic potential in idiopathic pulmonary fibrosis,  In the Phase II TOMORROW trial, treatment with 150 mg of nintedanib twice daily showed a trend to slow the decline in lung function and significantly decrease acute exacerbations in patients with IPF, while showing an acceptable safety profile. The Phase III INPULSIS trials demonstrated a significant decrease in the annual rate of decline in forced vital capacity in IPF patients treated with 150 mg nintedanib twice daily. In the INPULSIS-2 trial, the time to the first acute exacerbation significantly increased in IPF patients who were treated with 150 mg of nintedanib twice daily.,  Effects on collagen secretion were compared with those of the drugs nintedanib and pirfenidone, recently approved for IPF., Nintedanib, an orally available, small-molecule tyrosine kinase inhibitor with selectivity for vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) receptors has recently been shown, in two pivotal phase III studies, to effectively slow IPF disease progression. Consequently, nintedanib was given accelerated approval by the FDA in October 2014 for the treatment of IPF. , Most recently, pirfenidone and nintedanib, two compounds with pleiotropic anti-fibrotic properties, have been proven effective in reducing functional decline and disease progression in IPF. , Meningococcal group B vaccine (Trumenba) to prevent more types of invasive meningococcal disease; antihemophilic factor (recombinant), porcine sequence (Obizur) to treat bleeding from acquired hemophilia A; and pirfenidone (Esbriet) and nintedanib (Ofev) for idiopathic pulmonary fibrosis.,  More importantly, the period ends with the publication of two groundbreaking studies that confirmed that two drugs, pirfenidone and nintedanib, slowed disease progression, leading to a historic approval by the FDA. , Nintedanib (Ofev(®)) is an orally available, small, multiple receptor tyrosine kinase inhibitor developed by Boehringer Ingelheim for the treatment of idiopathic pulmonary fibrosis (IPF) and cancer. Nintedanib received its first global approval in the US in October 2014 for the treatment of IPF. Nintedanib has received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use for the treatment of IPF, and for the second-line treatment in combination with docetaxel of locally advanced, metastatic or locally recurrent non-small cell lung cancer of adenocarcinoma tumour histology. , This article summarizes the milestones in the development of nintedanib leading to this first approval for IPF., Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis., Nintedanib: a novel therapeutic approach for idiopathic pulmonary fibrosis., Nintedanib is in clinical development as a treatment for idiopathic pulmonary fibrosis (IPF)., Reducing lung function decline in patients with idiopathic pulmonary fibrosis: potential of nintedanib., These results suggest that nintedanib may impact the progressive course of fibrotic lung diseases such as idiopathic pulmonary fibrosis., Findings from recently published placebo-controlled trials in idiopathic pulmonary fibrosis have established that pirfenidone and nintedanib prevent about 50% of the decline in forced vital capacity typically seen in this disease; future trials are therefore unlikely to use placebo as a control group for ethical reasons., The tyrosine kinase inhibitor nintedanib (BIBF 1120) is in clinical development for the treatment of idiopathic pulmonary fibrosis., A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis., A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. , Data from the Phase II TOMORROW study suggested that nintedanib 150�mg twice daily had clinical benefits with an acceptable safety profile.METHODS: The INPULSIS� trials are replicate Phase III, randomized, double-blind, studies comparing the efficacy and safety of nintedanib 150�mg twice daily with placebo in patients with IPF. , Nintedanib received its first global approval in the US in October 2014 for the treatment of IPF. , The most frequent adverse event in the nintedanib groups was diarrhea, with rates of 61.5% and 18.6% in the nintedanib and placebo groups, respectively, in INPULSIS-1 and 63.2% and 18.3% in the two groups, respectively, in INPULSIS-2. CONCLUSIONS: In patients with idiopathic pulmonary fibrosis, nintedanib reduced the decline in FVC, which is consistent with a slowing of disease progression; nintedanib was frequently associated with diarrhea, which led to discontinuation of the study medication in less than 5% of patients. , A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. METHODS: We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis. , Nintedanib (Ofev(�)) is an orally available, small, multiple receptor tyrosine kinase inhibitor developed by Boehringer Ingelheim for the treatment of idiopathic pulmonary fibrosis (IPF) and cancer. Nintedanib received its first global approval in the US in October 2014 for the treatment of IPF. , Nintedanib: evidence for its therapeutic potential in idiopathic pulmonary fibrosis., A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis.[SEP]", "label": "yes"}
{"id": "converted_3349", "sentence1": "The LINCS L1000 data set contains gene expression data for drug treated human cells, yes or no?", "sentence2": " Library of Integrated Network-based Cellular Signatures (LINCS) L1000 dataset that measured changes in GE before and after treatment of human cells with over 20 000 small-molecule compounds including most of the FDA-approved drugs., The Library of Integrated Network-based Cellular Signatures (LINCS) L1000 big data provide gene expression profiles induced by over 10 000 compounds, shRNAs, and kinase inhibitors using the L1000 platform., The Library of Integrated Cellular Signatures (LINCS) project provides comprehensive transcriptome profiling of human cell lines before and after chemical and genetic perturbations.,  Recently, resources such as the Library of Integrated Network-Based Cellular Signatures (LINCS) L1000 database provide gene expression profiles induced by various chemical and genetic perturbations, The library of integrated network-based cellular signatures (LINCS) L1000 data set currently comprises of over a million gene expression profiles of chemically perturbed human cell lines., The LINCS L1000 data repository contains almost two million gene expression profiles for thousands of small molecules and drugs., The GE data is from the Library of Integrated Network-based Cellular Signatures (LINCS) L1000 dataset that measured changes in GE before and after treatment of human cells with over 20 000 small-molecule compounds including most of the FDA-approved drugs.[SEP]", "label": "yes"}
{"id": "converted_3697", "sentence1": "Is SATB1 necessary for T-cell maturation?", "sentence2": "Special AT-rich binding protein 1 (SATB1) nuclear protein, expressed predominantly in T cells, regulates genes through targeting chromatin remodeling during T-cell maturation., the transcription factor SATB1 that regulates the T-cell maturation, SATB1 is a transcriptional regulator controlling the gene expression that is essential in the maturation of the immune T-cell. , Special AT-rich sequence binding protein 1 (SATB1) regulates gene expression essential in immune T-cell maturation and switching of fetal globin species, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin remodeling. [SEP]", "label": "yes"}
{"id": "converted_2060", "sentence1": "Do brown fat cells produce heat?", "sentence2": "WAT and BAT are both involved in energy balance. WAT is mainly involved in the storage and mobilization of energy in the form of triglycerides, whereas BAT specializes in dissipating energy as heat during cold- or diet-induced thermogenesis., Because brown adipose tissue (BAT) dissipates energy in the form of heat, increasing energy expenditure by augmenting BAT-mediated thermogenesis may represent an approach to counter obesity and its complications., Classic brown fat and inducible beige fat both dissipate chemical energy in the form of heat through the actions of mitochondrial uncoupling protein 1. This nonshivering thermogenesis is crucial for mammals as a defense against cold and obesity/diabetes., Mitochondrial uncoupling protein 1 in brown fat cells produces heat by dissipating the energy generated by fatty acid and glucose oxidation., Brown fat biology and thermogenesis., Brown fat (brown adipose tissue, BAT) primary function is to produce heat. , Brown fat cells were classified into 6 types: Type 1 cells are fat-depleted cells filled with granular cytoplasm and are believed to be produced after oxidation of fat for heat production., Calorimetric measurements from cell suspensions showed that ATP increased basal heat production of isolated brown fat cells by approximately 40% but had no effect on the greater than fivefold increase in heat production seen with maximal adrenergic stimulation., Classic brown fat and inducible beige fat both dissipate chemical energy in the form of heat through the actions of mitochondrial uncoupling protein 1., Brown adipocytes oxidize fatty acids to produce heat in response to cold or to excessive energy intake; stimulation of brown fat development and function may thus counteract obesity., The occurrence of Types 1 and/or 6 cells that has been revealed in 65 out of the total 180 samples (36%), suggests that the oxidation of fat for the thermogenesis proceeds in the brown fat tissue and that brown fat cells partially undergo fat depletion., Brown fat cells were classified into 6 types: Type 1 cells are fat-depleted cells filled with granular cytoplasm and are believed to be produced after oxidation of fat for heat production., In response to cold, both classical brown fat and the newly identified \"beige\" or \"brite\" cells are activated by β-adrenergic signaling and catabolize stored lipids and carbohydrates to produce heat via UCP1, The ability of brown adipocytes (fat cells) to dissipate energy as heat shows great promise for the treatment of obesity and other metabolic disorders, Inappropriate heat dissipation ignites brown fat thermogenesis in mice with a mutant thyroid hormone receptor α1, Brown fat and vascular heat dissipation: The new cautionary tail, Brown adipose produces heat as a defense against hypothermia and obesity, and the appearance of brown-like adipocytes within white adipose tissue depots is associated with improved metabolic phenotypes. , In the same manner, marked ability to produce a considerable amount of heat was evidenced in  brown fat tissue of children and teenagers. , Brown fat cells were classified into 6 types: Type 1 cells are fat-depleted cells filled with granular cytoplasm and are believed to be produced after oxidation of fat for heat production. , It is inferred that brown-adipose-tissue heat production is reduced during (and probably also some time after) anesthesia. , Parallel measurements of heat production and thermogenin content in brown fat cells during cold acclimation of rats., The classical white adipose tissue builds up energy in the form of triglycerides and is useful for preventing fatigue during periods of low caloric intake and the brown adipose tissue instead of inducing fat accumulation can produce energy as heat., In response to cold, both classical brown fat and the newly identified \"beige\" or \"brite\" cells are activated by β-adrenergic signaling and catabolize stored lipids and carbohydrates to produce heat via UCP1., White adipose tissue stores energy reserves as fat, whereas the metabolic function of brown adipose tissue is lipid oxidation to produce heat., The main function of brown adipose tissue (BAT) is to produce heat in response to cold., Brown adipocytes oxidize fatty acids to produce heat in response to cold or caloric overfeeding., Brown fat (brown adipose tissue, BAT) primary function is to produce heat., Adipose tissue plays an active role in energy balance because it is not only a lipid storing and mobilizing tissue but consists of functionally specialized tissues able to produce heat (in brown adipose tissue) and to produce or release a vast number of so called adipokines or adipocytokines., Brown adipose tissue (BAT), a specialized fat that dissipates energy to produce heat, plays an important role in the regulation of energy balance., Brown adipose cells are specialized to dissipate chemical energy in the form of heat, as a physiological defence against cold and obesity., In the present study, the thermogenesis of human brown fat tissue was suggested chiefly with regard to the occurrence of Types 1 and/or 6 cells., In the same manner, marked ability to produce a considerable amount of heat was evidenced in  brown fat tissue of children and teenagers., Adult humans have heat-producing and energy-consuming brown adipose tissue in the clavicular region of the neck., Brown and beige adipocytes expend chemical energy to produce heat and are therefore important in regulating body temperature and body weight., In human perirenal brown fat tissue, darkly stained fat-depleted cells (D) occupy, with other cell types (CR, CR'), an important part in the reversible heat production cycle of the brown fat tissue., Brown fat is a specialized fat depot that can increase energy expenditure and produce heat.[SEP]", "label": "yes"}
{"id": "converted_3111", "sentence1": "Does Axitinib prolong survival of Pancreatic Cancer patients?", "sentence2": "CONCLUSIONS: Axitinib/gemcitabine, while tolerated, did not provide survival benefit over gemcitabine alone in patients with advanced pancreatic cancer from Japan or other regions., RESULTS: Among Japanese patients, median overall survival was not estimable (95% confidence interval, 7.4 months-not estimable) with axitinib/gemcitabine (n = 58) and 9.9 months (95% confidence interval, 7.4-10.5) with placebo/gemcitabine (n = 56) (hazard ratio 1.093 [95% confidence interval, 0.525-2.274]). Median survival follow-up (range) was 5.1 months (0.02-12.3) with axitinib/gemcitabine vs. 5.4 months (1.8-10.5) with placebo/gemcitabine. Similarly, no difference was detected in overall survival between axitinib/gemcitabine and placebo/gemcitabine in patients from North America or the European Union. , At an interim analysis in January, 2009, the independent data monitoring committee concluded that the futility boundary had been crossed. Median overall survival was 8·5 months (95% CI 6·9-9·5) for gemcitabine plus axitinib (n=314, data missing for two patients) and 8·3 months (6·9-10·3) for gemcitabine plus placebo (n=316; hazard ratio 1·014, 95% CI 0·786-1·309; one-sided p=0·5436). , INTERPRETATION: The addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer. , INTERPRETATION\nThe addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer., However, as with other tyrosine kinase inhibitors of the same class, axitinib does not prolong overall survival; therefore, selection of second-line tyrosine kinase inhibitor therapy, including axitinib, must be carefully considered to maximize outcomes for each patient., CONCLUSIONS\nAxitinib/gemcitabine, while tolerated, did not provide survival benefit over gemcitabine alone in patients with advanced pancreatic cancer from Japan or other regions., Similarly, no difference was detected in overall survival between axitinib/gemcitabine and placebo/gemcitabine in patients from North America or the European Union., Axitinib/gemcitabine, while tolerated, did not provide survival benefit over gemcitabine alone in patients with advanced pancreatic cancer from Japan or other regions., The addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer.[SEP]", "label": "no"}
{"id": "converted_2428", "sentence1": "Is autosomal dominant inheritanced form of Osteogenesis imperfecta caused by mutations in the genes associated with collagen production?", "sentence2": "steogenesis imperfecta (OI) is a heterogeneous bone disorder characterized by recurrent fractures. Although most cases of OI have heterozygous mutations inCOL1A1orCOL1A2and show autosomal dominant inheritance,, Osteogenesis imperfecta (OI) is a group of hereditary disorders characterized by decreased bone mass and increased fracture risk. The majority of OI cases have an autosomal dominant pattern of inheritance and are usually caused by mutations in genes encoding type I collagen,  Osteogenesis imperfecta (OI) is a group of hereditary disorders characterized by low bone mass and recurrent fractures. Most OI cases follow an autosomal dominant pattern of inheritance and are attributed to mutations in genes encoding type I collagen (COL1A1/COL1A2). , Osteogenesis imperfecta (OI) is a genetic disorder characterised by low bone mineral density resulting in fractures. 85-90% of patients with OI carry a variant in the type 1 collagen genes, COL1A1 and COL1A2, which follows an autosomal dominant pattern of inheritance., Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders that are characterized by susceptibility to bone fractures, and range in severity from a subtle increase in fracture frequency to death in the perinatal period. Most patients have defects in type I collagen biosynthesis with autosomal-dominant inheritance, but many autosomal-recessive genes have been reported., To investigate mutation of COL1A1 gene and analyze the relationship between genotype and clinical phenotype in a family with osteogenesis imperfecta, Dominant inheritance of osteogenesis imperfecta (OI) is caused by mutations in COL1A1 or COL1A2, the genes that encode type I collagen,, Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders of bone formation, resulting in low bone mass and an increased propensity to fracture. It exhibits a broad spectrum of clinical severity, ranging from multiple fractures in utero and perinatal death, to normal adult stature and low fracture incidence. Extra-skeletal features of OI include blue sclera, hearing loss, skin hyperlaxity, joint hyperextensibility, and dentinogenesis imperfecta. The proα1(I) and proα2(I) chains of collagen 1 are encoded by the COL1A1 and COL1A2 genes, respectively; quantitative or qualitative defects in type I collagen synthesis usually manifest as types of OI or some sub-types of EDS. The majority of patients (about 90%) with a clinical diagnosis of OI have a mutation in the COL1A1 or COL1A2, Osteogenesis imperfecta (OI) type I is characterized by bone fragility without significant deformity, osteopenia, normal stature, blue sclerae, and autosomal dominant inheritance. Dermal fibroblasts from most affected individuals produce about half the expected amount of type I collagen, suggesting that the OI type I phenotype results from a variety of mutations which alter the apparent expression of either COL1A1 or COL1A2, the genes encoding the chains of type I collagen., Autosomal dominant osteogenesis imperfecta is caused by mutations in the COL1A2 and COL1A1 genes of type I collagen. , Osteogenesis imperfecta is caused by dominant autosomal mutations in the type I collagen coding genes (COL1A1 and COL1A2) in about 85% of individuals, affecting collagen quantity or structure., Osteogenesis imperfecta (OI) is a heterogeneous group of disorders of connective tissue, mainly caused by mutations in the collagen type I genes (COL1A1 and COL1A2)., Autosomal dominant osteogenesis imperfecta (OI) is caused by mutations in the genes (COL1A1 or COL1A2) encoding the chains of type I collagen., In approximately 90% of individuals with osteogenesis imperfecta, mutations in either of the genes encoding the pro-alpha1 or pro-alpha2 chains of type I collagen (COL1A1 or COL1A2) can be identified., Autosomal dominant OI is caused by mutations in the genes (COL1A1 or COL1A2) encoding the chains of type I collagen., ext-generation sequencing technology was used to screen a panel of known OI genes.RESULTS: In 41 probands, we identified 28 different disease-causing variants of 9 different known OI genes. Eleven of the variants are novel. Ten of the 28 variants are located in COL1A1, five in COL1A2, three in BMP1, three in FKBP10, two in TMEM38B, two in P3H1, and one each in CRTAP, SERPINF1, and SERPINH1. , Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous disorder associated with bone fragility and susceptibility to fractures after minimal trauma. OI type V has an autosomal-dominant pattern of inheritance and is not caused by mutations in the type I collagen genes COL1A1 and COL1A2. , Detection of a high frequency RsaI polymorphism in the human pro alpha 2(I) collagen gene which is linked to an autosomal dominant form of osteogenesis imperfecta., Osteogenesis imperfecta due to recurrent point mutations at CpG dinucleotides in the COL1A1 gene of type I collagen., Osteogenesis imperfecta (OI), commonly known as \"brittle bone disease\", is a dominant autosomal disorder characterized by bone fragility and abnormalities of connective tissue. Biochemical and molecular genetic studies have shown that the vast majority of affected individuals have mutations in either the COL1A1 or COL1A2 genes that encode the chains of type I procollagen. , Osteogenesis imperfecta is normally caused by an autosomal dominant mutation in the type I collagen genes COL1A1 and COL1A2.[SEP]", "label": "yes"}
{"id": "converted_2324", "sentence1": "Are mutations in the nf1 gene associated with memory?", "sentence2": "We hypothesized that NF1 mutations disturb the expression of genes important for memory formation, Our previous work has shown that defective cAMP signaling leads to the learning phenotype in Drosophila Nf1 mutants. In the present report, our experiments showed that in addition to learning, long-term memory was also abolished in Nf1 mutants. , Distinct functional domains of neurofibromatosis type 1 regulate immediate versus long-term memory formation.[SEP]", "label": "yes"}
{"id": "converted_3363", "sentence1": "Is bortezomib a Proteasome inhibitor?", "sentence2": "The proteasome-inhibitor bortezomib, The proteasome inhibitor bortezomib is effective for a variety of tumors, but not for GBM. , Proteasome inhibitor bortezomib , The proteasome inhibitor bortezomib, registered for Multiple Myeloma treatment, is currently explored for activity in solid tumors including non-small cell lung cancer (NSCLC)., Regulation of osteoblastic differentiation by the proteasome inhibitor bortezomib., The proteasome inhibitor bortezomib (also known as Velcade and PS-341) is a clinically effective antineoplastic drug that is FDA approved for treatment of hematologic malignancies such as multiple myeloma and mantle cell lymphoma., Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives., The proteasome inhibitor bortezomib is emerging as a potent anti-cancer agent., Bortezomib (Velcade™) is a reversible proteasome inhibitor that is approved for the treatment of multiple myeloma (MM)., The proteasome inhibitor Bortezomib is used to treat multiple myeloma (MM).[SEP]", "label": "yes"}
{"id": "converted_3205", "sentence1": "Does RUNX2 inhibit astrocyte differentiation?", "sentence2": "The method was able to recapitulate experimentally validated cell-fate determinants, and validation of two predicted cell-fate determinants confirmed that overexpression of ESR1 and RUNX2 in mouse neural stem cells induces neuronal and astrocyte differentiation, respectively.[SEP]", "label": "no"}
{"id": "converted_3545", "sentence1": "Does the BRAFV600E mutation have an effect on clinical response to radioiodine therapy?", "sentence2": "Preclinical studies showed that BRAF mutation significantly reduced radioiodine uptake and decreased the sensitivity to radioactive iodine (RAI) therapy., The status of BRAF mutation may not affect the clinical response to RAI therapy for patients with PTMC with intermediate-risk to high-risk features. More trials examining the role of BRAF mutation in guiding postoperative RAI therapy are needed., our results suggest that the combination of BRAFV600E+ve mutation and MIBI-ve scintigraphy may be considered a negative prognostic clue, which predicts the absence of radioiodine uptake at pT-WBS in DTC patients with incomplete bio-chemical response to first RAIT, The results indicate that BRAF(V600E) mutation is correlated with a lower expression of NIS in PTCs without HT, suggesting the radioiodine-refractory effects during RIA therapy in these patients.[SEP]", "label": "yes"}
{"id": "converted_1294", "sentence1": "Are optogenetics tools used in the study and treatment of epilepsy?", "sentence2": "The emerging revolutionary technique of optogenetics enables manipulation of the activity of specific neuronal populations in vivo with exquisite spatiotemporal resolution using light. We used optogenetic approaches to test the role of hippocampal excitatory neurons in the lithium-pilocarpine model of acute elicited seizures in awake behaving rats., This chapter focuses on the development of optogenetics and on-demand technologies for the study of epilepsy and the control of seizures., We then turn to the use of optogenetics, including on-demand optogenetics in the study of epilepsies, which highlights the powerful potential of optogenetics for epilepsy research., Optogenetic techniques provide powerful tools for bidirectional control of neuronal activity and investigating alterations occurring in excitability disorders, such as epilepsy.,  Therefore, one could optogenetically activate specific or a mixed population of interneurons and dissect their selective or concerted inhibitory action on principal cells. We chose to explore a conceptually novel strategy involving simultaneous activation of mixed populations of interneurons by optogenetics and study their impact on ongoing epileptiform activity in mouse acute hippocampal slices., Our data suggest that global optogenetic activation of mixed interneuron populations is a more effective approach for development of novel therapeutic strategies for epilepsy, but the initial action potential generation in principal neurons needs to be taken in consideration., Recently, a number of experiments have explored the treatments for epilepsy with optogenetic control of neurons. Here, we discuss the possibility that an optogenetic approach could be used to control the release of gliotransmitters and improve astrocyte function such as glutamate and K(+) uptake, and thereby offer a potential strategy to investigate and treat astrocyte-related epilepsy., Optogenetic and designer receptor technologies provide unprecedented and much needed specificity, allowing for spatial, temporal and cell type-selective modulation of neuronal circuits. Using such tools, it is now possible to begin to address some of the fundamental unanswered questions in epilepsy, to dissect epileptic neuronal circuits and to develop new intervention strategies. , We then turn to the use of optogenetics, including on-demand optogenetics in the study of epilepsies, which highlights the powerful potential of optogenetics for epilepsy research., Moreover, optogenetics may be considered for developing potential treatment strategies for brain diseases, particularly for excitability disorders such as epilepsy., This chapter focuses on the development of optogenetics and on-demand technologies for the study of epilepsy and the control of seizures., How might novel technologies such as optogenetics lead to better treatments in epilepsy?, WONOEP appraisal: optogenetic tools to suppress seizures and explore the mechanisms of epileptogenesis., Finally, optogenetic tools allow rapid and reversible suppression of epileptic electroencephalography (EEG) activity upon photoactivation., Our data suggest that epileptiform activity in the hippocampus caused by impaired inhibition may be controlled by optogenetic silencing of principal neurons and potentially can be developed as an alternative treatment for epilepsy., Seizure suppression by high frequency optogenetic stimulation using in vitro and in vivo animal models of epilepsy., Optogenetic techniques provide powerful tools for bidirectional control of neuronal activity and investigating alterations occurring in excitability disorders, such as epilepsy. , We first discuss the benefits and caveats to using optogenetic approaches and recent advances in optogenetics related tools. We then turn to the use of optogenetics, including on-demand optogenetics in the study of epilepsies, which highlights the powerful potential of optogenetics for epilepsy research.[SEP]", "label": "yes"}
{"id": "converted_2721", "sentence1": "Is Brucella abortus the organism that causes brucillosis known to cause spontaneous abortions in humans?", "sentence2": ". Brucellosis is a major cause of pyrexia of unknown origin (PUO), Brucellosis is the most common bacterial zoonosis, and causes a considerable burden of disease in endemic countries. Cardiovascular involvement is the main cause of mortality due to infection with Brucella spp,, quite abruptly, he developed asthenia and hypersomnia without any apparent cause or symptoms like fever, chills, or night sweats. On November 14, 2009, he suffered from pain and edema in the right testicle that coincided with pain in the abdomen. Clinical, serological, and bacteriological investigations confirmed the first case of unilateral orchitis in man in Ecuador caused by Brucella abortus biovar 1, Brucellosis is not frequent in Chile but it may present with life threatening complications like endocarditis., Human brucellosis exhibits diverse pathological manifestations that can affect almost any organ. In particular, osteoarticular complications are the most common focal manifestation of brucellosis and occur in 40-80% of patients., Brucella. Human brucellosis often makes the diagnosis difficult. The symptoms and clinical signs most commonly reported are fever, fatigue, malaise, chills, sweats headaches, myalgia, arthralgia, and weight loss. Some cases have been presented with only joint pain, lower backache, and involuntary limb movement, burning feet, or ischemic heart attacks. , Forty-five cases were collected (31 acute and 14 sub-acute). Contamination was digestive in 62%. Symptoms of patients were fever (93%), sweating (82%), arthralgia (78%) and splenomegaly (51%). Elevated erythrocyte sedimentation rate was determined in 80%, leukopenia in 49% and anaemia in 37% of cases. Blood cultures were positives in 39% of cases. The four sequenced strains were identified as Brucella melitensis biovar abortus. , It is also known to cause persistent undulant fever, endocarditis, arthritis, osteomyelitis and meningitis in humans., Brucella abortus is a Gram-negative intracellular bacterial pathogen that causes a zoonosis of worldwide occurrence, leading to undulant fever in humans and abortion in domestic animals., Brucella abortus is a facultative intracellular bacterial pathogen that causes abortion in domestic animals and undulant fever in humans., Brucella abortus is a facultative, intracellular zoonotic pathogen which can cause undulant fever in humans and abortions in cattle., Brucella abortus is a Gram-negative, facultative intracellular bacterium that causes brucellosis, a worldwide zoonotic disease leading to undulant fever in humans and abortion in cattle., Brucella abortus is a facultative intracellular bacterial pathogen that causes abortion in domestic animals and undulant fever in humans., Brucella abortus is a gram-negative, facultative intracellular pathogen that causes brucellosis, a chronic zoonotic disease resulting in abortion in pregnant cattle and undulant fever in humans., Brucella abortus is a bacterium which causes abortions and infertility in cattle and undulant fever in humans., Brucella abortus is the etiologic agent of bovine brucellosis and causes a chronic disease in humans known as undulant fever., No case of acute Brucella infection was demonstrated; however, there were 5 cases in which the serological finding was consistent with chronic brucellosis (4%). In all these cases no positive evidence of close animal contact could be found; furthermore of the 12,1% of women who actually handled domestic animals, only 1 had a history of previous abortion[SEP]", "label": "no"}
{"id": "converted_345", "sentence1": "Are circRNAs associated with diseases and traits?", "sentence2": "Circ2Traits: a comprehensive database for circular RNA potentially associated with disease and traits., Circular RNAs play a crucial role in fine tuning the level of miRNA mediated regulation of gene expression by sequestering the miRNAs. Their interaction with disease associated miRNAs indicates that circular RNAs are important for disease regulation., Firstly, the interactions of circRNAs with disease associated miRNAs were identified, following which the likelihood of a circRNA being associated with a disease was calculated, Emerging evidence indicates that circRNAs might play important roles in atherosclerotic vascular disease risk, neurological disorders, prion diseases and cancer; exhibit aberrant expression in colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC); and serve as diagnostic or predictive biomarkers of some diseases, In this paper we studied the potential association of circular RNAs (circRNA) with human diseases in two different ways. Firstly, the interactions of circRNAs with disease associated miRNAs were identified, following which the likelihood of a circRNA being associated with a disease was calculated., Firstly, the interactions of circRNAs with disease associated miRNAs were identified, following which the likelihood of a circRNA being associated with a disease was calculated. For the miRNAs associated with individual diseases, we constructed a network of predicted interactions between the miRNAs and protein coding, long non-coding and circular RNA genes.[SEP]", "label": "yes"}
{"id": "converted_2009", "sentence1": "Can Pentraxin 3 predict outcomes of sepsis?", "sentence2": "As compared with low serum PTX3and sTWEAK cases, cirrhotic patients with high serum PTX3/sTWEAK levels a have higher probability of new severe infections, severe sepsis, septic shock, type 1 hepatorenal syndrome, in-hospital, and 3-month follow-up mortalities. , Neonates with high nPTX3 concentrations also have lowered APGAR scores, increased rate of respiratory distress syndrome, clinical sepsis, IVH, necrotizing enterocolitis and prolonged NICU stay., In terms of predicting the prognosis of sepsis with heart failure complications, the PTX3 value's area under ROC curve was larger than that of BNP (respectively 0. 844, 0. 472).CONCLUSION: The PTX3 is an objective biochemical marker in diagnosis of sepsis; it is helpful in assessment of severity and prognosis of sepsis; it also has a certain clinical value in the assessment of sepsis cardiovascular function damage., Severe Acinetobacter baumannii sepsis is associated with elevation of pentraxin 3., Together, these results suggest that elevation of PTX3 is associated with fulminant disease during A. baumannii sepsis., Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality., PTX3, as a mediator of inflammation, may represent an early marker of severity and outcome in sepsis., CONCLUSIONS: Persisting high levels of circulating PTX3 over the first days from sepsis onset may be associated with mortality. PTX3 correlates with severity of sepsis and with sepsis-associated coagulation/fibrinolysis dysfunction., Pentraxin 3 in patients with severe sepsis or shock: the ALBIOS trial., Pentraxin 3: an immune modulator of infection and useful marker for disease severity assessment in sepsis., Redox state of pentraxin 3 as a novel biomarker for resolution of inflammation and survival in sepsis., The prototypic long pentraxin, pentraxin 3, is an acute phase protein that is structurally related but distinct from C-reactive protein which has proven to correlate with the severity of bacterial infection in critically ill patients., Circulating levels of the long pentraxin PTX3 correlate with severity of infection in critically ill patients., Pentraxin 3 (PTX3) is associated with severe sepsis and fatal disease in emergency room patients with suspected infection: a prospective cohort study., In addition, high levels of PTX3 were associated with unfavorable outcome.CONCLUSIONS: The long pentraxin PTX3 is elevated in critically ill patients and correlates with severity of disease and infection., PTX3, as a mediator of inflammation, may represent an early marker of severity and outcome in sepsis., Redox state of pentraxin 3 as a novel biomarker for resolution of inflammation and survival in sepsis., Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality., Pentraxin 3 (PTX3) is associated with severe sepsis and fatal disease in emergency room patients with suspected infection: a prospective cohort study., The proteomic profile of circulating pentraxin 3 (PTX3) complex in sepsis demonstrates the interaction with azurocidin 1 and other components of neutrophil extracellular traps.[SEP]", "label": "yes"}
{"id": "converted_2205", "sentence1": "Does the Abelson-related gene (ARG) gene encode for a serine kinase?", "sentence2": "One isoform of Arg/Abl2 tyrosine kinase is nuclear and the other seven cytosolic isoforms differently modulate cell morphology, motility and the cytoskeleton., The non-receptor tyrosine kinase Abelson related gene (Arg/Abl2) regulates cell migration and morphogenesis by modulating the cytoskeleton. , The human Arg (Abl2) nonreceptor tyrosine kinase has a role in cytoskeletal rearrangements by its C-terminal F-actin- and microtubule-binding sequences. , The tyrosine kinase abl-related gene ARG is fused to ETV6 in an AML-M4Eo patient with a t(1;12)(q25;p13): molecular cloning of both reciprocal transcripts.,  The ARG gene encodes for a nonreceptor tyrosine kinase characterized by high homology with c-Abl in the TK, SH2, and SH3 domains. This is the first report on ARG involvement in a human malignancy., Ultraviolet-A and -B differentially modify the tyrosine-kinase profile of human keratinocytes and induce the expression of Arg+., Arg (Abelson-related gene, Abl2) was the PTK with the highest prevalence (30% of all PTKs) and UVA led to a further induction of Arg expression reaching nine-fold mRNA baseline expression at 17 h after irradiation., To investigate the expression profile of protein tyrosine kinases (PTKs) in normal human epidermal keratinocytes (NHEK) in response to UVA and UVB we employed a reversed transcriptase polymerase chain reaction (PCR) approach using degenerate primers derived from the conserved catalytic domain of PTKs. , By 3'rapid amplification of cDNA ends-polymerase chain reaction (3'RACE-PCR), a novel fusion transcript was identified between the ETV6 and the Abelson-related gene (ARG) at 1q25, resulting in a chimeric protein consisting of the HLH oligomerization domain of ETV6 and the SH2, SH3, and protein tyrosine kinase (PTK) domains of ARG., The non-receptor tyrosine kinase Abelson related gene (Arg/Abl2) regulates cell migration and morphogenesis by modulating the cytoskeleton., Arg (Abelson-related gene, Abl2) was the PTK with the highest prevalence (30% of all PTKs) and UVA led to a further induction of Arg expression reaching nine-fold mRNA baseline expression at 17 h after irradiation., We studied the relationship of direct karyotypes, determined at diagnosis and remission, to Abelson-related tyrosine kinase activity and the cytogenetic features of erythroid and myeloid colonies derived from remission marrow of six children with acute lymphoblastic leukemia (ALL)., ABL2/ARG (ABL-related gene) belongs to the ABL (Abelson tyrosine-protein kinase) family of tyrosine kinases, The non-receptor tyrosine kinase Abelson related gene (Arg/Abl2) regulates cell migration and morphogenesis by modulating the cytoskeleton, The ARG gene encodes for a nonreceptor tyrosine kinase characterized by high homology with c-Abl in the TK, SH2, and SH3 domains., ABL2/ARG (ABL-related gene) belongs to the ABL (Abelson tyrosine-protein kinase) family of tyrosine kinases., We report that the Abelson (Abl) and Abl-related gene (Arg) nonreceptor tyrosine kinases are required for maintenance of cortical dendrites in the mouse brain., The products of the human ARG gene and the human ABL gene characterize the Abelson family of non-receptor tyrosine protein kinases., The products of the human Arg gene and human, mouse, Drosophila, and nematode Abl genes characterize the Abelson family of nonreceptor tyrosine protein kinase., By 3'rapid amplification of cDNA ends-polymerase chain reaction (3'RACE-PCR), a novel fusion transcript was identified between the ETV6 and the Abelson-related gene (ARG) at 1q25, resulting in a chimeric protein consisting of the HLH oligomerization domain of ETV6 and the SH2, SH3, and protein tyrosine kinase (PTK) domains of ARG., The tyrosine kinase abl-related gene ARG is fused to ETV6 in an AML-M4Eo patient with a t(1;12)(q25;p13): molecular cloning of both reciprocal transcripts.[SEP]", "label": "no"}
{"id": "converted_3471", "sentence1": "Are the members of the KRAB-ZNF  gene family promoting gene repression?", "sentence2": " The proteins encoded by these genes, whose expression is often tissue-specific, act as epigenetic suppressors contributing to the addition of repressive chromatin marks and DNA methylation., Here, using a reporter system, we show that TRIM28/KRAB-ZNFs alter DNA methylation patterns in addition to H3K9me3 to cause stable gene repression during reprogramming. Using several expression datasets, we identified KRAB-ZNFs (ZNF114, ZNF483, ZNF589) in the human genome that maintain pluripotency., Further analyses of our data sets link GABPa to cognitive disorders, diabetes, KRAB zinc finger (KRAB-ZNF), and human-specific genes., The stem cell zinc finger 1 (SZF1)/ZNF589 protein belongs to the large family of Krüppel-associated box domain-zinc finger (KRAB-ZNF) transcription factors, which are present only in higher vertebrates and epigenetically repress transcription by recruiting chromatin-modifying complexes to the promoter regions of their respective target genes, Because KAP1 is recruited to the DNA via interaction with KRAB-ZNF proteins, we suggest that expression of KRAB-ZNF genes may be controlled via an auto-regulatory mechanism involving KAP1., Interestingly, although most KAP1 binding sites were within core promoter regions, the binding sites near ZNF genes were greatly enriched within transcribed regions of the target gene[SEP]", "label": "yes"}
{"id": "converted_1477", "sentence1": "Does HuR protein regulate the splicing process?", "sentence2": "HuR and TIA1/TIAL1 are involved in regulation of alternative splicing of SIRT1 pre-mRNA, Here we describe experiments showing that HuR and TIA1/TIAL1, two kinds of RNA-binding proteins, were involved in the regulation of alternative splicing of SIRT1 pre-mRNA under normal and stress circumstances, HuR increased SIRT1-∆Exon8 by promoting SIRT1 exon 8 exclusion, whereas TIA1/TIAL1 inhibition of the exon 8 exclusion led to a decrease in SIRT1-∆Exon8 mRNA levels. , HuR regulates alternative splicing of the TRA2β gene in human colon cancer cells under oxidative stress, Hu antigen R (HuR) regulates stress responses through stabilizing and/or facilitating the translation of target mRNAs, We show here that the RBP embryonic lethal abnormal vision like 1 (ELAVL1, also know as HuR) regulates the alternative splicing of eukaryotic translation initiation factor 4E nuclear import factor 1 (Eif4enif1), which encodes an eukaryotic translation initiation factor 4E transporter (4E-T) protein and suppresses the expression of capped mRNAs, Further, endothelial-specific Elavl1 knockout mice exhibited reduced revascularization after hind limb ischemia and tumor angiogenesis in oncogene-induced mammary cancer, resulting in attenuated blood flow and tumor growth, respectively. , Changes in cellular mRNA stability, splicing, and polyadenylation through HuR protein sequestration by a cytoplasmic RNA virus, Furthermore, significant changes can be observed in nuclear alternative polyadenylation and splicing events on cellular pre-mRNAs as a result of sequestration of HuR protein by the 3' UTR of transcripts of this cytoplasmic RNA virus., Here we demonstrate that expression of 2A(pro) induces a selective nucleo-cytoplasm translocation of several important RNA binding proteins and splicing factors. Subcellular fractionation studies, together with immunofluorescence microscopy revealed an asymmetric distribution of HuR and TIA1/TIAR in 2A(pro) expressing cells, which modulates splicing of the human Fas exon 6, knockdown of HuR or overexpression of TIA1/TIAR, leads to Fas exon 6 inclusion in 2A(pro)-expressing cells, The differential expression levels of T-cell intracellular antigens (TIA) and Hu antigen R (HuR) are concomitant with a splicing switch in apoptosis receptor Fas in HCT-116 cells, overexpression and knockdown of HuR led to Fas exon 6 skipping and inclusion, respectively. These results suggest that the TIA and HuR cellular ratio influences cell-type specific Fas exon 6 splicing pattern., Hu antigen R (HuR) functions as an alternative pre-mRNA splicing regulator of Fas apoptosis-promoting receptor on exon definition, antiapoptotic regulator Hu antigen R (HuR, ELAVL1), a member of the embryonic lethal, abnormal vision, Drosophila-like (ELAVL) family, promotes Fas exon 6 skipping by binding to an exonic splicing silencer, ELAV/Hu proteins bind to AU-rich elements (ARE) in mRNAs and regulate their stability from splicing to translation, and the ubiquitous HuR protein has been implicated in cancerous cell growth., The HuR protein regulates the expression of thousands of cellular transcripts by modulating mRNA splicing, trafficking, translation, and stability., Hu antigen R (HuR) functions as an alternative pre-mRNA splicing regulator of Fas apoptosis-promoting receptor on exon definition., I report that antiapoptotic regulator Hu antigen R (HuR, ELAVL1), a member of the embryonic lethal, abnormal vision, Drosophila-like (ELAVL) family, promotes Fas exon 6 skipping by binding to an exonic splicing silencer. , Changes in cellular mRNA stability, splicing, and polyadenylation through HuR protein sequestration by a cytoplasmic RNA virus., Further, the silencing capacity of HuR as splicing regulator resides in the RRM1 and hinge-RRM3 domains. , HuR and TIA1/TIAL1 are involved in regulation of alternative splicing of SIRT1 pre-mRNA., HuR regulates alternative splicing of the TRA2β gene in human colon cancer cells under oxidative stress., The HuR protein regulates the expression of thousands of cellular transcripts by modulating mRNA splicing, trafficking, translation, and stability. , Further, the silencing capacity of HuR as splicing regulator resides in the RRM1 and hinge-RRM3 domains. Taken together, these results support a functional link between HuR as repressor of alternative Fas splicing and the molecular mechanisms modulating programmed cell death., We are interested in interactions involving hnRNP proteins participating in several steps of mRNA processing (mainly pre-mRNA splicing) and HuR with an established role in stability/translation of associated mRNAs. hnRNP and HuR proteins have a major nucleoplasmic localization and ability to shuttle between nucleus and cytoplasm. We report here on interactions between hnRNP and HuR proteins that were identified in the context of isolated hnRNP and mRNP complexes. , Despite the fact that HuR sites are observed in intronic regions, our data do not support a role for HuR in regulating splicing.[SEP]", "label": "yes"}
{"id": "converted_3718", "sentence1": "Are there negative enhancers?", "sentence2": "Role of a YY-1 factor-binding negative enhancer, Mutations targeted to the CArG-like motif abolished the suppressive effect of the negative enhancer and the inducibility of the promoter during myogenic differentiation, Our results suggest that the activity of the negative enhancer may determine the level of expression of the COX Vb gene in different tissues., Coordinate regulation of Drosophila tropomyosin gene expression is controlled by multiple muscle-type-specific positive and negative enhancer elements., enhancer regions contain multiple muscle-type-specific positive and negative cis-acting elements which together contribute toward full expression of the gene. , We also show that this somatic/visceral muscle element(s) can be repressed through an adjacent negative control region, suggesting that the regulation of expression in these muscles is under dual control during both phases of myogenesis, We propose a model in which transcriptional regulation of the Drosophila TmI gene is controlled by the cooperative interaction of multiple positive and negative cis-acting regulatory elements that control the temporal and muscle-type pattern of expression., Tandemly reiterated negative enhancer-like elements regulate transcription of a human gene for the large subunit of calcium-dependent protease, Upstream of the promoter region are tandemly reiterated multiple regulatory regions (-2.5k to -690, -690 to -460, -460 to -260, and -260 to -202), each of which negatively regulates the CANP mL gene promoter as well as heterologous promoters in an orientation-independent manner, he negative regulation of transcription mediated by these reiterated cis-acting elements and trans-acting factor(s) may play an essential role in the expression of the CANP mL gene., Although LDB1-dependent activated genes are regulated at the level of transcriptional initiation, the LDB1-dependent repressed transcription units appear to be regulated primarily at the level of promoter pausing, with LDB1 regulating recruitment of metastasis-associated 1 family, member 2, a component of the nucleosome remodeling deacetylase complex, on these negative enhancers, required for the repressive enhancer function., The site was similar to silencers, or negative enhancers, in that it acted to repress transcription from outside the transcribed region, but was distinct in that the function of a canonical silencer was independent of orientation., Clones in which the transgene was down-regulated by dexamethasone survived and were designated AtT-20/NET (for negative enhancer trap)., The E1a gene of adenovirus encodes two proteins, 289 and 243 amino acids long, which have positive (transactivator) and negative (enhancer repressor) RNA polymerase II transcriptional regulatory properties and cell transformation activities including cooperation with an activated ras gene., Tandemly reiterated negative enhancer-like elements regulate transcription of a human gene for the large subunit of calcium-dependent protease., Upstream of the promoter region are tandemly reiterated multiple regulatory regions (-2.5k to -690, -690 to -460, -460 to -260, and -260 to -202), each of which negatively regulates the CANP mL gene promoter as well as heterologous promoters in an orientation-independent manner., The presence of a cellular factor(s) mediating the action of these positive (promoter) and negative regulatory elements was suggested by an in vivo competition assay., We have previously identified a silencer (negative enhancer) in glutathione transferase P (GST-P) gene which is strongly and specifically induced during hepatocarcinogenesis of the rat. , The possibility that SF-B/LAP/IL6-DBP functions as a dual positive and negative regulator is discussed., Coordinate regulation of Drosophila tropomyosin gene expression is controlled by multiple muscle-type-specific positive and negative enhancer elements, Together these enhancer regions contain multiple muscle-type-specific positive and negative cis-acting elements which together contribute toward full expression of the gene., We also show that this somatic/visceral muscle element(s) can be repressed through an adjacent negative control region, suggesting that the regulation of expression in these muscles is under dual control during both phases of myogenesis. We propose a model in which transcriptional regulation of the Drosophila TmI gene is controlled by the cooperative interaction of multiple positive and negative cis-acting regulatory elements that control the temporal and muscle-type pattern of expression., Mutations targeted to the CArG-like motif abolished the suppressive effect of the negative enhancer and the inducibility of the promoter during myogenic differentiation. Our results suggest that the activity of the negative enhancer may determine the level of expression of the COX Vb gene in different tissue[SEP]", "label": "yes"}
{"id": "converted_3682", "sentence1": "Is indinavir effective for treatment of amyotrophic lateral sclerosis?", "sentence2": "Group differences in the rate of decline were not significant between the groups for the ALS Functional Rating Scale (p = 0.36) or for the secondary variables. The toxicity and negative efficacy trends discourage further indinavir trials in ALS.[SEP]", "label": "no"}
{"id": "converted_2856", "sentence1": "Can exposure to heavy metals like lead(Pb) or cadmium(Cd) cause changes in DNA methylation patterns in Isoetes sinensis?", "sentence2": "DNA methylation in endangered plants after exposure to heavy metals, the Isoetes sinensis, an endangered plant, was stressed with three different concentrations of two heavy metals lead (Pb) and cadmium (Cd), The results showed that the DNA methylated profile of I. sinensis was affected by Pb and Cd stress., The proportion of DNA methylation (including hypermethylation) by both Pb and Cd stresses is nearly equal (39.04% and 39.71%), but the proportion of DNA demethylation by Cd is higher than that by Pb (46.86% than 33.92%)., There was no significant difference in the amount of DNA methylation among control check (CK), Pb stress group, and Cd stress group (CK 46.96%, Pb 48.23%, and Cd 48.1%)., However, full-methylation level of Pb stress group (28.34%) and Cd stress group (20.25%) was lower than control (33.91%), in contrast, hemi-methylation level Pb stress group (19.89%) and Cd stress group (27.85%) were higher than control (13.04%)., Consistently, a dramatic change in DNA methylation patterns was detected in excess Cu-exposed H. verticillata., Hydrilla verticillata employs two different ways to affect DNA methylation under excess copper stress.Because of the accumulation of heavy metals, Hydrilla verticillata (L.f.) Royle, a rooted submerged perennial aquatic herb, is being developed as a potential tool to clean the aquatic ecosystem polluted by heavy metals. , The proportion of DNA methylation (including hypermethylation) by both Pb and Cd stresses is nearly equal (39.04% and 39.71%), but the proportion of DNA demethylation by Cd is higher than that by Pb (46.86% than 33.92%).<br>[SEP]", "label": "yes"}
