{"id": "converted_2021", "sentence1": "Is siltuximab effective for Castleman disease?", "sentence2": "Siltuximab: a targeted therapy for idiopathic multicentric Castleman disease., The recent approvals in North America, Europe and Brazil of siltuximab, a monoclonal antibody against IL-6, for iMCD now provide a safe and effective therapy that targets a key aspect of pathogenesis. In the first ever randomized, placebo-controlled trial in iMCD, siltuximab significantly reduced disease burden and symptoms in a large portion (34%) of patients., Despite recent significant advances in our understanding of this disease and the increasing therapeutic experience with rituximab, tocilizumab and siltuximab, there are still difficult questions concerning its aetiology, prognosis and optimal treatment., Emerging treatments in Castleman disease - a critical appraisal of siltuximab.,  Siltuximab, a chimeric monoclonal antibody to IL-6, has thus emerged as a promising treatment option in a disease lacking efficacious therapy. Here, we review the findings of recent studies evaluating single-agent siltuximab treatment in CD, including the first-ever randomized clinical trial in this disease. Although much more work is needed to establish a standardized treatment approach, siltuximab appears to be a safe and effective treatment for patients with newly diagnosed and previously treated CD., FDA approval: siltuximab for the treatment of patients with multicentric Castleman disease., On April 22, 2014, the FDA granted full approval to siltuximab (SYLVANT for injection; Janssen Biotech, Inc.), a chimeric human-mouse monoclonal antibody to IL6, for the treatment of patients with multicentric Castleman disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative. , Currently, there are more effective therapeutic alternatives in multicentric Castleman disease: treatment with monotherapy of rituximab or in combination therapy with immunomodulatory drugs (thalidomide or lenalidomide, treatment with anti-IL-6 (siltuximab) or against its receptor (tocilizumab). , Currently, there are more effective therapeutic alternatives in multicentric Castleman disease: treatment with monotherapy of rituximab or in combination therapy with immunomodulatory drugs (thalidomide or lenalidomide, treatment with anti-IL-6 (siltuximab) or against its receptor (tocilizumab)., Siltuximab for multicentric Castleman disease., Siltuximab: A Review in Idiopathic (Human Herpesvirus-8-Negative) Multicentric Castleman Disease., Siltuximab (IL6 antibody) is approved for the treatment of multicentric Castleman disease (MCD)., A phase 2, open-label, multicenter study of the long-term safety of siltuximab (an anti-interleukin-6 monoclonal antibody) in patients with multicentric Castleman disease., A phase I, open-label study of siltuximab, an anti-IL-6 monoclonal antibody, in patients with B-cell non-Hodgkin lymphoma, multiple myeloma, or Castleman disease., Analysis of Inflammatory and Anemia-Related Biomarkers in a Randomized, Double-Blind, Placebo-Controlled Study of Siltuximab (Anti-IL6 Monoclonal Antibody) in Patients With Multicentric Castleman Disease., Siltuximab (Sylvant). Castleman's disease: good symptomatic efficacy in some patients., Siltuximab: a new option for the management of Castleman's disease., Siltuximab, a novel anti-interleukin-6 monoclonal antibody, for Castleman's disease., PURPOSE: To evaluate the safety and pharmacokinetics of siltuximab, an anti-interleukin-6 chimeric monoclonal antibody (mAb) in patients with B-cell non-Hodgkin lymphoma (NHL), multiple myeloma, or Castleman disease.EXPERIMENTAL DESIGN: In an open-label, dose-finding, 7 cohort, phase I study, patients with NHL, multiple myeloma, or symptomatic Castleman disease received siltuximab 3, 6, 9, or 12 mg/kg weekly, every 2 weeks, or every 3 weeks., Dose selection of siltuximab for multicentric Castleman's disease., Here, modeling and simulation of the pharmacokinetic (PK)/pharmacodynamic