{"id": "converted_3812", "sentence1": "Can secondary glioblastoma be caused by brain irradiation?", "sentence2": "Prolonged survival in secondary glioblastoma following local injection of targeted alpha therapy with , [Radiation induced glioblastoma: a case report]., We report a surgical case of a 54-year-old woman with a radiation induced glioblastoma., Glioblastoma multiforme following cranial irradiation and chemotherapy for acute lymphocytic leukaemia., The occurrence of glioblastoma multiforme following radiation and chemotherapy in acute lymphocytic leukaemia (ALL) is rare., Glioblastoma multiforme following cranial irradiation and chemotherapy for acute lymphocytic leukaemia. R, exact cause for the development of glioblastoma multiforme following therapy for ALL is not clear. A gen, ndary malignant and benign brain tumors such as astrocytoma, meningioma and glioblastoma have been described in long-term survivors of conventional myeloablative alloBMT. Here w, The authors consider irradiation-induced glioblastomas secondary to primarily verified medulloblastomas in patients who had previously undergone craniospinal irradiation as a component of combined treatment after tumor resection., The authors analyzed patterns of occurrence of irradiation-induced glioblastomas depending on the molecular genetic group and clinical characteristics of patients after primary surgery., Secondary brain tumors rarely arise after cranial irradiation; among them, meningiomas and glioblastomas are the most common and secondary oligodendroglial tumors the most rare., Secondary glioblastoma multiforme (sGBM) can occur after a long latency period following radiation treatment of various diseases including brain tumors, leukemia, and more benign disorders like tinea capitis., Irradiation, however, acts as an oncogenic factor as a delayed effect and it is rare that glioblastoma multiforme develops during the remission period of ALL., A cerebellar glioblastoma was discovered in a 28 year old woman, 5 years after a focal 50 grays brain irradiation for meningioma of the clivus., Glioblastoma multiforme following cranial irradiation and chemotherapy for acute lymphocytic leukaemia. Report of 3 cases., Secondary tumors including glioblastomas are under special attention since their occurrence is associated with a fatal outcome., We describe a case of radiation-induced glioblastoma after radiotherapy for germinoma., [A Case of Radiation-induced Glioblastoma 29 Years after Treatments for Germinoma]., Paradoxically, radiation is also a risk factor for GBM development, raising the possibility that radiotherapy of brain tumors could promote tumor recurrence or trigger secondary gliomas., An SMN may have a benign course, as in meningioma, or be a dilemma for the patient, as in glioblastoma., During a median of 2 years of follow-up review after the diagnosis of a secondary tumour, 3 patients died related to the secondary tumours (2 sarcomas, 1 glioblastoma), one died of a recurrent primary glioma, while the remaining 7 have been alive for from 10 months to 12 years after being treated for the secondary tumours (median: 3 years). , In particular, children treated with X-irradiation for acute lymphoblastic leukemia show a significantly elevated risk of developing gliomas and primitive neuroectodermal tumor (PNET), often within 10 years after therapy. TP53 mutations are frequent in low-grade gliomas and secondary glioblastomas derived therefrom., Pathologic diagnoses were one glioblastoma, two cases of anaplastic astrocytoma, one medulloblastoma, one low-grade glioma, one high-grade glial tumor, and one atypical meningioma., A 22 year-old-man with acute lymphoblastic leukaemia had received prophylactic cranial irradiation and intrathecal chemotherapy. Eighteen years later a cerebellar glioblastoma multiforme was diagnosed. , She developed glioblastoma 5.7 years after the initial GK surgery.[SEP]", "label": "yes"}
{"id": "converted_3799", "sentence1": "Can SMAD6 variants cause craniosynostosis?", "sentence2": "SMAD6 variants in craniosynostosis: genotype and phenotype evaluation., Enrichment of heterozygous missense and truncating SMAD6 variants was previously reported in nonsyndromic sagittal and metopic synostosis, and interaction of SMAD6 variants with a common polymorphism nearBMP2 (rs1884302) was proposed to contribute to inconsistent penetrance. We determined the occurrence of SMAD6 variants in all types of craniosynostosis, evaluated the impact of different missense variants on SMAD6 function, and tested independently whether rs1884302 genotype significantly modifies the phenotype.METHODS: We performed resequencing of SMAD6 in 795 unsolved patients with any type of craniosynostosis and genotyped rs1884302 in SMAD6-positive individuals and relatives. We examined the inhibitory activity and stability of SMAD6 missense variants.RESULTS: We found 18 (2.3%) different rare damaging SMAD6 variants, with the highest prevalence in metopic synostosis (5.8%) and an 18.3-fold enrichment of loss-of-function variants comparedwith gnomAD data (P < 10-7). Combined with eight additional variants, ≥20/26 were transmitted from an unaffected parent but rs1884302 genotype did not predict phenotype.CONCLUSION: Pathogenic SMAD6 variants substantially increase the risk of both nonsyndromic and syndromic presentations of craniosynostosis, especially metopic synostosis. Functional analysis is important to evaluate missense variants. Genotyping of rs1884302 is not clinically useful. Mechanisms to explain the remarkable diversity of phenotypes associated with SMAD6 variants remain obscure.[SEP]", "label": "yes"}
{"id": "converted_2630", "sentence1": "Is there any role of interleukin-11 in cardiovascular fibrosis?", "sentence2": "IL11 is a crucial determinant of cardiovascular fibrosis., Using integrated imaging-genomics analyses of primary human fibroblasts, we found that Interleukin 11 (IL11) upregulation is the dominant transcriptional response to TGFB1 exposure and required for its profibrotic effect. IL11 and its receptor (IL11RA) are expressed specifically in fibroblasts where they drive non-canonical, ERK-dependent autocrine signalling that is required for fibrogenic protein synthesis. In mice, fibroblast-specific Il11 transgene expression or Il11 injection causes heart and kidney fibrosis and organ failure whereas genetic deletion of Il11ra1 is protective against disease. Thus, inhibition of IL11 prevents fibroblast activation across organs and species in response to a range of important pro-fibrotic stimuli. These data reveal a central role of IL11 in fibrosis and we propose inhibition of IL11 as a new therapeutic strategy to treat fibrotic diseases., IL11 is a crucial determinant of cardiovascular fibrosis.[SEP]", "label": "yes"}
{"id": "converted_3803", "sentence1": "Is Tcf3 associated with the Wnt pathway?", "sentence2": "TCF3, a novel positive regulator of osteogenesis, plays a crucial role in miR-17 modulating the diverse effect of canonical Wnt signaling in different microenvironments, Furthermore, the role of miR-17 was because of its target gene TCF3 (transcription factor 3), a key transcription factor of canonical Wnt pathway., Consequently, Tcf3 knockdown in HCT-R cells restores their sensitivity to the effects of butyrate on Wnt activity and clonal cell growth. Interestingly, the effects of overexpressed Tcf3 differ between HCT-116 and HCT-R cells, In HCT-R cells, however, the overexpression of Tcf3 inhibits Wnt activity, and the cells are still able to proliferate due to the higher expression levels of cell cycle factors, particularly those driving the G(1) to S transition., TCF3 (also known as TCF7L1) is a member of the TCF/LEF transcription factor family that is central in regulating epidermal and embryonic stem cell identity., We found that in contrast to ES cells, where it represses Wnt-pathway target genes, TCF3 promotes the expression of a subset of Wnt-responsive genes in breast cancer cells while repressing another distinct target subset. In the normal mouse mammary gland, Tcf3 is highly expressed in terminal end buds, structures that lead duct development, Tcf3 is essential within the neural ectoderm to maintain anterior character and that its interaction with Hesx1 ensures the repression of Wnt targets in the developing forebrain., We report here that a terminal component of the canonical Wnt pathway in ES cells, the transcription factor T-cell factor-3 (Tcf3), co-occupies promoters throughout the genome in association with the pluripotency regulators Oct4 and Nanog. , Our results suggest that the Wnt pathway, through Tcf3, brings developmental signals directly to the core regulatory circuitry of ES cells to influence the balance between pluripotency and differentiation., The wnt pathway regulates the steady state level of beta-catenin, a transcriptional coactivator for the Tcf3/Lef1 family of DNA binding proteins., Along with evidence that a significant amount of Tcf protein is nonnuclear, these findings suggest that CK1epsilon can modulate wnt signaling in vivo by regulating both the beta-catenin-Tcf3 and the GBP-dsh interfaces., RA increases the expression of ligands and receptors of the noncanonical Wnt pathway (Wnt 5a, 7a, Fzd2 and Fzd6), downstream signaling, and Tcf3 expression., The noncanonical Wnt signaling pathway, through actions of Tcf3, can antagonize the canonical pathway., We report here that a terminal component of the canonical Wnt pathway in ES cells, the transcription factor T-cell factor-3 (Tcf3), co-occupies promoters throughout the genome in association with the pluripotency regulators Oct4 and Nanog., Both Tcf3 depletion and Wnt pathway activation cause increased expression of Oct4, Nanog, and other pluripotency factors and produce ES cells that are refractory to differentiation., Here, we show that injection of a hesx1 morpholino into a 'sensitised' zygotic headless (tcf3) mutant background leads to severe forebrain and eye defects, suggesting an interaction between Hesx1 and the Wnt pathway during zebrafish forebrain development., In addition, we reveal that Tcf3 is essential within the neural ectoderm to maintain anterior character and that its interaction with Hesx1 ensures the repression of Wnt targets in the developing forebrain., TCF3, a novel positive regulator of osteogenesis, plays a crucial role in miR-17 modulating the diverse effect of canonical Wnt signaling in different microenvironments., Our studies located the position of Wnts, downstream LEF1 and TCF3 and stem cell marker proteins, which provide new information in understanding the role of the Wnt singaling pathway in whisker follicles' growth., The transcription factor T-cell factor 3 (TCF3), one component of the Wnt pathway, is known as a cell-intrinsic inhibitor of many pluripotency genes in embryonic stem cells (ESCs) that influences the balance between pluripotency and differentiation., Overexpression of TCF3 attenuated the effect of miR-17 on modulating canonical Wnt signaling., We also find that TCF3 phosphorylation is triggered by canonical Wnt ligands, LRP6, and dominant negative mutants for Axin and GSK3, indicating that this process shares the same upstream regulators with β-catenin stabilization., Wnt pathway stimulation also triggers β-catenin association at regulatory elements with classic Lef/Tcf motifs associated with differentiation programs., We show that menin physically interacts with proteins involved in the canonical Wnt signaling pathway, including beta-catenin, TCF3 (TCFL1), and weakly with TCF4 (TCFL2)., T-cell factor 3 (Tcf3) is a component of the Wnt signaling and a dominant downstream effector in ESCs.,  factor 3 (Tcf3) is a component of the Wnt signaling and a dominant downstream effector in ESCs. Despit, rt here that a terminal component of the canonical Wnt pathway in ES cells, the transcription factor T-cell factor-3 (Tcf3), co-occupies promoters throughout the genome in association with the pluripotency regulators Oct4 and Nanog. Thus, Tc, Tcf3, is recruited to a palindromic motif enriched in the promoter of cell cycle repressor genes, such as p15Ink4b, p16Ink4a and p19Arf, which mediate the Wnt-dependent anti-proliferative effect in mESCs. Consistently, abl, nonical Wnt/β-catenin pathway controls mESC pluripotency via the Wnt-effector Tcf3. Howe, g increases the dissociation of Tcf1 and the association of Tcf3 at promoters of genes that regulate stemness (e.g., NR5A2, Lrh-1) or differentiation (e.g. Cyr61, Zic5). Knockdown of Tcf3 increases, pport the existence of a regulatory circuit whereby Wnt/β-catenin counteracts Tcf3 repression of Lef1, which subsequently activates target gene expression via Lef1-β-catenin complexes. We propose that the Tcf/,  with a requirement for Wnt signalling repression, we highlight a synergistic gene dosage-dependent interaction between Hesx1 and Tcf3, a transcriptional repressor of Wnt target genes, to maintain anterior forebrain identity during mouse embryogenesis. In addition, expression of ligands and receptors of the noncanonical Wnt pathway (Wnt 5a, 7a, Fzd2 and Fzd6), downstream signaling, and Tcf3 expression. RA reduces the phosp, BACKGROUND AND OBJECTIVES: Transcription factor 3 (TCF3) implicates Wnt signaling pathway and regulates E-cadherin expression, which is involved i, We demonstrate that mouse Tcf3 mediates repression of both moderate and high levels of canonical Wnt signaling, by either competing with other members of the Tcf/Lef family for binding to β-catenin, or for binding to DNA., TCF3 is a transcriptional repressor that has been implicated in Wnt signaling and plays key roles in embryonic axis specification and stem cell differentiation., Our data show for the first time that Wnt signaling down-regulates Tcf3 expression, possibly at both the transcriptional and post-transcriptional levels, and thus highlight a novel mechanism through which Wnt signaling inhibits neuro-ectodermal lineage differentiation in mouse embryonic stem cells., We found Tcf3 to be a repressor of Wnt signaling in neocortical NPCs in a reporter gene assay., We found that down-regulation of Tcf3, a member of the Tcf/Lef family and a key player in the control of self-renewal and pluripotency, represents a specific and primary response to Wnt activation in ESCs., Wnt16b also activated the RhoA/Rac1 signaling cascade suggesting the activation of a non-canonical Wnt pathway in TCF3-PBX1 cells., B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with TCF3-PBX1 fusion gene expression has constitutively elevated levels of Wnt16b and ROR1 (receptor tyrosine kinase-like orphan receptor), a ligand and a receptor from the Wnt signaling pathway, respectively., We found that in contrast to ES cells, where it represses Wnt-pathway target genes, TCF3 promotes the expression of a subset of Wnt-responsive genes in breast cancer cells while repressing another distinct target subset., Together, these results suggest that Tcf3 antagonizes Wnt signaling in NPCs, thereby maintaining their undifferentiated state in the neocortex and that Wnt signaling promotes the transition from Tcf3-mediated repression to Tcf1/Lef1-mediated enhancement of Wnt signaling, constituting a positive feedback loop that facilitates neuronal differentiation., We also found that Wnt signal stimulation reduces the level of Tcf3, and increases those of Tcf1 (also known as Tcf7) and Lef1, positive mediators of Wnt signaling, in NPCs., These data suggest that in the absence of Wnt signals, Tcf3 may function in skin SCs to maintain an undifferentiated state and, through Wnt signaling, directs these cells along the hair lineage.[SEP]", "label": "yes"}
{"id": "converted_1432", "sentence1": "Do U6-associated proteins Lsm4 and Lsm6 interact with SMN?", "sentence2": "SMN also interacts with at least two of the U6-associated Sm-like (Lsm) proteins, Lsm4 and Lsm6. , Interestingly, SMN also interacts with at least two of the U6-associated Sm-like (Lsm) proteins, Lsm4 and Lsm6, Furthermore, we present evidence for two separate binding sites in SMN for Sm/Lsm proteins., Interestingly, SMN also interacts with at least two of the U6-associated Sm-like (Lsm) proteins, Lsm4 and Lsm6. , Symmetrical dimethylation of arginine residues in spliceosomal Sm protein B/B' and the Sm-like protein LSm4, and their interaction with the SMN protein., Interestingly, SMN also interacts with at least two of the U6-associated Sm-like (Lsm) proteins, Lsm4 and Lsm6. Furthermore, the carboxyl-terminal arginine- and glycine-rich domain of Lsm4 directly interacts with SMN., This entity promotes the binding of a set of factors, termed LSm/Sm proteins, onto snRNA to form the core structure of these particles. , Toward an assembly line for U7 snRNPs: interactions of U7-specific Lsm proteins with PRMT5 and SMN complexes., In this report, we demonstrate that the coilin C-terminal domain binds directly to various Sm and Lsm proteins via their Sm motifs. We show that the region of coilin responsible for this binding activity is separable from that which binds to SMN., Thus, the ability to interact with free Sm (and Lsm) proteins as well as with intact snRNPs, indicates that coilin and CBs may facilitate the modification of newly formed snRNPs, the regeneration of 'mature' snRNPs, or the reclamation of unassembled snRNP components., Moreover this structure has important consequences for snRNP assembly that is mediated by two complexes containing the PRMT5 methyltransferase and the SMN (survival of motor neurons) protein, respectively., Arginine/glycine (RG)-rich domains in components of the SMN complex interact with Sm, like-Sm (LSm), fibrillarin, RNA helicase A (Gu), and coilin proteins, all of which are antigen targets in a variety of diseases. [SEP]", "label": "yes"}
{"id": "converted_2282", "sentence1": "Is dasatinib effective for treatment of glioblastoma?", "sentence2": "RESULTS: fourteen randomized clinical trials were identified (7 with bevacizumab, 2 cilengitide, 1 enzastaurin, 1 dasatinib, 1 vandetanib, 1 temsirolimus, 1 cediranib) including 4330 patients. Antiangiogenic drugs showed no improvement in overall survival with a pooled HR of 1.00, a trend for an inferior outcome, in terms of overall survival, was observed in the group of patients receiving antiangiogenic drug alone compared to cytotoxic drug alone (HR=1.24, p=0.056)., CONCLUSIONS: Intraparticipant dose escalation was feasible, but dasatinib was ineffective in recurrent GBM. , Median progression-free survival (PFS) was 1.35 months (95% confidence interval: 1.2-1.4) and 6-month PFS was 7.7%. In this phase I study of recurrent glioblastoma patients, the combination of CCNU and dasatinib showed significant hematological toxicities and led to suboptimal exposure to both agents., Dasatinib in conjunction with bevacizumab does not appear to have activity in patients with recurrent, heavily pretreated GBM.[SEP]", "label": "no"}
{"id": "converted_282", "sentence1": "Is the Wnt protein modified by notum?", "sentence2": "Notum deacylates Wnt proteins to suppress signalling activity., Kinetic and mass spectrometric analyses of human proteins show that Notum is a carboxylesterase that removes an essential palmitoleate moiety from Wnt proteins and thus constitutes the first known extracellular protein deacylase., the Wnt inhibitor notum, the WNT-inhibitor notum.[SEP]", "label": "yes"}
{"id": "converted_3024", "sentence1": "Is deletion at 6q24.2-26 associated with longer survival of patients with high-grade serous ovarian carcinoma (HGSOCs)?", "sentence2": "Deletion at 6q24.2-26 predicts longer survival of high-grade serous epithelial ovarian cancer patients., We found that loss at 6q24.2-26 was significantly associated with the cluster of longer survival independently from other confounding factors (HR = 0.06, 95%CI = 0.01-0.43, Padj = 0.005). The prognostic value of this deletion was validated in two independent series, one consisting of 36 HGSOCs analyzed by fluorescent in situ hybridization (P = 0.04) and another comprised of 411 HGSOCs from the Cancer Genome Atlas study (TCGA) (HR = 0.67, 95%CI = 0.48-0.93, Padj = 0.019). In addition, we confirmed the association of low expression of the genes from the region with longer survival in 799 HGSOCs (HR = 0.74, 95%CI = 0.61-0.90, log-rank P = 0.002) and 675 high-FIGO stage HGSOCs (HR = 0.76, 95%CI = 0.61-0.96, log-rank P = 0.02) available from the online tool KM-plotter. Finally, by integrating copy number, RNAseq and survival data of 296 HGSOCs from TCGA we propose a few candidate genes that can potentially explain the association. Altogether our findings indicate that the 6q24.2-26 deletion is an independent marker of favorable outcome in HGSOCs with potential clinical value as it can be analyzed by FISH on tumor sections and guide the selection of patients towards more conservative therapeutic strategies in order to reduce side-effects and improve quality of life., Altogether our findings indicate that the 6q24.2-26 deletion is an independent marker of favorable outcome in HGSOCs with potential clinical value as it can be analyzed by FISH on tumor sections and guide the selection of patients towards more conservative therapeutic strategies in order to reduce side-effects and improve quality of life., OBJECTIVE\nWe aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients., OBJECTIVE We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients., Altogether our findings indicate that the 6q24.2-26 deletion is an independent marker of favorable outcome in HGSOCs with potential clinical value as it can be analyzed by FISH on tumor sections and guide the selection of patients towards more conservative therapeutic strategies in order to reduce side-effects and improve quality of life.<br>, <b>OBJECTIVE</b>: We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients.<br><b>METHODS</b>: In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays., We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients.[SEP]", "label": "yes"}
{"id": "converted_3384", "sentence1": "Does the chromatin remodeling complex, RSC target H2A.Z nucleosomes?", "sentence2": "In contrast, the upstream nucleosome which covers the TATA box under repressed conditions is shifted approximately 50 bp further upstream by the ATP-dependent chromatin remodeler RSC upon activation. It is marked with the histone variant H2A.Z and H4K16 acetylation in active state, In RSC-depleted cells, NFRs shrink such that the average positions of flanking nucleosomes move toward predicted sites., In contrast, H2A.Z deposition is dispensable for nucleosome positioning. , Emerging lines of evidence indicate that histone variants (H2AX and H2A.Z), histone post-translational modifications (acetylation, phosphorylation, methylation and ubiquitination) and chromatin-remodeling complexes (INO80, SWR1, SWI/SNF, RSC and NuRD) are important and direct players in the DNA double-strand break (DSB) response as well., H2A.Z probably helps RSC in keeping the gene nucleosome-fre, Accordingly, the absence of SWR-C or histone H2A.Z results in compromised chromatin remodeling and impaired gene expression in the absence of RSC and H3K4 methylation.[SEP]", "label": "yes"}
{"id": "converted_2176", "sentence1": "Is dexamethasone recommended for treatment of intracerebral hemorrhage?", "sentence2": "Dexamethasone and other glucocorticoids should be avoided. , During the third interim analysis, the death rate at the 21st day was identical in the two groups (dexamethasone vs. placebo, 21 of 46 vs. 21 of 47; chi-square = 0.01, P = 0.93). In contrast, the rate of complications (mostly infections and complications of diabetes) was much higher in the dexamethasone group (chi-square = 10.89, P less than 0.001), leading to early termination of the study. In the light of the absence of a demonstrable beneficial effect and the presence of a significant harmful effect, current practices of using dexamethasone for treatment of primary supratentorial hemorrhage should be reconsidered., In the light of the absence of a demonstrable beneficial effect and the presence of a significant harmful effect, current practices of using dexamethasone for treatment of primary supratentorial hemorrhage should be reconsidered.[SEP]", "label": "no"}
{"id": "converted_3449", "sentence1": "Can Flotillin be used as exosomal marker?", "sentence2": "Flotillin 1 and tumor susceptibility gene 101 (TSG101), two exosomal marker proteins, , expressed exosomal marker tumor susceptibility gene (TSG) 101 and flotillin (Flot) 1.[SEP]", "label": "yes"}
{"id": "converted_2187", "sentence1": "Is edema a symptom of nephrotic syndrome?", "sentence2": "Nephrotic syndrome (NS) is a common clinical disease with four main clinical manifestations: hypoalbuminemia (<30 g/L), macro-proteinuria (>3.5 g/24 h), edema, and hyperlipidemia. , Nephrotic syndrome is an unusual manifestation of IgA Nephropathy (IgAN)., Twelve patients with IgAN with steroid-responsive nephrotic syndrome were evaluated and followed up. All patients presented with generalized edema. , The clinical features of sudden onset of generalized edema, initial heavy proteinuria and initial severe hypoalbuminemia might help identify the subset of patients, especially in low grade IgAN., Most patients presented within 3 months duration (61.4%) and the most common symptom was puffiness of face (98.45%) followed by pedal edema (91%). , We analyzed medical records of 290 patients with diagnosis of nephrotic syndrome as defined by International Study of Kidney Disease in Children (ISKDC), between January 1987 and December 2000, at the Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar. , He was admitted because of systemic edema and dyspnea on effort Laboratory data revealed renal failure and nephrotic syndrome, whereas there was no symptom of diabetic retinopathy., Nephrotic syndrome: more than just oedema., Oedema is the commonest presenting symptom and sign in nephrotic syndrome. , One of these five clinical syndromes is the nephrotic syndrome, which is characterized by proteinuria > 3.5 g/day accompanied by hypalbuminemia, hyperlipoproteinemia and pronounced edema, Tolvaptan therapy for massive edema in a patient with nephrotic syndrome, Nephrotic syndrome (NS) is characterized by water and sodium retention, which leads to edema, The non-osmotic stimulation of arginine vasopressin release from the pituitary gland has been implicated as one of the important factors in abnormal water retention in patients with NS.We present the initial description of a patient with massive edema caused by refractory nephrotic syndrome, which was effectively treated with tolvaptan, a selective oral vasopressin V2 receptor antagonist.Tolvaptan is effective for the treatment of massive edema caused by NS, We report a child with steroid-resistant nephrotic syndrome with diuretic-resistant nephrotic edema treated successfully using acute peritoneal dialysis as a means of UF, Albumin and Furosemide Combination for Management of Edema in Nephrotic Syndrome: A Review of Clinical Studies, The treatment of edema in patients with nephrotic syndrome is generally managed by dietary sodium restriction and loop diuretics, Nine months after introduction of tiopronin, the boy manifested generalized edema, oliguria, and biochemical indices of nephrotic syndrome, Blessed were the days when it all made sense and the apparent mechanism for edema formation in nephrotic syndrome was straightforward: the kidneys lost protein in the urine, which lowered the plasma oncotic pressure, The nephrotic syndrome is characterized by a combination of pathological lab values and clinical symptoms, i. e. pronounced proteinuria (usually more than 3 - 3,5 g protein/24 h), hypoalbuminemia, edema and hyperlipidemia., The patient was admitted with edema of both legs, and the nephrotic syndrome was discovered, leading to the diagnosis of AA amyloidosis on kidney biopsy., Linear regression to relate measures.Other signs and symptoms of nephrotic syndrome at baseline (serum albumin < 3.5 g/dL, serum total cholesterol > 260 mg/dL or use of a statin, and edema or use of a loop diuretic); progression of chronic kidney disease during follow-up (doubling of baseline serum creatinine level or requirement for dialysis or kidney transplantation)., A case of interstitial shadows associated with oral cyclophosphamide therapy in a 32-month-old girl with steroid-resistant nephrotic syndrome, who was admitted to the Nishi-Kobe Medical Center with systemic edema, is reported., Nephrotic syndrome represents a constellation of symptoms including hyperalbuminuria, hypoalbuminemia, edema formation, hypercholesterolemia, hypertension, hypercoagulopathy, and increased infection risk., Pathophysiology of edema formation in children with nephrotic syndrome not due to minimal change disease., To study the evidence-based therapy of edema in nephrotic syndrome by analyzing the literatures systematically., Edema is the prominent feature of nephrotic syndrome and initially develops around the eyes and legs., Intussusception should be considered in the differential diagnosis of abdominal pain in patients with nephrotic syndrome, especially in patients exhibiting prolonged edema., Oedema is the commonest presenting symptom and sign in nephrotic syndrome., Other signs and symptoms of nephrotic syndrome at baseline (serum albumin < 3.5 g/dL, serum total cholesterol > 260 mg/dL or use of a statin, and edema or use of a loop diuretic); progression of chronic kidney disease during follow-up (doubling of baseline serum creatinine level or requirement for dialysis or kidney transplantation).[SEP]", "label": "yes"}
{"id": "converted_317", "sentence1": "Have mutations in the Polycomb group been found in human diseases?", "sentence2": "We identify a novel mutation in PHC1, a human orthologue of the Drosophila polyhomeotic member of polycomb group (PcG), which significantly decreases PHC1 protein expression, increases Geminin protein level and markedly abolishes the capacity to ubiquitinate histone H2A in patient cells., In clinical specimens of head and neck cancer, we found that coamplification of BMI1 and AURKA correlated with poorer prognosis., Mutations of EZH2, RUNX1, TP53, and ASXL1 were associated with shorter overall survival independent of the LR-PSS., In this study, we show the high frequency of spontaneous γδ T-cell leukemia (T-ALL) occurrence in mice with biallelic deletion of enhancer of zeste homolog 2 (Ezh2)., Subsequently, analysis of deletion profiles of other PRC2 members revealed frequent losses of genes such as EZH2, AEBP2, and SUZ12; however, the deletions targeting these genes were large. We also identified two patients with homozygous losses of JARID2 and AEBP2. We observed frequent codeletion of AEBP2 and ETV6, and similarly, SUZ12 and NF1., A total of 25 different EZH2 mutations were detected in 5.9% of PMF, 1.2% of PPV-MF, and 9.4% of PET-MF patients; most were exonic heterozygous missense changes., In the present investigation we have focused on the candidate region in 6p23, a region that have been found linked to CL/P in several investigations, in the attempt to find out the susceptibility gene provisionally named OFC1. Gene expression experiments in mice embryo of positional candidate genes revealed that JARID2 was highly and specifically expressed in epithelial cells in merging palatal shelves., High expression of EZH2 and amplification of EZH2 was found in 54.1% and 12.0% of ESCCs, respectively., We also observed that HOXA9 levels were significantly inversely correlated with survival and that BMI-1 was overexpressed in cases with 11q23 rearrangements, suggesting that p19(ARF) suppression may be involved in MLL-associated leukemia., We demonstrate that in multiple experimental models of metastatic prostate cancer both BMI1 and Ezh2 genes are amplified and gene amplification is associated with increased expression of corresponding mRNAs and proteins., he EZH2 gene amplification was significantly (P < 0.05) associated with increased EZH2 protein expression., The third tumor showed a t(6p;10q;10p) as the sole karyotypic abnormality, leading to the fusion of PHF1 with another partner, the enhancer of polycomb (EPC1) gene from 10p11; EPC1 has hitherto not been associated with neoplasia.[SEP]", "label": "yes"}
{"id": "converted_4277", "sentence1": "Αre plants from the genus Strychnos the original source of curare?", "sentence2": "Poisons are widespread in plants and animals and humankind has often tried to turn them to its own advantage. Owing to their poisonous properties, some species of Strychnos genus have been employed mainly in hunting and fishing, as an adjunct to weapons used not only in the search of food and clothes, but also for preventing depredation by wild animals. They have been employed for martial and criminal purposes and also as a means of determining guilt or innocence. By their nature, poisons such as strychnine and curare affect the functioning of the victim's body; , The ethnobotanical uses of South American species of Strychnos L. (Loganiaceae) are reviewed, with the exception of their major rôle in the preparation of curare, which will be dealt with in detail elsewhere., VELOPMENT: Curare is prepared by boiling the roots, bark and stalks of different plants belonging to the Loganiaceae (Strychnos) and Menispermaceae families (Chondrodendron, Curarea and Abuta). , The history to about 1850 of the muscle-relaxant poison curare is discussed, especially the developments leading to the botanical identification of the plants that yield the alkaloidal active principles: Loganiaceae (Strychnos species) and Menispermaceae (Abuta, Chondrodendron, and Curarea species)., or centuries. The study reviews the historical and ethnographic aspects of the use of curares and timbós in the Amazonian region.DEVELOPMENT: Curare is prepared by boiling the roots, bark and stalks of different plants belonging to the Loganiaceae (Strychnos) and Menispermaceae families (Chondrod[SEP]", "label": "yes"}
{"id": "converted_3362", "sentence1": "Is CTCF bound at nucleosome free regions?", "sentence2": "Nucleosome depletion at 5'-HS4 was dependent on interaction of the insulator protein CCCTC-binding factor (CTCF) and was required for enhancer blocking. , Here, we show that promoter classes are significantly differentiated by nucleosome organization and chromatin structure. Dispersed promoters display higher associations with well-positioned nucleosomes downstream of the TSS and a more clearly defined nucleosome free region upstream, while focused promoters have a less organized nucleosome structure, yet higher presence of RNA polymerase II., hese differences extend to histone variants (H2A.Z) and marks (H3K4 methylation), as well as insulator binding (such as CTCF), independent of the expression levels of affected genes., nucleosome occupancy at nucleosome-free regions (NFRs), many of which are located at sites occupied by the multivalent factors Ctcf and cohesin. , This general architectural change correlates with enhanced binding of CTCF and cohesins and more pronounced insulation of contacts across chromatin boundaries in lineage-committed cells. , robust inter-nucleosomal interactions exist around transcription start site (TSS), transcription termination sites (TTS) or around CTCF binding sites[SEP]", "label": "yes"}
{"id": "converted_4566", "sentence1": "Is Otolin-1 a matrix protein?", "sentence2": "otoconia matrix protein, otolin-1, Otolin-1 is a collagen-like protein expressed in the inner ear of vertebrates. , Mammalian Otolin: a multimeric glycoprotein specific to the inner ear that interacts with otoconial matrix protein Otoconin-90 and Cerebellin-1, binds to otolin-1 and forming matrix protein architectures[SEP]", "label": "yes"}
{"id": "converted_375", "sentence1": "Is lambrolizumab effective for treatment of patients with melanoma ?", "sentence2": "However, through parallel efforts that have showcased the efficacy of small-molecule BRAF and MAP-ERK kinase (MEK) inhibitors, as well as the immune checkpoint inhibitors, namely ipilimumab and the anti-PD1/PDL1 antibodies (lambrolizumab, nivolumab, MPDL3280), an opportunity exists to transform the treatment of melanoma specifically and cancer generally by exploring rational combinations of molecularly targeted therapies, immunotherapies, and molecular targeted therapies with immunotherapies. , Programmed death-1 receptor (PD-1)/its ligand (PD-L1) antibodies have changed the landscape in oncology in 2013. The most mature results have been obtained in advanced melanoma patients. , Merck's lambrolizumab (MK-3475) monoclonal antibody received \"Breakthrough Therapy\" designation from the U.S. Food and Drug Administration in April for treating patients with advanced melanoma., The programmed death 1 (PD-1) receptor is a negative regulator of T-cell effector mechanisms that limits immune responses against cancer. We tested the anti-PD-1 antibody lambrolizumab (previously known as MK-3475) in patients with advanced melanoma. , In patients with advanced melanoma, including those who had had disease progression while they had been receiving ipilimumab, treatment with lambrolizumab resulted in a high rate of sustained tumor regression, with mainly grade 1 or 2 toxic effects. , Because of all these reasons PD-1/PD-L1 antibodies are considered 'drug of the year'.[SEP]", "label": "yes"}
{"id": "converted_22", "sentence1": "Are transcription and splicing connected?", "sentence2": ", as splicing is often cotranscriptional, a complex picture emerges in which splicing regulation not only depends on the balance of splicing factor binding to their pre-mRNA target sites but also on transcription-associated features such as protein recruitment to the transcribing machinery and elongation kinetics., recent evidence shows that chromatin structure is another layer of regulation that may act through various mechanisms, hese span from regulation of RNA polymerase II elongation, which ultimately determines splicing decisions, to splicing factor recruitment by specific histone marks., Chromatin may not only be involved in alternative splicing regulation but in constitutive exon recognition as well, Moreover, splicing was found to be necessary for the proper 'writing' of particular chromatin signatures, giving further mechanistic support to functional interconnections between splicing, transcription and chromatin structure., These links between chromatin configuration and splicing raise the intriguing possibility of the existence of a memory for splicing patterns to be inherited through epigenetic modifications., Spliceosome assembly occurs co-transcriptionally, raising the possibility that DNA structure may directly influence alternative splicing., upporting such an association, recent reports have identified distinct histone methylation patterns, elevated nucleosome occupancy and enriched DNA methylation at exons relative to introns, Moreover, the rate of transcription elongation has been linked to alternative splicing., ere we provide the first evidence that a DNA-binding protein, CCCTC-binding factor (CTCF), can promote inclusion of weak upstream exons by mediating local RNA polymerase II pausing both in a mammalian model system for alternative splicing, CD45, and genome-wide, We recently showed that cotranscriptional splicing occurs efficiently in Drosophila,, In recent years it became apparent that splicing is predominantly cotranscriptional, To determine the prevalence of cotranscriptional splicing in Drosophila, we sequenced nascent RNA transcripts from Drosophila S2 cells as well as from Drosophila heads. Eighty-seven percent of the introns assayed manifest >50% cotranscriptional splicing. The remaining 13% are cotranscriptionally spliced poorly or slowly, with ∼3% being almost completely retained in nascent pre-mRNA., We estimate that > or =90% of endogenous yeast splicing is posttranscriptional, consistent with an analysis of posttranscriptional snRNP-associated pre-mRNA., Notably, the topoisomerase I inhibitor camptothecin, which stalls elongating Pol II, increased cotranscriptional splicing factor accumulation and splicing in parallel. This provides direct evidence for a kinetic link between transcription, splicing factor recruitment and splicing catalysis., Recent evidence indicates that transcriptional elongation and splicing can be influenced reciprocally: Elongation rates control alternative splicing and splicing factors can, in turn, modulate pol II elongation., The presence of transcription factors in the spliceosome and the existence of proteins, such as the coactivator PGC-1, with dual activities in splicing and transcription can explain the links between both processes and add a new level of complexity to the regulation of gene expression in eukaryotes.[SEP]", "label": "yes"}
{"id": "converted_905", "sentence1": "Are viruses involved in the etiology of human subacute thyroiditis?", "sentence2": "he etiology of subacute (de Quervain's) thyroiditis (SAT) is uncertain, although it probably represents a nonspecific inflammatory response by the thyroid to a variety of viruses., Subacute thyroiditis is an inflammatory disorder of the thyroid caused probably by viruses. I, We believe that the etiologic agent was the Epstein-Barr virus because heterophile and Epstein-Barr virus-specific antibodies were positive., ltogether, these results indicate that the mechanism of inhibition of Spumavirinae infection by interferon differs from that described for the other Retroviridae, and particularly for types B, C and D viruses. Our data is of therapeutic interest since Spumavirinae have been linked to pathological processes such as de Quervain thyroiditis.[SEP]", "label": "yes"}
{"id": "converted_1929", "sentence1": "Can NADPH oxidase be inhibited by apocynin and diphenylene iodonium?", "sentence2": "Ang II treatment also led to a significant increment in intracellular reactive oxygen species generation, which could be fully abolished by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors apocynin or diphenylene iodonium, indicating that Ang II enhanced oxidative stress via a NADPH oxidase-dependent manner., NOX inhibitors (diphenylene iodonium (DPI) or apocynin) were able to achieve similar results to that of ML-7 except no effect on MLCK activity and MLC20 phosphorylation. , Significant reductions of AII effects on podocyte TRPC6 were also observed after pretreatment with NADPH oxidase inhibitors apocynin or diphenylene iodonium (DPI). , Furthermore, inhibition of NOX-mediated ROS production with apocynin, diphenylene iodonium (DPI) or NOX2 docking sequence (Nox2ds)-tat peptide during these first 4h of PE stimulation significantly inhibited PE-induced hypertrophy of H9c2 cells, both after 24 and 48h of PE stimulation. , Remarkably, Ang-II induced reactive oxygen species (ROS) via a NAD(P)H oxidase-dependent mechanism, as shown by inhibition of ROS production via the NAD(P)H oxidase inhibitors diphenylene iodonium (DPI) and apocynin. , Moreover, NADPH oxidase activation by beta CD (145.5+/-9.0%; control: 98.6+/-1.6%) was also abrogated by the NADPH oxidase inhibitors apocynin (100.4+/-3.2%) and diphenylene iodonium (9.5+/-3.3%)., We used structurally diverse NADPH oxidase inhibitors, aminoethyl-benzenesulfonylfluoride (AEBSF, 100-1000microM), apocynin (100-1000microM), and diphenylene iodonium (DPI, 3-30microM), to inhibit intrinsic NADPH oxidase activity in N27 cells., Paraquat-induced ROS production was inhibited by NADPH oxidase inhibitors, apocynin and diphenylene iodonium (DPI), but not the xanthine/xanthine oxidase inhibitor, allopurinol., With the use of dihydroethidium as a superoxide indicator, C(2)-ceramide was found to increase superoxide production in the endothelial cells of small coronary arteries, which was inhibited by the NADPH oxidase inhibitors N-vanillylnonanamide, apocynin, and diphenylene iodonium., The contractile responses to U46619 in isolated PA were inhibited by PEG-catalase and the NADPH oxidase inhibitors diphenylene iodonium (DPI) and apocynin., The effects of diphenylene iodonium (DPI) and apocynin, inhibitors of NADPH oxidase, on key parameters of PSC activation were evaluated in vitro., These effects could be inhibited by diphenylene iodonium and apocynin, indicating a self-cycle regulated by NADPH oxidase in microglial activation in response to oAâ., Diphenylene iodonium is an inhibitor of the respiratory burst-generating NADPH oxidase of phagocytes., NADPH oxidase inhibitors [diphenylene iodonium (DPI) and apocynin (4-hydroxy-3-methoxy-acetophenone)] prevented the microglial activation induced by oAâ, suggesting that NADPH oxidase activation was involved in microglial activation., In addition, inhibitors of NADPH oxidase (diphenylene iodonium or apocynin) also prevented microglia proliferation, suggesting that this may be the source of hydrogen peroxide., Inhibitors of NADPH oxidase (diphenylene iodonium, apocynin, D-(+)-neopterine) also significantly blunted the generation of reactive oxygen species, activation of K(+), Cl(-)-cotransport and apoptosis induced by N-ethylmaleimide., With the use of dihydroethidium as a superoxide indicator, C(2)-ceramide was found to increase superoxide production in the endothelial cells of small coronary arteries, which was inhibited by the NADPH oxidase inhibitors N-vanillylnonanamide, apocynin, and diphenylene iodonium., NADPH-dependent superoxide production by the solubilized oxidase of neutrophils was inhibited 36% by diphenylene iodonium at a 1:1 stoichiometry with the enzyme flavoprotein content., These effects could be inhibited by diphenylene iodonium and apocynin, indicating a self-cycle regulated by NADPH oxidase in microglial activation in response to oAβ, Moreover, CSE-regulated COX-2, PGE(2), and IL-6 generation was inhibited by pretreatment with TLR4 Ab; inhibitors of c-Src (PP1), NADPH oxidase (diphenylene iodonium chloride and apocynin), p38 MAPK (SB202190), MEK1/2 (U0126), JNK1/2 (SP600125), and NF-kappaB (helenalin); a ROS scavenger (N-acetyl-l-cysteine); and transfection with siRNA of TLR4, MyD88, TRAF6, Src, p47(phox), p38, p42, JNK2, or p65, Treatment of the cells with the NADPH oxidase inhibitors, apocynin and diphenylene iodonium, inhibited these effects, With the use of dihydroethidium as a superoxide indicator, C(2)-ceramide was found to increase superoxide production in the endothelial cells of small coronary arteries, which was inhibited by the NADPH oxidase inhibitors N-vanillylnonanamide, apocynin, and diphenylene iodonium, UVB irradiation generated ROS in a dose-dependent manner, and this was significantly inhibited by diphenylene iodonium (DPI), apocynin (Apo) and neopterine (Neo), inhibitors of the NADPH oxidase, and indomethacin (Indo), a cyclooxygenase (COX) inhibitor, but not by the mitochondrial electron transport inhibitors and other cytosolic enzyme inhibitors, In RBA-1 cells, JEV induced MMP-9 expression and promoter activity, which was inhibited by pretreatment with inhibitors of NADPH oxidase (diphenylene iodonium chloride or apocynin), MAPKs (U0126, SB203580 or SP600125) and a ROS scavenger (N-acetylcysteine), or transfection with siRNAs of p47(phox) , ERK1, JNK2 and p38, Such discharge of Dectin-1-reactive β-glucan from macrophage cells was inhibited by either NADPH oxidase inhibitors (apocynin and diphenylene iodonium) or radical scavengers (N-acetyl cysteine and MCI-186), The contractile responses to U46619 in isolated PA were inhibited by PEG-catalase and the NADPH oxidase inhibitors diphenylene iodonium (DPI) and apocynin, ANG II further increased superoxide production in LP only, and this was inhibited by coincubation with diphenylene iodonium or apocynin (inhibitor of NADPH oxidase complex), Our results showed that IL-1beta enhanced HTSMCs-monocyte adhesion through up-regulation of VCAM-1, which was inhibited by pretreatment with selective inhibitors of PKCalpha (Gö6976), c-Src (PP1), NADPH oxidase [diphenylene iodonium (DPI) and apocynin (APO)], intracellular calcium chelator (BAPTA/AM), PI-PLC (U73122), CaM (calmidazolium chloride), CaM kinase II (KN62), p300 (garcinol), NF-kappaB (Bay11-7082), HDAC (trichostatin A), and ROS scavenger [N-acetyl-L-cysteine (NAC)] or transfection with siRNAs of MyD88, PKCalpha, Src, p47(phox), p300, and HDAC4., Here we show that cAMP-dependent decidualization can be attenuated or enhanced upon treatment of primary cultures with a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor (diphenylen iodonium) or activator (apocynin), respectively. , With the use of dihydroethidium as a superoxide indicator, C(2)-ceramide was found to increase superoxide production in the endothelial cells of small coronary arteries, which was inhibited by the NADPH oxidase inhibitors N-vanillylnonanamide, apocynin, and diphenylene iodonium. , The inhibition of NAD(P)H oxidase by apocynin and diphenylene iodonium, and of the mitochondrial electron transport system at complex II by thenoyltrifluoroacetone (TTFA), significantly inhibited both AGE-induced ROS production and VCAM-1 expression, whereas these effects were potentiated by rotenone and antimycin A, specific inhibitors of mitochondrial complex I and III, respectively. , Paraquat-induced ROS production was inhibited by NADPH oxidase inhibitors, apocynin and diphenylene iodonium (DPI), but not the xanthine/xanthine oxidase inhibitor, allopurinol. , Treatment of the cells with the NADPH oxidase inhibitors, apocynin and diphenylene iodonium, inhibited these effects. , The G6PD inhibitor DHEA and the inhibitors of NADPH oxidase apocynin and diphenylene iodonium (DPI) prevented both superoxide generation and capacitation in human spermatozoa, but whereas DPI and DHEA inhibited PPP, apocynin did not influence it, suggesting that PPP activation during capacitation is not a response to increased oxidative stress but exerts a role by supplying reducing equivalents to oxygen., Ang II induced a time-dependent increase in Rac1 activation and O(2)(*-) production in Neuro-2A cells, and this was abolished by pretreatment with AdN17Rac1 or the NADPH oxidase inhibitors apocynin or diphenylene iodonium. , Paraquat-induced ROS production was inhibited by NADPH oxidase inhibitors, apocynin and diphenylene iodonium (DPI), but not the xanthine/xanthine oxidase inhibitor, allopurinol., In RBA-1 cells, JEV induced MMP-9 expression and promoter activity, which was inhibited by pretreatment with inhibitors of NADPH oxidase (diphenylene iodonium chloride or apocynin), MAPKs (U0126, SB203580 or SP600125) and a ROS scavenger (N-acetylcysteine), or transfection with siRNAs of p47(phox) , ERK1, JNK2 and p38., These effects could be inhibited by diphenylene iodonium and apocynin, indicating a self-cycle regulated by NADPH oxidase in microglial activation in response to oAβ., Treatment of the cells with the NADPH oxidase inhibitors, apocynin and diphenylene iodonium, inhibited these effects., UVB irradiation generated ROS in a dose-dependent manner, and this was significantly inhibited by diphenylene iodonium (DPI), apocynin (Apo) and neopterine (Neo), inhibitors of the NADPH oxidase, and indomethacin (Indo), a cyclooxygenase (COX) inhibitor, but not by the mitochondrial electron transport inhibitors and other cytosolic enzyme inhibitors., Such discharge of Dectin-1-reactive β-glucan from macrophage cells was inhibited by either NADPH oxidase inhibitors (apocynin and diphenylene iodonium) or radical scavengers (N-acetyl cysteine and MCI-186)., Our results showed that IL-1beta enhanced HTSMCs-monocyte adhesion through up-regulation of VCAM-1, which was inhibited by pretreatment with selective inhibitors of PKCalpha (Gö6976), c-Src (PP1), NADPH oxidase [diphenylene iodonium (DPI) and apocynin (APO)], intracellular calcium chelator (BAPTA/AM), PI-PLC (U73122), CaM (calmidazolium chloride), CaM kinase II (KN62), p300 (garcinol), NF-kappaB (Bay11-7082), HDAC (trichostatin A), and ROS scavenger [N-acetyl-L-cysteine (NAC)] or transfection w, Moreover, CSE-regulated COX-2, PGE(2), and IL-6 generation was inhibited by pretreatment with TLR4 Ab; inhibitors of c-Src (PP1), NADPH oxidase (diphenylene iodonium chloride and apocynin), p38 MAPK (SB202190), MEK1/2 (U0126), JNK1/2 (SP600125), and NF-kappaB (helenalin); a ROS scavenger (N-acetyl-l-cysteine); and transfection with siRNA of TLR4, MyD88, TRAF6, Src, p47(phox), p38, p42, JNK2, or p65., The use of diphenylene iodonium, an inhibitor of NADPH oxidase, to investigate the antimicrobial action of human monocyte derived macrophages., NADPH oxidase inhibitors [diphenylene iodonium (DPI) and apocynin (4-hydroxy-3-methoxy-acetophenone)] prevented the microglial activation induced by oAβ, suggesting that NADPH oxidase activation was involved in microglial activation., Furthermore, inhibition of NOX-mediated ROS production with apocynin, diphenylene iodonium (DPI) or NOX2 docking sequence (Nox2ds)-tat peptide during these first 4h of PE stimulation significantly inhibited PE-induced hypertrophy of H9c2 cells, both after 24 and 48h of PE stimulation., We compared the pharmacological profiles of the commonly used NADPH oxidase inhibitors, diphenylene iodonium (DPI), apocynin and 4-(2-amino-ethyl)-benzolsulphonyl-fluoride (AEBSF), as well as the novel triazolo pyrimidine VAS3947., IL-1beta and TNF-alpha rapidly stimulated the rate of hydrogen peroxide produced by isolated microglia, and this was inhibited by diphenylene iodonium, implying that the cytokines were acting directly on microglia to stimulate the NADPH oxidase., The fractions achieved the same effects that known NADPH oxidase inhibitors, such as diphenylene iodonium and apocynin, but they presented better hydrosolubility., Ang II induced a time-dependent increase in Rac1 activation and O(2)(*-) production in Neuro-2A cells, and this was abolished by pretreatment with AdN17Rac1 or the NADPH oxidase inhibitors apocynin or diphenylene iodonium.[SEP]", "label": "yes"}
{"id": "converted_1671", "sentence1": "Is LPS a microbial product?", "sentence2": "and microbial translocation [lipopolysaccaride (LPS), microbial 16S rDNA and sCD14] , Lipopolysaccharide sensing an important factor in the innate immune response to Gram-negative bacterial infections, bacterial lipopolysaccharide (LPS), sterile bacterial wall lipopolysaccharide (LPS) to investigate the changes in innate lung microbiota[SEP]", "label": "yes"}
{"id": "converted_3806", "sentence1": "Does head ct increase brain tumor risk?", "sentence2": "Excess relative risk of new brain tumor averaged 1.29 (95% confidence interval, 0.66-1.93) for pediatric patients exposed to one or more head CTs. Tumor incidence increased with number of pediatric head CTs in a dose-dependent manner, with measurable excess incidence even after a single scan. Converging evidence from epidemiological studies supported a small excess risk of brain tumor incidence after even a single CT exam in pediatric patients. , Recent epidemiologic evidence from a national registry of children who underwent CT scans suggests a higher-than-expected incidence of secondary tumors. , However, we found 1) a statistically significant correlation between radiation dose and age at procedure, as well as number and type of procedures, and 2) a substantial increase in lifetime predicted risk of tumor above baseline in the cohort of young children who undergo neurointerventions.CONCLUSIONS: Although neurointerventional procedures have dramatically improved the prognosis of children facing serious cerebrovascular conditions, the predicted risk of secondary tumors, particularly in the youngest patients and those undergoing multiple procedures, is sobering., Conclusion When prevalent cases of meningioma at first exposure to CT of the head are excluded, no statistically significant increase in risk of meningioma was found among exposed subjects compared with unexposed control subjects.,  data suggest that 1 excess brain malignancy occurred after 4000 brain CTs (40 mSv per scan) and that the estimated risk in the 10 years following CT exposure was 1 brain tumor per 10,000 patients exposed to a 10 mGy scan at less than 10 years of age.CONCLU, SIONS: The model predicts that the effective radiation dose from a single head CT is capable of inducing a thyroid or brain tumor in an infant or child. These, Neither whole head CT nor cumulative brain dose to the brain increased the risk of glioma or of all brain tumours., rison of exposed and unexposed cohorts showed that there was no statistically significant increase in the risk of meningioma after exposure to CT of the head (HR: 1.49; 95% confidence interval: 0.97, 2.30; P = .07). If incident c, from epidemiological studies supported a small excess risk of brain tumor incidence after even a single CT exam in pediatric patients. However, refined e, ve risk of new brain tumor averaged 1.29 (95% confidence interval, 0.66-1.93) for pediatric patients exposed to one or more head CTs. Tumor incidence,  CT nor cumulative brain dose to the brain increased the risk of glioma or of all brain tumours. Although this st, o for developing a brain tumour from having a brain CT was 0.93 (95% confidence interval: 0.38-1.82). This was har, Tumor incidence increased with number of pediatric head CTs in a dose-dependent manner, with measurable excess incidence even after a single scan., Converging evidence from epidemiological studies supported a small excess risk of brain tumor incidence after even a single CT exam in pediatric patients., Excess relative risk of new brain tumor averaged 1.29 (95% confidence interval, 0.66-1.93) for pediatric patients exposed to one or more head CTs., Epidemiological studies consistently cited increased tumor incidence in pediatric patients (ages 0-18) exposed to head CTs., RESULTS: A positive correlation between exposure to CT scans and developing central nervous system tumors was evident in all cohorts. The strength of the association varied across the studies. Exclusion of patients with predisposing factors to central nervous system tumors was examined in four studies with a decreased risk to develop central nervous system tumors noted in three studies. Two studies reported nonsignificant reduction in the excess relative risk per milliGray of brain dose after adjusting for predisposing factors, whereas the reduction was significant in one study. The frequency of CT exposure was proportional to the risk of developing tumors in two studies although not significantly maintained in two other studies. , RESULTS: The overall risk was not significantly different in the two cohorts (incidence rate=36.72 per 100 000 person-years in the exposed cohort, 28.48 per 100 000 person-years in the unexposed cohort, hazard ratio (HR)=1.29, 95% confidence interval (CI)=0.90-1.85). The risk of benign brain tumour was significantly higher in the exposed cohort than in the unexposed cohort (HR=2.97, 95% CI=1.49-5.93). The frequency of CT examination showed strong correlation with the subsequent overall risk of malignancy and benign brain tumour.CONCLUSIONS: We found that paediatric head CT examination was associated with an increased incidence of benign brain tumour., CONCLUSIONS: We found evidence that CT-related radiation exposure increases brain tumor risk. , Compared with the general population, incidence of brain tumors was higher in the cohort of children with CT scans, requiring cautious interpretation of the findings., BACKGROUND: Recent studies linking radiation exposure from pediatric computed tomography (CT) to increased risks of leukemia and brain tumors lacked data to control for cancer susceptibility syndromes (CSS). , IMPACT: Future studies should identify TSC patients in order to avoid overestimation of brain tumor risks due to radiation exposure from CT scans., The radiation-induced occurrence of meningiomas and other brain tumours most probably contributes to the continuously increasing incidence of these diseases which is observed in several industrial nations, as well as the exposure of the bone marrow by CT to the increase of childhood leukaemia., 1,000 annual paediatric CT investigations of the skull will lead to about 3 excess neoplasms in the head region, i.e., the probability of an induced late effect must be suspected in the range of some thousandths. [SEP]", "label": "yes"}
{"id": "converted_2461", "sentence1": "Does Evolocumab improve cognitive function?", "sentence2": "Conclusions In a randomized trial involving patients who received either evolocumab or placebo in addition to statin therapy, no significant between-group difference in cognitive function was observed over a median of 19 months. , Results A total of 1204 patients were followed for a median of 19 months; the mean (±SD) change from baseline over time in the raw score for the spatial working memory strategy index of executive function (primary end point) was -0.21±2.62 in the evolocumab group and -0.29±2.81 in the placebo group (P<0.001 for noninferiority; P=0.85 for superiority). There were no significant between-group differences in the secondary end points of scores for working memory (change in raw score, -0.52 in the evolocumab group and -0.93 in the placebo group), episodic memory (change in raw score, -1.53 and -1.53, respectively), or psychomotor speed (change in raw score, 5.2 msec and 0.9 msec, respectively). , Conclusions In a randomized trial involving patients who received either evolocumab or placebo in addition to statin therapy, no significant between-group difference in cognitive function was observed over a median of 19 months., There were no significant between-group differences in the secondary end points of scores for working memory (change in raw score, -0.52 in the evolocumab group and -0.93 in the placebo group), episodic memory (change in raw score, -1.53 and -1.53, respectively), or psychomotor speed (change in raw score, 5.2 msec and 0.9 msec, respectively).[SEP]", "label": "no"}
{"id": "converted_156", "sentence1": "Is the gene MAOA epigenetically modified by methylation?", "sentence2": "Evidence that the methylation state of the monoamine oxidase A (MAOA) gene predicts brain activity of MAO A enzyme in healthy men., We found significant interindividual differences in methylation status and methylation patterns of the core MAOA promoter. , In the present study, DNA methylation patterns in the MAOA regulatory and exon 1/intron 1 region were investigated for association with panic disorder with particular attention to possible effects of gender and environmental factors. ,  The present pilot data suggest a potential role of MAOA gene hypomethylation in the pathogenesis of panic disorder particularly in female patients, possibly mediating a detrimental influence of negative life events. , The MAOA promoter was hypermethylated immediately upstream of the start codon in cholangiocarcinoma samples and cell lines but not in nonmalignant counterparts. , MAOA promoter methylation and susceptibility to carotid atherosclerosis: role of familial factors in a monozygotic twin sample., Because twins reared together share early life experience, which may leave a long-lasting epigenetic mark, aberrant MAOA methylation may represent an early biomarker for unhealthy familial environment., Effects of MAOA promoter methylation on susceptibility to paranoid schizophrenia., In conclusion, abnormalities of DNA methylation at the MAOA promoter may be associated with schizophrenia in males., In our study we analyzed DNA methylation patterns of 14 neuropsychiatric genes (COMT, DAT1, GABRA1, GNB3, GRIN2B, HTR1B, HTR2A, 5-HTT, MAOA, MAOB, NOS1, NR3C1, TPH1 and TH). D, Our data suggest that aberrant epigenetic regulation of neuropsychiatric genes may contribute to the pathogenesis of BPD., We conclude that smoking reliably decreases MAOA methylation, but exact characterization of effects on level of methylation depend on genotype, smoking history, current smoking status, gender, and region of the promoter-associated CpG Island examined., Given that DNA methylation is linked to the regulation of gene expression, we hypothesized that epigenetic mechanisms factor into the MAOA expression,  the extended MAOA regulatory region contains two CpG islands (CGIs), one of which overlaps with the canonical MAOA promoter and the other is located further upstream; both CGIs exhibit sensitivity to differential methylation., Identification and characterization of putative methylation targets in the MAOA locus using bioinformatic approaches., DNA methylation is a key epigenetic mechanism involved in the developmental regulation of gene expression. , MAOA methylation is associated with nicotine and alcohol dependence in women., In recent years, the role of epigenetic phenomenon, such as methylation, in mediating vulnerability to behavioral illness has become increasingly appreciated. One prominent locus at which epigenetic phenomena are thought to be in play is the monoamine oxidase A (MAOA) locus. , We conclude that methylation of MAOA may play a significant role in common psychiatric illness and that further examination of epigenetic processes at this locus is in order., Analysis of CpG methylation in the MAOA promoter region revealed substantial methylation in females but not in males., Therefore, allelic mRNA expression is affected by genetic and epigenetic events, both with the potential to modulate biogenic amine tone in the CNS.[SEP]", "label": "yes"}
{"id": "converted_2476", "sentence1": "Can canagliflozin cause euglycemic diabetic ketoacidosis?", "sentence2": "CASE REPORT: We present a case of a 57-year-old woman with type 2 diabetes mellitus taking a combination of canagliflozin and metformin who presented with progressive altered mental status over the previous 2 days. Her work-up demonstrated a metabolic acidosis with an anion gap of 38 and a venous serum pH of 7.08. The serum glucose was 168 mg/dL. The urinalysis showed glucose>500 mg/dL and ketones of 80 mg/dL. Further evaluation demonstrated an elevated serum osmolality of 319 mOsm/kg and an acetone concentration of 93 mg/dL. She was treated with intravenous insulin and fluids, and the metabolic abnormalities and her altered mental status resolved within 36 h. This was the first episode of diabetic ketoacidosis (DKA) for this patient. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Diabetic patients on SGLT2 inhibitor medications are at risk for ketoacidosis. Due to the renal glucose-wasting properties of these drugs, they may present with ketoacidosis with only mild elevations in serum glucose, potentially complicating the diagnosis. , Euglycemic Diabetic Ketoacidosis with Persistent Diuresis Treated with Canagliflozin., We herein report the case of a 27-year-old Asian woman with type 2 diabetes who was treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor (canagliflozin) who developed euglycemic diabetic ketoacidosis and persistent diuresis in the absence of hyperglycemia., Canagliflozin raised the risk of amputations and the rate of fractures in the CANVAS trial, although more data are necessary before drawing definite conclusions. The risk of euglycemic diabetic ketoacidosis seems to be minimal when the drugs are prescribed properly., Severe Ketoacidosis Associated with Canagliflozin (Invokana): A Safety Concern.,  However, some serious side effects, including severe anion gap metabolic acidosis and euglycemic diabetic ketoacidosis (DKA), have been reported. , At present, the Food and Drug Administration (FDA) has only approved three medications (canagliflozin, dapagliflozin and empagliflozin) in this drug class for the management of Type 2 diabetes. In May 2015, the FDA issued a warning of ketoacidosis with use of this drug class., We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient., Nonconvulsive Status Epilepticus in Elderly Patients Receiving SSRIs; Euglycemic Diabetic Ketoacidosis Associated with Canagliflozin Use in a Type 1 Diabetic Patient; Duloxetine-Induced Galactorrhea; Canagliflozin-Associated Severe Hypercalcemia and Hypernatremia; Vemurafenib-Induced Fanconi Syndrome., Euglycemic Diabetic Ketoacidosis in a 27 year-old female patient with type-1-Diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor Canagliflozin., We are reporting a timely case of atypical euglycemic diabetic ketoacidosis in a type 1 diabetic patient treated with sodium-glucose cotransporter-2 (SGLT-2) inhibitor canagliflozin., Euglycemic ketoacidosis did not recur in our patient after discontinuing canagliflozin. , Euglycemic Diabetic Ketoacidosis With Prolonged Glucosuria Associated With the Sodium-Glucose Cotransporter-2 Canagliflozin., In this article, we present a case of a 50-year-old woman with type 2 diabetes who developed euglycemic DKA after initiating therapy with canagliflozin. , SGLT2 inhibitors such as canagliflozin may predispose patients not only to diabetic ketoacidosis but also to prolonged glucosuria., We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient.<br>, We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient., CONCLUSION Treatment with canagliflozin was associated with development of euglycemic ketoacidosis., Euglycemic Diabetic Ketoacidosis with Persistent Diuresis Treated with Canagliflozin., We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient.., Euglycemic Diabetic Ketoacidosis With Prolonged Glucosuria Associated With the Sodium-Glucose Cotransporter-2 Canagliflozin., Euglycemic Diabetic Ketoacidosis in a 27 year-old female patient with type-1-Diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor Canagliflozin.[SEP]", "label": "yes"}
{"id": "converted_1713", "sentence1": "Does the Oncotype DX test work with paraffin embedded tissues?", "sentence2": "The Oncotype-DX Breast Cancer Assay (Genomic Health, Redwood City, CA) quantifies gene expression for 21 genes in breast cancer tissue by performing reverse transcription polymerase chain reaction (RT-PCR) on formalin-fixed paraffin-embedded (FFPE) tumour blocks that are obtained during initial surgery (lumpectomy, mastectomy, or core biopsy) of women with early breast cancer that is newly diagnosed., Oncotype DXtrade mark, is a diagnostic test comprised of a 21-gene assay applied to paraffin-embedded breast cancer tissue, which allows physicians to predict subgroups of hormone-receptor-positive, node-negative patients who may benefit from hormonal therapy alone or require adjuvant chemotherapy to attain the best survival outcome., Oncotype DX is a clinically validated, high-complexity, multianalyte reverse transcription-PCR genomic test that predicts the likelihood of breast cancer recurrence in early-stage, node-negative, estrogen receptor-positive breast cancer. , We therefore investigated the analytical performance of the assay., Assays used a pooled RNA sample from fixed paraffin-embedded tissues to evaluate the analytical performance of a 21-gene panel with respect to amplification efficiency, precision, linearity, and dynamic range, as well as limits of detection and quantification., One such strategy is the 21-gene assay (Oncotype DX), which is currently in commercial use in the USA. One advantage of this test is the use of paraffin-embedded blocks instead of previous methods, which required fresh frozen tissue. , We used paraffin-embedded core biopsies from a completed phase II trial to identify genes that correlate with response to primary chemotherapy. , In addition to the individual genes, the correlation of the Oncotype DX Recurrence Score with pCR was examined, RNA was extracted from paraffin blocks, to develop the 21-gene Recurrence Score assay (Oncotype DX)[SEP]", "label": "yes"}
{"id": "converted_2129", "sentence1": "Is diphosphatidylglycerol (cardiolipin) a phospholipid of the mitochondrial membranes?", "sentence2": "A unique organelle for studying membrane biochemistry is the mitochondrion whose functionality depends on a coordinated supply of proteins and lipids. Mitochondria are capable of synthesizing several lipids autonomously such as phosphatidylglycerol, cardiolipin and in part phosphatidylethanolamine, phosphatidic acid and CDP-diacylglycerol., A small decrease of diphosphatidylglycerol also occurred in the hepatoma mitochondria inner membrane. , Diphosphatidylglycerol was confined to the mitochondrial fraction, where it represented about 7% of the total phosphoacylglycerols. , Mitochondrial membranes were isolated from the myocardium of young (4-month-old) and aged (33-month-old) male Long-Evans rats and compared in terms of cholesterol content and phospholipid and fatty acid composition. In aged rats, as compared to young, the major observations include: markedly higher cholesterol content; increased percentage of sphingomyelin and diphosphatidylglycerol (cardiolipin); , The polyglycerophosphatides (typified by diphosphatidylglycerol) were apparently synthesized in situ by intramitochondrial membrane-bound enzymes using CDP-diglycerides as intermediates. , Both the mitochondrial and microsomal fractions contained significant proportions of solvent front phospholipid (SFP) and whereas the mitochondrial SFP displayed the relatively unsaturated fatty acid composition characteristic of diphosphatidylglycerol (cardiolipin), the fatty acids of the microsomal SFP were distinctly more saturated., Ten to 15% of microsomal radioactive CDP-diglycerides was transferred to mitochondrial membranes and incorporated into mitochondrial radioactive lipids identified as phosphatidylglycerol, phosphatidylglycerophosphate, and, when [14C]linoleoyl CDP-diglycerides were used, diphosphatidylglycerol (cardiolipin)., The enzyme responsible for the conversion of phosphatidylglycerol to diphosphatidylglycerol (cardiolipin) in the presence of cytidine diphosphate diacylglycerol is firmly associated with mitochondrial membranes and is not extracted with hypotonic or hypertonic media or with nonionic detergents., The mechanism of cardiolipin (diphosphatidylglycerol) biosynthesis was examined in mitochondria and outer and inner mitochondrial membranes prepared from guinea pig and rat livers to determine whether this formation from phosphatidylglycerol was absolutely dependent on cytidinediphosphodiglyceride, as previously reported for intact mitochondria., In isolated mitochondrial outer membranes, cardiolipin (diphosphatidylglycerol) increased CPT1 activity 4-fold and the Km for carnitine 6-fold., Ten to 15% of microsomal radioactive CDP-diglycerides was transferred to mitochondrial membranes and incorporated into mitochondrial radioactive lipids identified as phosphatidylglycerol, phosphatidylglycerophosphate, and, when [14C]linoleoyl CDP-diglycerides were used, diphosphatidylglycerol (cardiolipin)., 90% or more of the phospholipid, cardiolipin was found in the mitochondrial membranes of wild type and petite yeast., Furthermore, the same mechanism for the biosynthesis of cardiolipin was operational in the outer and inner mitochondrial membranes., The mechanism of cardiolipin (diphosphatidylglycerol) biosynthesis was examined in mitochondria and outer and inner mitochondrial membranes prepared from guinea pig and rat livers to determine whether this formation from phosphatidylglycerol was absolutely dependent on cytidinediphosphodiglyceride, as previously reported for intact mitochondria, Cardiolipin (CL) is a key phospholipid in mitochondrial membranes, playing important roles in maintaining the functional integrity and dynamics of mitochondria in animals and yeasts, Cardiolipin, the specific phospholipid of mitochondria, is involved in the biogenesis, the dynamics, and the supramolecular organization of mitochondrial membranes, Cardiolipin (CL), the signature phospholipid of mitochondrial membranes, is crucial for both mitochondrial function and cellular processes outside of the mitochondria, Since it has been recognized that mitochondria are crucial not only for energy metabolism but also for other cellular functions, there has been a growing interest in cardiolipin, the specific phospholipid of mitochondrial membranes, Cardiolipin, the main anionic phospholipid in mitochondrial membranes, is expected to be a determinant in this adaptive mechanism since it modulates the activity of most membrane proteins, Ten to 15% of microsomal radioactive CDP-diglycerides was transferred to mitochondrial membranes and incorporated into mitochondrial radioactive lipids identified as phosphatidylglycerol, phosphatidylglycerophosphate, and, when [14C]linoleoyl CDP-diglycerides were used, diphosphatidylglycerol (cardiolipin), Cardiolipin is normally localized to the inner mitochondrial membrane; however, when cardiolipin becomes externalized to the surface of dysregulated mitochondria, it promotes inflammasome activation and stimulates the elimination of damaged or nonfunctional mitochondria by mitophagy, In isolated mitochondrial outer membranes, cardiolipin (diphosphatidylglycerol) increased CPT1 activity 4-fold and the Km for carnitine 6-fold. , Increasing levels of cardiolipin differentially influence packing of phospholipids found in the mitochondrial inner membrane., Here, we used Saccharomyces cerevisiae subjected to conditions that affect mitochondrial metabolism as a model to determine the possible role of cardiolipin in stress adaptation. , This decline of respiration was attributed to a progressive diminution of the number of mitochondria in copper-treated cells, based on the demonstration of the concomitant decline of (1) cardiolipin (diphosphatidylglycerol) and cytochrome aa3 (cytochrome oxidase), two specific markers of mitochondrial inner membrane, and (2) fumarase activity, a specific marker of mitochondrial matrix space., Diphosphatidylglycerol (DPG) or cardiolipin, a specific component of the inner mitochondrial membrane, represents about 4% of the total lipid content., Experimental results confirmed that the biosynthesis of cardiolipin, from the membrane-bound radioactive phosphatidylglycerol in intact mitochondria isolated from guinea pig and rat liver, was absolutely dependent on CDP-diglycerides and required the addition of divalent cations., We have shown that decrease of cardiolipin in mitochondrial membrane occurs early during ischemia, and only during the irreversible phase of ischemia are phosphatidylethanolamine and phosphatidylcholine broken down., Partial purification of diphosphatidylglycerol synthetase from liver mitochondrial membranes., A small decrease of diphosphatidylglycerol also occurred in the hepatoma mitochondria inner membrane.[SEP]", "label": "yes"}
{"id": "converted_4647", "sentence1": "Is telomestatin, a novel statin drug used to treat high cholesterol?", "sentence2": "Telomestatin is a natural product isolated from Streptomyces anulatus 3533-SV4 and has been shown to be a very potent telomerase inhibitor., Telomestatin, a potent telomerase inhibitor that interacts quite specifically with the human telomeric intramolecular g-quadruplex., Activity of a novel G-quadruplex-interactive telomerase inhibitor, telomestatin (SOT-095), ,  G-quadruplex-interactive telomerase inhibitor, telomestatin (SOT-095),,  We found that treatment with telomestatin reproducibly inhibited telomerase activity in the BCR-ABL-positive leukemic cell lines, A novel telomerase inhibitor, telomestatin, isolated from Streptomyces anulatus is the most potent telomerase inhibitor so far., Telomerase inhibitor, telomestatin, a specific mechanism to interact with telomere structure, Telomestatin specifically inhibited telomerase without affecting reverse transcriptases and polymerases., In addition, telomestatin induced telomere shortening, but its ratio was extremely faster than that observed in physiological telomere shortening., A novel telomerase inhibitor, telomestatin, isolated from Streptomyces anulatus is the most potent telomerase inhibitor so far. , ructure has been yet resolved for the complex with telomestatin, one of the most promising G-quadruplex-targeting anticancer drug candidates. Here, Telomestatin, a strong telomerase inhibitor with G-quadruplex stabilizing activity, is a potential therapeutic agent for treating cancers., Thus, telomestatin provide the novel therapeutic molecular target for cancer chemotherapy., Telomerase inhibition with a novel G-quadruplex-interactive agent, telomestatin: in vitro and in vivo studies in acute leukemia., Activity of a novel G-quadruplex-interactive telomerase inhibitor, telomestatin (SOT-095), against human leukemia cells: involvement of ATM-dependent DNA damage response pathways.[SEP]", "label": "no"}
{"id": "converted_4236", "sentence1": "Is SMOC2 expressed during wound healing?", "sentence2": "All three fibroblast populations were PDGFRα+/CD34 + but were distinct in their expression of Ngfr/Spon2/Angptl7 (F1), Cxcl14/Smoc2/Rgs2 (F2), and Clec3b/Col14a1/Mmp3 (F3), with potential functions in the regulation of immune responses, response to wounding, and organization of extracellular matrix, respectively., Deficiency of the SMOC2 matricellular protein impairs bone healing and produces age-dependent bone loss.[SEP]", "label": "yes"}
{"id": "converted_688", "sentence1": "Is Ctf4 involved in sister chromatid cohesion establishment?", "sentence2": "In addition to Eco1, several other factors contribute to cohesion establishment, including Ctf4, Ctf18, Tof1, Csm3, Chl1 and Mrc1, but little is known about their roles. Here, we show that each of these factors facilitates cohesin acetylation. Moreover, the absence of Ctf4 and Chl1, but not of the other factors, causes a synthetic growth defect in cells lacking Eco1. Distinct from acetylation defects, sister chromatid cohesion in ctf4Δ and chl1Δ cells is not improved by removing Wapl, Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment, Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1, Influence of the human cohesion establishment factor Ctf4/AND-1,  Here, we used Xenopus egg extracts to show that AND-1 and Tim1-Tipin, homologues of Saccharomyces cerevisiae Ctf4 and Tof1-Csm3, respectively, are associated with the replisome and are required for proper establishment of the cohesion observed in the M-phase extracts, These data defined two cohesion pathways, one containing CSM3, TOF1, CTF4, and CHL1, and the second containing MRC1, CTF18, CTF8, and DCC1, Our results suggest that Chl1 and Ctf4 are directly involved in homologous recombination repair rather than acting indirectly via the establishment of sister chromatid cohesion, Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks, WSS1 was also found to interact genetically with SGS1, TOP3, SRS2 and CTF4, which are involved in recombination, repair of replication forks and the establishment of sister chromatid cohesion, The catalytic subunit of budding yeast Polalpha (Pol1p) has been shown to associate in vitro with the Spt16p-Pob3p complex, a component of the nucleosome reorganization system required for both replication and transcription, and with a sister chromatid cohesion factor, Ctf4p, Constituents of the replication fork, such as the DNA polymerase alpha-binding protein Ctf4, contribute to cohesion in ways that are poorly understood, Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1 and the pathway involving the acetylation of Smc3., Our results suggest that Chl1 and Ctf4 are directly involved in homologous recombination repair rather than acting indirectly via the establishment of sister chromatid cohesion., Ctf4/AND-1 is a highly conserved gene product required for both DNA replication and the establishment of sister chromatid cohesion., Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks., Sister-chromatid cohesion mediated by the alternative RF-CCtf18/Dcc1/Ctf8, the helicase Chl1 and the polymerase-alpha-associated protein Ctf4 is essential for chromatid disjunction during meiosis II., Saccharomyces cerevisiae CTF18 and CTF4 are required for sister chromatid cohesion., We find that absence of either CTF4 or CTF18 causes sister chromatid cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint., We show here that CTF8, CTF4 and a helicase encoded by CHL1 are required for efficient sister chromatid cohesion in unperturbed mitotic cells, and provide evidence that Chl1 functions during S-phase., In budding yeast, a specialized replication factor C called RF-C(Ctf18/Dcc1/Ctf8) and the DNA-polymerase-alpha-associated protein Ctf4 are required to maintain sister-chromatid cohesion in cells arrested for long periods in mitosis., The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes observed in this study and others suggest that both gene products act in association with the replication fork to facilitate sister chromatid cohesion., Our results suggest that Chl1 and Ctf4 are directly involved in homologous recombination repair rather than acting indirectly via the establishment of sister chromatid cohesion., Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment., Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment., Ctf4/AND-1 is a highly conserved gene product required for both DNA replication and the establishment of sister chromatid cohesion, Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1 and the pathway involving the acetylation of Smc3, Establishment of sister chromatid cohesion at the S. cerevisiae replication fork.[SEP]", "label": "yes"}
{"id": "converted_4408", "sentence1": "Does UBE4B promote renal cancer?", "sentence2": "UBE4B might act as an oncogene in regulating RCC development. Therefore it could be served as an effective indicator to predict OS and a potential biomarker for targeted therapy of RCC patients.[SEP]", "label": "yes"}
{"id": "converted_2789", "sentence1": "Can gene therapy restore auditory function?", "sentence2": "Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c., We demonstrate recovery of gene and protein expression, restoration of sensory cell function, rescue of complex auditory function and recovery of hearing and balance behavior to near wild-type levels. The data represent unprecedented recovery of inner ear function and suggest that biological therapies to treat deafness may be suitable for translation to humans with genetic inner ear disorders.[SEP]", "label": "yes"}
{"id": "converted_4543", "sentence1": "Is CircRNA produced by back splicing of exon, intron or both, forming exon or intron circRNA?", "sentence2": "CircRNAs are a subclass of lncRNAs that have been found to be abundantly present in a wide range of species, including humans. CircRNAs are generally produced by a noncanonical splicing event called backsplicing that is dependent on the canonical splicing machinery, giving rise to circRNAs classified into three main categories: exonic circRNA, circular intronic RNA, and exon-intron circular RNA. , Circular RNA (circRNA) is a large class of covalently closed circRNA., Human transcriptome contains a large number of circular RNAs (circRNAs) that are mainly produced by back splicing of pre-mRNA., Analyses of the other reads revealed two origins for non-canonical circRNAs: (1) Intronic sequences for lariat-derived intronic circRNAs and intron circles, (2) Mono-exonic genes (mostly non-coding) for either a new type of circRNA (including only part of the exon: sub-exonic circRNAs) or, even more rarely, mono-exonic canonical circRNAs., Our objective was to characterize non-canonical circRNAs, namely not originating from back splicing and circRNA produced by non-coding genes., Recent studies have identified a new class of ncRNAs called circular RNAs (circRNAs), which are produced by back-splicing and fusion of either exons, introns, or both exon-intron into covalently closed loops., CircRNA is produced by the reverse splicing of exon, intron or both, forming exon or intron circRNA., Circular RNAs (circRNAs) belong to a recently re-discovered species of RNA that emerge during RNA maturation through a process called back-splicing. , Exonic circular RNAs (circRNAs) are RNA molecules that are covalently closed by back-splicing via canonical splicing machinery. , Human transcriptome contains a large number of circular RNAs (circRNAs) that are mainly produced by back splicing of pre-mRNA. , Circular RNAs (circRNAs) are a class of non‑coding RNAs formed by covalently closed loops through back‑splicing and exon‑skipping. , Here, we review the emerging understanding that both, circRNAs produced by co- and posttranscriptional head-to-tail \"backsplicing\" of a downstream splice donor to a more upstream splice acceptor, as well as circRNAs generated from intronic lariats during colinear splicing, may exhibit physiologically relevant regulatory functions in eukaryotes., Compared to the linear RNA, circRNAs are produced differentially by backsplicing exons or lariat introns from a pre-messenger RNA (mRNA) forming a covalently closed loop structure missing 3' poly-(A) tail or 5' cap, rendering them immune to exonuclease-mediated degradation., CircRNAs are a large class of endogenous single-stranded RNA that is different from other linear RNA, which are produced by back-splicing and fusion of either exons, introns, or both exon-intron into covalently closed loops., Circular RNAs (circRNAs) derived from back-spliced exons have been widely identified as being co-expressed with their linear counterparts.[SEP]", "label": "yes"}
{"id": "converted_406", "sentence1": "Can botulism poisoning of a pregnant woman harm her fetus?", "sentence2": "Two botulism outbreaks were attributed to commercial ready-to-eat meat products and 3 to foods served in restaurants; several cases were attributed to non-Native home-prepared foods. Three affected pregnant women delivered healthy infants., Botulinum toxin is not expected to be present in systemic circulation following proper intramuscular or intradermal injection. Moreover, BTX-A, which has a high molecular weight, does not appear to cross the placenta. From the 38 pregnancies reported in the literature, including women who had botulism poisoning during pregnancy, exposure to BTX-A does not appear to increase the risk of adverse outcome in the fetus., From the 38 pregnancies reported in the literature, including women who had botulism poisoning during pregnancy, exposure to BTX-A does not appear to increase the risk of adverse outcome in the fetus.[SEP]", "label": "no"}
{"id": "converted_573", "sentence1": "Are there telemedicine applications for chronic pain management?", "sentence2": "An integrated cognitive-behavioral and physical therapy group protocol has been developed and then implemented at remote sites using videoconferencing technology to provide pain management for veterans. , Tele-pain management: use of videoconferencing technology in the delivery of an integrated cognitive-behavioral and physical therapy group intervention., It is feasible to provide treatment to women veterans living in rural areas by utilizing video-teleconferencing technology between larger VA medical centers and facilities at CBOCs in more rural settings, The results suggest that a smartphone-delivered intervention with diaries and personalized feedback can reduce catastrophizing and prevent increases in functional impairment and symptom levels in women with chronic widespread pain following inpatient rehabilitation.,  Of the studies available, there are very few randomized trials of telehealth pain care and only one general overview of e-health and chronic pain, which dedicates just a few paragraphs to telehealth., therapy adaptation and the resultant specification for the SMART2 project-a technology-based self-management system for assisting long-term health conditions, including chronic pain, Results showed the use of videoconferencing for this group of patients is useable and satisfactory for both patients and staff, that the patients save time and money, and that for a system where videoconferencing equipment is already in use, it is also cost effective. Staff were able to identify new patient problems. , This pilot study indicates that telemedicine follow-up consultations for chronic pain patients are feasible and cost-saving. Patients and anesthesiologists were highly satisfied with telemedicine consultation.[SEP]", "label": "yes"}
{"id": "converted_238", "sentence1": "Can valproic acid act as an activator of AMPK?", "sentence2": "Here we demonstrate that VPA is a novel activator of AMP-activated protein kinase (AMPK), a key regulator of cellular metabolism, using primary mouse and human hepatocytes., These studies are the first to establish VPA and its metabolites as in vitro activators of AMPK.[SEP]", "label": "yes"}
{"id": "converted_2265", "sentence1": "Does echinacea increase anaphylaxis risk?", "sentence2": "Chicoric acid (dicaffeoyl-tartaric acid), is a natural phenolic compound found in a number of plants, such as chicory (Cichorium intybus) and Echinacea (Echinacea purpurea), which possesses antioxidant, anti-inflammatory, antiviral, and analgesic activities. Although these biological effects of chicoric acid have been investigated, there are no reports of its antiallergic-related anti-inflammatory effects in human mast cells (HMC)-1 or anaphylactic activity in a mouse model., BACKGROUND: Fifty percent of Australians use complementary and alternative medicines (other than vitamins) in any 12-month period, of which echinacea-containing products are increasingly popular. Recent reports have highlighted the risk of allergic reactions to complementary medicines in atopic patients., Two patients suffered anaphylaxis and a third had an acute asthma attack 10 minutes after their first ever dose of echinacea., Fifty-one Australian adverse drug reports implicating echinacea were also reviewed. There were 26 cases suggestive of possible immunoglobulin E-mediated hypersensitivity (4 anaphylaxis, 12 acute asthma, 10 urticaria/angioedema). , Echinacea-associated anaphylaxis., A woman with atopy experienced anaphylaxis after taking, among other dietary supplements, a commercial extract of echinacea., Risk of anaphylaxis in complementary and alternative medicine., Several culprits identified including Andrographis paniculata, Echinacea species, bee products, Ginkgo biloba and Ginseng are discussed here.SUMMARY: Knowing the factors that increase the risk of anaphylaxis allows reactions to be recognized, reported and further investigated.[SEP]", "label": "yes"}
{"id": "converted_3595", "sentence1": "Can LB-100 sensitize ovarian carcinoma to cisplatin?", "sentence2": "The protein phosphatase 2A inhibitor LB100 sensitizes ovarian carcinoma cells to cisplatin-mediated cytotoxicity., LB100 sensitized ovarian carcinoma lines to cisplatin-mediated cell death. , Our results suggest that LB100 sensitizes ovarian cancer cells to cisplatin in vitro and in vivo by modulation of the DDR pathway and cell-cycle checkpoint abrogation.[SEP]", "label": "yes"}
{"id": "converted_3406", "sentence1": "Does xaliproden improve prognosis of amyotrophic lateral sclerosis?", "sentence2": "Treatment for crampsThere is evidence (13 RCTs, N = 4012) that for the treatment of cramps in MND, compared to placebo:- memantine and tetrahydrocannabinol (THC) are probably ineffective (moderate-quality evidence);- vitamin E may have little or no effect (low-quality evidence); and- the effects of L-threonine, gabapentin, xaliproden, riluzole, and baclofen are uncertain as the evidence is either very low quality or the trial specified the outcome but did not report numerical data., The medications comprised vitamin E, baclofen, riluzole, L-threonine, xaliproden, indinavir, and memantine. Six studies assessed cramps as an adverse event. The medications comprised creatine, gabapentin, dextromethorphan, quinidine, and lithium. In all 20 studies no favourable effect for the treatment of cramps in ALS/MND could be demonstrated, but many studies were underpowered to draw a definite conclusion., . The six months intent-to-treat analysis showed no statistically significant effect but a trend in favour of 2 mg xaliproden compared to placebo for reduction in the rate of deterioration of FVC, limbs functional score, and manual muscle testing score (MMT)., These results support the use of a staging process to select suitable patients for phase II studies, and suggest that xaliproden may have potential effects in ALS and deserve further study., An effect of xaliproden on functional parameters, especially VC, was noted. Although this effect did not reach statistical significance, xaliproden had a small effect on clinically noteworthy aspects of disease progression in ALS., The six months intent-to-treat analysis showed no statistically significant effect but a trend in favour of 2 mg xaliproden compared to placebo for reduction in the rate of deterioration of FVC, limbs functional score, and manual muscle testing score (MMT)., An effect of xaliproden on functional parameters, especially VC, was noted., These results support the use of a staging process to select suitable patients for phase II studies, and suggest that xaliproden may have potential effects in ALS and deserve further study., The six months intent-to-treat analysis showed no statistically significant effect but a trend in favour of 2 mg xaliproden compared to placebo for reduction in the rate of deterioration of FVC, limbs functional score, and manual muscle testing score (MMT)., Although this effect did not reach statistical significance, xaliproden had a small effect on clinically noteworthy aspects of disease progression in ALS.[SEP]", "label": "no"}
{"id": "converted_146", "sentence1": "Is SLC22A3 expressed in the brain?", "sentence2": "The organic cation transporter (OCT) 3 is widely expressed in various organs in humans, and involved in the disposition of many exogenous and endogenous compounds. Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission. , The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain., In agreement with this distribution, OCT3/Slc22a3-deficient mice show evidence of altered monoamine neurotransmission in the brain, with decreased intracellular content and increased turnover of aminergic transmitters., CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF., The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain, The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain. , CRT may be a key factor facilitating blood-to-brain guanidinoacetate transport in patients deficient in S-adenosylmethionine:guanidinoacetate N-methyltransferase, the creatine biosynthetic enzyme, resulting in cerebral accumulation of guanidinoacetate. CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF., Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain., CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF. Interestingly, BBB efflux transport of GCs, including guanidinoacetate and creatinine, is negligible, though the BBB has a variety of efflux transport systems for synthetic precursors of GCs, such as amino acids and neurotransmitters.,  The organic cation transporter (OCT) 3 is widely expressed in various organs in humans, and involved in the disposition of many exogenous and endogenous compounds. Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission., CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF., Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission., The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain., OCT2-OCT-3 display differential tissue distribution: OCT1 is predominantly found in liver of humans, and liver and kidney in rodents; OCT2 is most strongly expressed in both human and rodent kidney, whereas is OCT3 primarily expressed in placenta, but also more widely detected in various tissues, including brain and lung.[SEP]", "label": "yes"}
{"id": "converted_3555", "sentence1": "Is AZD5153 active in prostate cancer?", "sentence2": "AZD5153 Inhibits Prostate Cancer Cell Growth in Vitro and in Vivo., Bromodomain-containing protein 4 (BRD4) overexpression participates in prostate cancer progression by enhancing the transcriptional activity and expression of several key oncogenes. AZD5153 is a novel BRD4 inhibitor.METHODS: Prostate cancer cells were treated with AZD5153. Cell survival was tested by MTT assay and clonogenicity assay. Cell proliferation was tested by [H3] DNA incorporation assay. Cell apoptosis was tested by caspase-3/-9 activity assay, Histone DNA ELISA assay, Annexin V FACS assay and TUNEL staining assay. Cell cycle progression was tested by propidium iodide (PI) FACS assay. Signaling was tested by Western blotting assay. The nude mice PC-3 xenograft model was applied to test AZD5153's activity in vivo.RESULTS: AZD5153 inhibited proliferation and survival of established and primary prostate cancer cells. AZD5153 induced apoptosis activation and cell cycle arrest in prostate cancer cells. AZD5153 was non-cytotoxic to the prostate epithelial cells. AZD5153 downregulated BRD4 targets (cyclin D1, Myc, Bcl-2, FOSL1 and CDK4) in PC-3 and primary prostate cancer cells. Further studies show that AKT could be the primary resistance factor of AZD5153. Pharmacological inhibition or genetic depletion of AKT induced BRD4 downregulation, sensitizing AZD5153-induced cytotoxicity in PC-3 cells. In vivo, AZD5153 oral administration inhibited PC-3 xenograft tumor growth in nude mice. Its anti-tumor activity was further enhanced with co-treatment of the AKT specific inhibitor MK-2206.CONCLUSION: Together, our results indicate a promising therapeutic value of the novel BRD4 inhibitor AZD5153 against prostate cancer cells., AZD5153 induced apoptosis activation and cell cycle arrest in prostate cancer cells., CONCLUSION\n\nTogether, our results indicate a promising therapeutic value of the novel BRD4 inhibitor AZD5153 against prostate cancer cells., AZD5153 downregulated BRD4 targets (cyclin D1, Myc, Bcl-2, FOSL1 and CDK4) in PC-3 and primary prostate cancer cells., RESULTS\n\nAZD5153 inhibited proliferation and survival of established and primary prostate cancer cells., RESULTS AZD5153 inhibited proliferation and survival of established and primary prostate cancer cells., AZD5153 induced apoptosis activation and cell cycle arrest in prostate cancer cells., AZD5153 downregulated BRD4 targets (cyclin D1, Myc, Bcl-2, FOSL1 and CDK4) in PC-3 and primary prostate cancer cells., CONCLUSION Together, our results indicate a promising therapeutic value of the novel BRD4 inhibitor AZD5153 against prostate cancer cells., AZD5153 Inhibits Prostate Cancer Cell Growth in Vitro and in Vivo, AZD5153 induced apoptosis activation and cell cycle arrest in prostate cancer cells.[SEP]", "label": "yes"}
{"id": "converted_2509", "sentence1": "Is creatinine assessment included in the MELD score?", "sentence2": "Model For End-Stage Liver Disease (MELD) scores were calculated as 3.78×ln[TB] + 11.2×ln[INR] + 9.57×ln[creatinine] + 6.43. , A corrected creatinine was derived from the mGFR after application of the Modification of Diet in Renal Disease formula. Subsequently, a corrected MELD was calculated and compared with the conventionally calculated MELD., Among patients with MELD score>35, a new prognostic model based on serum creatinine, need for hemodialysis and moderate ascites could identify the sickest one., Patient risk factors evaluated include age, INR (international normalized ratio), creatinine, bilirubin, and MELD score (Model for End-of-stage Liver Disease). , Limited comparability of creatinine assays in patients with liver cirrhosis and their impact on the MELD score., The model of end-stage liver disease (MELD) score is used for this purpose in most countries and incorporates bilirubin, International Normalized ratio, and creatinine. , The MELD score was calculated using international normalized ratio, serum billirubin and creatinine., Regression analysis identified high creatinine and INR, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. , This study aimed to evaluate the impact of two creatinine measurement methods on the Model for End Stage Liver Disease (MELD) score and glomerular filtration rate estimation (eGFR) in cirrhotic patients., <b>OBJECTIVES</b>: The model for end-stage liver disease score (MELD = 3.8*LN[total bilirubin] + 9.6*LN[creatinine] + 11.2*[PT-INR] + 6.4) predicts mortality for tricuspid valve surgery., Simplified MELD score = 3.8*LN[total bilirubin] + 9.6*LN[creatinine] + 6.4.<br><b>METHODS</b>: A total of 172 patients (male: 66, female: 106; mean age, 63.8 ± 10.3 years) who underwent tricuspid replacement (n = 18) or repair (n = 154) from January 1991 to July 2011 at a single centre were included., CONCLUSION Incorporating eGFR obtained by the 6-variable MDRD equation into the MELD score showed an equal predictive performance in in-hospital mortality compared to a creatinine-based MELD score., Simplified MELD score = 3.8*LN[total bilirubin] + 9.6*LN[creatinine] + 6.4.[SEP]", "label": "yes"}
{"id": "converted_1563", "sentence1": "Are cyclophilins ubiquitously expressed?", "sentence2": "Cyclophilin from Leishmania donovani (LdCyp) is a ubiquitous peptidyl-prolyl cis-trans isomerase, Cyclophilins (CYPs) and FK506-binding proteins (FKBPs) are ubiquitous proteins belonging to the peptidyl-prolyl cis/trans isomerase (PPIase) family.,  However, their wide distribution and ubiquitous nature signifies their fundamental importance in plant survival., Cyclophilins (Cyps) are ubiquitous proteins that effect the cis-trans isomerization of Pro amide bonds, and are thus crucial to protein folding., FK506 binding proteins (FKBPs) and cyclophilins (CYPs) are abundant and ubiquitous proteins belonging to the peptidyl-prolyl cis/trans isomerase (PPIase) superfamily, which regulate much of metabolism through a chaperone or an isomerization of proline residues during protein folding., Cyclophilin is a ubiquitous peptidyl prolyl cis/trans isomerase that plays critical roles in many biological processes., The receptor for cyclosporin is the protein cyclophilin, which is a ubiquitous peptidylprolyl isomerase. , Cyps (cyclophilins) are ubiquitous proteins of the immunophilin superfamily with proposed functions in protein folding, protein degradation, stress response and signal transduction. , Cyclophilins are folding helper enzymes belonging to the class of peptidyl-prolyl cis-trans isomerases (PPIases; EC 5.2.1.8) that catalyze the cis-trans isomerization of peptidyl-prolyl bonds in proteins. They are ubiquitous proteins present in almost all living organisms analyzed to date, with extremely rare exceptions., Immunophilins are ubiquitous enzymes responsible for proline isomerisation during protein synthesis and for the chaperoning of several membrane proteins., Cyclophilins (CyPs) are a large class of highly conserved ubiquitous peptidyl-prolyl cis-trans isomerases., Cyclophilins belong to the family of peptidyl-prolyl cis/trans isomerases (PPIases), which are ubiquitous and highly conserved enzymes capable of cis/trans isomerizing Xaa-Pro peptide bonds. , Originally identified as the cellular targets of immunosuppressant drugs, the immunophilins encompass two ubiquitous protein families: the FK-506 binding proteins or FKBPs, and the cyclosporin-binding proteins or cyclophilins.[SEP]", "label": "yes"}
{"id": "converted_478", "sentence1": "Can vitamin B1 deficiency cause encephalopathy?", "sentence2": "Wernicke's encephalopathy (WE) is a severe neurological syndrome caused by thiamine (vitamin B1) deficiency and clinically characterized by the sudden onset of mental status changes, ocular abnormalities, and ataxia, Wernicke encephalopathy (or Wernicke-Korsakoff encephalopathy) is a rarely diagnosed neurological disorder, which is caused by vitamin B1 deficiency, Wernicke's encephalopathy (WE) is a potentially reversible yet serious neurological manifestation caused by vitamin B1(thiamine) deficiency, Wernicke encephalopathy is caused by thiamine (vitamin B1) deficiency, Both the thyrotoxicosis and a catabolic state due to the hyperemesis were thought to have induced a vitamin B1 deficiency, causing the Wernicke encephalopathy., Wernicke encephalopathy (or Wernicke-Korsakoff encephalopathy) is a rarely diagnosed neurological disorder, which is caused by vitamin B1 deficiency., Wernicke encephalopathy is caused by thiamine (vitamin B1) deficiency., Wernicke's encephalopathy is a neurological disorder caused by thiamine (vitamin B1) deficiency characterized by vertigo, ataxia, and mental confusion., Wernicke's encephalopathy (WE) is caused by thiamine (vitamin B1) deficiency and most commonly found in individuals with chronic alcoholism and malnutrition., Wernicke's encephalopathy (WE) is an acute neurological disease resulting from thiamine (vitamin B1) deficiency., Post-mortem findings demonstrate that thiamine (vitamin B1) deficiency sufficient to cause irreversible brain damage is not diagnosed ante mortem in 80-90% of these patients., Wernicke's encephalopathy is an acute neuropsychiatric disorder, due to thiamine (vitamin B1) deficiency., Wernicke's encephalopathy (WE) is a severe neurological syndrome caused by thiamine (vitamin B1) deficiency and clinically characterized by the sudden onset of mental status changes, ocular abnormalities, and ataxia., Wernicke's encephalopathy, a pathology caused by vitamin B1 (thiamin) deficiency, is often difficult to diagnose and can lead to severe cognitive sequels if left untreated., Wernicke's encephalopathy-Korsakoff syndrome (WE-KS) is common in alcoholics, caused by thiamine deficiency (TD; vitamin B1) and associated with lesions to the thalamus (THAL)., Wernicke encephalopathy is caused by thiamine (vitamin B1) deficiency, Thiamine (vitamin B1) deficiency, associated with a variety of conditions, including chronic alcoholism and bariatric surgery for morbid obesity, can result in the neurological disorder Wernicke&apos;s encephalopathy (WE), Wernicke's encephalopathy is caused by thiamin deficiency and can be recognized by severe neurological symptoms that are occasionally accompanied by systemic signs. , INTRODUCTION: Wernicke's encephalopathy, a pathology caused by vitamin B1 (thiamin) deficiency, is often difficult to diagnose and can lead to severe cognitive sequels if left untreated. , OBSERVATION: We report a case of encephalopathy due to dual vitamin deficiency of both thiamine (vitamin B1) and niacin (vitamin PP) in an 80-year-old women, hospitalized for severe sepsis caused by aspiration pneumonia. , Acute Wernicke's encephalopathy (WE) is caused by profound vitamin B1 (thiamine) deficiency and commonly presents with the classic clinical triad of mental confusion, ataxia, and ophthalmoplegia. , [Wernicke´s encephalopathy and polyneuropathy associated with vitamin B complex deficiency after a bariatric surgery]., BACKGROUND: Thiamine deficiency in patients who abuse alcohol can cause Wernicke's encephalopathy (WE). , Wernicke encephalopathy--a debilitating acute or subacute neurological disorder-is caused by a deficiency in thiamine (vitamin B(1)). , Wernicke's encephalopathy is a serious neurological manifestation of vitamin B1 deficiency., Both the thyrotoxicosis and a catabolic state due to the hyperemesis were thought to have induced a vitamin B1 deficiency, causing the Wernicke encephalopathy., Wernicke encephalopathy is caused by thiamine (vitamin B1) deficiency., Wernicke encephalopathy (or Wernicke-Korsakoff encephalopathy) is a rarely diagnosed neurological disorder, which is caused by vitamin B1 deficiency., Wernicke's encephalopathy is a neurological disorder caused by thiamine (vitamin B1) deficiency characterized by vertigo,, Post-mortem findings demonstrate that thiamine (vitamin B1) deficiency sufficient to cause irreversible brain damage is not diagnosed ante mortem in 80-90% of these patients. The causes of vitamin deficiency are reviewed with special attention to the inhibition of oral thiamine hydrochloride absorption in man caused by malnutrition present in alcoholic patients or by the direct effects of ethanol on intestinal transport., Wernicke's encephalopathy is a serious neurologic disorder caused by vitamin-B1 or thiamine deficiency., Wernicke's encephalopathy results from thiamine (vitamin B1) deficiency. Common causes include alcoholism and gastric disorders., Wernicke's encephalopathy is a neurological disorder caused by thiamine (vitamin B1) deficiency characterized by vertigo, ataxia, and mental confusion., Wernicke's encephalopathy (WE) is caused by thiamine (vitamin B1) deficiency and most commonly found in individuals with chronic alcoholism and malnutrition., Post-mortem findings demonstrate that thiamine (vitamin B1) deficiency sufficient to cause irreversible brain damage is not diagnosed ante mortem in 80-90% of these patients., Wernicke's encephalopathy, a pathology caused by vitamin B1 (thiamin) deficiency, is often difficult to diagnose and can lead to severe cognitive sequels if left untreated.[SEP]", "label": "yes"}
{"id": "converted_1152", "sentence1": "Does thyroid hormone affect cardiac remodeling ?", "sentence2": "Thyroid hormones exert important effects on heart remodeling through mir-208., RV and RA function and mechanics are significantly affected by SHT. l-T4 therapy and 1-year maintenance of euthyroid status improved but did not completely recover RV and RA function and deformation in the SHT patients, which implies that right heart remodeling caused by SHT is not reversible in a 1-year period., These results suggest that long-term T4 treatment after MI has beneficial effects on myocyte, arteriolar, and collagen matrix remodeling in the non-infarcted area. Most importantly, results suggest improved survival of myocytes in the peri-infarct area.[SEP]", "label": "yes"}
{"id": "converted_809", "sentence1": "Are conserved noncoding elements associated with developmental genes?", "sentence2": "Some characteristics of CNEs include their high frequency in mammalian genomes, their potential regulatory role in gene expression, and their enrichment in gene deserts nearby master developmental genes, we review recent findings that disruptions of CNEs, within or at long distance from the coding sequences of key genes involved in NCC development, result in neurocristopathies via the alteration of tissue- or stage-specific long-distance regulation of gene expression, Genomic regulatory blocks are chromosomal regions spanned by long clusters of highly conserved noncoding elements devoted to long-range regulation of developmental genes, Analysis of CNEs, at least some of which are candidate regulatory elements, suggests that ancestral CNEs partitioned between gene duplicates. These results help explain the evolutionary pathways by which the developmentally important family of FgfD molecules arose and the deduced principles that guided FgfD evolution are likely applicable to the evolution of developmental regulation in many vertebrate multigene families, Pan-vertebrate developmental cis-regulatory elements are discernible as highly conserved noncoding elements (HCNEs) and are often dispersed over large areas around the pleiotropic genes whose expression they control. On the loci of two developmental transcription factor genes, SOX3 and PAX6, we demonstrate that HCNEs conserved between human and zebrafish can be systematically and reliably tested for their regulatory function in multiple stable transgenes in zebrafish, and their genomic reach estimated with confidence using synteny conservation and HCNE density along these loci. HCNEs of both human and zebrafish function as specific developmental enhancers in zebrafish, We show that human HCNEs result in expression patterns in zebrafish equivalent to those in mouse, establishing zebrafish as a suitable model for large-scale testing of human developmental enhancers, HCNEs from the same area often drive overlapping patterns, suggesting that multiple regulatory inputs are required to achieve robust and precise complex expression patterns exhibited by developmental genes, Organization of conserved elements near key developmental regulators in vertebrate genomes, Further positional analysis of these conserved noncoding elements (CNEs) in the genome demonstrates that they cluster around genes involved in developmental regulation, Ancora: a web resource for exploring highly conserved noncoding elements and their association with developmental regulatory genes, Metazoan genomes contain arrays of highly conserved noncoding elements (HCNEs) that span developmental regulatory genes and define regulatory domains, The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development, We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated \"bystander\" genes., Ancora: a web resource for exploring highly conserved noncoding elements and their association with developmental regulatory genes., Pan-vertebrate developmental cis-regulatory elements are discernible as highly conserved noncoding elements (HCNEs) and are often dispersed over large areas around the pleiotropic genes whose expression they control., Metazoan genomes contain arrays of highly conserved noncoding elements (HCNEs) that span developmental regulatory genes and define regulatory domains., Further positional analysis of these conserved noncoding elements (CNEs) in the genome demonstrates that they cluster around genes involved in developmental regulation., The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs)., Disruption of long-distance highly conserved noncoding elements in neurocristopathies., Fish-mammal genomic comparisons have proved powerful in identifying conserved noncoding elements likely to be cis-regulatory in nature, and the majority of those tested in vivo have been shown to act as tissue-specific enhancers associated with genes involved in transcriptional regulation of development., Despite this, attempts at unearthing genome-wide regulatory elements conserved throughout the vertebrate lineage using BLAST-like approaches have thus far detected noncoding conservation in only a few hundred genes, mostly associated with regulation of transcription and development., Further positional analysis of these conserved noncoding elements (CNEs) in the genome demonstrates that they cluster around genes involved in developmental regulation., We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated \"bystander\" genes., Organization of conserved elements near key developmental regulators in vertebrate genomes., Pan-vertebrate developmental cis-regulatory elements are discernible as highly conserved noncoding elements (HCNEs) and are often dispersed over large areas around the pleiotropic genes whose expression they control[SEP]", "label": "yes"}
{"id": "converted_828", "sentence1": "Is muscle lim protein (MLP) involved in cardiomyopathies?", "sentence2": "Muscle LIM protein (MLP) has been proposed to be a central player in the pathogenesis of heart muscle disease. In line with this notion, the homozygous loss of MLP results in cardiac hypertrophy and dilated cardiomyopathy. Moreover, MLP is induced in several models of cardiac hypertrophy such as aortic banding and myocardial infarction. , Muscle LIM protein (MLP) null mice are often used as a model for human dilated cardiomyopathy., A lack of MLP leads to an age-dependent impairment of excitation-contraction coupling with resulting contractile dysfunction and secondary fibrosis., Loss of murine MLP results in dilated cardiomyopathy, and mutations in human MLP lead to cardiac hypertrophy, indicating a critical role for MLP in maintaining normal cardiac function., Our data indicate that MLP contributes to muscle stiffness and is necessary for maximum work and power generation., Interestingly, MLP was also found to be down-regulated in humans with heart failure (Zolk et al. Circulation 101:2674-2677, 2000) and MLP mutations are able to cause hypertrophic and dilated forms of cardiomyopathy in humans (Bos et al. Mol Genet Metab 88:78-85, 2006; Geier et al. Circulation 107:1390-1395, 2003; Hershberger et al. Clin Transl Sci 1:21-26, 2008; Knöll et al. Cell 111:943-955, 2002; Knöll et al. Circ Res 106:695-704, 2010; Mohapatra et al. Mol Genet Metab 80:207-215, 2003)., MLP soon became an important model for experimental cardiology when it was first demonstrated that MLP deficiency leads to myocardial hypertrophy followed by a dilated cardiomyopathy and heart failure phenotype (Arber et al. Cell 88:393-403, 1997). , Previous studies have shown an association between CSRP3 missense mutations and either dilated cardiomyopathy (DCM) or HCM, but all these studies were unable to provide comprehensive genetic evidence for a causative role of CSRP3 mutations. , We used a newly designed monoclonal antibody to show that muscle LIM protein (MLP), the protein encoded by CSRP3, is mainly a cytosolic component of cardiomyocytes and not tightly anchored to sarcomeric structures. Our functional data from both in vitro and in vivo analyses suggest that at least one of MLP's mutated forms seems to be destabilized in the heart of HCM patients harbouring a CSRP3 missense mutation., Muscle LIM protein (MLP) is a cytoskeletal protein located at the Z-disc of sarcomeres. Mutations in the human MLP gene are associated with hypertrophic and dilated cardiomyopathy., Our data demonstrate that Mlp84B is essential for normal cardiac function and establish the Drosophila model for the investigation of the mechanisms connecting defective cardiac Z-disc components to the development of cardiomyopathy., Muscle LIM protein (MLP) is a cytoskeletal LIM-only protein expressed in striated muscle. Mutations in human MLP are associated with cardiomyopathy;, TTN-encoded titin, CSRP3-encoded muscle LIM protein, and TCAP-encoded telethonin are Z-disc proteins essential for the structural organization of the cardiac sarcomere and the cardiomyocyte's stretch sensor. All three genes have been established as cardiomyopathy-associated genes for both dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). , Approximately 4.1% of unrelated patients had HCM-associated MLP or TCAP mutations. MLP/TCAP-HCM phenotypically mirrors myofilament-HCM and is more severe than the subset of patients who still remain without a disease-causing mutation. The precise role of W4R-MLP in the pathogenesis of either DCM or HCM warrants further investigation., MLP (muscle-LIM-protein) deficient mice develop DCM and changes in the mechanical coupling of cardiomyocytes result in alterations at the intercalated disks and enhanced accumulation of adherens junction proteins., Targeted deletion of cytoskeletal muscle LIM protein (MLP) in mice consistently leads to dilated cardiomyopathy (DCM) after one or more months. , In summary, young MLPKO mice revealed substantial alterations in passive myocardial properties and relaxation time, but not in most systolic characteristics. These results indicate that the progression to heart failure in the MLPKO model may be driven by diastolic myocardial dysfunction and abnormal passive properties rather than systolic dysfunction., Mice lacking the muscle LIM protein (MLP) develop morphological and clinical signs resembling human dilated cardiomyopathy and heart failure., Our results show that the absence of MLP causes a local loss of mitochondria. We hypothesize that this is caused by a disturbed interaction between cytoskeleton and mitochondria, which interferes with energy sensing and energy transfer. Recovery of energy depletion by stimulating mitochondrial biogenesis might be a useful therapeutic strategy for improving the energy imbalance in heart failure., Previous work has shown that mutations in muscle LIM protein (MLP) can cause hypertrophic cardiomyopathy (HCM). In order to gain an insight into the molecular basis of the disease phenotype, we analysed the binding characteristics of wild-type MLP and of the (C58G) mutant MLP that causes hypertrophic cardiomyopathy., The molecular basis for HCM-causing mutations in the MLP gene might therefore be an alteration in the equilibrium of interactions of the ternary complex MLP-N-RAP-alpha-actinin., Muscle LIM protein (MLP) is a member of the cysteine-rich protein (CRP) family and has been implicated in both myogenesis and sarcomere assembly. In the latter role, it binds zyxin and alpha-actinin, both of which are involved in actin organization. An MLP-deficient mouse has been described; these mice develop dilated cardiomyopathy and heart failure., We identified a patient with DCM and EFE, having a mutation in MLP with the residue lysine 69 substituted by arginine (K69R). , MLP-knockout mice develop a marked cardiac hypertrophy reaction and dilated cardiomyopathy (DCM). MLP is therefore a candidate gene for heritable forms of hypertrophic cardiomyopathy (HCM) and DCM in humans., Family studies revealed cosegregation of clinically affected individuals with the respective mutations in MLP. CONCLUSION: Here, we present evidence that mutations in the CRP3/MLP gene can cause HCM., The skeletal muscle LIM protein 1 (SLIM1) is highly expressed in skeletal and cardiac muscle, and its expression is downregulated significantly in dilated human cardiomyopathy. , Targeted disruption of muscle LIM protein (MLP) has previously been shown to result in dilated cardiomyopathy with many of the clinical signs of heart failure, although the effects of MLP disruption on passive ventricular mechanics and myocyte architecture are not known., These results suggest that the disruption of the cytoskeletal protein MLP results in less compliant passive tissue and concomitant structural alterations in the three-dimensional myocyte architecture that may in part explain the ventricular dysfunction in the dilated heart.,  Mutations in cysteine and glycine-rich protein 3 (CSRP3), the gene encoding MLP, have been directly associated with human cardiomyopathies, whereas aberrant expression patterns are reported in human cardiac and skeletal muscle diseases., Muscle LIM protein (MLP) has been proposed to be a central player in the pathogenesis of heart muscle disease., Previous work has shown that mutations in muscle LIM protein (MLP) can cause hypertrophic cardiomyopathy (HCM)[SEP]", "label": "yes"}
{"id": "converted_2186", "sentence1": "Can acupuncture cause spinal epidural hematoma?", "sentence2": "RESULTS: A 54-year-old woman, a 38-year-old woman, and a 60-year-old man with hemiplegia by cervical subdural or epidural hematoma after cervical posterior paraspinal muscle needling without direct invasion (intramuscular stimulation, acupuncture, or intramuscular lidocaine) were observed., Acute spinal subdural hematoma with hemiplegia after acupuncture: a case report and review of the literature., Although acupuncture has been a popular method for the management of pain control, we encountered the first case of SDH after acupuncture.PURPOSE: The purpose of this case report was to present the first case of subdural hematoma after acupuncture and the reasons for the risks of blind cervical acupuncture., SUMMARY OF BACKGROUND DATA: Epidural hematomas after dry needling are quite unusual and only a few cases of epidural hematoma after acupuncture have been reported in the literature., Spinal epidural hematoma is a rare complication associated with pain control procedures such as facet block, acupuncture, epidural injection, etc. , Unintentional acupuncture needling of the thoracic spinal canal produced a spinal epidural hematoma and subarachnoid hemorrhage., Spinal epidural hematoma is a rare complication associated with pain control procedures such as facet block, acupuncture, epidural injection, etc., Spinal epidural hematoma with subarachnoid hemorrhage caused by acupuncture., However, subarachnoid hemorrhage and spinal epidural hematoma have been reported to occur after acupuncture in the posterior neck., A retrospective case report.The objective of this article is to report an unusual complication of dry needling.Epidural hematomas after dry needling are quite unusual and only a few cases of epidural hematoma after acupuncture have been reported in the literature, Spinal epidural hematoma with subarachnoid hemorrhage caused by acupuncture, Spinal epidural hematoma is a rare complication associated with pain control procedures such as facet block, acupuncture, epidural injection, etc, Unintentional acupuncture needling of the thoracic spinal canal produced a spinal epidural hematoma and subarachnoid hemorrhage, Spinal epidural hematoma with subarachnoid hemorrhage caused by acupuncture.[SEP]", "label": "yes"}
{"id": "converted_67", "sentence1": "Is TENS machine effective in pain?", "sentence2": "Transcutaneous electrical nerve stimulation is widely used in pain management but its effectiveness depends on the stimulation being targeted appropriately, hypoalgesic effects of transcutaneous electrical nerve stimulation upon experimentally induced ischaemic pain., The results of this study have provided evidence of the hypoalgesic effects of TENS upon experimental ischaemic pain which were found to be frequency specific with the lower frequency used here (4 Hz) demonstrating the only significant effect[SEP]", "label": "yes"}
{"id": "converted_1880", "sentence1": "Are alterations in ultraconserved elements implicated in breast cancer?", "sentence2": "SNPs in ultraconserved elements and familial breast cancer risk,  In the present study, we investigated the influence of six SNPs within UCEs on familial breast cancer risk. Two out of six SNPs showed an association with familial breast cancer risk, This is the first study indicating that SNPs in UCEs might be associated with cancer risk, SNPs in ultraconserved elements and familial breast cancer risk., Recent studies have indicated that UCEs are not mutation cold regions and likely to be concerned with cancers, including breast cancer (BC). , SNPs in ultraconserved elements and familial breast cancer risk., Genetic variants in ultraconserved elements and risk of breast cancer in Chinese population.[SEP]", "label": "yes"}
{"id": "converted_2078", "sentence1": "Is the number of described human nuclear mutations less than 50000?", "sentence2": "The number of known mutations in human nuclear genes, underlying or associated with human inherited disease, has now exceeded 100,000 in more than 3700 different genes (Human Gene Mutation Database)., The Human Gene Mutation Database (HGMD®) is a comprehensive collection of germline mutations in nuclear genes that underlie, or are associated with, human inherited disease. By June 2013, the database contained over 141,000 different lesions detected in over 5,700 different genes, with new mutation entries currently accumulating at a rate exceeding 10,000 per annum., By March 2012, the database contained in excess of 123,600 different lesions (HGMD Professional release 2012.1) detected in 4,514 different nuclear genes, with new entries[SEP]", "label": "no"}
{"id": "converted_3834", "sentence1": "Does the use of bDMARDs during pregnancy impact neonatal development?", "sentence2": "Exposure to bDMARDs during pregnancy does not seem to interfere with post-natal development up to infancy., Long-term follow-up data about newborns exposed to bDMARDs during pregnancy are however scarce. [SEP]", "label": "no"}
{"id": "converted_4183", "sentence1": "Is Tranexamic acid effective for intracerebral haemorrhage?", "sentence2": "Tranexamic acid did not increase the risk of post-intracerebral haemorrhage seizures in the first 90 days., The primary outcome was not different between the two groups: 26 (52%) patients in the placebo group and 22 (44%) in the tranexamic acid group had intracerebral haemorrhage growth (odds ratio [OR] 0·72 [95% CI 0·32-1·59], p=0·41). There was no evidence of a difference in the proportions of patients who died or had thromboembolic complications between the groups: eight (16%) in the placebo group vs 13 (26%) in the tranexamic acid group died and two (4%) vs one (2%) had thromboembolic complications. None of the deaths was considered related to study medication.INTERPRETATION: Our study does not provide evidence that tranexamic acid prevents intracerebral haemorrhage growth, although the treatment was safe with no increase in thromboembolic complications. , CONCLUSIONS: Tranexamic acid did not affect a patient's functional status at 90 days after ICH, despite there being significant modest reductions in early death (by 7 days), haematoma expansion and SAEs, which is consistent with an antifibrinolytic effect. , INTERPRETATION: Functional status 90 days after intracerebral haemorrhage did not differ significantly between patients who received tranexamic acid and those who received placebo, despite a reduction in early deaths and serious adverse events. , Of these, two randomised controlled trials (RCTs) comparing intravenous tranexamic acid to placebo (n = 54) reported no significant difference in death or dependency. Three observational studies (n = 281) suggested less haematoma growth with rapid tranexamic acid infusion. [SEP]", "label": "no"}
{"id": "converted_2159", "sentence1": "Is autophagy the process where bacteria ingest viral particles?", "sentence2": "Autophagy, a cellular degradation process, Autophagy, a form of lysosomal degradation capable of eliminating dysfunctional proteins and organelles, is a cellular process associated with homeostasis., Autophagy, a programmed process in which cell contents are delivered to lysosomes for degradation, appears to have both tumor-suppressive and tumor-promoting functions; both stimulation and inhibition of autophagy have been reported to induce cancer cell death, and particular genes and proteins have been associated both positively and negatively with autophagy, Autophagy is a lysosome-mediated catabolic process involving the degradation of intracellular contents (e.g., proteins and organelles) as well as invading microbes (e.g., parasites, bacteria and viruses)., Autophagy is a cellular process that targets proteins, lipids and organelles to lysosomes for degradation, but it has also been shown to combat infection with various pathogenic bacteria., Autophagy, an intracellular degradation process highly conserved from yeast to humans, is viewed as an important defence mechanism to clear intracellular bacteria., Autophagy has intracellular anti-viral and anti-bacterial functions, and plays a role in the initiation of innate and adaptive immune system responses to viral and bacterial infections., documented abundant autophagy within VZV-infected cells throughout the infectious cycle but also demonstrated that VZV-induced autophagy facilitated VZV glycoprotein biosynthesis and processing., Autophagy is a highly conserved process by which cells can recycle organelles and proteins by degrading them in the lysosomes.[SEP]", "label": "yes"}
{"id": "converted_3704", "sentence1": "Does radiotherapy for prostate cancer increase bladder cancer risk?", "sentence2": "External Beam Radiotherapy Increases the Risk of Bladder Cancer When Compared with Radical Prostatectomy in Patients Affected by Prostate Cancer: A Population-based Analysis., On multivariable competing risk regression analyses, treatment with EBRT was independently associated with the risk of developing a second primary BCa (hazard ratio: 1.35, CI: 1.18-1.55; p<0.001), but not RCa (p=0.4). , CONCLUSIONS: Patients treated with EBRT are at increased risk of developing a second primary BCa compared with those treated with RP. However, no differences were found considering RCa incidence in patients treated with RP or EBRT within the first 5 yr after primary therapy. , We found that those treated with external beam radiotherapy are at an increased risk of developing a second primary bladder cancer tumor., All radiation modalities were found to have an increased RR of developing BlCa after 10 years, with brachytherapy having a significantly higher RR than external beam radiation (EBRT) or combined EBRT and brachytherapy in Caucasian men and a significantly higher RR than EBRT in men of other/unknown ethnicity. , CONCLUSIONS: The increased risk of BlCa after prostate radiation occurs predominantly after 10 years, regardless of ethnicity. The RR of developing BlCa after 10 years is significantly higher following brachytherapy than after EBRT or EBRT and brachytherapy. , Based on the data in the literature, there is a consistently increased risk of bladder cancer (HR: 1.67, 95% CI 1.55-1.80), rectal cancer (HR: 1.79, 95% CI 1.34-2.38), and colorectal cancer (HR: 1.79, 95% CI 1.34-23.8) following percutaneous radiation therapy. Following brachytherapy only an increased for the development of bladder cancer (HR: 2.14, 95% CI 1.03-3.94) has been observed., When comparing with a matched general French population, the standard incidence ratio (SIR) for bladder cancer was 1.02 (95% CI: 0.46-1.93)., LDR resulted in lower bladder cancer risks than HDR, and lower or similar risks of rectal cancer., Compared to external beam techniques, second rectal and bladder cancer risks were lowest for brachytherapy., OBJECTIVE: Although it is well known that radiotherapy for prostate cancer increases comorbid rate of secondary bladder cancer, the effect of aging and smoking with radiotherapy on incidence rate of secondary bladder cancer remains unknown. , RESULTS: During the median follow-up period of 4.3 and 3.1 years, secondary bladder cancer occurred in 11 (3.4%) and 5 (1.1%) of patients with prostate cancer treated with external beam radiotherapy and radical prostatectomy, respectively. , CONCLUSIONS\n\nMen who receive radiotherapy for localized prostate cancer have an increased risk of bladder cancer compared to patients undergoing radical prostatectomy and compared to the general population., Radiation therapy for prostate cancer increases subsequent risk of bladder and rectal cancer: a population based cohort study., RESULTS\n\nThe relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively., Compared to the general United States population the standardized incidence ratio for bladder cancer developing after radical prostatectomy, external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy was 0.99, 1.42, 1.10 and 1.39, respectively., OBJECTIVE\n\nAlthough it is well known that radiotherapy for prostate cancer increases comorbid rate of secondary bladder cancer, the effect of aging and smoking with radiotherapy on incidence rate of secondary bladder cancer remains unknown., OBJECTIVE\nAlthough it is well known that radiotherapy for prostate cancer increases comorbid rate of secondary bladder cancer, the effect of aging and smoking with radiotherapy on incidence rate of secondary bladder cancer remains unknown., CONCLUSIONS\nMen who receive radiotherapy for localized prostate cancer have an increased risk of bladder cancer compared to patients undergoing radical prostatectomy and compared to the general population., PURPOSE\nPre-prostate specific antigen era series demonstrated an increased risk of bladder cancer and rectal cancer in men who received radiotherapy for prostate cancer., RESULTS\nThe relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively., CONCLUSIONS: Taken together, these findings suggest that smoking history might be one of criteria to choose radical prostatectomy than external beam radiotherapy for prostate cancer, and that age would not be a criterion for therapeutic selection in terms of secondary bladder cancer., PURPOSE: Pre-prostate specific antigen era series demonstrated an increased risk of bladder cancer and rectal cancer in men who received radiotherapy for prostate cancer., RESULTS: The relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively., Compared to the general United States population the standardized incidence ratio for bladder cancer developing after radical prostatectomy, external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy was 0.99, 1.42, 1.10 and 1.39, respectively., Pre-prostate specific antigen era series demonstrated an increased risk of bladder cancer and rectal cancer in men who received radiotherapy for prostate cancer., Men who receive radiotherapy for localized prostate cancer have an increased risk of bladder cancer compared to patients undergoing radical prostatectomy and compared to the general population., The relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively., Radiotherapy for prostate cancer is associated with an increased incidence of secondary bladder cancer (BC)., Radiation therapy for prostate cancer is associated with an increased risk of bladder cancer., Radiotherapy for prostate cancer was associated with higher risks of developing second malignancies of the bladder, colon, and rectum compared with patients unexposed to radiotherapy, but the reported absolute rates were low.[SEP]", "label": "yes"}
{"id": "converted_3210", "sentence1": "Are cardenolides inhibitors of Na+/K+ ATPase?", "sentence2": ". Previously, we reported that a variety of cardenolides impart anti-transmissible gastroenteritis coronavirus (TGEV) activity in swine testicular (ST) cells, through targeting of the cell membrane sodium/potassium pump, Na+/K+-ATPase. , : We found evidence for low cardenolides by HPLC, but substantial toxicity when extracts were assayed on Na+ /K+ -ATPases., Cardenolides have shown significant antitumor activity due to their ability to inhibit the Na+K+ATPase enzyme, and the expression of this enzyme is increased in tumor cells. [SEP]", "label": "yes"}
{"id": "converted_581", "sentence1": "Is CD99 encoded by MIC2 gene?", "sentence2": "We report 2 unusual cytogenetic findings in a pediatric Ewing sarcoma, an insertion of the MIC2 gene encoding CD99 from Xp to 10p and a submicroscopic deletion of the well-known tumor supressor gene KLF6, We obtained the final diagnosis of ES/PNET by immunohistochemical molecular study with positive staining for the MIC2 gene product (CD99) and a Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangement, CD99, a transmembrane protein encoded by MIC2 gene is involved in multiple cellular events including cell adhesion and migration, apoptosis, cell differentiation and regulation of protein trafficking either in physiological or pathological conditions, CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene, The surgical specimens showed small round cell tumor with positive staining for MIC2 gene product (CD99), CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene., The leukocyte surface molecule CD99 is an integral membrane glycoprotein encoded by the E2/MIC2 gene., Human CD99, which is encoded by the mic2 gene, is a ubiquitous 32 kDa transmembrane protein., Human CD99 is a 32-kDa cell surface protein that is encoded by the MIC2 gene localized to the PAR1., The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene., CD99, a transmembrane protein encoded by MIC2 gene is involved in multiple cellular events including cell adhesion and migration, apoptosis, cell differentiation and regulation of protein trafficking either in physiological or pathological conditions., CD99, the product of the MIC2 gene, exhibits an erythroid-specific quantitative polymorphism coregulated with the polymorphism of the XG blood group gene., CD99, the product of the MIC2 gene, exhibits an erythroid-specific quantitative polymorphism co-regulated with the Xga blood group polymorphism., Homology searches resulted in finding homologous sequences (totally about 40% homology) in the human MIC2 gene product (CD99; 32-kDa) of T lymphocytes., Although considered a specific marker for Ewing's sarcoma/peripheral neuroectodermal tumour, the MIC2 gene product (CD99) has been immunolocalised in a variety of human tumours., MIC2, the gene encoding the CD99 antigen, is found in the pseudoautosomal region of both the X and Y chromosomes., Human CD99 is a 32-kDa cell surface protein that is encoded by the MIC2 gene localized to the PAR1., The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene., CD99 (MIC2) regulates the LFA-1/ICAM-1-mediated adhesion of lymphocytes, and its gene encodes both positive and negative regulators of cellular adhesion., Relation of neurological marker expression and EWS gene fusion types in MIC2/CD99-positive tumors of the Ewing family., The Ewing family of tumors (EFT) is characterized by high MIC2/CD99 expression and specific EWS/ETS gene rearrangements, resulting in different chimeric transcripts., The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene., Monoclonal antibody (MAb) HBA71, which was raised against Ewing's sarcoma cells, recognizes a cell-surface glycoprotein, p30/32MIC2, that is encoded by the MIC2 gene in the pseudoautosomal region of human chromosomes X and Y., Monoclonal antibodies (mAbs) directed against E2, a 32-kDa transmembrane protein encoded by the MIC2 gene located in the pseudoautosomal region, induce a transbilayer movement of phosphatidylserine and, to a lesser extent, phosphatidylethanolamine in human thymocytes and a Jurkat T lymphocytes., Homology searches resulted in finding homologous sequences (totally about 40% homology) in the human MIC2 gene product (CD99; 32-kDa) of T lymphocytes., CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene, CD99, a transmembrane protein encoded by MIC2 gene is involved in multiple cellular events including cell adhesion and migration, apoptosis, cell differentiation and regulation of protein trafficking either in physiological or pathological conditions, The surgical specimens showed small round cell tumor with positive staining for MIC2 gene product (CD99), We report 2 unusual cytogenetic findings in a pediatric Ewing sarcoma, an insertion of the MIC2 gene encoding CD99 from Xp to 10p and a submicroscopic deletion of the well-known tumor supressor gene KLF6, MIC2, the gene encoding the CD99 antigen, is found in the pseudoautosomal region of both the X and Y chromosomes, Immunohistochemical analysis showed weak to moderate and partial staining for MIC2 (CD99) and WT1, respectively, Human CD99, which is encoded by the mic2 gene, is a ubiquitous 32 kDa transmembrane protein, The leukocyte surface molecule CD99 is an integral membrane glycoprotein encoded by the E2/MIC2 gene, The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene, Human CD99 is a 32-kDa cell surface protein that is encoded by the MIC2 gene localized to the PAR1, MIC2, the gene encoding the CD99 antigen, is found in the pseudoautosomal region of both the X and Y chromosomes, CD99, the product of the MIC2 gene, exhibits an erythroid-specific quantitative polymorphism co-regulated with the Xga blood group polymorphism[SEP]", "label": "yes"}
{"id": "converted_3357", "sentence1": "Is SARS virus interacting with ACE2 encoded protein?", "sentence2": "The trimeric SARS coronavirus (SARS-CoV) surface spike (S) glycoprotein consisting of three S1-S2 heterodimers binds the cellular receptor angiotensin-converting enzyme 2 (ACE2) and mediates fusion of the viral and cellular membranes through a pre- to postfusion conformation transition, The viral spike glycoprotein (S) utilizes angiotensin-converting enzyme 2 (ACE2) as a host protein receptor and mediates fusion of the viral and host membranes, making S essential to viral entry into host cells and host species tropism., Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, Angiotensin-converting enzyme 2 (ACE2), a relatively new member of the RAS, has drawn extensive attention since 2003, because of the findings that ACE2 is the receptor for SARS Corona virus and that maintenance of normal ACE2 levels in the lung is beneficial for the host to combat inflammatory lung disease., The infection of target cells by the SARS CoV is mediated through the interaction of the viral Spike (S) protein (1255 amino acids) and its cellular receptor, angiotensin-converting enzyme 2 (ACE2).[SEP]", "label": "yes"}
{"id": "converted_4266", "sentence1": "Is cytokeratin a tumor marker?", "sentence2": "cytokeratin fragment antigen 21-1 (CYFRA21-1) in patients with laryngeal squamous cell carcinoma (LSCC) and its correlation with tumorigenesis and progression,  cytokeratin fragment 19 (AUC=0.6882, p<0.0001) proved best in detecting relapse., The immunohistochemistry staining for cancer antigen 19-9, carcinoembryonic antigen, cytokeratin 20, and Ki-67 showed comparable intensities in both groups., evels of inflammatory and tumor markers, including carbohydrate antigen (CA) 19-9, CA125, carcinoembryonic antigen (CEA), CA153, and cytokeratin 19 fragments (CYFRA21-1), [SEP]", "label": "yes"}
{"id": "converted_2216", "sentence1": "Is Hepatic mesenchymal hamartoma usually a malignant tumor?", "sentence2": "Mesenchymal hamartoma of the liver (MHL) is a benign and rare hepatic lesion, , Mesenchymal hamartoma of the liver (MHL) is an uncommon benign hepatic tumor typically affecting children under 2 years of age, This review on the pathology of hepatic tumors in childhood, from a personal series of 245 tumors, focuses on incidence, management, description of frequent tumors such as hepatoblastoma, fibrolamellar carcinoma, and undifferentiated sarcoma for malignant tumors, focal nodular hyperplasia, hepatocellular adenoma, and mesenchymal hamartoma for benign tumors., Mesenchymal hamartoma of the liver is a rare benign liver tumor in children, usually arising from the right liver lobe and represents about 5 to 6% of all primary hepatic tumors, Hepatic mesenchymal hamartoma (HMH) is the second most common benign hepatic tumor in children, Hepatic mesenchymal hamartoma is a rare benign tumor in children, and infantile hepatic hemangioendothelioma is also a rare liver neoplasm, This review on the pathology of hepatic tumors in childhood, from a personal series of 245 tumors, focuses on incidence, management, description of frequent tumors such as hepatoblastoma, fibrolamellar carcinoma, and undifferentiated sarcoma for malignant tumors, focal nodular hyperplasia, hepatocellular adenoma, and mesenchymal hamartoma for benign tumors, Mesenchymal hamartoma is a rare and benign tumor.. Representing 5 to 8 % of childrens hepatic tumors, it is rarely described in adults, We report a case of hepatic mesenchymal hamartoma, a rare benign tumour, in a 10-month-old infant., Hepatic mesenchymal hamartoma is a rare benign tumour in children., Mesenchymal hamartoma is a benign lesion best treated by surgical resection, which usually results in cure., Hepatic mesenchymal hamartoma are rare benign tumors., Hepatic mesenchymal hamartoma is a rare benign tumor in children, and infantile hepatic hemangioendothelioma is also a rare liver neoplasm., Mesenchymal hamartoma is an uncommon benign hepatic tumor arising from the mesenchyme of the portal triad., esenchymal hamartoma of the liver (MHL) is an uncommon benign tumor found primarily in children younger than 2 years of age,  case of a prenatally recognized hepatic mesenchymal hamartoma is presented and the literature reviewed. These tumors are benign and usually present in early infancy with symptoms that are related to the mass effect on adjacent organ[SEP]", "label": "no"}
{"id": "converted_3130", "sentence1": "Are apoE mimetics being considered as a treatment against Alzheimer's disease?", "sentence2": "The apolipoprotein-E-mimetic COG112 protects amyloid precursor protein intracellular domain-overexpressing animals from Alzheimer's disease-like pathological features., Studies show that administration of apolipoprotein E (apoE) and apoE-derived small peptide mimetics protect AD mouse models against these AD-like features.[SEP]", "label": "yes"}
{"id": "converted_4608", "sentence1": "Is Benralizumab effective for Chronic Spontaneous Urticaria?", "sentence2": "Finally, treatments aimed at reducing eosinophil accumulation and activation, such as the anti-IL-5 antibodies mepolizumab, reslizumab, and benralizumab, have been reported to reduce CSU symptoms. , The treatments that are under clinical trials for CSU are anti-IgE treatments such as ligelizumab, molecules targeting intracellular signaling pathways such as spleen tyrosine kinase inhibitors, surface inhibitory molecules such as siglec-8, anti-IL-1s such as canakinumab, Bruton kinase (BTK) inhibitors such as GDC-0853 and anti-IL-5s such as benralizumab and mepolizumab., f-label use of dupilumab, reslizumab, mepolizumab, and benralizumab can be effective in CU. Ligel, Finally, treatments aimed at reducing eosinophil accumulation and activation, such as the anti-IL-5 antibodies mepolizumab, reslizumab, and benralizumab, have been reported to reduce CSU symptoms., ments aimed at reducing eosinophil accumulation and activation, such as the anti-IL-5 antibodies mepolizumab, reslizumab, and benralizumab, have been reported to reduce CSU symptoms. Clearly, a new pi, ormation on the effects of the off-label use, in CSU, of biologics licensed for the treatment of other diseases, including dupilumab, benralizumab, mepolizumab, reslizumab, and secukinumab. Finally, we discuss, , B cells, T cells and eosinophils. The treatments that are under clinical trials for CSU are anti-IgE treatments such as ligelizumab, molecules targeting intracellular signaling pathways such as spleen tyrosine kinase inhibitors, surface inhibitory molecules such as siglec-8, anti-IL-1s such as canakinumab, Bruton kinase (BTK) inhibitors such as GDC-0853 and anti-IL-5s such as benralizumab and mepolizumab.SUMMARY: The ongoing clinical trials on new targets of treatment hold new hopes not only for a better care of the disease but also a better understan[SEP]", "label": "yes"}
{"id": "converted_1138", "sentence1": "Does surgery for ovarian endometriomas improve fertility?", "sentence2": "CONCLUSION: Endometriomas per se appear to be the main cause of the reduced long-term reproductive performance of the affected patients, with little or no contribution from surgery. Furthermore, endometrioma surgery seems to improve the success rates of fertility treatment., Amongst the 38 women desiring pregnancy after endometrioma surgery, 19 (50%) achieved a spontaneous pregnancy during the follow-up period. , Of 33 women who wished to conceive, 67% became pregnant, spontaneously in 59%, CONCLUSIONS: Recurrence and pregnancy rates are encouraging in that they seem comparable to the best reported results after endometrioma cystectomy. , While laparoscopic excision is known to improve fertility, recurrence can cause significant ovarian damage and adverse affects on fertility., Surgery is considered to play a role within the framework of the therapeutic options to cure infertile women with the disease even though its effectiveness is generally modest. , Randomized controlled trials showed that the excision technique is associated with a higher pregnancy rate and a lower rate of recurrence although it may determine severe injury to the ovarian reserve. , Surgical treatment is associated with a high recurrence rate and its employment for women undergoing assisted conception has recently been challenged., Laparoscopic excision of ovarian endometrioma prior to IVF does not offer any additional benefit over expectant management. , For those women subsequently attempting to conceive it was also associated with a subsequent increased spontaneous pregnancy rate in women who had documented prior sub-fertility (OR 5.21 CI 2.04-13.29)., here is insufficient evidence to favour excisional surgery over ablative surgery with respect to the chance of pregnancy after controlled ovarian stimulation and intra-uterine insemination (OR 1.40 CI 0.47-4.15) . , CONCLUSIONS: These findings suggest that in a context of more than one year infertility only related to endometriosis, it is reasonable to offer these patients a complete operative laparoscopic treatment of their lesions, which enables 65% of them to be pregnant within a 8.5 months post-surgical median time to pregnancy and spontaneously in 60%. ,  It was also associated with a subsequent increased rate of spontaneous pregnancy women who had documented prior sub-fertility (OR 5.21 CI 2.04-13.29). AUTHORS' CONCLUSIONS: There is some evidence that excisional surgery for endometriomata provides for a more favourable outcome than drainage and ablation, with regard to the recurrence of the endometrioma, recurrence of symptoms and subsequent spontaneous pregnancy in women who were previously subfertile. , Surgery is an option for treatment, but there is no convincing evidence that it promotes a significant improvement in fertility., In conclusion, ovarian surgery for the treatment of endometriosis reduces the ovarian outcome in IVF/ICSI cycles in women >35 years old, and might also decrease pregnancy rates. , Improvement of pain symptoms occurred in 87% of the patients and fertility rate was 45%., The long-term results, especially the fertility outcome, have been promising: 12 of 20 women (60%) achieved a term pregnancy following a laparoscopic endometrioma procedure alone. , Among this group, 115 patients (54%) conceived following surgery; of these conceptions, 109 resulted in a living child., WIDER IMPLICATIONS OF THE FINDINGS: Despite the available evidence that surgery for endometriomas does not improve the outcome of ART and may damage ovarian reserve, it seems that the majority of gynaecologists in the UK offer ovarian cystectomy to their patients., Ovarian endometriomas does not exclude fertility., Removal of endometriomas before in vitro fertilization does not improve fertility outcomes: a matched, case-control study., Conclusion(s): Laparoscopic cystectomy for endometriomas before commencing an IVF cycle does not improve fertility outcomes., Despite the available evidence that surgery for endometriomas does not improve the outcome of ART and may damage ovarian reserve, it seems that the majority of gynaecologists in the UK offer ovarian cystectomy to their patients., Furthermore, laparoscopic removal of endometriomas does not improve IVF results, but may cause a decrease of ovarian responsiveness to gonadotropins., Furthermore, endometrioma surgery seems to improve the success rates of fertility treatment., Laparoscopic cystectomy for endometriomas before commencing an IVF cycle does not improve fertility outcomes[SEP]", "label": "yes"}
{"id": "converted_1876", "sentence1": "Has small pox been eradicated from the world?", "sentence2": "small pox has been eradicated., smallpox is now eradicated, In May 1980 the World Health Assembly in Geneva announced in solemn form the world-wide eradication of the small-pox and gave recommendations to the member countries for concluding measures concerning the small-pox vaccination, the foundation of vaccine reserves and the control of the epidemiological situation in the world., As a result of vaccination, diseases such as polio and measles have been controlled and small pox has been eradicated, Small pox eradication from the world is the perfect example of the role of mass vaccination of the entire community of the universe. , The French owe a lot to this Central Committee of Vaccine, which greatly contributed to fighting small pox and eradicating the disease finally., Small pox eradication from the world is the perfect example of the role of mass vaccination of the entire community of the universe., Also, the vaccine that Jenner used, which decreased the prevalence of Small Pox worldwide in his own time, and later was used to eradicate Small Pox altogether, is discussed in light of recent data.., the only known cases of smallpox happened from an outbreak in Birmingham, England caused by a laboratory accident in the year of 1979. On May the 8 th 1980 the disease was declared as eliminated from the world by the WHO (WHO-Resolution 33.33).[SEP]", "label": "yes"}
{"id": "converted_1059", "sentence1": "Are piRNAs involved in gene silencing?", "sentence2": "In Drosophila ovaries, the nuclear Piwi protein is required for transcriptional silencing of transposons, though the precise mechanisms by which this occurs are unknown., Here we show that the CG9754 protein is a component of Piwi complexes that functions downstream of Piwi and its binding partner, Asterix, in transcriptional silencing. Enforced tethering of CG9754 to nascent messenger RNA transcripts causes cotranscriptional silencing of the source locus and the deposition of repressive chromatin marks., We have named CG9754 \"Panoramix,\" and we propose that this protein could act as an adaptor, scaffolding interactions between the piRNA pathway and the general silencing machinery that it recruits to enforce transcriptional repression., piRNA-guided slicing of transposon transcripts enforces their transcriptional silencing via specifying the nuclear piRNA repertoire, Caenorhabditis elegans piRNAs interact with both transposon and nontransposon mRNAs to initiate sustained silencing via the RNAi pathway., To assess the dysregulation of gene silencing caused by lack of piRNAs, we restored RNA silencing in RNAi-defective animals in the presence or absence of piRNAs., Thus, by reanimating RNAi, we uncovered a role for piRNAs in protecting essential genes from RNA silencing., In different organisms, small RNAs were shown to be implicated in the posttranscriptional degradation of mRNA and/or transcriptional repression of the homologous locus. In Drosophila, the mechanism of piRNA-mediated silencing is still far from being understood, Analyses of piRNA-mediated transcriptional transposon silencing in Drosophila, Transcriptional silencing implies a piRNA-mediated formation of repressive chromatin which diminishes the transcriptional capacity of the target locus., In mice, piRNA-guided transposon repression correlates with establishment of CpG DNA methylation on their sequences, yet the mechanism and the spectrum of genomic targets of piRNA silencing are unknown, Using a candidate gene KD-approach, we identified differences in the spatio-temporal requirements of the piRNA pathway components for piRNA-mediated silencing., Spatio-temporal requirements for transposable element piRNA-mediated silencing during Drosophila oogenesis, In contrast, piRNA-mediated silencing is strong in germline stem cells in which TE mobilization is tightly repressed ensuring the continued production of viable germline cysts., Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state., In germ cells, early embryos, and stem cells of animals, PIWI-interacting RNAs (piRNAs) have an important role in silencing retrotransposons, which are vicious genomic parasites, through transcriptional and post-transcriptional mechanisms., Our results show that the piRNA pathway can be used as a tool for sequence-specific gene silencing in germ cells and support the idea that the piRNA generating regions serve as traps for retrotransposons, enabling the host cell to generate piRNAs against active retrotransposons.,  Our observations confirm the pivotal role of piRNA-mediated silencing in defending the genome against selfish transposition, yet also suggest limits to the optimization of host genome defense., Analysis of piRNA-mediated silencing of active TEs in Drosophila melanogaster suggests limits on the evolution of host genome defense, The Piwi-interacting RNA (piRNA) pathway defends animal genomes against the harmful consequences of transposable element (TE) infection by imposing small-RNA-mediated silencing., A novel organelle, the piNG-body, in the nuage of Drosophila male germ cells is associated with piRNA-mediated gene silencing., Proteins of the PIWI subfamily Aub and AGO3 associated with the germline-specific perinuclear granules (nuage) are involved in the silencing of retrotransposons and other selfish repetitive elements in the Drosophila genome. , Telomeric retroelements HeT-A, TART and TAHRE, which are involved in telomere maintenance in Drosophila, are also the targets of piRNA-mediated silencing, Mechanism of the piRNA-mediated silencing of Drosophila telomeric retrotransposons., Gene silencing mechanisms mediated by Aubergine piRNA complexes in Drosophila male gonad., The epigenetic trans-silencing effect in Drosophila involves maternally-transmitted small RNAs whose production depends on the piRNA pathway and HP1., Here, we show that mutations in squash and zucchini, which are involved in the piwi-interacting RNA (piRNA) silencing pathway, strongly affect TSE, MVH in piRNA processing and gene silencing of retrotransposons, piRNA-mediated silencing in Drosophila germlines., These have shed light not only on the molecular mechanisms of gene silencing mediated by piRNAs and PIWI proteins, but also on their intriguing relationship with cellular genes that have been shown to be important for gametogenesis and fertility., The most abundant piRNAs were those corresponding to antisense transcripts of Suppressor of Stellate [Su(Ste)] genes known to be involved in Stellate gene silencing, To determine the capacity of piRNA-mediated silencing, we introduced reporter genes into Drosophila OSS cells, which express microRNAs (miRNAs) and piRNAs, and compared the Piwi pathway to the Argonaute pathway in gene regulation, PIWI-interacting small non-coding RNAs (piRNAs) are genetic and epigenetic regulatory factors in germline cells, where they maintain genome stability, are involved in RNA silencing and regulate gene expression, The piNG-body contains ribonucleoprotein complexes involved in piRNA-silencing of genome repeats including transposons in premeiotic spermatocytes with aid of short piRNAs, Our results show that the piRNA pathway can be used as a tool for sequence-specific gene silencing in germ cells and support the idea that the piRNA generating regions serve as traps for retrotransposons, enabling the host cell to generate piRNAs against active retrotransposons, Recent studies have revealed not only the biogenesis of piRNAs and their roles in transposon silencing, but also the function of the Piwi-piRNA pathway in epigenetic and post-transcriptional regulation of gene expression, A growing number of studies on piRNAs have investigated piRNA-mediated gene silencing, including piRNA biogenesis, These have shed light not only on the molecular mechanisms of gene silencing mediated by piRNAs and PIWI proteins, but also on their intriguing relationship with cellular genes that have been shown to be important for gametogenesis and fertility, Telomeric retroelements HeT-A, TART and TAHRE, which are involved in telomere maintenance in Drosophila, are also the targets of piRNA-mediated silencing. , MVH in piRNA processing and gene silencing of retrotransposons., To determine the capacity of piRNA-mediated silencing, we introduced reporter genes into Drosophila OSS cells, which express microRNAs (miRNAs) and piRNAs, and compared the Piwi pathway to the Argonaute pathway in gene regulation. , Therefore piRNA-mediated transcriptional mode of silencing is involved in the control of retrotransposon expression in the Drosophila germline., Panoramix enforces piRNA-dependent cotranscriptional silencing., The most abundant piRNAs were those corresponding to antisense transcripts of Suppressor of Stellate [Su(Ste)] genes known to be involved in Stellate gene silencing., Our results indicate that piRNAs are involved in a posttranscriptional gene-silencing mechanism resulting in RNA nuclear accumulation.[SEP]", "label": "yes"}
{"id": "converted_4355", "sentence1": "Is Mycobacterium abscessus a human pathogen?", "sentence2": "Mycobacterium abscessus is unique in terms of its high morbidity and treatment failure rates, Mycobacterium abscessus has emerged as a successful pathogen owing to its intrinsic drug resistance. , Mycobacterium abscessus lung disease is difficult to treat due to intrinsic drug resistance and the persistence of drug-tolerant bacteria., Mycobacterium abscessus has been recognised as a dreadful respiratory pathogen among the non-tuberculous mycobacteria (NTM) because of misdiagnosis, prolonged therapy with poor treatment outcomes and a high cost. [SEP]", "label": "yes"}
{"id": "converted_999", "sentence1": "Has single guide RNA been used on human cells?", "sentence2": "We used a library containing 73,000 sgRNAs to generate knockout collections and performed screens in two human cell lines., Here we engineer this system to enable RNA-guided genome regulation in human cells by tethering transcriptional activation domains either directly to a nuclease-null Cas9 protein or to an aptamer-modified single guide RNA (sgRNA)., The type II CRISPR/Cas system from Streptococcus pyogenes and its simplified derivative, the Cas9/single guide RNA (sgRNA) system, have emerged as potent new tools for targeted gene knockout in bacteria, yeast, fruit fly, zebrafish and human cells., Here we engineer this system to enable RNA-guided genome regulation in human cells by tethering transcriptional activation domains either directly to a nuclease-null Cas9 protein or to an aptamer-modified single guide RNA (sgRNA). , Using synthetic single RNA guides, Cas9 can be reprogrammed to create specific double-stranded DNA breaks in the genomes of a variety of organisms, ranging from human cells to bacteria, and thus constitutes a powerful tool for genetic engineering. , Here we engineer this system to enable RNA-guided genome regulation in human cells by tethering transcriptional activation domains either directly to a nuclease-null Cas9 protein or to an aptamer-modified single guide RNA (sgRNA).[SEP]", "label": "yes"}
{"id": "converted_1551", "sentence1": "Can we use platelet biomarkers to study Alzheimer's disease?", "sentence2": "Platelet biomarkers in Alzheimer's disease., platelets are the most important source of circulating forms of the amyloid precursor protein and other important proteins such as Tau and glycogen synthase kinase-3B., Alternative plasma and platelet measures are described,, The success of these studies led to the application of platelet proteomics to the study of several pathologies where platelets play a fundamental role. Those include platelet-related disorders, such as storage pool disease, gray platelet syndrome, and Quebec platelet disorder; diseases where unwanted platelet activation is highly relevant, such as thrombosis and cardiovascular disease; and other diseases, such as cystic fibrosis, uremia, or Alzheimer's disease. [SEP]", "label": "yes"}
{"id": "converted_3377", "sentence1": "Is KAT2A involved in Acute myeloid leukemia (AML)?", "sentence2": "Acute myeloid leukemia (AML) is an aggressive cancer with a poor prognosis, for which mainstream treatments have not changed for decades. To identify additional therapeutic targets in AML, we optimize a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screening platform and use it to identify genetic vulnerabilities in AML cells. We identify 492 AML-specific cell-essential genes, including several established therapeutic targets such as DOT1L, BCL2, and MEN1, and many other genes including clinically actionable candidates. We validate selected genes using genetic and pharmacological inhibition, and chose KAT2A as a candidate for downstream study. KAT2A inhibition demonstrated anti-AML activity by inducing myeloid differentiation and apoptosis, and suppressed the growth of primary human AMLs of diverse genotypes while sparing normal hemopoietic stem-progenitor cells. Our results propose that KAT2A inhibition should be investigated as a therapeutic strategy in AML and provide a large number of genetic vulnerabilities of this leukemia that can be pursued in downstream studies., Our results propose that KAT2A inhibition should be investigated as a therapeutic strategy in AML and provide a large number of genetic vulnerabilities of this leukemia that can be pursued in downstream studies., KAT2A inhibition demonstrated anti-AML activity by inducing myeloid differentiation and apoptosis, and suppressed the growth of primary human AMLs of diverse genotypes while sparing normal hemopoietic stem-progenitor cells., Our results propose that KAT2A inhibition should be investigated as a therapeutic strategy in AML and provide a large number of genetic vulnerabilities of this leukemia that can be pursued in downstream studies., KAT2A inhibition demonstrated anti-AML activity by inducing myeloid differentiation and apoptosis, and suppressed the growth of primary human AMLs of diverse genotypes while sparing normal hemopoietic stem-progenitor cells.[SEP]", "label": "yes"}
{"id": "converted_3465", "sentence1": "Are lamina-associated domains (LADs) associated with transcriptional activation?", "sentence2": "Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains., Extensive changes in DNA methylation are common in cancer and may contribute to oncogenesis through transcriptional silencing of tumor-suppressor genes., Such lamina-associated domains (LADs) are thought to help organize chromosomes inside the nucleus and have been associated with gene repression., The nuclear lamina contributes to the regulation of gene expression and to chromatin organization.[SEP]", "label": "no"}
{"id": "converted_3695", "sentence1": "Are Chernobyl survivors at increased risk for breast cancer?", "sentence2": "Results: A more aggressive course of breast cancer is observed in patients exposed to radiation from the Chernobyl accident under the age of 30 years (P < .01). , A significant excess of multiple myeloma incidence [standardized incidence rate (SIR) 1.61 %, 95% confidence interval (CI) 1.01-2.21], thyroid cancer (SIR 4.18, 95% CI 3.76-4.59), female breast cancer (SIR 1.57 CI 1.40-1.73), and all cancers combined (SIR 1.07; 95% CI 1.05-1.09) was registered. , Possible effects for further study include increased rates of thyroid, breast, and lung cancers and multiple myeloma; reduction of radiation risks of leukemia to population levels; and increased morbidity and mortality of cleanup workers from cardio- and cerebrovascular pathology., Furthermore, the upward trends of increases in a variety of other tumors including breast cancer, cancers of central nervous system and renal cancer have been reported in the persons exposed to Chornobyl fallout., Epidemiological cohort studies found increased incidence (1990-2012 gg.) of thyroid cancer in victims of Chernobyl accident (liquidators - in 4.6 times, evacuated - in 4.0 times, residents of contaminated areas - in 1.3 times) and increased incidence of breast cancer in female workers of 1986-1987., Historically, data from the Chernobyl reactor accident 27 years ago demonstrated a strong correlation with thyroid cancer, but data on the radiation effects of Chernobyl on breast cancer incidence have remained inconclusive., Re-analyzing the data reveals that the incidence of breast cancer in Chernobyl-disaster-exposed women could be higher than previously thought. , For breast cancer, the rates and age of onset appear to vary significantly in regions differentially affected by the Chernobyl accident. , In contrast, millions of people were exposed to radioactive isotopes in the fallout from the Chernobyl accident, within the first 20 years there was a large increase in thyroid carcinoma incidence and a possible radiation-related increase in breast cancer, but as yet there is no general increase in malignancies. , The study demonstrated increases in breast cancer incidence in all areas following the Chernobyl accident, reflecting improvements in cancer diagnosis and registration., An increase in breast cancer incidence has been reported in areas of Belarus and Ukraine contaminated by the Chernobyl accident and has become an issue of public concern., The study demonstrated increases in breast cancer incidence in all areas following the Chernobyl accident, reflecting improvements in cancer diagnosis and registration.[SEP]", "label": "yes"}
{"id": "converted_1125", "sentence1": "Does smoking increase risk for glioblastoma?", "sentence2": "Glioma risk has consistently been inversely associated with allergy history but not with smoking history despite putative biologic plausibility., No relation was observed between glioma risk and smoking (odds ratio = 0.92, 95% confidence interval: 0.77, 1.10; P = 0.37), and there were no interactions for glioma risk of smoking history with any of the risk alleles. , Non-smokers with G/A and A/A genotype showed increased glioma risk compared with G/G genotype (adjusted OR = 1.72, 95%CI: 1.29-2.30, p = 0.0002 and adjusted OR = 1.81, 95%CI: 1.10-2.99, p = 0.020, respectively). This association was not found in ever- or current-smokers. , There was no significant association between glioma and alcohol consumption, smoking and mobile phone use. , RESULTS: We found no associations between the GSTM3, GSTP1, NQO1, CYP1A1, GSTM1, or GSTT1 polymorphisms and adult brain tumor risk with the possible exception of a weak association between the G-C (Val-Ala) GSTP1 105/114 haplotype and glioma [odds ratio (OR), 0.73; 95% confidence interval (95% CI), 0.54, 0.99], nor was there an interaction between the effects of the GSTM3 or GSTP1 polymorphisms and cigarette smoking., We did not find any evidence for an association with life-style characteristics such as cigarette smoking, alcohol consumption, use of drugs of any kind, or dietary intake of cured or smoked meat or fish., No relation was observed between glioma risk and smoking (odds ratio = 0, Glioma risk has consistently been inversely associated with allergy history but not with smoking history despite putative biologic plausibility, Compared with nonsmokers, duration of cigarette smoking, number of cigarettes smoked per day and pack-years of smoking were associated with increased glioma risk, although the increases in risk were relatively modest, Among ever smokers, women who reported having quit smoking had a 51% increase in risk of glioma compared with never smokers (HR = 1.51, 95% CI = 0.97-2.34), while current smokers did not appear to have an increase in risk[SEP]", "label": "no"}
{"id": "converted_4433", "sentence1": "Should perampanel be used for amyotrophic lateral sclerosis?", "sentence2": "RESULTS: Six participants were enrolled. All had adverse events, mostly behavioral. Two completed the trial and the other four withdrew due to adverse events. All participants reported resolution of these events after discontinuation of the drug. The trial was halted due to the large number of adverse events.DISCUSSION: The use of perampanel in this study of ALS was limited by its poor tolerability, CONCLUSIONS: Perampanel was associated with a significant decline in ALSFRS-R score and was linked to worsening of the bulbar subscore in the 8 mg group., DISCUSSION: The use of perampanel in this study of ALS was limited by its poor tolerabilit[SEP]", "label": "no"}
{"id": "converted_4482", "sentence1": "Is neurofilament light marker for disease?", "sentence2": "sNfL levels during the first demyelinating event of MS are associated with greater impairment of BBB integrity, immune cell extravasation, and brain lesion activity on MRI., Neurofilament light chain (NfL) has recently been proposed as a promising biomarker in frontotemporal dementia (FTD). We investigated the correlation of both cerebrospinal fluid (CSF) and serum NfL with detailed neuropsychological data and cognitive decline in a cohort of sporadic and familial FTD., Neurofilament light chain has a potential role in differentiating patients with frontotemporal dementia from healthy controls, patients with Alzheimer's dementia, and psychiatric disorders. ,  Serum neurofilament light chain (sNfL) is a marker of neuroaxonal injury., sNfL is associated with ongoing neuroinflammation and predictive of future neurodegeneration in early MS., Neurofilament light chain (NfL) is a relatively new biomarker for MS diagnosis and follow up. [SEP]", "label": "yes"}
{"id": "converted_4428", "sentence1": "Is there a dependence between chromatin organization and dorsoventral gene expression in Drosophila?", "sentence2": "Independence of chromatin conformation and gene regulation during Drosophila dorsoventral patterning., Here, using the dorsoventral patterning of the Drosophila melanogaster embryo as a model system, we provide evidence for the independence of chromatin organization and dorsoventral gene expression. We define tissue-specific enhancers and link them to expression patterns using single-cell RNA-seq. Surprisingly, despite tissue-specific chromatin states and gene expression, chromatin organization is largely maintained across tissues. Our results indicate that tissue-specific chromatin conformation is not necessary for tissue-specific gene expression but rather acts as a scaffold facilitating gene expression when enhancers become active.[SEP]", "label": "no"}
{"id": "converted_1865", "sentence1": "Is adalimumab effective for hidradenitis suppurativa?", "sentence2": "If patient is not improved, then Adalimumab 160 mg at week 0, 80 mg at week 2; then 40 mg subcutaneously weekly should be administered (LOE Ib, SOR A). If improvement occurs then therapy should be maintained as long as HS lesions are present., Reduction in pain scores and improvement in depressive symptoms in patients with hidradenitis suppurativa treated with adalimumab in a phase 2, randomized, placebo-controlled trial., Adalimumab treatment for 16 weeks improved HS lesions significantly versus placebo (NCT00918255)., CONCLUSION: Patients with moderate to severe HS had a high degree of pain and depressive symptoms at baseline. Adalimumabtherapy was associated with decreased pain and depressive symptoms compared to baseline., Spotlight on adalimumab in the treatment of active moderate-to-severe hidradenitis suppurativa., Adalimumab, a recombinant, fully humanized, anti-tumor necrosis factor alpha (anti-TNF-α) monoclonal antibody, is the only officially approved treatment for the management of moderate-to-severe HS. Case reports, concerning 42 patients who received adalimumab for severe HS (with the standard dose regimen for psoriasis), reported a cumulative response rate of 58% (≥50% in 23 patients) with a relapse rate of 71% (10 out of 14 patients). The most recent and most well-powered phase III, randomized placebo-controlled trials for the evaluation of the efficacy and safety of adalimumab in treatment of moderate-to-severe HS (PIONEER studies I and II) showed that the Hidradenitis Suppurativa Clinical Response (HiSCR) rate at week 12 was significantly higher for patients randomized to adalimumab compared to placebo., In conclusion, adalimumab, to date, holds the most robust data regarding treatment efficacy in HS. , Adalimumab (Humira) for the Treatment of Hidradenitis Suppurativa., Adalimumab (Humira®) is a novel therapy approved by the US Food and Drug Administration, Health Canada, and the European Commission for the treatment of hidradenitis suppurativa (HS)., Taken together, these data conclude that treatment of HS with adalimumab is a safe and effective therapy resulting in a significant decrease in abscess and inflammatory nodule counts within the first 12 weeks of treatment., Effective long-term control of refractory hidradenitis suppurativa with adalimumab after failure of conventional therapy., Hidradenitis suppurativa managed with adalimumab., Treatment of severe recalcitrant hidradenitis suppurativa with adalimumab., Long-term successful adalimumab therapy in severe hidradenitis suppurativa., Comparing treatment outcome of infliximab and adalimumab in patients with severe hidradenitis suppurativa., HiSCR (Hidradenitis Suppurativa Clinical Response): a novel clinical endpoint to evaluate therapeutic outcomes in patients with hidradenitis suppurativa from the placebo-controlled portion of a phase 2 adalimumab study, Adalimumab in treatment-resistant hidradenitis suppurativa following recurrence after extensive affected area excision: a review of biologics therapy, Adalimumab (antitumour necrosis factor-α) treatment of hidradenitis suppurativa ameliorates skin inflammation: an in situ and ex vivo study, Treatment of severe recalcitrant hidradenitis suppurativa with adalimumab, In a phase 2 trial, adalimumab, an antibody against tumor necrosis factor α, showed efficacy against hidradenitis suppurativa.PIONEER I and II were similarly designed, phase 3 multicenter trials of adalimumab for hidradenitis suppurativa, with two double-blind, placebo-controlled periods., Here we report a case of a patient with severe recalcitrant hidradenitis suppurativa successfully treated with adalimumab., Recent reports have demonstrated that adalimumab, a tumor necrosis factor (TNF) antagonist, may be effective in the treatment of patients with HS who have failed conventional therapy., Conclusion Adalimumab appears to be an effective and safe treatment for refractory HS., Effective long-term control of refractory hidradenitis suppurativa with adalimumab after failure of conventional therapy., Hidradenitis suppurativa managed with adalimumab., Treatment of severe recalcitrant hidradenitis suppurativa with adalimumab., Two Phase 3 Trials of Adalimumab for Hidradenitis Suppurativa., Adalimumab treatment for hidradenitis suppurativa associated with Crohn's disease., Long-term successful adalimumab therapy in severe hidradenitis suppurativa., Conclusion Adalimumab appears to be an effective and safe treatment for refractory HS.., Comparing treatment outcome of infliximab and adalimumab in patients with severe hidradenitis suppurativa., Here we report a case of a patient with severe recalcitrant hidradenitis suppurativa successfully treated with adalimumab.., Adalimumab is suitable for the long-term treatment of hidradenitis suppurativa and presents a further conservative treatment approach.., HiSCR (Hidradenitis Suppurativa Clinical Response): a novel clinical endpoint to evaluate therapeutic outcomes in patients with hidradenitis suppurativa from the placebo-controlled portion of a phase 2 adalimumab study., Spotlight on adalimumab in the treatment of active moderate-to-severe hidradenitis suppurativa.[SEP]", "label": "yes"}
{"id": "converted_3656", "sentence1": "Can Systemic Lupus Erythematosus cause seizures?", "sentence2": "The mean ± SD age at SLE diagnosis and at onset of PRES was 25.02 ± 13.78 and 28.31 ± 12.61 years, respectively. Seizure was the most common presenting symptom, as seen in 28 episodes, followed by acute severe headache in 17,, Epilepsy is characterized by a relevant epidemiological and clinical burden. In the extant literature, an increased risk of seizures has been described in several inflammatory/autoimmune disorders, including systemic lupus erythematosus (SLE)., Seizures are one of the most serious neuropsychiatric manifestations of systemic lupus erythematous (SLE). , The aim of this study was to describe the frequency , attribution , outcome and predictors of seizures in systemic lupus erythematosus ( SLE, OBJECTIVE\nTo evaluate the frequency and risk factors of epileptic seizures in a large cohort of patients with systemic lupus erythematosus (SLE)., Epileptic seizures occurred at the onset of SLE symptoms in 19 (31.6%) and after the onset of SLE in 41 of 60 (68.3%) patients., Epileptic seizures and EEG features in juvenile systemic lupus erythematosus., CONCLUSIONS\nEpileptic seizures were observed in 11.2% of systemic lupus erythematosus (SLE) patients., CONCLUSIONS\nSeizures tend to occur early in the course of systemic lupus erythematosus, and contribute to damage accrual., Seizures tend to occur early in the course of systemic lupus erythematosus, and contribute to damage accrual., To determine the factors associated with seizures in systemic lupus erythematosus (SLE)., Neurologic manifestations, in special epileptic seizures, are frequent in systemic lupus erythematosus.[SEP]", "label": "yes"}
{"id": "converted_2277", "sentence1": "Are TAD boundaries in Drosophila depleted in highly-expressed genes?", "sentence2": "Furthermore, we find that these TAD boundaries are present irrespective of the expression and looping of genes located between them., In particular, Hi-C revealed that chromosomes of animals are organized into topologically associating domains (TADs), evolutionary conserved compact chromatin domains that influence gene expression., Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes. , The insulator-like, TAD-boundary-like, and TAD-interior-like regions are each enriched for distinct epigenetic marks and are each correlated with different gene expression levels, We conclude that epigenetic modifications, gene density, and transcriptional activity combine to shape the local packing of the A. thaliana nuclear genome., Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions., Our results demonstrate the functional importance of TADs for orchestrating gene expression via genome architecture and indicate criteria for predicting the pathogenicity of human structural variants, particularly in non-coding regions of the human genome., The three-dimensional organization of a genome plays a critical role in regulating gene expression, yet little is known about the machinery and mechanisms that determine higher-order chromosome structure., Ectopically expressed roX1 and roX2 RNAs target HAS on the X chromosome in trans and, via spatial proximity, induce spreading of the MSL complex in cis, leading to increased expression of neighboring autosomal genes. , Collectively, our results suggest that TADs are condensed chromatin domains depleted in active chromatin marks, separated by regions of active chromatin., However, Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes.[SEP]", "label": "no"}
{"id": "converted_1380", "sentence1": "Can chronological age be predicted by measuring telomere length?", "sentence2": "Human somatic cells gradually lose telomeric repeats with age. This study investigated if one could use a correlation between telomere length and age, to predict the age of an individual from their DNA., Therefore, telomere length measurement by real-time quantitative PCR cannot be used to predict age of a person, due to the presence of large inter-individual variations in telomere lengths., ur results provide the first clear and unambiguous evidence of a relationship between telomere length and mortality in the wild, and substantiate the prediction that telomere length and shortening rate can act as an indicator of biological age further to chronological age when exploring life history questions in natural conditions.[SEP]", "label": "no"}
{"id": "converted_2197", "sentence1": "Is Pfh1 a component of the replisome?", "sentence2": "Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to Facilitate Fork Progression and Preserve Genome Integrity, Although the Schizosaccharomyces pombe 5'-to-3' DNA helicase Pfh1 is known to promote fork progression, its genomic targets, dynamics, and mechanisms of action are largely unknown. Here we address these questions by integrating genome-wide identification of Pfh1 binding sites, comprehensive analysis of the effects of Pfh1 depletion on replication and DNA damage, and proteomic analysis of Pfh1 interaction partners by immunoaffinity purification mass spectrometry., DNA replication through hard-to-replicate sites, including both highly transcribed RNA Pol II and Pol III genes, requires the S. pombe Pfh1 helicase., Here, we show that Pfh1 is required for efficient fork movement in the ribosomal DNA, the mating type locus, tRNA, 5S ribosomal RNA genes, and genes that are highly transcribed by RNA polymerase II. ,  Thus, Pfh1 promotes DNA replication and separation of converged replication forks and suppresses DNA damage at hard-to-replicate sites., Cells depleted of Pfh1 were inviable if they also lacked the human TIMELESS homolog Swi1, a replisome component that stabilizes stalled forks., Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to Facilitate Fork Progression and Preserve Genome Integrity., Thus, we conclude that Pfh1 is an accessory DNA helicase that interacts with the replisome and promotes replication and suppresses DNA damage at hard-to-replicate sites., Consistent with this interpretation, Pfh1 co-purified with many key replisome components, including the hexameric MCM helicase, replicative DNA polymerases, RPA, and the processivity clamp PCNA in an S phase dependent manner., Although Pfh1 affected replication and suppressed DNA damage at discrete sites throughout the genome, Pfh1 and the replicative DNA polymerase bound to similar extents to both Pfh1-dependent and independent sites, suggesting that Pfh1 is proximal to the replication machinery during S phase., Cells depleted of Pfh1 were inviable if they also lacked the human TIMELESS homolog Swi1, a replisome component that stabilizes stalled forks, Here, we show that Pfh1 is required for efficient fork movement in the ribosomal DNA, the mating type locus, tRNA, 5S ribosomal RNA genes, and genes that are highly transcribed by RNA polymerase II, Thus, Pfh1 promotes DNA replication and separation of converged replication forks and suppresses DNA damage at hard-to-replicate sites, Cells depleted of Pfh1 were inviable if they also lacked the human TIMELESS homolog Swi1, a replisome component that stabilizes stalled forks., Thus, we conclude that Pfh1 is an accessory DNA helicase that interacts with the replisome and promotes replication and suppresses DNA damage at hard-to-replicate sites., Consistent with this interpretation, Pfh1 co-purified with many key replisome components, including the hexameric MCM helicase, replicative DNA polymerases, RPA, and the processivity clamp PCNA in an S phase dependent manner., Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to Facilitate Fork Progression and Preserve Genome Integrity.[SEP]", "label": "no"}
{"id": "converted_3348", "sentence1": "Is Figitumumab effective for non-small cell lung cancer?", "sentence2": "A phase III study failed for carboplatin, paclitaxel, with or without figitumumab in first-line treating metastatic non-small cell lung cancer (NSCLC)., CONCLUSION: Adding figitumumab to standard chemotherapy failed to increase OS in patients with advanced nonadenocarcinoma NSCLC., Median OS was 8.6 months for figitumumab plus chemotherapy and 9.8 months for chemotherapy alone (hazard ratio [HR], 1.18; 95% CI, 0.99 to 1.40; P = .06); median progression-free survival was 4.7 months (95% CI, 4.2 to 5.4) and 4.6 months (95% CI, 4.2 to 5.4), respectively (HR, 1.10; P = .27); the objective response rates were 33% and 35%, respectively. , Phase III trials of the anti-insulin-like growth factor-1 receptor (IGF1R) antibody figitumumab in non-small cell lung cancer (NSCLC) patients have been discontinued owing to lack of survival benefit., Two phase III trials of the anti-IGF-1R monoclonal antibody, figitumumab (CP-751,871), were discontinued in 2010 as it was considered unlikely either trial would meet their primary endpoints. In light of disappointing clinical data with figitumumab and other targeted agents, it is likely that the use of molecular markers will become important in predicting response to treatment. , Phase III trials of the anti-insulin-like growth factor-1 receptor ( IGF1R ) antibody figitumumab in non-small cell lung cancer ( NSCLC ) patients have been discontinued owing to lack of survival benefit . , Phase III trials of the anti-insulin-like growth factor type 1 receptor ( IGF-IR ) antibody figitumumab ( F ) in unselected non-small-cell lung cancer ( NSCLC ) patients were recently discontinued owing to futility . , One recent phase III trial of the IGF-1R inhibitor figitumumab in patients with non-small-cell lung cancer was discontinued after an interim analysis showed no survival improvement . , The insulin-like growth factor receptor ( IGF-1R ) monoclonal antibody figitumumab , while initially promising , appears to increase toxicity and death in combination with chemotherapy in the treatment of patients with NSCLC of squamous histology; therefore , clinical development of this class of agents will need to proceed with caution . , Two phase III trials of the anti-IGF-1R monoclonal antibody , figitumumab ( CP-751,871) , were discontinued in 2010 as it was considered unlikely either trial would meet their primary endpoints . , A phase III study failed for carboplatin , paclitaxel , with or without figitumumab in first-line treating metastatic non-small cell lung cancer ( NSCLC) . , Median OS was 8.6 months for figitumumab plus chemotherapy and 9.8 months for chemotherapy alone (hazard ratio [HR], 1.18; 95% CI, 0.99 to 1.40; P = .06); median progression-free survival was 4.7 months (95% CI, 4.2 to 5.4) and 4.6 months (95% CI, 4.2 to 5.4), respectively (HR, 1.10; P = .27); the objective response rates were 33% and 35%, respectively.[SEP]", "label": "no"}
{"id": "converted_1766", "sentence1": "Is ocrelizumab effective for treatment of multiple sclerosis?", "sentence2": " Advances made in immunomodulation are driving the progress being made in the treatment of MS. Ocrelizumab is the first treatment with positive results in the primarily progressive forms and tocilizumab, a drug product for rheumatoid arthritis, stands out as a potential candidate for the treatment of neuromyelitis optica.,  Expert commentary: The recent encouraging results of the ocrelizumab trial in PP MS, the first to reach the primary disability endpoint, indicate B cells as a promising therapeutic target to prevent disease progression. , Ocrelizumab also shows efficacy in the primary progressive form of multiple sclerosis., Ocrelizumab for the treatment of relapsing-remitting multiple sclerosis., Expert commentary: The topline results of two phase-III randomized clinical trials demonstrate superiority of ocrelizumab over interferon beta in RRMS patients with regards to clinical and paraclinical outcome parameters. , The efficacy of three of them, rituximab, ocrelizumab and ofatumumab in MS has been confirmed by placebo-controlled clinical trials demonstrating a significant reduction of the annualized relapsing rate (ARR), new gadolinium-enhancing (GdE) and T2 lesions. , Ongoing PMS trials are currently being conducted with the phosphodiesterase inhibitor ibudilast, S1P modulator siponimod and anti-B-cell therapy ocrelizumab. , RECENT FINDINGS: Novel and imminently emerging DMTs for the treatment of RRMS include alemtuzumab, daclizumab, ocrelizumab, pegylated interferon-β-1a, and three times weekly glatiramer acetate. , To summarize mechanisms of action, efficacy, and safety of novel and imminently emerging disease-modifying treatments (DMTs) intended to be used in relapsing-remitting multiple sclerosis (RRMS).Novel and imminently emerging DMTs for the treatment of RRMS include alemtuzumab, daclizumab, ocrelizumab, pegylated interferon-β-1a, and three times weekly glatiramer acetate, Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial., We aimed to assess efficacy and safety of two dose regimens of the humanised anti-CD20 monoclonal antibody ocrelizumab in patients with relapsing-remitting multiple sclerosis. , In multiple sclerosis (MS), B cell-depleting therapy using monoclonal anti-CD20 Abs, including rituximab (RTX) and ocrelizumab, effectively reduces disease activity. , Ocrelizumab also shows efficacy in the primary progressive form of multiple sclerosis.Most of the presented cell-depleting and myeloablative therapies are highly effective treatment options but are also accompanied by significant risks., The armamentarium of approved disease-modifying therapies in MS and those in development include: (1) the first approved, moderately effective, injectable interferon-β and glatiramer acetate; (2) oral drugs (fingolimod, laquinimod, teriflunomide, dimethyl fumarate); (3) monoclonal antibodies (rituximab, ocrelizumab, ofatumumab, daclizumab, alemtuzumab); and (4) immunosuppressive agents (e.g. mitoxantrone)., BACKGROUND: B lymphocytes are implicated in the pathogenesis of multiple sclerosis. We aimed to assess efficacy and safety of two dose regimens of the humanised anti-CD20 monoclonal antibody ocrelizumab in patients with relapsing-remitting multiple sclerosis.METHODS: We did a multicentre, randomised, parallel, double-blind, placebo-controlled study involving 79 centres in 20 countries. Patients aged 18-55 years with relapsing-remitting multiple sclerosis were randomly assigned (1:1:1:1) via an interactive voice response system to receive either placebo, low-dose (600 mg) or high-dose (2000 mg) ocrelizumab in two doses on days 1 and 15, or intramuscular interferon beta-1a (30 ìg) once a week., Ocrelizumab for the treatment of relapsing-remitting multiple sclerosis., The potential role for ocrelizumab in the treatment of multiple sclerosis: current evidence and future prospects., Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial., Ocrelizumab also shows efficacy in the primary progressive form of multiple sclerosis.[SEP]", "label": "yes"}
{"id": "converted_402", "sentence1": "Is paroxetine effective for treatment of premenstrual dysphoric disorder?", "sentence2": "To evaluate the cost effectiveness of the four medications with a US FDA-approved indication for PMDD: fluoxetine, sertraline, paroxetine and drospirenone plus ethinyl estradiol (DRSP/EE)., All SSRIs (fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and clomipramine) were effective in reducing premenstrual symptoms., Paroxetine has been approved for the treatment of major depressive disorder (MDD), obsessive-compulsive disorder, panic disorder (PD), generalised anxiety disorder, post traumatic stress disorder (PTSD), and social anxiety disorder (SAD) in adults, whereas paroxetine CR is approved for the treatment of MDD, SAD, PD and premenstrual dysphoric disorder in adults., Selective serotonin-reuptake inhibitors (SSRIs) have been proven safe and effective for the treatment of PMDD and are recommended as first-line agents when pharmacotherapy is warranted. Currently fluoxetine, controlled-release paroxetine, and sertraline are the only Food and Drug Administration-approved agents for this indication., When compared with placebo, patients treated with paroxetine 20 mg attained a significant reduction in irritability (difference in median percent change: -23.9, 95% CI = -51.3 to -6.2, p = .014; difference in mean absolute change: -18.6, 95% CI = -32.5 to -4.6, p = .007). A statistically significant difference was not observed when the patients treated with the lower dose of paroxetine (10 mg) were compared with placebo. Treatment was well tolerated with no unexpected side effects., Intermittent administration of paroxetine 20 mg significantly reduced irritability symptoms in patients with PMDD., All these women had significant improvements in the HAMA, HAMD, CGI, and PRISM calendar. The rate of response to paroxetine treatment lay between 50% and 78.6% in the continuous-treatment group, and 37.5-93.8% in the intermittent-treatment group, as determined at the study end-point., The present results indicate that paroxetine is effective in both continuous and intermittent treatment of oriental PMDD women, and that the effects of active treatment lasted for six consecutive treatment menstrual cycles., Paroxetine CR is approved for the treatment of major depression, social anxiety disorder, panic disorder and premenstrual dysphoric disorder in adults., Continuous treatment with paroxetine reduced premenstrual symptoms effectively with a response rate of 85%., Intermittent treatment was as effective as continuous treatment in reducing irritability, affect lability, and mood swings, but had a somewhat weaker effect on depressed mood and somatic symptoms., Daily Record of Severity of Problems scores were lower in the paroxetine group compared with the placebo group, although the differences were not statistically significant., However, the mean on-treatment Inventory of Depressive Symptomatology (clinician-rated) score for the paroxetine group was 17.9 +/- 8.3 compared with 31.5 +/- 11.2 in the placebo group (adjusted mean difference = 13.6, P = 0.009)., Response (Clinical Global Impressions Scale score of 1 or 2) occurred in 70% of subjects randomized to paroxetine CR and 10% of those assigned to placebo (chi2(1) = 7.5, P = 0.006)., The US Food and Drug Administration and Health Canada recently approved paroxetine for the treatment of premenstrual dysphoric disorder., Patients treated with either dose of paroxetine CR demonstrated significantly greater improvements on the primary efficacy measure (change from baseline in mean luteal phase VAS-Mood scores) and on the majority of secondary efficacy measures compared with patients randomly assigned to placebo., For the treatment of PMDD, luteal phase dosing with 12.5 mg and 25 mg of paroxetine CR is effective and generally well tolerated., A statistically significant difference was observed in favor of paroxetine CR 25 mg versus placebo on the VAS-Mood (adjusted mean difference = -12.58 mm, 95% CI = -18.40 to -6.76; p < .001) and for paroxetine CR 12.5 mg versus placebo (adjusted mean difference = -7.51 mm, 95% CI = -13.40 to -1.62; p = .013)., Paroxetine CR doses of 12.5 mg/day and 25 mg/day are effective in treating PMDD and are well tolerated., At end point, subjects treated with paroxetine CR (12.5 mg and 25 mg) demonstrated significant improvement in VAS-Mood scores compared with those who received placebo (paroxetine CR 12.5 mg mean treatment difference vs. placebo, -8.7 mm; 95% CI, -15.7, -1.7; p =.015; paroxetine CR 25 mg mean treatment difference vs. placebo, -12.1 mm; 95% CI, -18.9, -5.3; p <.001)., Both doses of paroxetine CR 12.5 mg and 25 mg daily are effective and well tolerated in patients who suffer from PMDD., Of these agents, sertraline, fluoxetine and paroxetine (as an extended-release formulation) are approved by the US FDA for luteal phase, as well as continuous, administration., In well designed placebo-controlled trials in patients with major depressive disorder (including a study in the elderly), social anxiety disorder or premenstrual dysphoric disorder (PMDD), paroxetine CR was consistently superior to placebo with regards to primary endpoints (i.e. mean Hamilton Rating Scale for Depression total score [major depressive disorder], Liebowitz social anxiety scale total score and Clinical Global Impressions-Global Improvement score [social anxiety disorder] and Visual Analogue Scale-Mood score [PMDD])., Paroxetine is a potent selective serotonin reuptake inhibitor (SSRI) with indications for the treatment of depression, obsessive- compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post-traumatic stress disorder, premenstrual dysphoric disorder and chronic headache., Studies having compared the efficiency of antidepressants according to their serotonin activity (paroxetine or sertraline versus maprotiline, that is a selective noradrenaline re-uptake inhibitor), showed that serotonin re-uptake inhibitors were significantly more efficient on all symptoms than maprotiline, that was not more efficient than placebo., Paroxetine is a potent and selective serotonin reuptake inhibitor (SSRI) with currently approved indications for the treatment of depression, obsessive-compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post traumatic stress disorder, premenstrual dysphoric disorder and chronic headache., Preliminary data suggest that paroxetine has potential in the treatment of social phobia, premenstrual dysphoric disorder and chronic headache., The effects of active treatment were marked by the first active cycle with luteal phase 17-item Hamilton Rating Scale for Depression scores decreasing from 14.9 (+/- 5.3) to 8.2 (+/- 4.9) in the first, 7.8 (+/- 5.1) in the second, and 7.8 (+/- 6.8) in the third active treatment cycles (F[1,13] = 17.6; p < 0.0001)., The most conservative measure, the Clinical Global Impression (CGI), revealed that 7 of 14 patients had a complete response (CGI = 1 or 2) whereas 4 patients had a partial response (CGI = 3)., These open trial findings are consistent with the notion that paroxetine is effective in the acute phase for the treatment of PDD., The rating of premenstrual irritability, depressed mood, increase in appetite, and anxiety/tension was markedly lower during treatment with paroxetine than before, and this reduction in symptomatology appeared unabated for the entire treatment period.[SEP]", "label": "yes"}
{"id": "converted_2605", "sentence1": "Does verubecestat activate BACE?", "sentence2": "Verubecestat is a potent BACE1 enzyme inhibitor currently being investigated in Phase III trials for the treatment of mild-to-moderate and prodromal Alzheimer's disease. [SEP]", "label": "no"}
{"id": "converted_1497", "sentence1": "Is depression associated with poor prognosis of brain tumor patients?", "sentence2": "Before surgery 27 patients (35%) had BDI scores indicating the presence of depression. These scores were significantly higher in patients with a history of depression (p = 0.017) and in those with a lower functional outcome (p = 0.015)., A lower functional status (KPS score < or = 70) in patients was significantly associated with high depression scores at the 3-month (p = 0.000) and 1-year (p = 0.005) assessments., At all follow-ups, depressed low-grade glioma patients had a significantly shorter survival time, 3.3-5.8 years, compared to non-depressed low-grade glioma patients, 10.0-11.7 years., The results suggest that depression and decreased QOL among low-grade glioma patients is related to shorter survival at long-term follow-up., The adverse impact of depression in relation to survival among cancer patients is currently a subject of great interest in research., In the subgroup of patients with low-grade gliomas, depressive patients had a significantly shorter survival time compared with nondepressive subjects (P = 0.031, Kaplan-Meier survival analysis)., Preoperative depression seemed to be a significant prognostic factor for worse survival in low-grade glioma patients., Major depressive disorder was marginally associated with outcomes, while surgical interventions and radiotherapy did not show strong associations with test performances.[SEP]", "label": "yes"}
{"id": "converted_3686", "sentence1": "Does saracatinib promote oncogenesis?", "sentence2": "Antitumor activity of saracatinib (AZD0530), a c-Src/Abl kinase inhibitor, alone or in combination with chemotherapeutic agents in gastric cancer., We evaluated the antitumor effect of a c-Src/Abl kinase inhibitor, saracatinib (AZD0530), alone or combined with chemotherapeutic agents in gastric cancer cell lines and a NCI-N87 xenograft model. Among 10 gastric cancer cell lines, saracatinib specifically inhibited the growth and migration/invasion of SNU216 and NCI-N87 cells. Saracatinib blocked the Src/FAK, HER family, and oncogenic signaling pathways, and it induced G(1) arrest and apoptosis in SNU216 and NCI-N87 cells. , Consistent with our in vitro findings, cotreatment with saracatinib and 5-FU resulted in enhanced antitumor activity in the NCI-N87 xenografts. These data indicate that the inhibition of Src kinase activity by saracatinib alone or in combination with other agents can be a strategy to target gastric cancer.[SEP]", "label": "no"}
{"id": "converted_76", "sentence1": "Is CD56 useful in Ewing sarcoma prognosis?", "sentence2": "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.[SEP]", "label": "yes"}
{"id": "converted_831", "sentence1": "Have 5q35 microdeletions been implicated in Sotos syndrome development?", "sentence2": "Loss-of-function mutations of NSD1 and 5q35 microdeletions encompassing NSD1 are a major cause of Sotos syndrome (Sos), which is characterized by overgrowth, macrocephaly, characteristic facies, and variable intellectual disability (ID), We observed a novel 3.5 Mb 5q subtelomeric deletion in a 3-year-old girl with developmental delay, hypotonia and multiple minor anomalies. Comparison of her phenotype with the few published patients with terminal 5q35 deletions revealed several overlapping features, but also showed remarkable differences such as shortness of stature versus macrosomia. After the report of 5q35.3 microdeletions in Sotos syndrome we integrated the published BACs into the public draft sequence and exactly mapped the deletion size in our patient by FISH analysis with 15 BAC probes. We demonstrated that the deletion in our patient is immediately adjacent to the reported Sotos syndrome deletion site, Switch in FGFR3 and -4 expression profile during human renal development may account for transient hypercalcemia in patients with Sotos syndrome due to 5q35 microdeletions., Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome., After the report of 5q35.3 microdeletions in Sotos syndrome we integrated the published BACs into the public draft sequence and exactly mapped the deletion size in our patient by FISH analysis with 15 BAC probes., Clinical and genetic spectrum of 18 unrelated Korean patients with Sotos syndrome: frequent 5q35 microdeletion and identification of four novel NSD1 mutations., Here we describe a new case of Sotos syndrome with a 5q35 microdeletion, affecting the fibroblast growth factor receptor 4 (FGFR4) gene, presenting with infantile hypercalcemia., Microdeletions at 5q35.3, encompassing NSD1, are responsible for approximately 10% of non-Japanese cases of Sotos., Alu-related 5q35 microdeletions in Sotos syndrome., Most cases of Sotos syndrome are caused by intragenic NSD1 mutations or 5q35 microdeletions., Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome, Clinical and genetic spectrum of 18 unrelated Korean patients with Sotos syndrome: frequent 5q35 microdeletion and identification of four novel NSD1 mutations, Microdeletions at 5q35.3, encompassing NSD1, are responsible for approximately 10% of non-Japanese cases of Sotos, A case of Sotos syndrome with 5q35 microdeletion and novel clinical findings., Here we describe a new case of Sotos syndrome with a 5q35 microdeletion, affecting the fibroblast growth factor receptor 4 (FGFR4) gene, presenting with infantile hypercalcemia. , There are two types of mutations that cause NSD1 haploinsufficiency: mutations within the NSD1 gene (mutation type) and a 5q35 submicroscopic deletion encompassing the entire NSD1 gene (deletion type). , aCGH and metaphase FISH are useful for rapid diagnosis of 5q35 microdeletion associated with Sotos syndrome., Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome., Switch in FGFR3 and -4 expression profile during human renal development may account for transient hypercalcemia in patients with Sotos syndrome due to 5q35 microdeletions., A case of Sotos syndrome with 5q35 microdeletion and novel clinical findings., Most cases of Sotos syndrome are caused by intragenic NSD1 mutations or 5q35 microdeletions., aCGH and metaphase FISH are useful for rapid diagnosis of 5q35 microdeletion associated with Sotos syndrome., Alu-related 5q35 microdeletions in Sotos syndrome.[SEP]", "label": "yes"}
{"id": "converted_2832", "sentence1": "Is durvalumab used for lung cancer treatment?", "sentence2": " In the phase III PACIFIC trial consolidation with durvalumab, an anti-PDL-1 antibody, was associated with survival benefit in patients diagnosed with LA-NSCLC who responded to concurrent chemoradiotherapy., METHODS: An electronic literature search was performed of public databases (MEDLINE, Excerpta Medica dataBASE [EMBASE], and Cochrane) and conference proceedings for trials using PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab, durvalumab, and avelumab) in patients with NSCLC., Durvalumab in non-small-cell lung cancer patients: current developments., Single-agent durvalumab showed clinical efficacy and a manageable safety profile in advanced non-small-cell lung cancer, particularly the ≥25% PD-L1+ population., Six drugs including one CTLA-4 blocker (ipilimumab), two PD-1 blockers (nivolumab and pembrolizumab) and three PD-L1 blockers (atezolizumab, avelumab and durvalumab) are approved for the treatment of different types of cancers including both solid tumors such as melanoma, lung cancer, head and neck cancer, bladder cancer and Merkel cell cancer as well as hematological tumors such as classic Hodgkin's lymphoma. , PURPOSE OF REVIEW: The therapeutic armamentarium for advanced non-small-cell lung cancer has evolved considerably over the past years. Immune checkpoint inhibitors targeting programmed cell death-1 such as pembrolizumab and nivolumab or programmed cell death ligand 1 such as atezolizumab, durvalumab and avelumab have shown favorable efficacy results in this patient population in the first-line and second-line setting., In addition, preclinical and early clinical evidence suggests that chemotherapy and radiation may work synergistically with anti-PD-1/PD-L1 therapy to promote antitumor immunity, which has led to the initiation of clinical trials testing these drugs in patients with stage III NSCLC. A preliminary report of a randomized phase III trial, the PACIFIC trial, demonstrated an impressive increase in median progression-free survival with consolidative durvalumab, a PD-L1 inhibitor, compared with observation after cCRT. , ICI, such as the PD-1 inhibitors nivolumab and pembrolizumab and the PD-L1 inhibitor atezolizumab, have already been marketed for the treatment of pretreated patients with advanced NSCLC., The PACIFIC trial assessing durvalumab after standard chemoradiotherapy for locally advanced NSCLC has already met its primary endpoint and the potential of durvalumab will be reinforced if phase III randomized studies of first-line (MYSTIC trial) and second or subsequent (ARCTIC trial) lines of therapy demonstrate superiority over the current standard of care.<br>[SEP]", "label": "yes"}
{"id": "converted_618", "sentence1": "Does molindone affect body weight?", "sentence2": "Mean weight increased by 0.54 kg, and mean body mass index by 0.24 kg/m(2). , A large-scale trial comparing a first-generation antipsychotic (molindone) with newer agents did not find significant differences in treatment response, although the newer antipsychotics were associated with more severe weight gain. , No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. , The three treatment arms did not significantly differ in symptom decrease or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment. , Olanzapine and risperidone were associated with significantly greater weight gain. Olanzapine showed the greatest risk of weight gain and significant increases in fasting cholesterol, low density lipoprotein, insulin, and liver transaminase levels. Molindone led to more self-reports of akathisia. , Molindone is no more or less likely than typical drugs to cause movement disorders, but it does cause significantly more weight loss (2RCTs n=60 RR 2.78, CI 1.10 to 6.99, NNH 5 CI 2 to 77). , Molindone may be an effective antipsychotic but its adverse effect profile does not differ significantly from that of typical antipsychotics (apart from the event of weight loss). , Convergent evidence suggests a hierarchy in the magnitude of BWG that may be induced by diverse agents, being very high for clozapine and olanzapine; high for quetiapine, zotepin, chlorpromazine, and thioridazine; moderate for risperidone and sertindole; and low for ziprazidone, amisulpiride, haloperidol, fluphenazine, pimozide, and molindone. , Loxapine and molindone induce weight decreases, and these exceptions are difficult to explain., It is no more or less likely than typical drugs to cause movement disorders, but causes significantly more weight loss (RR 2.78, CI 1.10 to 6.99)., Molindone may be an effective antipsychotic; however, its adverse effect profile does not differ significantly from that of typical antipsychotics, apart from the event of weight loss. , Among conventional agents, mean weight change ranged from a reduction of 0.39 kg with molindone to an increase of 3.19 kg with thioridazine., Weight gain has been reported with nearly every antipsychotic drug on the market (molindone is an exception). , Although almost all antipsychotics induce bodyweight gain, molindone and loxapine appear to induce bodyweight loss. , Clozapine and low-potency phenothiazines are associated with the largest gains and molindone with weight loss, but the mechanism is not known. , On average, molindone patients lost 5 pounds over the 6 weeks of treatment, whereas thioridazine patients gained 6 pounds. , Clinically, molindone has a tendency to cause weight loss and may have less effect on seizure threshold than conventional antipsychotic agents,  Monthly weights and neuroleptic dosages during the first three months of psychiatric hospitalization were compared between matched groups of patients receiving molindone, a combination of molindone and other neuroleptics, or other neuroleptic drugs. We found no significant differences in weight gain among the three groups. , The weight-reducing property of molindone, a recently introduced antipsychotic drug, was tested in 9 hospitalized chronic schizophrenic patients. There was an average weight loss of 7.6 kg after 3 months on molindone; most of the loss occurred during the first month.[SEP]", "label": "yes"}
{"id": "converted_4701", "sentence1": "Is ASF1 phopshorylated by  the Tousled-like kinases?", "sentence2": "Asf1, a key histone H3-H4 chaperone required for this process, is phosphorylated by Tousled-like kinases (TLKs). , The Tousled-like kinases 1 and 2 (TLK1/2) control histone deposition through the ASF1 histone chaperone, The Tousled-like kinases (TLKs) are involved in chromatin assembly, DNA repair, and transcription. Two TLK genes exist in humans, and their expression is often dysregulated in cancer. TLKs phosphorylate Asf1 , TLKs interact specifically (and phosphorylate) with the chromatin assembly factor Asf1, a histone H3-H4 chaperone, TLK1 substrates were identified as the histone H3 and Asf1 (a histone H3/H4 chaperone)[SEP]", "label": "yes"}
{"id": "converted_2247", "sentence1": "Does TFIIS affect nucleosome positioning?", "sentence2": "Transcript cleavage factor TFIIS reactivates the backtracked complexes and promotes pol II transcription through the nucleosome. , The same nucleosomes transcribed in the opposite orientation form a weaker, more diffuse barrier that is largely relieved by higher salt, TFIIS, or FACT, The system contains natural or recombinant histones, chromatin assembly factors, the histone-acetyltransferase p300, all components of the general transcription machinery, general coactivators and the elongation factor SII (TFIIS)., Efficient and rapid nucleosome traversal by RNA polymerase II depends on a combination of transcript elongation factors., We now show that although TFIIF or TFIIS alone is modestly stimulatory for nucleosome traversal, both factors together increase transcription through nucleosomes in a synergistic manner., Significantly, we found that nucleosomes with a Sin mutant histone are traversed to the same extent and at nearly the same rate as equivalent pure DNA templates if both TFIIS and TFIIF are present., After partial uncoiling of nucleosomal DNA from histone octamer by Pol II and backtracking of the enzyme, nucleosomal DNA recoils on the octamer, locking Pol II in the arrested state. Histone chaperones and transcription factors TFIIS, TFIIF and FACT facilitate transcription through chromatin using different molecular mechanisms., Transcript cleavage factor TFIIS reactivates the backtracked complexes and promotes pol II transcription through the nucleosome., The highly conserved eukaryotic transcriptional elongation factor TFIIS enables RNA polymerase II (RNAPII) to read though pause or termination sites, nucleosomes and sequence-specific DNA-binding proteins., We also studied the effect of TFIIF and TFIIS on transcription of nucleosomes containing a Sin mutant histone., The same nucleosomes transcribed in the opposite orientation form a weaker, more diffuse barrier that is largely relieved by higher salt, TFIIS, or FACT.[SEP]", "label": "yes"}
{"id": "converted_1272", "sentence1": "Is curcumin a phytochemical?", "sentence2": "we analyzed turmeric from different agroclimatic regions for influence of various factors on its growth and yield of important phytochemicals, The phytochemical, curcumin, has been reported to play many beneficial roles., Curcumin (CUR), the major component in Curcuma longa, has been shown as a potent chemopreventive phytochemical that modulates various signaling pathways. , Curcumin (CUR) is a phytochemical that inhibits the xenobiotic ABC efflux transporters implicated in cancer multidrug resistance (MDR), such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins 1 and 5 (MRP1 and MRP5). , In this study, we tested the efficacy of combining temozolomide with curcumin, a phytochemical known to inhibit glioblastoma growth, and investigated the mechanisms involved.,  In the present study, we investigate whether curcumin (cur), a phytochemical compound with potent anti-inflammatory effect, the Phytochemicals Curcumin , in combination with the phytochemicals curcumin and quercetin, Curcumin is a phytochemical derived from rhizome of turmeric Curcuma longa, present in the curry spice. , Curcumin, a naturally occurring polyphenolic phytochemical isolated from the medicinal plant Curcuma longa, has anti-inflammatory activities, In the present study curcumin (CUR), a known anticancer phytochemical, ,  Curcumin, a natural phytochemical, exhibits potent anticancer activities., hat curcumin, a phytochemical compound with potent anti-inflammatory properties , curcumin, a phytochemical[SEP]", "label": "yes"}
{"id": "converted_1623", "sentence1": "Is the Histidine-Rich Calcium Binding protein (HRC) related to arrhythmias and cardiac disease?", "sentence2": "A human genetic variant (Ser96Ala) in the sarcoplasmic reticulum (SR) histidine-rich Ca(2+)-binding (HRC) protein has been linked to ventricular arrhythmia and sudden death in dilated cardiomyopathy. , These findings suggest that aberrant SR Ca2+ release and increased susceptibility to delayed afterdepolarizations underlie triggered arrhythmic activity in human Ala96 HRC carriers., The histidine-rich calcium binding protein (HRC) Ser96Ala polymorphism was shown to correlate with ventricular arrhythmias and sudden death only in dilated cardiomyopathy patients but not in healthy human carriers., These findings indicate that the HRC Ser96Ala variant increases the propensity of arrhythmogenic Ca(2+) waves in the stressed failing heart, suggesting a link between this genetic variant and life-threatening ventricular arrhythmias in human carriers., HRC plays an important role in myocyte differentiation and in antiapoptotic cardioprotection against ischemia/reperfusion induced cardiac injury. Interestingly, HRC has been linked with familiar cardiac conduction disease and an HRC polymorphism was shown to associate with malignant ventricular arrhythmias in the background of idiopathic dilated cardiomyopathy., This review summarizes studies, which have established the critical role of HRC in Ca(2+)-homeostasis, suggesting its importance in cardiac physiology and pathophysiology., HRC is a SR luminal Ca(2+) binding protein known to associate with both triadin and the sarcoplasmic reticulum Ca(2+)-ATPase, and may thus mediate the crosstalk between SR Ca(2+) uptake and release. Indeed, evidence from genetic models of JCN and HRC indicate that they are important in cardiophysiology as alterations in these proteins affect SR Ca(2+) handling and cardiac function. In addition, downregulation of JCN and HRC may contribute to Ca(2+) cycling perturbations manifest in the failing heart, where their protein levels are significantly reduced., The Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias in idiopathic DCM and may serve as an independent predictor of susceptibility to arrhythmogenesis in the setting of DCM., AAV-mediated knock-down of HRC exacerbates transverse aorta constriction-induced heart failure., Chronic overexpression of HRC that may disrupt intracellular Ca(2+) homeostasis is implicated in pathogenesis of cardiac hypertrophy, Ablation of HRC showed relatively normal phenotypes under basal condition, but exhibited a significantly increased susceptibility to isoproterenol-induced cardiac hypertrophy, Our results present evidence that down-regulation of HRC could deteriorate cardiac function in TAC-FH through perturbed SR-mediated Ca(2+) cycling, However, AAV9-mediated HRC-KD in TAC-FH was associated with decreased fractional shortening and increased cardiac fibrosis compared with control., Histidine-rich calcium binding protein (HRC) is a high capacity, low affinity Ca(2+) binding protein, specifically expressed in striated muscles of mammals. In rabbit skeletal and cardiac muscles, HRC binds to sarcoplasmic reticulum (SR) membranes via triadin, a junctional SR protein. Recently, a potential role in heart failure and arrhythmogenesis has been assigned to HRC due to its activity as regulator of SR Ca(2+) uptake and Ca(2+) release., In addition, HRC null mice displayed a significantly exaggerated response to the induction of cardiac hypertrophy by isoproterenol compared to their wild-type littermates. The exaggerated response of HRC knockout mice to the induction of cardiac hypertrophy is consistent with a regulatory role for HRCBP in calcium handling in vivo and suggests that mutations in HRC, in combination with other genetic or environmental factors, might contribute to pathological hypertrophy and heart failure., We observed that the levels of HRC were reduced in animal models and human heart failure., Collectively, these data indicate that alterations in expression levels of HRC are associated with impaired cardiac SR Ca homeostasis and contractile function., Abnormal calcium cycling and cardiac arrhythmias associated with the human Ser96Ala genetic variant of histidine-rich calcium-binding protein., The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy., Interestingly, HRC has been linked with familiar cardiac conduction disease and an HRC polymorphism was shown to associate with malignant ventricular arrhythmias in the background of idiopathic dilated cardiomyopathy[SEP]", "label": "yes"}
{"id": "converted_4053", "sentence1": "Does hypofractionated radiotherapy offers any benefit for DIPG?", "sentence2": "CONCLUSION: Hypofractionated RT for children with newly diagnosed DIPG is well tolerated and feasible from the viewpoint of reducing a patient's burden of treatment. Re-irradiation at first progression is suggested to be beneficial., Median OS and time to progression were similar between conventionally fractionated and hypofractionated RT groups.(9.7 [95% confidence interval(CI): 7.1-11.2] versus 11.0[95% CI: 5.2-13.6] months, P = 0.60; 4.2[95% CI: 1.8-8.3] versus 7.1 [95% CI:4.5-8.7] months, P = 0.38). , The median overall survival (OS) was 11 months (95% CI - 7.5 to 14.5 months) in the conventional arm and 12 months (95% CI - 10.5 to 13.5 months) in the experimental arm (p = 0.208). 28% (n = 5) patients in the experimental arm developed grade 3 or 4 hematological toxicity.CONCLUSION: The above study shows that hypofractionated radiotherapy with concurrent and adjuvant temozolomide does not improve OS and has higher hematological toxicity. , CONCLUSIONS: The results of this meta-analysis suggest that CFRT and HFRT provide similar survival outcomes for patients with DIPG., CONCLUSIONS: Hypofractionated radiotherapy offers lesser burden on the patients, their families and the treating departments, with nearly comparable results to conventional fractionation, though not fulfilling the non-inferiority assumption., xternal radiotherapy with a radical hypofractionated regimen is feasible and well tolerated in children with newly diagnosed DIPG. However, this regimen does not seem to change overall survival in this setting.[SEP]", "label": "no"}
{"id": "converted_2308", "sentence1": "Is there an RNAi drug being developed to treat amyloidosis?", "sentence2": "Patisiran is an investigational RNA interference (RNAi) therapeutic in development for the treatment of hereditary ATTR (hATTR) amyloidosis, a progressive disease associated with significant disability, morbidity, and mortality.[SEP]", "label": "yes"}
{"id": "converted_2549", "sentence1": "Are stress granules membraneous?", "sentence2": "PMLOs are different in size, shape, and composition, and almost invariantly contain intrinsically disordered proteins (e.g., eIF4B and TDP43 in stress granules,, Liquid-liquid phase separation (LLPS) of RNA-binding proteins plays an important role in the formation of multiple membrane-less organelles involved in RNA metabolism, including stress granules., Stress granules (SG) are membrane-less compartments involved in regulating mRNAs during stress.,  In addition to membrane delimited organelles, proteins and RNAs can organize themselves into specific domains. Some examples include stress granules and subnuclear bodies. [SEP]", "label": "no"}
{"id": "converted_3168", "sentence1": "Tocilizumab is an anti-TNF antibody, yes or no?", "sentence2": "was treated with tocilizumab, an anti-interleukin-6 receptor monoclonal antibody , Tocilizumab (TCZ) is a humanized monoclonal antibody against IL-6 receptor licensed in 2009 that has demonstrated clinical efficacy in various adult RA populations. RA management guidelines and recommendations consider TCZ as one of the bDMARDS indicated after methotrexate or other conventional synthetic DMARDs and/or TNF inhibitors failure in adult RA, Tocilizumab (RoActemra or Actemra) is a recombinant humanized monoclonal antibody that acts as an interleukin (IL)-6 receptor antagonist., METHODS\nPatients (n = 93) were treated with an anti-IL-6 receptor antibody (tocilizumab) or TNF-α inhibitors for 16 weeks., The recent development of biological agents, namely, anti-tumour necrosis factor alpha (TNF-α) agents (infliximab, adalimumab and etanercept), anti- CD20 monoclonal antibody (rituximab) and anti-interleukin 6 receptor (IL-6R) monoclonal antibody (tocilizumab), represents a major breakthrough for the treatment of immune-mediated disorders., Recently, an anti-IL-6 receptor monoclonal antibody, tocilizumab, has been licensed for the treatment as monotherapy or in combination with methotrexate of moderate to severe RA, when disease modifying anti-rheumatic drugs or anti-tumour necrosis factors (TNF) have failed., Tocilizumab is a monoclonal humanized anti-IL-6-receptor antibody used for the treatment of rheumatoid arthritis., Indeed, worldwide clinical trials of TNF inhibiting biologic disease modifying antirheumatic drugs (bDMARDs) including infliximab, adalimumab, golimumab, certolizumab pegol, and etanercept as well as the humanized anti-human IL-6 receptor antibody, tocilizumab, have demonstrated outstanding clinical efficacy and tolerable safety profiles, resulting in worldwide approval for using these bDMARDs to treat moderate to severe active RA in patients with an inadequate response to synthetic disease modifying antirheumatic drugs (sDMARDs)., Tocilizumab is a humanized anti-IL-6 receptor monoclonal antibody, which binds to circulating soluble IL-6 receptor and membrane-expressed IL-6 receptor, inhibiting IL-6 binding to both forms of IL-6 receptor., Subsequent options include a TNF-alpha antagonist, followed by rituximab or possibly abatacept; (2) Tocilizumab, a monoclonal antibody, inhibits interleukin-6 receptors., Tocilizumab (TCZ) is a monoclonal antibody which inhibits the interleukin-6 receptor.[SEP]", "label": "no"}
{"id": "converted_3810", "sentence1": "Can AGY be used as antidiuretic replacement therapy?", "sentence2": "AGY, a Novel Egg Yolk-Derived Anti-gliadin Antibody, Is Safe for Patients with Celiac Disease., Oral egg yolk anti-gliadin antibody (AGY) is a novel treatment to neutralize gluten and may improve the efficacy of the GFD., To determine the safety, tolerability, and potential efficacy of AGY in patients with CD., Most patients had fewer celiac symptoms (especially tiredness, headache, and bloating), improved quality of life, lowered antibodies, and lowered LMER when taking AGY compared to the run-in period., In our cohort, AGY was safe and potentially associated with improved CD-related outcome measures in patients on a GFD. [SEP]", "label": "no"}
{"id": "converted_2512", "sentence1": "Is celiac disease caused by gliadin-induced transglutaminase-2 (TG2)-dependent events ?", "sentence2": "Celiac disease (CD) is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. , Celiac disease (CD) is an autoimmune enteropathy initiated and sustained by the ingestion of gluten in genetically susceptible individuals. It is caused by a dysregulated immune response toward both dietary antigens, the gluten proteins of wheat, rye, and barley, and autoantigens, the enzyme tissue transglutaminase (TG2), Celiac disease (CD) is an autoimmune gastrointestinal disorder characterized by the presence of anti-transglutaminase 2 (TG2) and anti-gliadin antibodies, Transglutaminase 2 (TG2) catalyzes cross-linking or deamidation of glutamine residues in peptides and proteins. The in vivo deamidation of gliadin peptides plays an important role in the immunopathogenesis of celiac disease (CD)., Tissue transglutaminase (TG2) modifies proteins and peptides by transamidation or deamidation of specific glutamine residues. TG2 also has a central role in the pathogenesis of celiac disease. The enzyme is both the target of disease-specific autoantibodies and generates deamidated gliadin peptides recognized by intestinal T cells from patients.[SEP]", "label": "yes"}
{"id": "converted_4703", "sentence1": "Does sphingosine-1 phosphoate suppress epiregulin?", "sentence2": "S1P-induced FOXO1 and EREG gene expression suggests that the activation of S1P-S1PR axis may cooperate with gonadotropins in modulating follicle development., S1P-dependent CREB phosphorylation induced FOXO1 and the EGF-like epiregulin-encoding gene (EREG), confirming the exclusive role of gonadotropins and interleukins in this process, but did not affect steroidogenesis. [SEP]", "label": "no"}
{"id": "converted_885", "sentence1": "Does  thyroid hormone receptor beta1 affect insulin secretion?", "sentence2": "We demonstrated that thyroid hormone T3 rapidly induces Akt activation in pancreatic beta cells rRINm5F and hCM via thyroid hormone receptor (TR) beta1., The silencing of TRbeta1 expression through RNAi confirmed this receptor to be crucial for the T3-induced activation of Akt., T3 is able to specifically activate Akt in the islet beta cells rRINm5F and hCM through the interaction between TRbeta1 and PI3K p85alpha, demonstrating the involvement of TRbeta1 in this novel T3 non-genomic action in islet beta cells.[SEP]", "label": "no"}
{"id": "converted_253", "sentence1": "Can life style changes reduce oxidative stress", "sentence2": "The CFS group had an unfavorable lipid profile and signs of oxidative stress induced damage to lipids and proteins. These results might be indicative of early proatherogenic processes in this group of patients who are otherwise at low risk for atherosclerosis. Antioxidant treatment and life style changes are indicated for women with CFS, as well as closer observation in order to assess the degree of atherosclerosis., Once detected, these patients may be offered more aggressive treatment strategies such as early pharmacotherapy in addition to life style changes targeted to maintaining pericyte integrity., Our results suggested that life style changes which related to migration might reduce DNA damage in Hasake nationalities., Low levels of antioxidants and increased oxidative stress with insulin resistance in metabolic syndrome suggests that besides therapeutic life style changes (TLC) as suggested in ATP III guidelines inclusion of antioxidant vitamins, fruits and vegetable could be beneficial to ward off the consequences of metabolic syndrome.[SEP]", "label": "yes"}
{"id": "converted_3399", "sentence1": "Does CXorf21 escape X chromosome inactivation?", "sentence2": "This revealed a 637-kb tandem duplication that in addition to DAX1 includes the four MAGEB genes, the hypothetical gene CXorf21, GK, and part of the MAP3K7IP3 gene, Among statin users, diabetes cases had marginal but insignificantly different expression of ZNF532 (up-regulated 15%, Q-value=0.0584), CXORF21 (up-regulated 11%, Q-value=0.0584), and ZNHIT3 (up-regulated 19%, Q-value=0.0959), compared with controls.,  For this, we selected five SNPs (rs1801274 in FCGR2A and rs2286672 in PLD2, rs887369 in CXorf21, rs9782955 in LYST, and rs3794060 in NADSYN1), Examination of X-linked DEGs, such as GTPBP6, TAF9L, and CXORF21, that show verbal cognition-gene expression correlations may establish a causal link between these genes, neurodevelopment, and language function.[SEP]", "label": "yes"}
{"id": "converted_2785", "sentence1": "Are whole-genome duplications more divergent than small-scale duplications in yeast?", "sentence2": " Also, we observe that transporter and glycolytic genes have a higher probability to be retained in duplicate after WGD and subsequent gene loss, both in the model as in S. cerevisiae, which leads to an increase in glycolytic flux after WGD, We show that the retention of genes in duplicate in the model, corresponds nicely with those retained in duplicate after the ancestral WGD in S. cerevisiae, Thus, our model confirms the hypothesis that WGD has been important in the adaptation of yeast to the new, glucose-rich environment that arose after the appearance of angiosperms., Whole-genome duplicates tend to exhibit less profound phenotypic effects when deleted, are functionally less divergent, and are associated with a different set of functions than their small-scale duplicate counterparts., The results uncover the WGD as a major source for the evolution of a complex interconnected block of transcriptional pathways., These selected pairs, both WGD and SSD, tend to have decelerated functional evolution, have higher propensities of co-clustering into the same protein complexes, and share common interacting partners., Moreover, we find additional transcriptional profiles that are suggestive of neo- and subfunctionalization of duplicate gene copies. These patterns are strongly correlated with the functional dependencies and sequence divergence profiles of gene copies., Functional and transcriptional divergence between the copies after gene duplication has been considered the main driver of innovations ., Whole-genome duplicates tend to exhibit less profound phenotypic effects when deleted, are functionally less divergent, and are associated with a different set of functions than their small-scale duplicate counterparts., Empirical data shows that whole-genome duplications (WGDs) are more likely to be retained than small-scale duplications (SSDs), though their relative contribution to the functional fate of duplicates remains unexplored.[SEP]", "label": "yes"}
{"id": "converted_3544", "sentence1": "Is AND-1/Ctf4 essential for proliferation?", "sentence2": "AND-1 fork protection function prevents fork resection and is essential for proliferation., AND-1/Ctf4 bridges the CMG helicase and DNA polymerase alpha, facilitating replication. Using an inducible degron system in avian cells, we find that AND-1 depletion is incompatible with proliferation, owing to cells accumulating in G2 with activated DNA damage checkpoint. Replication without AND-1 causes fork speed slow-down and accumulation of long single-stranded DNA (ssDNA) gaps at the replication fork junction, with these regions being converted to DNA double strand breaks (DSBs) in G2. Strikingly, resected forks and DNA damage accumulation in G2, but not fork slow-down, are reverted by treatment with mirin, an MRE11 nuclease inhibitor. Domain analysis of AND-1 further revealed that the HMG box is important for fast replication but not for proliferation, whereas conversely, the WD40 domain prevents fork resection and subsequent DSB-associated lethality. Thus, our findings uncover a fork protection function of AND-1/Ctf4 manifested via the WD40 domain that is essential for proliferation and averts genome instability., Thus , our findings uncover a fork protection function of AND-1/Ctf4 manifested via the WD40 domain that is essential for proliferation and averts genome instability, Thus, our findings uncover a fork protection function of AND-1/Ctf4 manifested via the WD40 domain that is essential for proliferation and averts genome instability.[SEP]", "label": "yes"}
{"id": "converted_1978", "sentence1": "Do histone variant mH2A (macro-H2A) levels decrease upon differentiation?", "sentence2": "Through manipulation of macroH2A isoforms, we further demonstrate that macroH2A2 is the predominant barrier to reprogramming., In particular, we find macroH2A isoforms to be highly enriched at target genes of the K27me3 demethylase, Utx, which are reactivated early in iPS reprogramming,  Therefore, we propose that macroH2A isoforms provide a redundant silencing layer or terminal differentiation 'lock' at critical pluripotency genes that presents as an epigenetic barrier when differentiated cells are challenged to reprogram., Histone variant macroH2A confers resistance to nuclear reprogramming, Resistance to reprogramming is associated with incorporation of the histone variant macroH2A, which is retained on the Xi of differentiated cells, but absent from the Xi of EpiSCs., We highlight the role of macroH2A in the establishment and maintenance of differentiated states and we discuss its still poorly recognized function in transcriptional activation., Histone variant macroH2A marks embryonic differentiation in vivo and acts as an epigenetic barrier to induced pluripotency., MacroH2A.1 was found to be present at low levels upon the establishment of pluripotency in the inner cell mass and epiblast, but it was highly enriched in the trophectoderm and differentiated somatic cells later in mouse development., Chromatin immunoprecipitation revealed that macroH2A.1 is incorporated in the chromatin of regulatory regions of pluripotency genes in somatic cells such as mouse embryonic fibroblasts and adult neural stem cells, but not in embryonic stem cells., In addition, overexpression of macroH2A isoforms prevented efficient reprogramming of epiblast stem cells to naïve pluripotency. , Macro histone variants are critical for the differentiation of human pluripotent cells, Here we show that the knockdown of macro histone variants impaired the in vitro and in vivo differentiation of human pluripotent cells, likely through defects in the silencing of pluripotency-related genes, Furthermore, male and female mH2A-deficient ESCs proliferate normally under pluripotency culture conditions, and respond to several standard differentiation procedures efficiently.[SEP]", "label": "no"}
{"id": "converted_4075", "sentence1": "Has AZD9668 been tested in clinical trials?", "sentence2": "Efficacy, safety and tolerability of AZD9668 (5, 20 and 60 mg bid) were compared with placebo in a randomised, double-blind, placebo-controlled, 12-week, Phase IIb trial (NCT00949975: approved by an Investigational Review Board), in patients with symptomatic COPD receiving maintenance tiotropium. , A randomised, placebo-controlled, dose-finding study of AZD9668, an oral inhibitor of neutrophil elastase, in patients with chronic obstructive pulmonary disease treated with tiotropium.[SEP]", "label": "yes"}
{"id": "converted_2786", "sentence1": "Do yeast LTR give rise to circular DNA?", "sentence2": "Circular retrotransposition products generated by a LINE retrotransposon, Formation of Extrachromosomal Circular DNA from Long Terminal Repeats of Retrotransposons in Saccharomyces cerevisiae, Ty eccDNA can arise from the circularization of extrachromosomal linear DNA during the transpositional life cycle of retrotransposons, or from circularization of genomic Ty DNA, Circularization may happen through nonhomologous end-joining (NHEJ) of long terminal repeats (LTRs) flanking Ty elements, by Ty autointegration, or by LTR-LTR recombination, We have recently shown that yeast LTR elements generate circular DNAs through recombination events between their flanking long terminal repeats (LTRs)., Similarly, circular DNAs can be generated by recombination between LTRs residing at different genomic loci, in which case the circular DNA will contain the intervening sequence., A recent study on circular DNAs in yeast found that transposable element sequence residing in circular structures mostly corresponded to full-length transposable elements.[SEP]", "label": "yes"}
{"id": "converted_4184", "sentence1": "Are interferons defensive proteins?", "sentence2": "In response to viral infections, various pattern recognition receptors (PRRs) are activated for the production of type I interferon (IFN I). ,  activating interferon (IFN) production and positively regulating antiviral response in mammals. , The innate immune system, in particular the type I interferon (IFN) response, is a powerful defence against virus infections. , The interferon-induced GTP-binding protein Mx is responsible for a specific antiviral state against a broad spectrum of viral infections that are induced by type-I interferons (IFN α/β) in different vertebrates[SEP]", "label": "yes"}
{"id": "converted_245", "sentence1": "Is the Drosophila Translational Control Element (TCE) involved in spermatogenesis?", "sentence2": "Gene regulation in Drosophila spermatogenesis: analysis of protein binding at the translational control element TCE., We have previously identified a 12 nucleotide long sequence element, the TCE, that was demonstrated to be necessary for translational control of expression in the male germ line of Drosophila melanogaster (Schäfer et al., 1990)., Gene regulation in Drosophila spermatogenesis: analysis of protein binding at the translational control element TCE, The Drosophila Translational Control Element (TCE) is required for high-level transcription of many genes that are specifically expressed in testes, Bioinformatic analyses of core promoter sequences from 190 genes that are specifically expressed in testes identified a 10 bp A/T-rich motif that is identical to the translational control element (TCE), The Drosophila Translational Control Element (TCE) is required for high-level transcription of many genes that are specifically expressed in testes.[SEP]", "label": "yes"}
{"id": "converted_4194", "sentence1": "Is adenosine signaling prognostic for cancer outcome?", "sentence2": "Adenosine Signaling Is Prognostic for Cancer Outcome and Has Predictive Utility for Immunotherapeutic Response., There are several agents in early clinical trials targeting components of the adenosine pathway including A2AR and CD73. The identification of cancers with a significant adenosine drive is critical to understand the potential for these molecules. However, it is challenging to measure tumor adenosine levels at scale, thus novel, clinically tractable biomarkers are needed.EXPERIMENTAL DESIGN: We generated a gene expression signature for the adenosine signaling using regulatory networks derived from the literature and validated this in patients. We applied the signature to large cohorts of disease from The Cancer Genome Atlas (TCGA) and cohorts of immune checkpoint inhibitor-treated patients.RESULTS: The signature captures baseline adenosine levels in vivo (r 2 = 0.92, P = 0.018), is reduced after small-molecule inhibition of A2AR in mice (r 2 = -0.62, P = 0.001) and humans (reduction in 5 of 7 patients, 70%), and is abrogated after A2AR knockout. Analysis of TCGA confirms a negative association between adenosine and overall survival (OS, HR = 0.6, P < 2.2e-16) as well as progression-free survival (PFS, HR = 0.77, P = 0.0000006). Further, adenosine signaling is associated with reduced OS (HR = 0.47, P < 2.2e-16) and PFS (HR = 0.65, P = 0.0000002) in CD8+ T-cell-infiltrated tumors. Mutation of TGFβ superfamily members is associated with enhanced adenosine signaling and worse OS (HR = 0.43, P < 2.2e-16). Finally, adenosine signaling is associated with reduced efficacy of anti-PD1 therapy in published cohorts (HR = 0.29, P = 0.00012).CONCLUSIONS: These data support the adenosine pathway as a mediator of a successful antitumor immune response, demonstrate the prognostic potential of the signature for immunotherapy, and inform patient selection strategies for adenosine pathway modulators currently in development.[SEP]", "label": "yes"}
{"id": "converted_3042", "sentence1": "Is Semagacestat effective for treatment of Alzheimer's disease?", "sentence2": "However, a large phase 3 trial of semagacestat, a potential non-transition state analog (non-TSA) GSI, in patients with Alzheimer's disease (AD) was terminated due to unexpected aggravation of cognitive deficits and side effects., BACKGROUND: In a recent report, 76 weeks' treatment with a gamma-secretase inhibitor (semagacestat) was associated with poorer cognitive outcomes in Alzheimer's disease (AD)., A clinical trial with the wide-spectrum γ-secretase inhibitor semagacestat has, however, demonstrated that global inhibition of all γ-secretases causes serious toxicity. , OBJECTIVE: Semagacestat, a γ-secretase inhibitor, demonstrated an unfavorable risk-benefit profile in a Phase 3 study of patients with Alzheimer's disease (IDENTITY trials), and clinical development was halted. , CONCLUSIONS: As compared with placebo, semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability. Semagacestat was associated with more adverse events, including skin cancers and infections., BACKGROUND\nIn a recent report, 76 weeks' treatment with a gamma-secretase inhibitor (semagacestat) was associated with poorer cognitive outcomes in Alzheimer's disease (AD)., Semagacestat was associated with more adverse events, including skin cancers and infections., CONCLUSIONS\nAs compared with placebo, semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability., OBJECTIVE\nSemagacestat, a γ-secretase inhibitor, demonstrated an unfavorable risk-benefit profile in a Phase 3 study of patients with Alzheimer's disease (IDENTITY trials), and clinical development was halted., Recently disclosed Phase III findings on semagacestat indicated that Alzheimer's disease (AD) patients on this drug showed significantly worsened cognitive function compared to those treated with placebo., The recent failure of semagacestat in two large Phase III studies questions the value of γ-secretase inhibitors in treating Alzheimer's disease., A phase 3 trial of semagacestat for treatment of Alzheimer's disease.As compared with placebo, semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability. , Preliminary results from Phase III studies showed that semagacestat failed to slow disease progression, and it was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living. , Changes in Neuropsychiatric Inventory Associated with Semagacestat Treatment of Alzheimer's Disease.In participants with mild to moderate AD, high dose semagacestat treatment was associated with greater severity and faster worsening of NPS in a pattern resembling an agitated depression. , Patients treated with semagacestat lost more weight and had more skin cancers and infections, treatment discontinuations due to adverse events, and serious adverse events (P<0.001 for all comparisons with placebo)., <b>OBJECTIVE</b>: Semagacestat, a γ-secretase inhibitor, demonstrated an unfavorable risk-benefit profile in a Phase 3 study of patients with Alzheimer's disease (IDENTITY trials), and clinical development was halted., Other relevant safety findings associated with semagacestat treatment included cognitive and functional worsening, skin-related TEAEs, renal and hepatic changes, increased QT interval, and weight loss., Patients treated with semagacestat lost more weight and had more skin cancers and infections, treatment discontinuations due to adverse events, and serious adverse events (P&lt;0.001 for all comparisons with placebo)., Semagacestat, a γ-secretase inhibitor, demonstrated an unfavorable risk-benefit profile in a Phase 3 study of patients with Alzheimer's disease (IDENTITY trials), and clinical development was halted.[SEP]", "label": "no"}
{"id": "converted_3080", "sentence1": "Is treatment with Bacillus Calmette Guerin used for bladder cancer?", "sentence2": "Intravesical Bacillus Calmette-Guerin (BCG) is the best treatment modality for progression of non-muscle invasive bladder cancer. , this result indicates that they may be used as putative biomarkers for monitoring changes in bladder carcinogenesis in response to BCG immunotherapy., response of urothelial precancerous lesions to intravesical BCG treatment, bladder cancer (BC) is a major clinical issue.METHODS: We performed immunohistochemistry to assess the role of human epidermal growth factor receptor-2 (HER-2) and microsatellite instability (MSI) factors MutL homologue 1 (MLH1) and MutS homologue 2 (MSH2) in predicting recurrence and progression of T1 high-grade BCs having undergone transurethral resection of bladder tumor (TURBT) alone or TURBT + intravesical instillations of bacillus Calmette-Guerin (BCG)., To evaluate the efficacy and safety of a tailored endovesical immunotherapy protocol with biweekly BCG for elderly Patients with high risk non muscle invasive bladder cancer , Bacillus of Calmette-Guerin (BCG) therapy for high risk non muscle invasive bladder cancer treatment in older patients., BCG (Bacillus of Calmette Guerin) has been used for more than 20 years and is currently the most active agent for superficial bladder cancer therapy., BCG (Bacillus of Calmette Guerin) therapy of high-risk superficial bladder cancer., Production of IL-5, a classical T(H)2 cytokine, following bacillus Calmette guerin immunotherapy of bladder cancer., Intravesical Bacillus Calmette-Guerin is used to treat patients with superficial bladder cancer., There is some evidence that BCG therapy improves survival and progression rates of patients with high-risk superficial bladder cancer decreasing the proportion who require radical cystectomy., Local immunotherapy with bacillus Calmette-Guerin (BCG) is an effective and frequently used treatment for superficial bladder cancer., CONCLUSIONS\nIntravesical bacillus Calmette-Guerin is a viable therapeutic option in patients with high risk superficial bladder cancer and concomitant lymphoma or chronic lymphocytic leukemia, treatment with low dose oral steroids or treatment with inhaled steroids., PURPOSE\nBacillus Calmette-Guerin is the most effective therapy for nonmuscle invasive bladder cancer., INTRODUCTION\nBacillus Calmette-Guerin (BCG) is a live attenuated strain of Mycobacterium bovis that has been used to treat urothelial carcinoma since 1976, and has been reported to eradicate disease in more than 70% of patients with in situ and stage I disease., Intravesical administration of bacillus Calmette-Guerin has been shown to be highly effective treatment of superficial bladder cancer., Intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer: effect of bacillus Calmette-Guerin viability on treatment results., We describe a 53 year- old man with a disseminated bacillus Calmette-Guerin (BCG) infection after intravescical instillation for bladder carcinoma., We tested the hypothesis that tumor expression of natural cytotoxicity receptor ligands can serve as a predictive factor for the response to intravesical bacillus Calmette-Guerin in patients with nonmuscle invasive, high grade bladder cancer., Bacillus Calmette-Guerin immunotherapy has been found by a number of investigators to be effective in the treatment and prevention of superficial bladder cancer., Pancreatic and psoas abscesses as a late complication of intravesical administration of bacillus Calmette-Guerin for bladder cancer: a case report and review of the literature.This case illustrates the fact that although intravesical administration of bacillus Calmette-Guerin is generally considered to be safe, it is not exempt from complications and these could appear immediately after treatment or as a delayed complication many years later., Effects of local bacillus Calmette-Guerin therapy in patients with bladder carcinoma on immunocompetent cells of the bladder wall.The antitumoral effects of intravesical bacillus Calmette-Guerin against recurrent superficial urothelial bladder cancer seem to be linked to immunological effector mechanisms. , Fatal sepsis following intravesical bacillus Calmette-Guerin administration for bladder cancer.Intravesical administration of bacillus Calmette-Guerin has been shown to be highly effective treatment of superficial bladder cancer. , Intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer: effect of bacillus Calmette-Guerin viability on treatment results.We treated 40 patients with superficial bladder cancer via intravesical bacillus Calmette-Guerin for 1) prophylaxis against tumor recurrence, 2) residual carcinoma or 3) flat carcinoma in situ. , Bacillus Calmette-Guerin immunotherapy for bladder cancer.Bacillus Calmette-Guerin immunotherapy has been found by a number of investigators to be effective in the treatment and prevention of superficial bladder cancer. , Safety and efficacy of intravesical bacillus Calmette-Guerin instillations in steroid treated and immunocompromised patients.Intravesical bacillus Calmette-Guerin is a viable therapeutic option in patients with high risk superficial bladder cancer and concomitant lymphoma or chronic lymphocytic leukemia, treatment with low dose oral steroids or treatment with inhaled steroids. , Our results suggest that intralesional bacillus Calmette-Guerin immunotherapy can afford long term protection from transplanted bladder cancer, and that live bacillus Calmette-Guerin is superior to levamisole and P3 + Re-glycolipid + bacillus Calmette-Guerin cell walls in the treatment of bladder cancer., A randomized controlled prospective evaluation of intravesical and percutaneous bacillus Calmette-Guerin immunotherapy was done in 57 patients with transitional cell carcinoma of the bladder., Up to 90% of patients with high grade superficial bladder tumors experience tumor recurrence and up to 50% have progression despite bacillus Calmette-Guerin treatment., We review how the bacillus Calmette-Guerin vaccine evolved to become standard therapy for superficial bladder cancer., We reviewed the historical literature describing the origin of the bacillus Calmette-Guerin vaccine as an anticancer agent and its singular success as the most effective immunotherapy used against a human neoplasm.[SEP]", "label": "yes"}
{"id": "converted_4190", "sentence1": "Do honey contain diastases/amylases?", "sentence2": "A new rapid method for the determination of honey diastase activity using direct potentiometric principles has been proposed. , The major alpha-amylase in honey was characterized. , Separation of honey amylase[SEP]", "label": "yes"}
{"id": "converted_2483", "sentence1": "Are the human bombesin receptors, GRPR and NMBR, frequently overexpressed G-protein-coupled-receptors by lung-cancers?", "sentence2": "Members of the gastrin-releasing peptide (GRP) family and its analogs bombesin (BBN) have been implicated in the biology of several human cancers including prostate, breast, colon and lung., All 3 bombesin receptor subtypes (GRPR, NMBR, and BRS-3) were present on pulmonary and intestinal carcinoids by immunohistochemistry, There is increased interest in the Bn-receptor family because they are frequently over/ectopically expressed by tumors and thus useful as targets for imaging or receptor-targeted-cytotoxicity. , ML-18 is a non-peptide bombesin receptor subtype-3 antagonist which inhibits lung cancer growth., Gastrin-releasing peptide (GRP), a member of the bombesin family of peptides, has been shown to have mitogenic activity in small cell lung carcinoma (SCLC), and to be produced by SCLC in an autocrine fashion.[SEP]", "label": "yes"}
{"id": "converted_2491", "sentence1": "Has ATF4 transcription factor been linked to cancer and neoplastic transformation?", "sentence2": "aken together, we discovered a novel axis of BCL10-regulated OSCC progression via STAT1/ATF4/S100P/P65 signaling, which could predict the prognosis of OSCC and will be beneficial for developing therapeutic strategy against advanced OSCC, s a result, the level of phosphorylated Eukaryotic Initiation Factor 2 alpha (eIF2α) is markedly elevated, resulting in the promotion of a pro-adaptive signaling pathway by the inhibition of global protein synthesis and selective translation of Activating Transcription Factor 4 (ATF4). , Many cancers overexpress ATF4, a stress-induced transcription factor that promotes cell survival under hypoxic conditions and other stresses of the tumor microenvironment, but the potential contributions of ATF4 to oncogenesis itself have been little explored. Here, we report that ATF4 promotes oncogene-induced neoplastic transformation by suppressing the expression of cellular senescence-associated genes. , Here, we report that ATF4 promotes oncogene-induced neoplastic transformation by suppressing the expression of cellular senescence-associated genes., Elevated levels of ATF4 were sufficient to suppress expression of these proteins and drive oncogenic transformation., Our findings define a central function for ATF4 in promoting oncogenic transformation by suppressing a central pathway of cellular senescence.<br>, ATF4 expression is upregulated in cancer., Activating transcription factor 4 (ATF4), an endoplasmic reticulum stress-inducible transcription factor, plays important roles in cancer progression and resistance to therapy., Activating transcription factor 4 (ATF4) is a stress-induced transcription factor that is frequently upregulated in cancer cells., Our findings define a central function for ATF4 in promoting oncogenic transformation by suppressing a central pathway of cellular senescence., Stress-regulated transcription factor ATF4 promotes neoplastic transformation by suppressing expression of the INK4a/ARF cell senescence factors., Activating transcription factor 4 (ATF4), a member of the ATF/CREB family, has been reported to be related to tumor angiogenesis[SEP]", "label": "yes"}
{"id": "converted_3486", "sentence1": "Are there lncRNAs that control the extent of neuronal outgrowth?", "sentence2": "Regulation of Neuroregeneration by Long Noncoding RNAs., Here, we profiled gene expression following sciatic nerve crush in mice and identified long noncoding RNAs (lncRNAs) that act in the regenerating neurons and which are typically not expressed in other contexts. We show that two of these lncRNAs regulate the extent of neuronal outgrowth. We then focus on one of these, Silc1, and show that it regulates neuroregeneration in cultured cells and in vivo, through cis-acting activation of the transcription factor Sox11.[SEP]", "label": "yes"}
{"id": "converted_813", "sentence1": "Does a selective sweep increase genetic variation?", "sentence2": "An East African population that gave rise to non-Africans underwent a selective sweep affecting the subcentromeric region where MTMR8 is located. This and similar sweeps in four other regions of the X chromosome, documented in the literature, effectively reduced genetic diversity of non-African chromosomes, a selective sweep that has removed genetic variation from much of the drive X chromosome., evidence of reduced diversity and an excess of fixed replacement sites, consistent with a species-wide selective sweep., recent independent selective sweeps in AGO2 have reduced genetic variation, episodes of natural selection (likely a selective sweep) predating the coalescent of human lineages, within the last 25 million years, account for the observed reduced diversity, reduced variation or deviations from neutrality that might indicate a recent selective sweep, Consider a genetic locus carrying a strongly beneficial allele which has recently fixed in a large population. As strongly beneficial alleles fix quickly, sequence diversity at partially linked neutral loci is reduced. This phenomenon is known as a selective sweep., a local selective sweep or demographic process that reduced variability, reduced variation (a selective sweep), the mtDNA diversity, but not the nuclear DNA diversity, has been reduced relative to the neutral expectation of molecular evolution, suggesting the action of a selective sweep, Furthermore, the amount of genetic variation after a selective sweep is expected to be unequal over demes: a greater reduction in expected heterozygosity occurs in the subpopulation from which the beneficial mutation originates than in its neighboring subpopulations., Our observation of reduction in variation at both intragenic and flanking loci of mutant pfcrt gene confirmed the selective sweep model of natural selection in chloroquine resistant P., A selective sweep describes the reduction of linked genetic variation due to strong positive selection., In these situations, adaptation should commonly produce 'soft' selective sweeps, where multiple adaptive alleles sweep through the population at the same time, either because the alleles were already present as standing genetic variation or arose independently by recurrent de novo mutations., CONCLUSIONS: The severe reduction in nucleotide variation at OsAMT1;1 in rice was caused by a selective sweep around OsAMT1;1, which may reflect the nitrogen uptake system under strong selection by the paddy soil during the domestication of rice., A selective sweep describes the reduction of linked genetic variation due to strong positive selection[SEP]", "label": "no"}
{"id": "converted_24", "sentence1": "Is Alu hypomethylation associated with breast cancer?", "sentence2": "Alu and LINE-1 hypomethylation is associated with HER2 enriched subtype of breast cancer, In IBC, Alu hypomethylation correlated with negative estrogen receptor (ER) status, In survival analyses, low Alu methylation status tended to be associated with poor disease-free survival of the patients., Alu hypomethylation is probably a late event during breast cancer progression, prominent hypomethylation of Alu and LINE-1 in HER2 enriched subtype may be related to chromosomal instability of this specific subtype., DNA methylation for three repetitive elements (LINE1, Sat2 and Alu) were analyzed in invasive ductal carcinoma of the breast, paired adjacent normal tissue and WBC from 40 breast cancer patients, DNA methylation for the three repetitive elements was lower in tumor compared to adjacent tissue and WBC DNA.[SEP]", "label": "yes"}
{"id": "converted_3184", "sentence1": "Are Crocus sativus compounds being considered against Alzheimer's disease?", "sentence2": "Previous evidence suggested that Crocus sativus is linked to improving cognitive function in Alzheimer's disease (AD) patients. The aim of this study was to in vitro and in vivo investigate the mechanism(s) by which Crocus sativus exerts its positive effect against AD. , Collectively, findings from this study support the positive effect of Crocus sativus against AD by reducing Aβ pathological manifestations.[SEP]", "label": "yes"}
{"id": "converted_3643", "sentence1": "Is Selumetinib effective for low-grade glioma?", "sentence2": "Conclusion: Selumetinib has promising antitumor activity in children with LGG., INTERPRETATION\n\nSelumetinib is active in recurrent, refractory, or progressive pilocytic astrocytoma harbouring common BRAF aberrations and NF1-associated paediatric low-grade glioma., These results show that selumetinib could be an alternative to standard chemotherapy for these subgroups of patients, and have directly led to the development of two Children's Oncology Group phase 3 studies comparing standard chemotherapy to selumetinib in patients with newly diagnosed paediatric low-grade glioma both with and without NF1., Conclusion Selumetinib has promising antitumor activity in children with LGG., INTERPRETATION Selumetinib is active in recurrent, refractory, or progressive pilocytic astrocytoma harbouring common BRAF aberrations and NF1-associated paediatric low-grade glioma., Conclusion\n\nSelumetinib has promising antitumor activity in children with LGG., INTERPRETATION\nSelumetinib is active in recurrent, refractory, or progressive pilocytic astrocytoma harbouring common BRAF aberrations and NF1-associated paediatric low-grade glioma., These results show that selumetinib could be an alternative to standard chemotherapy for these subgroups of patients, and have directly led to the development of two Children's Oncology Group phase 3 studies comparing standard chemotherapy to selumetinib in patients with newly diagnosed paediatric low-grade glioma both with and without NF1., These results show that selumetinib could be an alternative to standard chemotherapy for these subgroups of patients, and have directly led to the development of two Children's Oncology Group phase 3 studies comparing standard chemotherapy to selumetinib in patients with newly diagnosed paediatric low-grade glioma both with and without NF1., INTERPRETATION: Selumetinib is active in recurrent, refractory, or progressive pilocytic astrocytoma harbouring common BRAF aberrations and NF1-associated paediatric low-grade glioma., Selumetinib is active in recurrent, refractory, or progressive pilocytic astrocytoma harbouring common BRAF aberrations and NF1-associated paediatric low-grade glioma., These results show that selumetinib could be an alternative to standard chemotherapy for these subgroups of patients, and have directly led to the development of two Children's Oncology Group phase 3 studies comparing standard chemotherapy to selumetinib in patients with newly diagnosed paediatric low-grade glioma both with and without NF1.[SEP]", "label": "yes"}
{"id": "converted_2970", "sentence1": "Does allele phasing improve the phylogenetic utility of ultraconserved elements?", "sentence2": "Allele Phasing Greatly Improves the Phylogenetic Utility of Ultraconserved Elements., Our empirical analyses of Ultraconserved Element (UCE) locus data collected from the South American hummingbird genus Topaza demonstrate that phased allele sequences carry sufficient phylogenetic information to infer the genetic structure, lineage divergence, and biogeographic history of a genus that diversified during the last three million years. The phylogenetic results support the recognition of two species, and suggest a high rate of gene flow across large distances of rainforest habitats but rare admixture across the Amazon River. Our simulations provide evidence that analyzing allele sequences leads to more accurate estimates of tree topology and divergence times than the more common approach of using contig sequences., Allele Phasing Greatly Improves the Phylogenetic Utility of Ultraconserved Elements.Advances in high-throughput sequencing techniques now allow relatively easy and affordable sequencing of large portions of the genome, even for nonmodel organisms. [SEP]", "label": "yes"}
{"id": "converted_277", "sentence1": "Is apixaban effective for treatment of acute venous thromboembolism?", "sentence2": "Apixaban is a direct inhibitor of factor Xa, and is a potential alternative for the treatment of acute venous thromboembolism. , These results suggest a lack of clear superiority of apixaban relative to enoxaparin. Apixaban is an oral alternative with similar efficacy and safety to existing anticoagulant therapies., A fixed-dose regimen of apixaban alone was noninferior to conventional therapy for the treatment of acute venous thromboembolism and was associated with significantly less bleeding, To critically review the effectiveness of the novel oral anticoagulants (rivaroxaban, dabigatran, ximelagatran, and apixaban) in the treatment of acute venous thromboembolism., ompared with vitamin K antagonists, the novel oral anticoagulants had a similar risk of recurrence of acute venous thromboembolism and all cause mortality, though rivaroxaban was associated with a reduced risk of bleeding, Nowadays, the new anticoagulants, such as dabigatran, rivaroxaban and apixaban, show potential advantages over classical treatments. These agents inhibit specific coagulation factors and are administered orally at fixed doses., In a recently completed phase III trial, apixaban also demonstrated promising efficacy and safety in that indication, the most advanced oral direct inhibitors to factor Xa (rivaroxaban and apixaban) and IIa (dabigatran)[SEP]", "label": "yes"}
{"id": "converted_3031", "sentence1": "Is cabozantinib effective for Hepatocellular Carcinoma?", "sentence2": "However, clinical trials of nonselective kinase inhibitors with c-Met activity (tivantinib, cabozantinib, foretinib, and golvatinib) in patients with HCC have failed so far to demonstrate significant efficacy. , Rationale for use, clinical trial data, and current recommendations for cabozantinib in renal cell cancer, thyroid cancer, prostate cancer, hepatocellular cancer, and lung cancer are detailed in this article., More recently, promising outcomes have also been reported with new agents, such as nivolumab and cabozantinib., Positive results in recent phase III clinical trials have confirmed the high value of anti-angiogenic therapies for HCC in both first (sorafenib and lenvatinib) and second line (regorafenib and cabozantinib) treatment modalities. , More recently, regorafenib and nivolumab have received approval in the second-line setting after sorafenib, with further positive phase 3 studies emerging in the first line (lenvatinib non-inferior to sorafenib) and second line versus placebo (cabozantinib and ramucirumab). , The rapidly changing treatment landscape due to the emergence of new treatment options (sorafenib and lenvatinib equally effective in first line; regorafenib, cabozantinib, and ramucirumab showing OS benefit in second line with nivolumab approved by the FDA based on response rate) underscores the importance of re-assessing the role of the first approved systemic agent in HCC, sorafenib., Positive phase III-study data have been published for lenvatinib as first-line and cabozantinib as second-line therapy. , Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma., BACKGROUND: Cabozantinib inhibits tyrosine kinases, including vascular endothelial growth factor receptors 1, 2, and 3, MET, and AXL, which are implicated in the progression of hepatocellular carcinoma and the development of resistance to sorafenib, the standard initial treatment for advanced disease. , CONCLUSIONS: Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo., Expert opinion: Based on favorable phase III clinical trial data, sorafenib and lenvatinib are considered promising agents for HCC as first-line systemic chemotherapy. Moreover, regorafenib and cabozantinib are useful second-line therapies after the failure of sorafenib., CONCLUSIONS: Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo. , Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma.Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo. , Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo., Median overall survival was 10.2 months with cabozantinib and 8.0 months with placebo (hazard ratio for death, 0.76; 95% confidence interval [CI], 0.63 to 0.92; P=0.005). Median progression-free survival was 5.2 months with cabozantinib and 1.9 months with placebo (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.52; P<0.001), and the objective response rates were 4% and less than 1%, respectively (P=0.009)., The most common high-grade events were palmar-plantar erythrodysesthesia (17% with cabozantinib vs. 0% with placebo), hypertension (16% vs. 2%), increased aspartate aminotransferase level (12% vs. 7%), fatigue (10% vs. 4%), and diarrhea (10% vs. 2%).<br><b>CONCLUSIONS</b>: Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo., CONCLUSIONS Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo., CONCLUSIONS The tyrosine kinase inhibitors sorafenib (first line) and regorafenib (second line) have been approved for hepatocellular carcinoma, and the immune checkpoint inhibitor nivolumab obtained conditional approval for sorafenib-experienced patients in the United States., The principal advancements in the treatment of hepatocellular carcinoma (HCC) are the use of new systemic treatments such as lenvatinib in first-line treatment and regorafenib, cabozantinib and ramucirumab in second-line treatment due to their benefits in terms of overall survival., Recently, a few systemic chemotherapies proved to be effective for advanced stage HCC in phase III studies: lenvatinib as the first line of therapy, and regorafenib, cabozantinib, and ramucirumab as second-line therapy., <b>BACKGROUND</b>: The approval of the tyrosine kinase inhibitor sorafenib in 2007 marked a milestone in the treatment of hepatocellular carcinoma, as sorafenib was the first systemic therapy to show a survival benefit in patients with advanced hepatocellular carcinoma., We also elaborate the unmet need of biomarkers to guide treatment decisions and discuss the emerging field of immunotherapy in hepatocellular carcinoma.<br><b>CONCLUSIONS</b>: The tyrosine kinase inhibitors sorafenib (first line) and regorafenib (second line) have been approved for hepatocellular carcinoma, and the immune checkpoint inhibitor nivolumab obtained conditional approval for sorafenib-experienced patients in the United States., Cabozantinib in the treatment of hepatocellular carcinoma., The approval of the tyrosine kinase inhibitor sorafenib in 2007 marked a milestone in the treatment of hepatocellular carcinoma, as sorafenib was the first systemic therapy to show a survival benefit in patients with advanced hepatocellular carcinoma.[SEP]", "label": "yes"}
{"id": "converted_3457", "sentence1": "Is Rad4/XPC a DNA damage sensing protein?", "sentence2": "Twist-open mechanism of DNA damage recognition by the Rad4/XPC nucleotide excision repair complex., Kinetic gating mechanism of DNA damage recognition by Rad4/XPC.,  These findings indicate that the lesions recognized by Rad4/XPC thermodynamically destabilize the Watson-Crick double helix in a manner that facilitates the flipping-out of two base pairs.[SEP]", "label": "yes"}
{"id": "converted_4691", "sentence1": "Is HYDIN (Hydrocephalus-inducing protein homolog) an axonemal protein?", "sentence2": "Hydin was recently identified as an axonemal protein; however, its function is as yet unknown., precise axonemal location of hydin, a protein that, when mutated, causes hydrocephalus, and defined a unique role for hydin in ciliary motility.[SEP]", "label": "yes"}
{"id": "converted_2271", "sentence1": "Is davunetide being considered for the treatment of progressive supranuclear palsy?", "sentence2": "Critical appraisal of the role of davunetide in the treatment of progressive supranuclear palsy., Davunetide's efficacy and tolerability are being tested in a placebo-controlled study in PSP patients, making it the most advanced drug candidate in this indication. This review examines the disease characteristics of PSP, the rationale for treating PSP with davunetide and assesses some of the challenges of clinical trials in this patient population.[SEP]", "label": "yes"}
{"id": "converted_1013", "sentence1": "Is  farnesoid X receptor (FXR) a nuclear receptor?", "sentence2": "Farnesoid X receptor (FXR) belongs to the ligand-activated nuclear receptor superfamily, and functions as a transcription factor regulating the transcription of numerous genes involved in bile acid homeostasis, lipoprotein and glucose metabolism,  Farnesoid X receptor (FXR) is an ascending target for metabolic and inflammatory diseases. As a nuclear receptor, FXR exhibits many physiological effects in transcription control of several genes.,  FXR is a member of the nuclear receptor superfamily which is also highly expressed in the liver. , Farnesoid X receptor (FXR) is a bile acid nuclear receptor described through mouse knockout studies as a tumor suppressor for the development of colon adenocarcinomas, Farnesoid X receptor (FXR, Nr1h4) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily., the nuclear receptor farnesoid X receptor ,  farnesoid X receptor (FXR), a nuclear receptor activated by bile acid ligands. , T-β-MCA is an farnesoid X receptor (FXR) nuclear receptor antagonist,,  Farnesoid X receptor (FXR), a nuclear receptor (NR) and originally considered as a bile acid-activated transcriptional factor, ,  The nuclear receptor farnesoid X receptor (FXR) plays a major role in the enterohepatic cycling of bile acids, Liver X receptors, LXRs, are ligand-activated transcription factors that belong to the group H nuclear receptor (NR) superfamily. , The intracellular nuclear receptor farnesoid X receptor and the transmembrane G protein-coupled receptor TGR5 respond to bile acids by activating transcriptional networks and/or signalling cascades., ncluding those of nuclear receptors, primarily farnesoid X receptor (FXR), , ile acids and their cognate nuclear receptor, FXR,, Farnesoid X receptor (FXR, Nr1h4) and small heterodimer partner (SHP, Nr0b2) are nuclear receptors that are critical to liver homeostasis., he activation of the nuclear receptor farnesoid X receptor (FXRα), bile acid-activated nuclear receptor farnesoid X receptor (FXR),  nuclear receptor signaling, notably by the farnesoid X receptor (FXR, FXR (farnesoid X receptor, NRIH4), a nuclear receptor, plays a major role in the control of cholesterol metabolism., The role of the nuclear receptor FXR is unclear., nuclear receptor FXR , a member of the nuclear receptor superfamily of ligand-activated transcription factors,, Farnesoid X receptor (FXR) is a nuclear receptor that functions as a bile acid sensor controlling bile acid homeostasis.[SEP]", "label": "yes"}
{"id": "converted_2796", "sentence1": "Does vesatolimod inhibit TLR7?", "sentence2": "Vesatolimod (GS-9620) is an oral agonist of toll-like receptor 7, an activator of innate and adaptive immune responses. [SEP]", "label": "no"}
{"id": "converted_4367", "sentence1": "Can bergapten cross the blood-brain barrier?", "sentence2": "Moreover, pharmacokinetic studies showed that bergapten has higher absolute bioavailability and can cross the blood-brain barrier and has a great potential for treating brain disease, but the mechanism needs further clarification to make greater use of its ability to treat brain diseases. [SEP]", "label": "yes"}
{"id": "converted_2315", "sentence1": "Is propranolol used for treatment of infantile hemangioma?", "sentence2": "Low-dose propranolol for infantile hemangioma of the head and neck: Analysis of 23 consecutive patients., BACKGROUND: More and more infantile hemangiomas (IH) are being treated with propranolol, but the effectiveness, dosage, and treatment course are still in dispute., CONCLUSIONS: Low-dose propranolol appears to be effective and safe for IH, especially for those patients previously treated with corticosteroid and who had no response or severe side-effects., Cardiovascular Profile of Propranolol after Multiple Dosing in Infantile Hemangioma., Propranolol is becoming the treatment of choice for complicated infantile hemangioma., In conclusion, propranolol 2 mg/kg of body weight daily causes a statistically though not clinically relevant decrease in blood pressure and heart rate in cardially healthy infants affected by infantile hemangioma. , Importance: Propranolol hydrochloride has become the primary medical treatment for problematic infantile hemangioma; however, the expression of propranolol's target receptors during growth, involution, and treatment of hemangioma remains unclear., BACKGROUND: Infantile hemangiomas (IHs) are the most common benign vascular tumors of childhood. Propranolol is an effective drug in treating IH. , Ultrasonography as an objective tool for assessment of infantile hemangioma treatment with propranolol., CONCLUSION: Ultrasonographic measurements contribute to demonstrate tumor regression and IH response to propranolol., Propranolol treatment was recently reported to be successful for the management of severe infantile hemangioma., We conclude that the initial use of propranolol as the sole treatment for infantile airway hemangioma is promising., Propranolol has been proposed for the treatment of infantile hemangiomas., Propranolol therapy is changing the treatment paradigm for infantile hemangioma., Propranolol has been successfully used recently in a limited number of children with Infantile hemangioma., Propranolol has been proposed for the treatment of infantile hemangiomas., CONCLUSIONS This is the first report of successful therapy of an intracranial infantile hemangioma with propranolol., PURPOSE The successful use of nadolol as an alternative to propranolol therapy in three cases of infantile hemangioma is reported., Propranolol has been used successfully in a limited number of children with infantile hemangiomas., CONCLUSIONS High-dose Propranolol is very effective in the treatment of infantile hemangioma with minor side effects and short disease period., Propranolol is novel and safe medication for treatment of infantile hemangioma., Propranolol is the only Food and Drug Administration approved therapy for treatment of patients with this vascular anomaly and should be considered first-line therapy for genital infantile hemangiomas., CONCLUSION Propranolol may be a promising therapeutic modality for infantile hemangioma., Propranolol, which is often used to treat cutaneous infantile hemangiomas, is not currently standard treatment for intracranial infantile hemangiomas., Preliminary results of propranolol treatment for patients with infantile hemangioma., Propranolol therapy is changing the treatment paradigm for infantile hemangioma., Propranolol should be considered as a first-line treatment of infantile hemangiomas.., Propranolol, a non-selective beta-blocker, has recently been introduced as a treatment for infantile hemangiomas.[SEP]", "label": "yes"}
{"id": "converted_2533", "sentence1": "Are paralog genes co-regulated?", "sentence2": "Co-regulation of paralog genes in the three-dimensional chromatin architecture., Consequently, paralogs show correlation in gene expression whereby the mechanisms of co-regulation remain unclear. In eukaryotes, genes are regulated in part by distal enhancer elements through looping interactions with gene promoters. These looping interactions can be measured by genome-wide chromatin conformation capture (Hi-C) experiments, which revealed self-interacting regions called topologically associating domains (TADs). We hypothesize that paralogs share common regulatory mechanisms to enable coordinated expression according to TADs. To test this hypothesis, we integrated paralogy annotations with human gene expression data in diverse tissues, genome-wide enhancer-promoter associations and Hi-C experiments in human, mouse and dog genomes. We show that paralog gene pairs are enriched for co-localization in the same TAD, share more often common enhancer elements than expected and have increased contact frequencies over large genomic distances. Combined, our results indicate that paralogs share common regulatory mechanisms and cluster not only in the linear genome but also in the three-dimensional chromatin architecture. This enables concerted expression of paralogs over diverse cell-types and indicate evolutionary constraints in functional genome organization., Paralog genes arise from gene duplication events during evolution, which often lead to similar proteins that cooperate in common pathways and in protein complexes. Consequently, paralogs show correlation in gene expression, We hypothesize that paralogs share common regulatory mechanisms to enable coordinated expression according to TADs., Further, interspecific changes in testis bias of expression are generally correlated within the co-regulated pairs and are anti-correlated within the anti-regulated pairs, suggesting coordinated regulation within both types of paralogous gene pairs., Analysis of the Drosophila melanogaster testes transcriptome reveals coordinate regulation of paralogous genes., Further, interspecific changes in testis bias of expression are generally correlated within the co-regulated pairs and are anti-correlated within the anti-regulated pairs, suggesting coordinated regulation within both types of paralogous gene pairs.<br>, Consequently, paralogs show correlation in gene expression whereby the mechanisms of co-regulation remain unclear., Co-regulation of paralog genes in the three-dimensional chromatin architecture., Further, interspecific changes in testis bias of expression are generally correlated within the co-regulated pairs and are anti-correlated within the anti-regulated pairs, suggesting coordinated regulation within both types of paralogous gene pairs.., We show that paralog gene pairs are enriched for co-localization in the same TAD, share more often common enhancer elements than expected and have increased contact frequencies over large genomic distances. , MiRNA genes are often subject to co-evolutionary changes together with their target transcripts, which may be reflected by differences between paralog mouse and primate miRNA/mRNA pairs., We characterize the collapse over time through the distribution of runs of reduced paralog pairs in duplicated segments., In addition, we identified 81 co-regulated regions on the human genome (RIDGEs) by using expression data from all cancers. Some RIDGEs (28%) consist of paralog genes while another subset (30%) are specifically dysregulated in tumors but not in normal tissues., We conclude that the similarity of hoxb3a/Hoxa3 regulatory mechanisms reflect the shared descent of both genes from a single ancestral paralog group 3 gene., Conserved co-regulation and promoter sharing of hoxb3a and hoxb4a in zebrafish., By analyzing paralogs of testis-biased genes, we identified \"co-regulated\" paralogous pairs in which both genes are testis biased, \"anti-regulated\" pairs in which one paralog is testis biased and the other downregulated in testes, and \"neutral\" pairs in which one paralog is testis biased and the other constitutively expressed.[SEP]", "label": "yes"}
{"id": "converted_2658", "sentence1": "Does International Citicoline Trial on acUte Stroke trial supports efficacy of citicoline for stroke treatment?", "sentence2": "The meta-analysis showed that no significant differences were found in the long-term mortality (OR=0.91, 95% CI 0.07 to 1.09, P=0.30), the rate of dependency (OR=1.02, 95% CI 0.87 to 1.24, P=0.85), and the effective rate (OR=0.98, 95% CI 0.84 to 1.14, P=0.82) between citicoline group and control group. ,  In conclusion, citicolne cannot reduce long-term mortality and dependence rate in the treatment of acute stroke, and the effective rate of citivoline may be not better than that of controls but with reliable safety., In humans, although a recent trial International Citicoline Trial on Acute Stroke (ICTUS) has shown that global recovery is similar in CDP-choline and placebo groups, CDP-choline was shown to be more beneficial in some patients, such as those with moderate stroke severity and not treated with t-PA. , INTERPRETATION: Under the circumstances of the ICTUS trial, citicoline is not efficacious in the treatment of moderate-to-severe acute ischaemic stroke., The trial was stopped for futility at the third interim analysis on the basis of complete data from 2078 patients., Global recovery was similar in both groups (odds ratio 1·03, 95% CI 0·86-1·25; p=0·364)., INTERPRETATION Under the circumstances of the ICTUS trial, citicoline is not efficacious in the treatment of moderate-to-severe acute ischaemic stroke., In humans, although a recent trial International Citicoline Trial on Acute Stroke (ICTUS) has shown that global recovery is similar in CDP-choline and placebo groups, CDP-choline was shown to be more beneficial in some patients, such as those with moderate stroke severity and not treated with t-PA. Several mechanisms have been proposed to explain the beneficial actions of CDP-choline., In humans, although a recent trial International Citicoline Trial on Acute Stroke (ICTUS) has shown that global recovery is similar in CDP-choline and placebo groups, CDP-choline was shown to be more beneficial in some patients, such as those with moderate stroke severity and not treated with t-PA.[SEP]", "label": "no"}
{"id": "converted_676", "sentence1": "Has proteomics been used in the study of Pick's disease?", "sentence2": "In Pick's disease, increased AGE, CML, CEL, HNE and MDAL bands of about 50 kDa were observed in the frontal cortex (but not in the occipital cortex) in association with increased density of glial acidic protein bands., Thus, brain and cerebrospinal fluid (CSF) samples from patients with Alzheimer's disease, Down syndrome, Pick's disease, Parkinson's disease, schizophrenia, and other disorders as well as brain and CSF from animals serving as models of neurological disorders have been analyzed by proteomics. , The present study is designed to investigate expression of peroxiredoxins (Prxs), the newly characterized family of highly conserved antioxidant enzymes, and other antioxidant enzymes in frontal cortex and cerebellum of DS, AD and PD patients using the technique of proteomics. , HMT levels were measured in the frontal cortex and cerebellum of brains of patients with AD, DS, and PiD, and normal aged subjects using proteomics techniques. [SEP]", "label": "yes"}
{"id": "converted_1775", "sentence1": "Is exon skipping correlated with exon circularization?", "sentence2": "Exon Skipping Is Correlated with Exon Circularization, We find that circularization of exons is widespread and correlates with exon skipping, a feature that adds considerably to the regulatory complexity of the human transcriptome, Exon Skipping Is Correlated with Exon Circularization., We find that circularization of exons is widespread and correlates with exon skipping, a feature that adds considerably to the regulatory complexity of the human transcriptome. <CopyrightInformation>Copyright © 2015 Elsevier Ltd. All rights reserved.</, We find that circularization of exons is widespread and correlates with exon skipping, a feature that adds considerably to the regulatory complexity of the human transcriptome. <CopyrightInformation>Copyright © 2015 Elsevier Ltd. All rights reserved.</C, Exon Skipping Is Correlated with Exon Circularization.[SEP]", "label": "yes"}
{"id": "converted_428", "sentence1": "Have gnotobiotic animal models been used for the study of bowel disease?", "sentence2": "Host gene expression in the colon of gnotobiotic interleukin-2-deficient mice colonized with commensal colitogenic or noncolitogenic bacterial strains: common patterns and bacteria strain specific signatures.,  Specific pathogen-free (SPF), but not germfree (GF), interleukin (IL)-2-deficient (IL-2-/-) mice develop inflammatory bowel disease (IBD) at 10 to 15 weeks of age. Gnotobiotic IL-2-/- mice monocolonized with E. coli mpk develop IBD at 25 to 33 weeks of age but not B. vulgatus mpk, E. coli Nissle 1917, or mice cocolonized with both E. coli mpk and B. vulgatus, Lactobacillus reuteri promotes Helicobacter hepaticus-associated typhlocolitis in gnotobiotic B6.129P2-IL-10(tm1Cgn) (IL-10(-/-) ) mice., To model inflammatory bowel disease, we assessed infection with Helicobacter hepaticus 3B1 (ATCC 51449) and a potential probiotic Lactobacillus reuteri (ATCC PTA-6475) in gnotobiotic B6.129P2-IL-10(tm1Cgn) (IL-10(-/-) ) mice. No typhlocolitis developed in germ-free controls (n=21) or in L. reuteri (n=8) or H. hepaticus (n=18) mono-associated mice for 20 weeks post-infection. As positive controls, three specific pathogen-free IL-10(-/-) mice dosed with H. hepaticus developed severe typhlocolitis within 11 weeks. , These data support that the development of typhlocolitis in H. hepaticus-infected IL-10(-/-) mice required co-colonization with other microbiota and in this study, required only L. reuteri. , When transferred to gnotobiotic mice, gut microbiomes from mice with active disease versus treatment-induced remission elicited varying degrees of colitis. , The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases., The immunomodulatory effects of microbiota and probiotics for inflammatory bowel diseases and the role of bacteria in their etiologies are being studied in gnotobiotic systems., To model inflammatory bowel disease, we assessed infection with Helicobacter hepaticus 3B1 (ATCC 51449) and a potential probiotic Lactobacillus reuteri (ATCC PTA-6475) in gnotobiotic B6.129P2-IL-10(tm1Cgn) (IL-10(-/-) ) mice., Gnotobiotic piglets may be used as a suitable animal model to study colitis induced by C. jejuni, The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases, We investigated the changes in renal expression of Kl as a consequence of colitis. METHODS: We studied 3 mouse models of IBD: colitis induced by trinitrobenzene sulfonic acid, colitis induced by microflora (in gnotobiotic interleukin-10(-/-)), and colitis induced by adoptive transfer of CD4(+)CD45RB(high) T cells. , METHODS: We studied 3 mouse models of IBD: colitis induced by trinitrobenzene sulfonic acid, colitis induced by microflora (in gnotobiotic interleukin-10(-/-)), and colitis induced by adoptive transfer of CD4(+)CD45RB(high) T cells. [SEP]", "label": "yes"}
{"id": "converted_1664", "sentence1": "Is the protein FAK (Focal Adhesion Kinase) phosphorylated?", "sentence2": "Overexpression of NEDD9 led to tyrosine phosphorylation of FAK and SRC oncoproteins, , yrosine phosphorylated FAK, TNFα contributes for attenuating both Y397FAK and Y416Src phosphorylations in osteoblasts.,  It was possible to show that TNFα provokes attenuation at Y-phosphorylation of both FAK (at Y397 ), ownregulation of G3BP significantly inhibited the phosphorylation of Src, FAK, Periodic mechanical stress significantly induced sustained phosphorylation of FAK at Tyr(397) and Tyr(576/577). , oss of αSNAP impaired Golgi-dependent glycosylation and trafficking of β1 integrin and decreased phosphorylation of focal adhesion kinase (FAK) and paxillin resulting in FA disassembly., functional characterization of many of today's best-known Src substrates (for example, p85-Cortactin, p110-AFAP1, p130Cas, p125FAK and p120-catenin), Western blots were used for P-FAK, e first time, that the EGF-dependent EGFR activation led to increased P-FAKSer732, . P-FAKSer732 presence was crucial for the maintenance of the proliferation rate and its levels were inversely related to the levels of acetylated α-tubulin. P-FAKSer732 localized at the microtubules (MTs) of the spindle, biochemically associated with MTs and contributed to MT depolymerization., specially, phosphorylation of Tyr925-FAK that is required for full activation of FAK was nearly completely suppressed even with 1nM of methyl violet 2B in A375P cancer cells. ,  The protein expression of PTPN13, focal adhesion kinase (FAK) and phosphorylated FAK (P-FAK) was evaluated using immunohistochemical staining and western blotting., Curcumin inhibits focal adhesion kinase (FAK) phosphorylation and enhances the expressions of several extracellular matrix components which play a critical role in invasion and metastasis. , uppressed both the phosphorylation of FAK ,  A GEF-inactive Rgnef mutant rescues FAK-Y397 phosphorylation [SEP]", "label": "yes"}
{"id": "converted_3768", "sentence1": "Is tocilizumab a tumor necrosis factor inhibitor?", "sentence2": "For the first-line bDMARD/tsDMARD, either tumor necrosis factor inhibitors (TNFi), non-TNFi (abatacept, tocilizumab, rituximab), or tsDMARDs, may be considered.[SEP]", "label": "no"}
{"id": "converted_2275", "sentence1": "Is Drk essential for anesthesia-resistant memory (ARM) in Drosophila?", "sentence2": "Anesthesia-resistant memory (ARM) was described decades ago, but the mechanisms that underlie this protein synthesis-independent form of consolidated memory inDrosophilaremain poorly understood. Whether the several signaling molecules, receptors, and synaptic proteins currently implicated in ARM operate in one or more pathways and how they function in the process remain unclear. We present evidence that Drk, theDrosophilaortholog of the adaptor protein Grb2, is essential for ARM within adult mushroom body neurons., We present evidence that Drk, the Drosophila ortholog of the adaptor protein Grb2, is essential for ARM within adult mushroom body neurons.[SEP]", "label": "yes"}
{"id": "converted_128", "sentence1": "Is MammaPrint cleared by the United States Food and Drug Administration? ", "sentence2": "Real-time RT-PCR confirmed the 5-gene prognostic signature that was distinct from an FDA-cleared 70-gene signature of MammaPrint panel and from the Oncotype DX recurrence score assay panel.[SEP]", "label": "yes"}
{"id": "converted_4279", "sentence1": "Are variants in FHF2 (also known as FGF13) associated with encephalopathy?", "sentence2": "Missense variants in the N-terminal domain of the A isoform of FHF2/FGF13 cause an X-linked developmental and epileptic encephalopathy., Whole-exome sequencing identified hemi- and heterozygous variants in the N-terminal domain of the A isoform of FHF2 (FHF2A). The X-linked FHF2 gene (also known as FGF13) has alternative first exons which produce multiple protein isoforms that differ in their N-terminal sequence. The variants were located at highly conserved residues in the FHF2A inactivation particle that competes with the intrinsic fast inactivation mechanism of Nav channels. Functional characterization of mutant FHF2A co-expressed with wild-type Nav1.6 (SCN8A) revealed that mutant FHF2A proteins lost the ability to induce rapid-onset, long-term blockade of the channel while retaining pro-excitatory properties. These gain-of-function effects are likely to increase neuronal excitability consistent with the epileptic potential of FHF2 variants. Our findings demonstrate that FHF2 variants are a cause of infantile-onset developmental and epileptic encephalopathy and underline the critical role of the FHF2A isoform in regulating Nav channel function.[SEP]", "label": "yes"}
{"id": "converted_2797", "sentence1": "Is selenocysteine an aminoacid?", "sentence2": "Selenocysteine (Sec), a rare genetically encoded amino acid with unusual chemical properties, is of great interest for protein engineering., Selenocysteine (SeC) is a naturally available Se-containing amino acid that displays splendid anticancer activities against several human tumors. [SEP]", "label": "yes"}
{"id": "converted_4368", "sentence1": "Does TIMELESS-TIPIN participate in replisome disassembly?", "sentence2": "TIMELESS-TIPIN and UBXN-3 promote replisome disassembly during DNA replication termination in Caenorhabditis elegans., We show that UBXN-3 is important in vivo for replisome disassembly in the absence of TIMELESS-TIPIN. Correspondingly, co-depletion of UBXN-3 and TIMELESS causes profound synthetic lethality. Since the human orthologue of UBXN-3, FAF1, is a candidate tumour suppressor, these findings suggest that manipulation of CMG disassembly might be applicable to future strategies for treating human cancer.[SEP]", "label": "yes"}
{"id": "converted_3899", "sentence1": "Is erabutoxin b usually found in plants?", "sentence2": "The variants are the curaremimetic toxin alpha from Naja nigricollis and erabutoxin a or b from Laticauda semifasciata, The three-dimensional structure of erabutoxin b, a short-chain neurotoxic peptide purified from the venom of the sea snake Laticauda semifasciata, , THe characteristic feature of the crystal structure of erabutoxin b, a short neurotoxin from Laticauda semifasciata, and alpha-cobratoxin, a long neurotoxin from Naja naja siamensis, is the presence of a triple-stranded antiparallel pleated beta-sheet structure formed by the central and the third peptide loops., Here we examine the actions of six snake neurotoxins (alpha-cobratoxin from Naja naja siamensis, erabutoxin-a and b from Laticauda semifasciata; CM12 from N. haje annulifera, toxin III 4 from Notechis scutatus and a long toxin from N. haje) on nicotinic acetylcholine receptors in the cercal afferent, giant interneuron 2 synapse of the cockroach, Periplaneta americana., The method was applied to a study of erabutoxin b molecule, a neurotoxic protein from a sea snake, to analyze the microenvironments of its single tryptophan and tyrosine residues., The area of greatest similarity centered on residue position 25 of erabutoxin b, a locale that is conserved throughout the snake alpha-neurotoxins and their homologues., A systematic computer search of the three-dimensional structure of erabutoxin b (an alpha-neurotoxin from the false sea snake Laticauda semifasciata) was performed to identify the locality that most closely matched the amino acid compositions of the smaller alpha-conotoxins (from the marine snails Conus magus and Conus geographus)., Erabutoxin b is one of a family of snake venom neurotoxins, all low-molecular-weight proteins, which block neuromuscular transmission at the postsynaptic membrane., Erabutoxins a and b are neurotoxins isolated from venom of a sea snake Laticauda semifasciata (erabu-umihebi)., The three-dimensional structure of erabutoxin b, a neurotoxin in the venom of the sea snake Laticauda semifasciata, has been determined from a 2.75 A resolution electron density map., Erabutoxin c, a minor neurotoxic component of the venom of a sea snake Laticauda semifasciata, was isolated in pure form by repeated column chromatography on CM-cellulose columns., The study has established complete structural identity of the two sea-snake venom toxins, erabutoxin b and neurotoxin b, isolated from Laticauda semifasciata snakes taken in different Pacific Ocean waters., Studies on sea-snake venoms. Crystallization of erabutoxins a and b from Laticauda semifasciata venom.[SEP]", "label": "no"}
{"id": "converted_4681", "sentence1": "Is paxillin affected by RANKL?", "sentence2": "Western blotting assays presented upregulated expressions of TNF receptor-activating factor 6 (TRAF6) and integrin β3 induced by gingipains and RANKL compared to RANKL alone. Enhanced integrin-related signaling was also demonstrated by elevated phosphorylations of FAK and paxillin compared to control. Moreover, the pit resorption assays showed that gingipains augmented bone resorptive function of osteoclasts induced by RANKL. , paxillin levels induced by RANKL in murine bone marrow cells., RANKL promotes paxillin serine and tyrosine phosphorylation,[SEP]", "label": "yes"}
{"id": "converted_3280", "sentence1": "Is Protoporphyrinogen oxidase localized to the mitochondrium?", "sentence2": "We showed that 28 amino acids in the amino terminus of PPOX contain an independently functioning signal for mitochondrial targeting., Based on our results we propose a mechanism for protoporphyrinogen oxidase targeting to the mitochondrion., Mitochondrial targeting of human protoporphyrinogen oxidase., In the present study, PfPPO has been cloned, expressed and shown to be localized to the mitochondrion by immunofluorescence microscopy. [SEP]", "label": "yes"}
{"id": "converted_1340", "sentence1": "Are there enhancer RNAs (eRNAs)?", "sentence2": "active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription,  eRNAs may then facilitate enhancer-promoter interaction or activate promoter-driven transcription, Enhancer RNAs: a class of long noncoding RNAs synthesized at enhancers, Enhancer RNAs and regulated transcriptional programs, enhancers have been found to be broadly transcribed, resulting in the production of enhancer-derived RNAs, or eRNAs, The emerging roles of eRNAs in transcriptional regulatory networks, we found certain enhancer RNAs (eRNAs) regulate chromatin accessibility of the transcriptional machinery at loci encoding master regulators of myogenesis (i.e., MyoD/MyoG), thus suggesting their significance and site-specific impact in cellular programming, Enhancer RNAs: the new molecules of transcription,  the discovery that distal regulatory elements known as enhancers are transcribed and such enhancer-derived transcripts (eRNAs) serve a critical function in transcriptional activation has added a new dimension to transcriptional regulation, eRNAs reach the heart of transcription, Recent studies have disclosed the function of enhancer RNAs (eRNAs), which are long non-coding RNAs transcribed from gene enhancer regions, in transcriptional regulation., Since the discovery that many transcriptional enhancers are transcribed into long noncoding RNAs termed \"enhancer RNAs\" (eRNAs), their putative role in enhancer function has been debated., Recent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs)., Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers, whose function and action mechanism are yet to be firmly established., In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs)., In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). , A subset of enhancers are occupied by RNA polymerase II (RNAP II) and transcribed to produce long non-coding RNAs termed eRNAs. , Very recent evidence has indicted that some eRNAs play a role in initiating or activating transcription, possibly by helping recruit and/or stabilize binding of the general transcription machinery to the proximal promoter of their target genes. , In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). However, it has remained unclear whether these eRNAs are functional or merely a reflection of enhancer activation. , Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4. The level of eRNA expression at neuronal enhancers positively correlates with the level of messenger RNA synthesis at nearby genes, suggesting that eRNA synthesis occurs specifically at enhancers that are actively engaged in promoting mRNA synthesis., A function of CBP at enhancers may be to recruit RNA polymerase II (RNAPII), as we also observed activity-regulated RNAPII binding to thousands of enhancers. Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4.,  Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers, whose function and action mechanism are yet to be firmly established. Here we show that eRNAs facilitate the transition of paused RNA polymerase II (RNAPII) into productive elongation by acting as a decoy for the negative elongation factor (NELF) complex upon induction of immediate early genes (IEGs) in neurons., Recent studies have disclosed the function of enhancer RNAs (eRNAs), which are long non-coding RNAs transcribed from gene enhancer regions, in transcriptional regulation., Recent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription., Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers,, In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). However, it has remained unclear whether these eRNAs are functional or merely a reflection of enhancer activation.,  Recent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription.[SEP]", "label": "yes"}
{"id": "converted_404", "sentence1": "Is endostatin a proangiogenic factor?", "sentence2": "endostatin (antiangiogenic factor, antiangiogenic factors include thrombospondin-1, angiostatin, and endostatin,  human endostatin (rh-endostatin), a potential antiangiogenic agent, , antiangiogenic PF4 and endostatin, Angiostatin and endostatin are endogenous inhibitors of angiogenesis with anticancer effects, the antiangiogenic factors, cystatin C and endostatin, were measured, accumulation of endostatin and Abeta peptides which have been shown to be antiangiogenic, antioangiogenic factors such as pigment epithelial derived factor (PEDF), angiostatin, endostatin, Endostatin is an antiangiogenic growth factor., angiogenesis inhibitor endostatin, Circulating and cellular proangiogenic and antiangiogenic proteins such as vascular endothelial growth factor (VEGF) and endostatin contribute to the local angiogenic balance, Thrombospondin-1 (Tsp1), endostatin, and tumstatin are extracellular matrix-associated proteins that inhibit angiogenesis, specific inhibitors of angiogenesis such as platelet factor, angiostatin, endostatin, endostatin, an endogenous inhibitor of angiogenesis., antiangiogenic factors (pigment epithelium-derived factor [PEDF]; angiostatin; restin; and endostatin, endostatin peptide, a potent inhibitor of angiogenesis derived from type XVIII collagen,, endogenous angiogenesis inhibitors endostatin , ndostatin is a potent inhibitor of angiogenesis and tumor growth., endogenous angiogenesis inhibitor - endostatin , Endostatin (ES), a fragment of collagen XVIII, is an endogenous inhibitor of angiogenesis, antiangiogenic protein endostatin, A number of endogenous inhibitors of angiogenesis are found in the body. Some of these are synthesized by specific cells in different organs, and others are created by extracellular proteolytic cleavage of plasma-derived or extracellular matrix-localized proteins. In this review, we focus on angiostatin, endostatin,, endostatin (a direct inhibitor of angiogenesis) , endogenous angiogenesis inhibitor endostatin, Endostatin, a peptide derived from proteolysis of collagen XVIII, is an endogenous inhibitor of angiogenesis and tumor growth. , anti-angiogenic factor endostatin, Endostatin is the first endogenous angiogenesis inhibitor to enter clinical trials, angiogenic inhibitors such as endostatin, endostatin inhibits the angiogenic switch, antiangiogenic endostatin , direct acting antiangiogenic agents (e.g., endostatin) , Endostatin is an antiangiogenic fragment of the basement membrane protein, collagen XVIII., specific inhibitors of angiogenesis such as platelet factor-4, angiostatin, endostatin, Endostatin, which is a natural inhibitor of angiogenesis, Angiostatin and endostatin are two powerful inhibitors of angiogenesis in experimental models[SEP]", "label": "no"}
{"id": "converted_2090", "sentence1": "Can methylenetetrahydrofolate reductase (MTHFR) gene mutations cause homocystinuria?", "sentence2": "Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive disorder. , Several mutations seen in methylenetetrahydrofolate reductase (MTHFR) give rise to the formation of hyperhomocysteinemia and homocystinuria, a considerable risk factor for cardiovascular and cerebrovascular disorders, by leading to enzymatic inactivation., At admission, he had significantly elevated plasma and urine levels of total homocysteine, significantly decreased levels of folate in serum and cerebrospinal fluid, and a normal blood concentration of methionine., Response to treatment demonstrated B(6)-non-responsive homocystinuria. Molecular study showed compound heterozygous T353 N and D444 N mutations of the cystathionine beta-synthase (CBS) gene, and also a C667T homozygous mutation of the methylenetetrahydrofolate-reductase (MTHFR) gene. , Our case is atypical because of the absence of thromboembolism and the mild phenotype, in spite of being B(6)-non-responsive, and the association of a rare compound heterozygous mutation of the CBS gene and also an homozygous mutation of the MTHFR gene., Molecular characterization of five patients with homocystinuria due to severe methylenetetrahydrofolate reductase deficiency., Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme in folate and homocysteine metabolism. Research performed during the past decade has clarified our understanding of MTHFR deficiencies that cause homocystinuria or mild hyperhomocysteinemia. Our cloning of the MTHFR coding sequence was initially followed by the identification of the first deleterious mutations in MTHFR, in patients with homocystinuria and marked hyperhomocysteinemia., Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the regulation of plasma homocysteine levels. MTHFR deficiency, an autosomal recessive disorder, results in homocystinuria and hypomethioninaemia and presents with highly variable symptoms affecting many organs but predominantly the central nervous system. , Some methylenetetrahydrofolate reductase (MTHFR) gene mutations cause hyperhomocysteinemia and homocystinuria., Rare mutations in the MTHFR gene have been associated with autosomal recessive MTHFR deficiency leading to homocystinuria., Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria., Five patients suspected of having non-classical homocystinuria due to MTHFR deficiency were examined with respect to their symptoms, MTHFR enzyme activity and genotypes of the MTHFR gene., The results of our study render the full-length characterisation of affected alleles in severe homocystinuria and moderate hyperhomocysteinaemia due to MTHFR deficiency and provide a basis for investigating the regulation of the human MTHFR gene., Our cloning of the MTHFR coding sequence was initially followed by the identification of the first deleterious mutations in MTHFR, in patients with homocystinuria and marked hyperhomocysteinemia., Different MTHFR mutations lead either to severe homocystinuria as a multisystem disorder or to moderate hyperhomocysteinaemia, which is a common risk factor for disorders ranging from cardiovasculopathy to spina bifida., We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis., On the contrary, thermolabile MTHFR caused by the 677C-->T mutation, was frequently observed among homocystinuria patients, especially among those with thromboembolic complications: three of six homocystinuria patients who had suffered from a thromboembolic event had thermolabile MTHFR., We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis., Some methylenetetrahydrofolate reductase (MTHFR) gene mutations cause hyperhomocysteinemia and homocystinuria, We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis, Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria, The most common genetic cause of hyperhomocysteinemia is the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, The 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is an important cause of mild hyperhomocysteinemia, but this polymorphism does not seem to be a risk factor for venous thrombosis, Hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) gene mutation have been postulated as a possible cause of recurrent miscarriage (RM), The 677C>T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is an important cause of mild hyperhomocysteinaemia, We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis. , AIM: Some methylenetetrahydrofolate reductase (MTHFR) gene mutations cause hyperhomocysteinemia and homocystinuria. , Betaine for treatment of homocystinuria caused by methylenetetrahydrofolate reductase deficiency., Severe deficiency of methylenetetrahydrofolate reductase (MTHFR) with homocystinuria can result in early demise or later-onset neurological impairment, including developmental delay, motor dysfunction, and seizures. , Deficiency of 5,10-methylenetetrahydrofolate reductase (MTHFR) leads to deficient remethylation of homocysteine and is one of the causes of homocystinuria. , Neurological disturbances have been described in homocystinuria caused by severe MTHFR deficiency. , The 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is an important cause of mild hyperhomocysteinemia, but this polymorphism does not seem to be a risk factor for venous thrombosis., Research performed during the past decade has clarified our understanding of MTHFR deficiencies that cause homocystinuria or mild hyperhomocysteinemia., The 677C>T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is an important cause of mild hyperhomocysteinaemia., The most common genetic cause of hyperhomocysteinemia is the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene., Our cloning of the MTHFR coding sequence was initially followed by the identification of the first deleterious mutations in MTHFR, in patients with homocystinuria and marked hyperhomocysteinemia., Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria., Molecular characterization of five patients with homocystinuria due to severe methylenetetrahydrofolate reductase deficiency., On the contrary, thermolabile MTHFR caused by the 677C-->T mutation, was frequently observed among homocystinuria patients, especially among those with thromboembolic complications: three of six homocystinuria patients who had suffered from a thromboembolic event had thermolabile MTHFR.[SEP]", "label": "yes"}
{"id": "converted_4587", "sentence1": "Does atemoya juice inhibit the CYP1A2 enzyme?", "sentence2": "Atemoya juice significantly inhibited CYP1A2 activity in human liver microsomes, but not the activities of CYP2C9 and CYP3A., This suggests that the intake of an excess amount of atemoya juice is necessary to cause a change in the pharmacokinetics of phenacetin when the IC50 values for CYP1A2 inhibition by atemoya and fluvoxamine are taken into account[SEP]", "label": "yes"}
{"id": "converted_1974", "sentence1": "Does mTOR regulate the translation of MAPKAPK2?", "sentence2": "mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype., Senescent cells secrete a combination of factors collectively known as the senescence-associated secretory phenotype (SASP). The SASP reinforces senescence and activates an immune surveillance response, but it can also show pro-tumorigenic properties and contribute to age-related pathologies. In a drug screen to find new SASP regulators, we uncovered the mTOR inhibitor rapamycin as a potent SASP suppressor. Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1. In turn, MAPKAPK2 phosphorylates the RNA-binding protein ZFP36L1 during senescence, inhibiting its ability to degrade the transcripts of numerous SASP components. Consequently, mTOR inhibition or constitutive activation of ZFP36L1 impairs the non-cell-autonomous effects of senescent cells in both tumour-suppressive and tumour-promoting contexts. Altogether, our results place regulation of the SASP as a key mechanism by which mTOR could influence cancer, age-related diseases and immune responses., Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1., mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype, Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1, Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1., Both Beclin1-PI3KIII and Beclin1-MAPKAPK2 interactions as were remarkably affected by silencing either ATM or MAPK14.ATM promoted IR-induced autophagy via the MAPK14 pathway, mTOR pathway and Beclin1/PI3KIII complexes., mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype.[SEP]", "label": "yes"}
{"id": "converted_3875", "sentence1": "Is MK-1602 a CGRP antagonist?", "sentence2": "The aim of this trial was to evaluate the efficacy and tolerability of ubrogepant (MK-1602), a calcitonin gene-related peptide receptor antagonist (CGRP-RA), for the acute treatment of migraine., This trial supports ubrogepant's efficacy and provides further evidence that CGRP-RAs are viable options for the acute treatment of migraine.[SEP]", "label": "yes"}
{"id": "converted_1599", "sentence1": "Is there any protein that undergoes both mono-ubiquitination and poly-ubiquitination?", "sentence2": "The yeast G protein alpha subunit Gpa1 represents a rare example of a protein that undergoes both mono- and poly-ubiquitination. , Expression of p34 promotes PTEN poly-ubiquitination, leading to PTEN protein degradation, whereas p34 knockdown results in PTEN mono-ubiquitination., These fingers possess E3 activities of mono-ubiquitination and poly-ubiquitination, respectively, with ubiquitin-conjugating enzyme (E2)-binding capabilities. , Instead of promoting poly-ubiquitination and degradation, we show that Smurf2 actually induces multiple mono-ubiquitination of Smad3 in vivo., mono-ubiquitination of CIITA dramatically increases its transactivity whereas poly-ubiquitination leads to CIITA degradation., This leads to a model in which Lys134 of LDB1 can be either mono-ubiquitinated, leading to stabilization, or poly-ubiquitinated, leading to degradation by the proteasome pathway. ,  mono-ubiquitination of CIITA increases its transactivity, whereas poly-ubiquitination of CIITA leads to its degradation, PS1 ubiquitination after PI3K inhibition is represented by the multiple mono-ubiquitination, instead of poly-ubiquitination, Our observations support a novel functional relationship between parkin and Hsc/Hsp70 and support the notion that parkin is a multi-purpose E3 ubiquitin ligase capable of modifying proteins either via attachment of alternatively linked poly-ubiquitin chains or through multiple mono-ubiquitination to achieve alternate biological outcomes, our results indicate that Hsp70 facilitates CHIP-mediated poly-ubiquitination of Smad1 whereas it attenuates CHIP-meditated mono-ubiquitination of Smad1., Whereas poly-ubiquitination targets protein substrates for proteasomal degradation, mono-ubiquitination is known to regulate protein trafficking in the endosomal system and to target cargo proteins for lysosomal degradation., Our results suggest that oxidative stress induces not only poly-ubiquitination but also mono-ubiquitination of LDH-A, which may be involved in its lysosomal degradation during unloading., wild type Smad4 is a relatively stable protein that undergoes mono- or oligo-ubiquitination, a modification not linked to protein degradation, These data suggest that oligo-ubiquitination positively regulates Smad4 function, whereas poly-ubiquitination primarily occurs in unstable cancer mutants and leads to protein degradation., We found that Ro52 was strongly conjugated by a single molecule of ubiquitin in cells. Although the biological relevance of this mono-ubiquitination was not defined, the function of Ro52 might be modified by the mono-ubiquitination. We also found that Ro52 was conjugated with poly-ubiquitin chain in cells (poly-ubiquitination)[SEP]", "label": "yes"}
{"id": "converted_3479", "sentence1": "Is modified vaccinia Ankara effective for smallpox?", "sentence2": "BACKGROUND: Modified Vaccinia Ankara (MVA) is a live, viral vaccine under advanced development as a non-replicating smallpox vaccine. , The three MVA lots induced equivalent antibody titers two weeks after the second vaccination, with seroconversion rates of 99·8% (PRNT) and 99·7% (ELISA). , INTRODUCTION: To guide the use of modified vaccinia Ankara (MVA) vaccine in response to a release of smallpox virus, the immunogenicity and safety of shorter vaccination intervals, and administration by jet injector (JI), were compared to the standard schedule of administration on Days 1 and 29 by syringe and needle (S&N)., Erratum: Safety and Immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine in Vaccinia-Naive and Experienced Human Immunodeficiency Virus-Infected Individuals: An Open-Label, Controlled Clinical Phase II Trial., Modified vaccinia Ankara virus (MVA) is a smallpox vaccine candidate. , A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN®) in 56-80-Year-Old Subjects., BACKGROUND: Modified Vaccinia Ankara MVA-BN® is a live, highly attenuated, viral vaccine under advanced development as a non-replicating smallpox vaccine. , CONCLUSIONS: One or two doses of MVA were safe and immunogenic in a 56-80 years old vaccinia-experienced population. , The results suggest that a single dose of MVA in a 56-80 years old population was well tolerated and sufficient to rapidly boost the long-term B cell memory response induced by a prior vaccination with a traditional smallpox vaccine., Modified Vaccinia Ankara (MVA) poxvirus has been assessed for cardiac safety in a large placebo-controlled clinical trial., BACKGROUND: Modified vaccinia Ankara (MVA) is being developed as a safer smallpox vaccine and is being placed in the US Strategic National Stockpile (SNS) as a liquid formulation for subcutaneous (SC) administration at a dose of 1×10(8) TCID50 in a volume of 0.5mL. , IMVAMUNE, an attenuated modified vaccinia Ankara virus vaccine for smallpox infection., Bavarian Nordic is developing IMVAMUNE, which is based on a live attenuated modified vaccinia Ankara virus, for the potential prevention of smallpox infection, particularly in those patients contraindicated to traditional smallpox vaccines, such as the immunocompromised and those with eczema or dermatitis., IMVAMUNE: modified vaccinia Ankara strain as an attenuated smallpox vaccine., Modified vaccinia Ankara: potential as an alternative smallpox vaccine., Evaluation of modified vaccinia virus Ankara as an alternative vaccine against smallpox in chronically HIV type 1-infected individuals undergoing HAART., Modified vaccinia Ankara: potential as an alternative smallpox vaccine, Modified vaccinia Ankara ( MVA ) is being developed as a safer smallpox vaccine and is being placed in the US Strategic National Stockpile ( SNS ) as a liquid formulation for subcutaneous ( SC ) administration at a dose of 1×10 ( 8 ) TCID50 in a volume of 0.5mL, Modified vaccinia Ankara was safe and immunogenic in subjects infected with HIV and represents a promising smallpox vaccine candidate for use in immunocompromised populations, Bavarian Nordic is developing IMVAMUNE , which is based on a live attenuated modified vaccinia Ankara virus , for the potential prevention of smallpox infection , particularly in those patients contraindicated to traditional smallpox vaccines , such as the immunocompromised and those with eczema or dermatitis, One of the most advanced and most promising vectors is the attenuated , non-replicating poxvirus MVA ( modified vaccinia virus Ankara) , a safer derivative of the uniquely successful smallpox vaccine, Modified vaccinia virus Ankara ( MVA ) is a highly attenuated vaccinia virus that is under consideration as an alternative to the conventional smallpox vaccine Dryvax, Modified Vaccinia virus Ankara ( MVA ) is an attenuated derivative , also used in the smallpox eradication campaign and now being developed as a recombinant viral vector to produce vaccines against infectious diseases and cancer, While modified vaccinia virus Ankara ( MVA ) is currently in clinical development as a safe vaccine against smallpox and heterologous infectious diseases , its immunogenicity is likely limited due to the inability of the virus to replicate productively in mammalian hosts, Modified vaccinia Ankara was safe and immunogenic in subjects infected with HIV and represents a promising smallpox vaccine candidate for use in immunocompromised populations., Modified Vaccinia virus Ankara (MVA) is a replication-deficient and attenuated derivative, also used in the smallpox eradication campaign and now being developed as a recombinant viral vector to produce vaccines against infectious diseases and cancer.,  Modified vaccinia Ankara was safe and immunogenic in subjects infected with HIV and represents a promising smallpox vaccine candidate for use in immunocompromised populations.[SEP]", "label": "yes"}
{"id": "converted_2096", "sentence1": "Is Cryptococcus neoformans a frequent cause of isolated skin infections in immunocompromised individuals", "sentence2": " Cryptococcus is an opportunistic yeast with a worldwide distribution that primarily causes significant infections in immunocompromised individuals, generally by affecting the respiratory tract. But primary cutaneous cryptococcosis (PCC) without systemic infection is rare. , Cryptococcus is a ubiquitous fungus and is known for causing meningitis and cutaneous infections in immunocompromised individuals., Cryptococcus neoformans is an encapsulated yeast that can cause primary pulmonary infections or disseminate and cause infections of the central nervous system, meninges, skin, and bone in the immunocompromised host., The authors report a male patient, a seller with no detected immunosuppression, with an extensive ulcerated skin lesion localized on the left forearm, caused by Cryptococcus neoformans var.[SEP]", "label": "no"}
{"id": "converted_523", "sentence1": "Is stop codon bypass possible?", "sentence2": "In 1999, proof-of-concept for treating these disorders was obtained in a mouse model of muscular dystrophy, when administration of aminoglycosides restored protein translation by inducing the ribosome to bypass a PTC., Aminoglycosides can bypass nonsense mutations and are the prototypic agents for translational bypass therapy (TBT)., Expression of retroviral replication enzymes (Pol) requires a controlled translational recoding event to bypass the stop codon at the end of gag. This recoding event occurs either by direct suppression of termination via the insertion of an amino acid at the stop codon (readthrough) or by alteration of the mRNA reading frame (frameshift)., Recent studies on translation termination in the yeast Saccharomyces cerevisiae have not only enabled the identification of the key components of the termination machinery, but have also revealed several regulatory mechanisms that might enable the controlled synthesis of C-terminally extended polypeptides via stop-codon readthrough. , The effects of all possible single-base mutations in the codons flanking the stop indicated that 3' contexts of the form CAR-YYA confer leakiness and that the 3' context permits read through of UAA and UGA stop codons as well as UAG., As a first step to elucidate the mechanism(s) by which ribosomes bypass leaky stop codons in vivo, we have devised a system in which readthrough is coupled to the transient expression of beta-glucuronidase (GUS) in tobacco protoplasts. [SEP]", "label": "yes"}
{"id": "converted_4463", "sentence1": "Is EuroQol 5-Dimension Health Assessment (EQ-5D) [a widely used, simple instrument that monitors the general health-related quality of life (HRQoL) in chronic disease] a 5 question assessment?", "sentence2": "The 6-question EuroQol 5-Dimension Health Assessment (EQ-5D) is a widely used, simple instrument that monitors general health-related quality of life (HRQoL) in chronic disease. , OBJECTIVE: The 6-question EuroQol 5-Dimension Health Assessment (EQ-5D) is a widely used, simple instrument that monitors general health-related quality of life (HRQoL) in chronic disease., OBJECTIVE: The 6-question EuroQol 5-Dimension Health Assessment (EQ-5D) is a widely used, simple instrument that monitors general health-related quality of life (HRQoL) in chronic d, OBJECTIVE: The 6-question EuroQol 5-Dimension Health Assessment (EQ-5D) is a widely used, simple instrument that monitors general health-related quality of life (HRQoL) in chron[SEP]", "label": "no"}
{"id": "converted_225", "sentence1": "Is it safe to take isotretinoin during pregnancy?", "sentence2": "Isotretinoin is a remarkably effective drug for severe, recalcitrant acne vulgaris., a number of important adverse effects were reported, even the most recent pregnancy prevention program (iPledge) is no more successful than prior programs; there will likely always be a small number of female patients becoming pregnant while receiving isotretinoin for acne vulgaris., Isotretinoin has revolutionized the management of acne vulgaris., The adverse effect(s) that led to patients stopping isotretinoin were cheilitis (22 patients), mood change (13), tiredness (12), eczema (6) and pregnancy (2)., Downregulation of FGFR2b-signaling by isotretinoin explains its therapeutic effect in acne. Downregulation of FGFR2b-signaling during the first trimester of pregnancy disturbs branched morphogenesis and explains retinoid embryotoxicity., The isotretinoin, a 13-cis-retinoic acid, has revolutionized the management of severe treatment-resistant acne and it has been widely used for a range of dermatological conditions, in 90% of the time in young women between 13 and 45 years of age. This agent has severe teratogenic effects, as serious craniofacial, cardiovascular, thymic and central nervous system malformations., malformations is 3-5%, but it increases to almost 30% in women exposed to isotretinoin during the first trimester of pregnancy. Generally, patients in treatment with isotretinoin avoid eventual pregnancy during assumption and, after its stopping, fertility and foetal development are normal once circulating isotretinoin levels return to normal., After 3 months of pharmacological wash out, patient become pregnant and manifested this severe malformation. Woman interrupted gestation, by labour induction., Clindamycin phosphate 1.2% together with tretinoin 0.025% as a gel (CTG) is a topical formulation of a fixed and stable combination approved by the FDA for the treatment of acne vulgaris in patients 12 years of age or older., Safety of CTG use in pregnancy has not been established., To estimate the population-based incidence rates of pregnancy, spontaneous and elective abortions, and birth defects associated with isotretinoin use, and to determine predictors of pregnancy while on isotretinoin, Pregnancies, spontaneous and elective abortions, and birth defects were identified using procedure codes and medical diagnoses., 90 women who became pregnant while on the drug, 76 terminated the pregnancy (84%), three had a spontaneous abortion (3%), two had trauma during delivery resulting in neonatal deaths (2%) and nine had a live birth (10%). Among the live births, only one had a congenital anomaly of the face and neck (11%)., elective abortion rates were also much higher in our study., Topical antibiotics, isotretinoin or systemic antibiotics are usually used for acne therapy. However, isotretinoin cannot be used during pregnancy because it can cause significant birth defects while systemic antibiotics can have adverse side effects such as gastrointestinal irritation, photosensitivity and tetracycline sensitivity., Isotretinoin has been used to treat acne since 1982. Its current indications in the package insert are limited and many physicians still feel uncomfortable prescribing it because of its side effects., Aside from its teratogenic effect, isotretinoin is a safe and excellent drug for acne therapy. I, a pregnancy test in females., Vitamin A and its derivatives, retinoic acid, tretinoin and isotretinoin, are currently used in dermatological treatments. The administration of high doses of this vitamin provokes congenital malformations in mice: cleft palate, maxillary and mandibular hypoplasia and total or partial fusion of the maxillary incisors., Twelve 60-day-old female Mus musculus were divided into two groups on the 7th day of pregnancy: treated group--1 mg isotretinoin per kg body weight, dissolved in vegetable oil, was administered from the 7th to the 13th day of pregnancy; control group--vegetable oil in equivalent volume was administered orally for the same period. On the 16th day of pregnancy, the females were sacrificed, the fetuses were removed and their heads amputated., The results showed that both groups had closed palates with no reminiscence of epithelial cells; however, the first molar germs of the isotretinoin-treated animals showed delayed development compared to the control animals., Isotretinoin (13-cis-RA) is teratogenic in all species examined; based on administered dose, humans appear most sensitive, followed by (in order or decreasing sensitivity) monkey, rabbit, hamster, mouse, and rat., Based on embryonic delivered dose, we suggest that 13-cis-RA is an equipotent teratogen in hamster and rabbit., its safety in humans is occasionally questioned because oral ingestion of retinoids at therapeutic levels is known to entail teratogenic risks., topical tretinoin is not a potential human developmental toxicant., Teratogenicity of vitamin A was firstly detected in experimental animals in 1953. Nearly 30 years later, teratogenicity of vitamin A analogue-isotretinoin was reported in humans. Isotretinoin induces serious birth defects of craniofacial and central nervous system, cardiovascular system and thymic malformations--in about 25% of babies exposed during the first trimester of their prenatal development., high vitamin A intake in pregnant woman: Women who use daily vitamin A supplements during early pregnancy have approximately a two-fold increased risk of giving birth to a malformed baby., Vitamin A started to affect development between doses 0.3-0.3 microm [corrected] per embryo. Malformations of head, extremities and heart were detected similarly like in laboratory mammals and in man, the minimal embryotoxic doses of vitamin A in mammals were estimated to be between 0.1-1 mg/kg of maternal weight, Human epidemiological studies have proved teratogenicity of vitamin A after daily doses 25,000 i.u.-8.3 mg (0.13 mg/kg)- and reduction of its maximum intake has been recommended to 10,000 i.u. per day (0.05 mg/kg). The results about teratogenicity of vitamin A achieved in the chick embryo are in agreement with such a recommendation. Intake of vitamin A in the food is sufficient for pregnant woman in common Czech population. Therefore, an artificial supplementation of vitamin A brings risk of overdosage. If supplementation by vitamin A is unavoidable during pregnancy, B-carotene should be preferred., a teratogenic dosing regimen with 13-cis-RA [Hummler et al. (1994) Teratology 50:184-193]., plasma AUC values of all-trans-RA were 2- to 7-fold higher after all-trans-RA administration (present study) than after dosing with the teratogenic dose of 13-cis-RA. These results strengthen our recent suggestion that the teratogenic effects induced in cynomolgus monkeys by 13-cis-RA treatment cannot solely result from the action of all-trans-RA, but may involve 13-cis-RA and 13-cis-4-oxo-RA, which could act directly or function as transport vehicle., VITA, among others, is involved in the process of morphogenesis. In contrast, synthetic derivatives of VITA, specifically Tigasone (etretinate, TIG) and Roaccutane (isotretinoin, ROA), are regarded as major teratogens., A biphasic maximal inhibition was present at 1 microM concentrations when the retinoids VITA, TIG and ROA were added for 16 h (52, 58 and 57%, respectively; P < 0.01 by one-way analysis of variance). In contrast, the addition of the three retinoids at 1 microM concentrations for 16 h had no significant effect on HCG secretion by placental explants of 11-13 weeks gestational age., Inhibition of HCG secretion by retinoids may contribute either directly or indirectly to their teratogenicity., Isotretinoin is a potent retinoic acid used in the treatment of skin disorders. Though very effective, it is teratogenic if administered during pregnancy, and its teratogenic effect may be related to the normal activity of retinoids as signalling molecules in the embryo., defects that includes heart defects, by inhibiting the migration of neural crest cells., Proliferation in heart tissue of whole embryo cultures was inhibited in medium with 10(-6) M isotretinoin to 62% of the control level in myocardium., The results suggest multiple effects of retinoids on growth, morphogenesis, and differentiation of early cardiac tissue, and are discussed in relation to the potential role of retinoids in early embryogenesis., Oral administration of 400 mg/kg of 13-cis retinoic acid to 9 day pregnant mice gives rise to important maxillofacial malformations. The first manifestation of teratogenic effect is an increase of density of cell death arising in the dorsal part of the first two branchial arches at day 9.5. These two arches become hypoplastic at days 10 and 11, and the preskeletal anlagen appear too late in comparison to control embryos. Meckel's cartilage is too curvilinear and medially situated. Pre-ossicular and pre-mandibular blastemata develop with spatial distortions which are well analyzable at days 16 and 17, Isotretinoin (13-cis-retinoic acid, Accutane) increases the risk of major congenital malformations in infants exposed to isotretinoin during pregnancy. However, there have been no epidemiologic reports to date on the effect of a subsequent pregnancy after discontinuation of isotretinoin., analysis of pregnancy case reports from patients in whom conception occurred after isotretinoin treatment had been discontinued, spontaneous and missed abortions from all pregnancies was 9.1% (eight patients), and the incidence rate of congenital malformation among the live births was 5.0% (four patients)., were not significantly different from the rates reported for women of reproductive age in the general population. In addition, the malformations reported were not characteristic of retinoic acid-induced congenital anomalies., Keratolenticular dysgenesis (Peters' anomaly) was induced in mice by exposure to the human teratogens, ethanol or 13-cis retinoic acid (isotretinoin, Accutane). Acute teratogen exposure on the seventh day of gestation (corresponding to the third week of human gestation) resulted in an eye malformation incidence of 46% to 100% in day 14 fetuses, This secondary effect on neural crest derivatives is exhibited in the adult animals as corneal opacities associated with defects in Descemet's membrane and endothelium, and anterior polar cataracts., 13-cis-retinoic acid (13-cis-RA, or isotretinoin) is responsible for various craniofacial malformations in the rodent and human embryo., In whole embryo culture, 13-cis-RA caused significant overall embryonic growth retardation, especially in the primary and secondary palatal processes., subsequent cell growth was decreased at concentrations of 13-cis-RA greater than 1 X 10(-5) M. After a 40-hr treatment period, labeling indices in retinoid-treated cells were significantly lower than control values (25% compared with 40%). Retinoic acid also caused a significant, concentration-dependent decrease in 3H-thymidine incorporation. The inhibitory effect of 13-cis-RA on proliferation of oral-nasal mesenchymal cells appears to be related to the production of craniofacial malformations., Reports of adverse human pregnancy outcomes including cleft palate have increased as the clinical use of isotretinoin (13-cis-retinoic acid) and other retinoic acid (RA) derivatives have increased, but the mechanisms by which their effects are exerted are not understood., In shelves exposed to EGF and trans-RA early in their development, DNA synthesis appears to terminate prematurely as compared to shelves cultured in control media, and this effect is accompanied by excessive mesenchymal extracellular space expansion. Exposure of shelves to EGF alone is sufficient to block degeneration and induce hyperplasia of the medial epithelial cells but does not induce other ultrastructural changes seen with both EGF and RA. The observed alterations in medial cell morphology could interfere with adhesion of the palatal shelves and may play a role in retinoid-induced cleft palate in the human embryo., Recent clinical observations strongly suggest that isotretinoin [13-cis-retinoic acid (cis RA)] is a human teratogen causing primarily heart and craniofacial malformations including ear and palatal defects., Our results demonstrate that labeled cis RA enters the tissues of the embryo both in vivo and in vitro. Cis RA inhibited proliferation of the frontonasal mesenchyme cells in primary culture with 31% inhibition occurring at 2 X 10(-5) M cis RA., Retinoic acid, an analogue of vitamin A, is known to be teratogenic in laboratory animals and has recently been implicated in a few clinical case reports. To study the human teratogenicity of this agent, we investigated 154 human pregnancies with fetal exposure to isotretinoin, a retinoid prescribed for severe recalcitrant cystic acne. The outcomes were 95 elective abortions, 26 infants without major malformations, 12 spontaneous abortions, and 21 malformed infants. A subset of 36 of the 154 pregnancies was observed prospectively., Exposure to isotretinoin was associated with an unusually high relative risk for a group of selected major malformations (relative risk = 25.6; 95 per cent confidence interval, 11.4 to 57.5)., It is possible that a major mechanism of isotretinoin teratogenesis is a deleterious effect on cephalic neural-crest cell activity that results in the observed craniofacial, cardiac, and thymic malformations.[SEP]", "label": "no"}
{"id": "converted_2496", "sentence1": "Does prolactinoma increase osteoporosis risk?", "sentence2": "Prolactinoma: A Massive Effect on Bone Mineral Density in a Young Patient., Osteoporosis has been noted to be an issue in postmenopausal women with prolactinomas. This case shows a similar impact on bone health in a young male resulting in low bone mineral density for age based on Z-score. This case report highlights the possible mechanisms for the bone loss in the setting of prolactinoma and the need for assessing bone health in such patients.,  Hyperprolactinaemia related to prolactinoma significantly (more than functional hyperprolactiaemia) increases the risk of osteopenia, osteoporosis and bone fractures. , Prolactinomas are the most common type of functional pituitary tumor. Effective hyperprolactinemia treatment is of great importance, due to its potential deleterious effects including infertility, gonadal dysfunction and osteoporosis. , Prolactinomas cause hypogonadism, infertility, osteoporosis, and tumor mass effects, and are the most common type of neuroendocrine tumor., We present a 22-year-old man with multiple osteoporotic fractures associated with prolactinoma despite the use of teriparatide for 18 months. We emphasize and highlight the importance of hyperprolactinemia and fractures caused by high prolactin levels., OBJECTIVE: Patients with prolactinoma seem to be at high risk for osteopenia. , RESULTS: Compared to the matched controls, BMD of patients with prolactinoma or craniopharyngioma significantly decreased. , CONCLUSION: In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma., Data on osteoporotic fractures in hyperprolactinemia are limited. An increased prevalence of radiological vertebral fractures was recently observed in women with prolactin (PRL)-secreting adenoma, whereas it is unknown whether this observation may reflect a more general increased risk of fractures in this disease and whether the prevalence of fractures in males is affected by gonadal status., Prolactinoma presenting as chronic anaemia with osteoporosis: a case report., Six years later, he was evaluated and diagnosed with a prolactinoma and resultant osteoporosis. Prolactinoma in old people may present insidiously with chronic anaemia and osteoporosis with or without sexual dysfunction., The relative risk for developing osteoporosis in women with prolactinoma was found to be 4.5, indicating that hyperprolactinemia in women is a major risk factor for osteoporosis.<br>, <b>INTRODUCTION</b>: Osteopenia and osteoporosis because of hyperprolactinaemia caused by prolactinoma may be followed by an increased risk of fracture., Univariate and multivariate regression analysis indicated that the bone loss in prolactinomas was significantly correlated to disease duration and hypogonadism.<br><b>CONCLUSION</b>: In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma., High serum prolactin levels lead to increase of the risk of osteopenia or/and osteoporosis., Prolactinoma in old people may present insidiously with chronic anaemia and osteoporosis with or without sexual dysfunction.<br><b>CASE PRESENTATION</b>: We describe the case of a 70-year-old Caucasian man who presented with mild anaemia and tiredness., In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma., The relative risk for developing osteoporosis in women with prolactinoma was found to be 4.5, indicating that hyperprolactinemia in women is a major risk factor for osteoporosis., CONCLUSION In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma., Prolactinoma in old people may present insidiously with chronic anaemia and osteoporosis with or without sexual dysfunction., Hyperprolactinaemia related to prolactinoma significantly (more than functional hyperprolactiaemia) increases the risk of osteopenia, osteoporosis and bone fractures., INTRODUCTION Osteopenia and osteoporosis because of hyperprolactinaemia caused by prolactinoma may be followed by an increased risk of fracture., In conclusion, men with prolactinoma have high prevalence of osteopenia and osteoporosis., Humans with prolactinoma are at risk for osteoporosis., Osteopenia and osteoporosis because of hyperprolactinaemia caused by prolactinoma may be followed by an increased risk of fracture., The relative risk for developing osteoporosis in women with prolactinoma was found to be 4.5, indicating that hyperprolactinemia in women is a major risk factor for osteoporosis.., In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma.[SEP]", "label": "yes"}
{"id": "converted_68", "sentence1": "Is there any algorithm for enhancer identification from chromatin state?", "sentence2": "RFECS: a random-forest based algorithm for enhancer identification from chromatin state., However, only a limited number of cell types or chromatin marks have previously been investigated for this purpose, leaving the question unanswered whether there exists an optimal set of histone modifications for enhancer prediction in different cell types. Here, we address this issue by exploring genome-wide profiles of 24 histone modifications in two distinct human cell types, embryonic stem cells and lung fibroblasts. We developed a Random-Forest based algorithm, RFECS (Random Forest based Enhancer identification from Chromatin States) to integrate histone modification profiles for identification of enhancers, and used it to identify enhancers in a number of cell-types. We show that RFECS not only leads to more accurate and precise prediction of enhancers than previous methods, but also helps identify the most informative and robust set of three chromatin marks for enhancer prediction., We developed a Random-Forest based algorithm, RFECS (Random Forest based Enhancer identification from Chromatin States) to integrate histone modification profiles for identification of enhancers, and used it to identify enhancers in a number of cell-types., Here, we address this issue by exploring genome-wide profiles of 24 histone modifications in two distinct human cell types, embryonic stem cells and lung fibroblasts. We developed a Random-Forest based algorithm, RFECS (Random Forest based Enhancer identification from Chromatin States) to integrate histone modification profiles for identification of enhancers, and used it to identify enhancers in a number of cell-types. , ChromaGenSVM selects optimum combinations of specific histone epigenetic marks to predict enhancers. , We developed a Random-Forest based algorithm, RFECS (Random Forest based Enhancer identification from Chromatin States) to integrate histone modification profiles for identification of enhancers, and used it to identify enhancers in a number of cell-types.[SEP]", "label": "yes"}
{"id": "converted_4250", "sentence1": "Is Ozanimod effective for Ulcerative Colitis?", "sentence2": "Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis., CONCLUSIONS: Ozanimod was more effective than placebo as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis., CONCLUSIONS: There was a high rate of continued study participation and long-term benefit with ozanimod HCl 1 mg daily based on clinical, histological and biomarker measures in patients with moderately to severely active UC in the TOUCHSTONE OLE. [NCT02531126]., Ozanimod: A First-in-Class Sphingosine 1-Phosphate Receptor Modulator for the Treatment of Ulcerative Colitis., CONCLUSION: Ozanimod is another option in the growing arsenal of UC treatment., RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Ozanimod is the first sphingosine 1-phosphate modulator to be approved for UC and is administered orally. Its efficacy profile is comparable with other UC medications., Compared with placebo, ozanimod led to clinical remission in a significantly higher proportion of patients in both the induction and maintenance phase. Additionally, for secondary end points of clinical response, endoscopic improvement, corticosteroid-free remission, and mucosal healing, ozanimod performed significantly better than placebo. , Ozanimod interferes with migrations of activated T cells to the site of inflammation and is a promising drug for the UC treatment.Key words: Crohns disease - mongersen - monoclonal antibodies - ozanimod - tofacitinib - ulcerative colitis., SIONS: Ozanimod was more effective than placebo as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. (Fund, The sphingosine-1-phosphate receptor-1 (S1P1) agonist ozanimod ameliorates ulcerative colitis, yet its mechanism of action is unknown. , Ozanimod (RPC1063) is a specific and potent small molecule modulator of the sphingosine 1-phosphate receptor 1 (S1PR1) and receptor 5 (S1PR5), which has shown therapeutic benefit in clinical trials of relapsing multiple sclerosis and ulcerative colitis. Ozan, SIONS: Ozanimod was more effective than placebo as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. (Fun, SIONS: In this preliminary trial, ozanimod at a daily dose of 1 mg resulted in a slightly higher rate of clinical remission of ulcerative colitis than placebo. The [SEP]", "label": "yes"}
{"id": "converted_1980", "sentence1": "Could divalent metal transporter 1 deficiency lead to anemia?", "sentence2": "The divalent metal transporter 1 (DMT1) is a major iron transporter required for iron absorption and erythropoiesis. Loss of DMT1 function results in microcytic anemia. , Dysfunction of human DMT1 is associated with several pathologies such as iron deficiency anemia hemochromatosis, Parkinson's disease and Alzheimer's disease, as well as colorectal cancer and esophageal adenocarcinoma, making DMT1 an attractive target for drug discovery., Deficiency of the divalent metal transporter 1 (DMT1) leads to hypochromic microcytic anemia. We have previously shown that DMT1 deficiency impairs erythroid differentiation and induces apoptosis of erythroid cells. , We propose that DMT1 deficiency negatively affects metabolism and life span of mature erythrocytes; two other aspects of defective erythropoiesis which contribute to the pathophysiology of the disease., Hypochromic microcytic anemia associated with ineffective erythropoiesis caused by recessive mutations in divalent metal transporter 1 (DMT1) can be improved with high-dose erythropoietin supplementation. , Belgrade rats exhibit microcytic, hypochromic anemia and systemic iron deficiency due to a glycine-to-arginine mutation at residue 185 in a metal ion transporter of a divalent metal transporter/divalent cation transporter/solute carrier 11 group A member 2 or 3 (DMT1/DCT1/SLC11A2), a member of the natural-resistance-associated macrophage protein (Nramp) family., Deficiency of the divalent metal transporter 1 (DMT1) leads to hypochromic microcytic anemia, Belgrade rats exhibit microcytic, hypochromic anemia and systemic iron deficiency due to a glycine-to-arginine mutation at residue 185 in a metal ion transporter of a divalent metal transporter/divalent cation transporter/solute carrier 11 group A member 2 or 3 (DMT1/DCT1/SLC11A2), a member of the natural-resistance-associated macrophage protein (Nramp) family, BACKGROUND/AIMS: Deficiency of the divalent metal transporter 1 (DMT1) leads to hypochromic microcytic anemia. , Microcytic anemia (mk/mk) mice defective in DMT1 and wild-type mice were exposed to either bleomycin or saline via intratracheal instillation and the resultant lung injury was compared. , Deficiency of the divalent metal transporter 1 (DMT1) leads to hypochromic microcytic anemia., The divalent metal transporter 1 (DMT1) is a major iron transporter required for iron absorption and erythropoiesis., This mutation severely impairs the iron transport capability of DMT1, leading to systemic iron deficiency and anemia.[SEP]", "label": "yes"}
{"id": "converted_2590", "sentence1": "Does temsirolimus improve survival of glioblastoma patients?", "sentence2": "RESULTS: fourteen randomized clinical trials were identified (7 with bevacizumab, 2 cilengitide, 1 enzastaurin, 1 dasatinib, 1 vandetanib, 1 temsirolimus, 1 cediranib) including 4330 patients. Antiangiogenic drugs showed no improvement in overall survival with a pooled HR of 1.00, a trend for an inferior outcome, in terms of overall survival, was observed in the group of patients receiving antiangiogenic drug alone compared to cytotoxic drug alone (HR=1.24, p=0.056)., CONCLUSIONS: Temsirolimus was not superior to temozolomide in patients with an unmethylated MGMT promoter., The actuarial 1-year survival was 72.2% [95% confidence interval (CI), 58.2-82.2] in the temozolomide arm and 69.6% (95% CI, 55.8-79.9) in the temsirolimus arm [hazard ratio (HR) 1.16; 95% CI, 0.77-1.76; P = 0.47]., CONCLUSION: The combination of bevacizumab with temsirolimus was well-tolerated and resulted in stable disease of at least four months/partial response in three out of six pediatric patients with chemorefractory CNS tumors., CONCLUSIONS: Temsirolimus administered weekly at the dose of 75 mg/m(2) did not meet the primary objective efficacy threshold in children with high-grade glioma, neuroblastoma or rhabdomyosarcoma; however, meaningful prolonged stable disease merits further evaluation in combination therapy., Novel targeted agents such as bevacizumab, imatinib, erlotinib, temsirolimus, immunotherapy, cilengitide, talampanel, etc. are helping classical chemotherapeutic agents, like temozolomide, to achieve an increase in overall survival., CONCLUSIONS: CCI-779 was well tolerated at this dose schedule; however, there was no evidence of efficacy in patients with recurrent GBM, The addition of temsirolimus to interferon did not improve survival., CONCLUSIONS Temsirolimus was not superior to temozolomide in patients with an unmethylated MGMT promoter., The addition of temsirolimus to interferon did not improve survival.[SEP]", "label": "no"}
{"id": "converted_704", "sentence1": "Are CD44 variants (CD44v) associated with poor prognosis of metastasis?", "sentence2": "CD44 variants and prognosis, The CD44 variant (CD44v) isoforms have been noted as markers for tumour metastasis and prognosis in several adenocarcinomas., Positive CD44v3 expression was associated with more advanced pathological stage and poorer prognosis than negative CD44v3 expression, CD44v6 expression in the adenocarcinoma component may directly affect the behavior of carcinoma and the prognosis of patients, D44 variant 6 in endometrioid carcinoma of the uterus: its expression in the adenocarcinoma component is an independent prognostic marker, CD44v5 expression is independently positively correlated with the aggressiveness of thymic epithelial tumors. The expression of CD44v5 may be a potential trigger of tumor invasion in thymomas, analysis of CD44v expression provides indications of biological and clinical relevance also in low grade lymphoproliferative disorders, clinical relevance of CD44 variant isoform expression on B-cell chronic lymphocytic leukemia, CD44 variants and its association with survival in pancreatic cancer, CD44 variant 6(v6) molecule has been noted as a marker for tumor metastasis and prognosis in several tumors, CD44v2 and CD44v6 may be useful markers for poor prognosis in curatively resected primary pancreatic cancer, CD44v8-10 may play an important role in the adhesion of tumor cells to the capillaries of distant organs in the metastatic process, and that immunohistochemical detection of CD44v8-10 may be a biologic marker of prognostic significance., combined expression of CD44v8-10 and SLX may be a biologic marker of prognostic significance, variant isoforms (CD44v) are expressed on different malignant cells and tissues. Their upregulation has been implicated, in the progression and metastasis of malignomas., expression of the CD44 variant exon 6 is associated with lymph node metastasis in non-small cell lung cancer, a number of variant forms of CD44 are frequently expressed, although these variants are infrequently expressed in normal lung tissue, and that the expression of CD44v6 is particularly associated with lymph node metastasis in NSCLC, Expression of CD44v6 may suggest an increased risk for local lymph node metastasis in NSCLCs, different CD44 isoforms are found in human skin cancers and are modulated during carcinogenesis, D44 isoforms correlate with cellular differentiation but not with prognosis in human breast cancer, Correlations between prognosis and expression of CD44v have been reported for gastric and colon carcinoma, for non-Hodgkin's lymphoma, and recently for breast carcinoma, Certain splice variants (CD44v) can promote the metastatic behaviour of cancer cells. In human colon and breast cancer the presence of epitopes encoded by exon v6 on primary resected tumour material indicates poor prognosis, In human mammary carcinomas and colorectal carcinomas, the expression of CD44v has also been correlated with more progressed tumor stages.[SEP]", "label": "yes"}
{"id": "converted_2665", "sentence1": "Is Lysyl oxidase crosslinking collagen?", "sentence2": "Lysyl oxidase (LOX) and LOX-like (LOXL) proteins play crucial roles in ECM remodeling due to their collagen crosslinking and intracellular functions. , Lysyl oxidase-like 1, a crosslinking enzyme implicated in collagen and elastin biogenesis, LOXL2 mediates collagen crosslinking, The same was true for assaying lysyl oxidase, an enzyme involved in crosslinking of matrix molecules.,  In addition, collagen fibers in metastatic lung tumors exhibit greater linearity and organization as a result of collagen crosslinking by the lysyl oxidase (LOX) family of enzymes. [SEP]", "label": "yes"}
{"id": "converted_818", "sentence1": "Is there evidence to suggest that triiodothyronine has neuroprotective properties in traumatic brain injury?", "sentence2": "Exogenous T3 administration provides neuroprotection in a murine model of traumatic brain injury., Treatment with T3 (1.2μg/100g body weight, i.p.) 1h after TBI resulted in a significant improvement in motor and cognitive recovery after CCI, as well as in marked reduction of lesion volumes. , Western blot analysis revealed the ability of T3 to reduce brain trauma through modulation of cytoplasmic-nuclear shuttling of nuclear factor-κB (NF-κB). Twenty-four hours after brain trauma, T3-treated mice also showed significantly lower number of TUNEL(+) apoptotic neurons and curtailed induction of Bax, compared to vehicle control. In addition, T3 significantly enhanced the post-TBI expression of the neuroprotective neurotrophins (BDNF and GDNF) compared to vehicle. , The stimulating effect of T3 on peripheral nerve regeneration may have considerable therapeutic potential., The present study provides evidence that the peripheral nervous system has its own system responsible for the local production of 3,5,3'-triiodothyronine, which may play a key role during the regeneration process., Although it has been hypothesized that T3 may facilitate neuronal regeneration after CNS injury, the 5'-D2 response to brain injury is unknown., The outcome after brain injury is closely correlated with the intensity of these changes, particularly with catecholamine plasma levels and the severity of the low triiodothyronine syndrome., The thyroid hormones triiodothyronine (T3) and L-thyroxine appear to enhance regeneration in the peripheral and central nervous system (CNS). , T3 treatment influenced the general levels of incorporation of all treated groups over all days postoperation., T3 effects appear to involve an increased sensitivity of the cells of the injured nervous system to the hormone., T3, when administered over an 8 week period, stimulated axonal regeneration in the dorsal cortex and corpus callosum and promoted healing of the wound in the corpus callosum. The results of this investigation suggest that the use of T3 in the clinical treatment of injury to the central nervous system may be of less value than the work of earlier authors had indicated., In addition, T3 significantly enhanced the post-TBI expression of the neuroprotective neurotrophins (BDNF and GDNF) compared to vehicle[SEP]", "label": "yes"}
{"id": "converted_3584", "sentence1": "Can PRL3-zumab inhibit PRL3+ cancer cells in vitro and in vivo?", "sentence2": "Here we show that PRL3-zumab specifically inhibits PRL3+ cancer cells in vivo, but not in vitro.[SEP]", "label": "no"}
{"id": "converted_1105", "sentence1": "Are thyroid hormone receptor alpha1 mutations  implicated in thyroid hormone resistance syndrome?", "sentence2": "Mutations in human TRα1 mediate RTH with features of hypothyroidism in particular tissues (e.g. skeleton, gastrointestinal tract), but are not associated with a markedly dysregulated pituitary-thyroid axis., Clinical phenotype of a new type of thyroid hormone resistance caused by a mutation of the TRα1 receptor[SEP]", "label": "yes"}
{"id": "converted_2802", "sentence1": "Does gepotidacin activate bacterial topoisomerase?", "sentence2": "GSK2140944 is a novel bacterial topoisomerase inhibitor in development for the treatment of bacterial infections.[SEP]", "label": "no"}
{"id": "converted_2246", "sentence1": "Is NEMO a zinc finger protein?", "sentence2": "To better understand the thermodynamics and dynamics of the zinc finger of NEMO (NF-κB essential modulator), an alteration in the zinc finger domain of NEMO (K392R) , CYLD and the NEMO Zinc Finger Regulate Tumor Necrosis Factor Signaling and Early Embryogenesis., our simulations of the zinc finger NEMO, An important regulatory domain of NF-[Formula: see text]B Essential Modulator (NEMO) is a ubiquitin-binding zinc finger, with a tetrahedral CYS3HIS1 zinc-coordinating binding site., NEMO function is mediated by two distal ubiquitin binding domains located in the regulatory C-terminal domain of the protein: the coiled-coil 2-leucine zipper (CC2-LZ) domain and the zinc finger (ZF) domain. ,  We show here that the NEMO C terminus, comprising the ubiquitin binding region and a zinc finger,[SEP]", "label": "yes"}
{"id": "converted_3706", "sentence1": "Do genes with monoallelic expression contribute proportionally to genetic diversity in humans?", "sentence2": "Genes with monoallelic expression contribute disproportionately to genetic diversity in humans., An unexpectedly large number of human autosomal genes are subject to monoallelic expression (MAE). Our analysis of 4,227 such genes uncovers surprisingly high genetic variation across human populations. This increased diversity is unlikely to reflect relaxed purifying selection. Remarkably, MAE genes exhibit an elevated recombination rate and an increased density of hypermutable sequence contexts. However, these factors do not fully account for the increased diversity. We find that the elevated nucleotide diversity of MAE genes is also associated with greater allelic age: variants in these genes tend to be older and are enriched in polymorphisms shared by Neanderthals and chimpanzees. Both synonymous and nonsynonymous alleles of MAE genes have elevated average population frequencies. We also observed strong enrichment of the MAE signature among genes reported to evolve under balancing selection. We propose that an important biological function of widespread MAE might be the generation of cell-to-cell heterogeneity; the increased genetic variation contributes to this heterogeneity., Genes with monoallelic expression contribute disproportionately to genetic diversity in humans[SEP]", "label": "no"}
{"id": "converted_3952", "sentence1": "Has ubrogepant entered clinical phase III trials?", "sentence2": "Ubrogepant (MK-1602) is a novel, oral, calcitonin gene-related peptide receptor antagonist in clinical development with positive phase III outcomes for acute treatment of migraine., A population pharmacokinetic model describing the effect of formulations was included in the E-R simulation framework to assess potential dose implications of a formulation switch from phase II to phase III. , The understanding of E-R helped support the dose selection for the phase III clinical trials., The CGRP receptor antagonist ubrogepant, also known as MK-1602, has been recently evaluated in phase III clinical trials for clinical efficacy and long-term safety as an abortive migraine treatment., Two pivotal phase III clinical trials (ACHIEVE I and ACHIEVE II) demonstrated effectiveness and safety of ubrogepant in acute migraine attacks.[SEP]", "label": "yes"}
{"id": "converted_3960", "sentence1": "Is avelumab effective for urothelial carcinoma?", "sentence2": "ince then, additional checkpoint inhibitors, including avelumab, durvalumab, and nivolumab, have gained approval. , Avelumab, an anti-programmed death-ligand 1 monoclonal antibody approved for the treatment of metastatic Merkel cell carcinoma and platinum-treated urothelial carcinoma, was initially approved with a 10 mg/kg weight-based dose. , Five new PD-1/PD-L1 checkpoint inhibitors have been approved for the treatment of metastatic urothelial carcinoma (UC): pembrolizumab, atezolizumab, durvalumab, nivolumab, and avelumab. , We reviewed the literature for prospective studies evaluating PD-1/PD-L1 inhibitors in refractory urothelial carcinoma patients, which formed the basis for US Food and Drug Administration approval of 5 different antagonistic antibodies targeting PD-1 or PD-L1 (atezolizumab, durvalumab, avelumab, nivolumab, and pembrolizumab)., Nowadays, five immune checkpoint inhibitors blocking PD-1 (pembrolizumab, nivolumab) or PD-L1 (atezolizumab, durvalumab, and avelumab) have been approved by the United States Food and Drug Administration (US FDA) for the first- or second-line use in urothelial carcinoma, based on durable response and manageable safety profiles observed in relevant clinical trials. , RETATION: Avelumab showed antitumour activity in the treatment of patients with platinum-refractory metastatic urothelial carcinoma; a manageable safety profile was reported in all avelumab-treated patients. These, data provide the rationale for therapeutic use of avelumab in metastatic urothelial carcinoma and it has received accelerated US FDA approval in this setting on this basis.FUNDIN, BACKGROUND: Anti-programmed cell death ligand 1 (PD-L1)/programmed cell death 1 antibodies have shown clinical activity in platinum-treated metastatic urothelial carcinoma, resulting in regulatory approval of several agents, including avelumab (anti-PD-L1)., Avelumab as second-line therapy for metastatic, platinum-treated urothelial carcinoma in the phase Ib JAVELIN Solid Tumor study: 2-year updated efficacy and safety analysis., BACKGROUND: Avelumab has recently been approved by the Food and Drug Administration for the therapy of Merkel cell carcinoma and urothelial carcinoma., SIONS: Maintenance avelumab plus best supportive care significantly prolonged overall survival, as compared with best supportive care alone, among patients with urothelial cancer who had disease that had not progressed with first-line chemotherapy. (Fund, By the emergence of modern immunotherapies with active agents like PD-1 (nivolumab, pembrolizumab) and PD-L1 immune checkpoint blockers (atezolizumab, avelumab, durvalumab), new therapeutic options have become available for the treatment of patients with locally advanced and metastatic urothelial carcinoma., Avelumab, an anti-programmed death-ligand 1 monoclonal antibody approved for the treatment of metastatic Merkel cell carcinoma and platinum-treated urothelial carcinoma, was initially approved with a 10 mg/kg weight-based dose., By the emergence of modern immunotherapies with active agents like PD-1 (nivolumab, pembrolizumab) and PD-L1 immune checkpoint blockers (atezolizumab, avelumab, durvalumab), new therapeutic options have become available for the treatment of patients with locally advanced and metastatic urothelial carcinoma. Accor, ACQUISITION: Five antibodies including pembrolizumab (PD-L1 antibody), atezolizumab (PD-1 antibody), nivolumab (PD-1 antibody), avelumab and durvalumab (PD-L1 antibodies) have been approved in the treatment of advanced urothelial carcinoma in first- and second-line treatment setting., INTERPRETATION: Avelumab showed antitumour activity in the treatment of patients with platinum-refractory metastatic urothelial carcinoma; a manageable safety profile was reported in all avelumab-treated patients., Conclusion Avelumab was well tolerated and associated with durable responses and prolonged survival in patients with refractory metastatic UC., Avelumab: A Novel Anti-PD-L1 Agent in the Treatment of Merkel Cell Carcinoma and Urothelial Cell Carcinoma., In early 2017, avelumab (BAVENCIO®), a PD-L1-blocking monoclonal antibody agent, was approved for the treatment of metastatic MCC and UC., Expert opinion: Avelumab has shown clinical efficacy for metastatic and advanced UC in phase I studies after the failure of platinum-based therapy with a well-tolerated safety profile., Avelumab has been approved by the U.S. FDA for the treatment of metastatic Merkel cell carcinoma and metastatic urothelial carcinoma that has progressed during or following treatment with a platinum-based regimen.[SEP]", "label": "yes"}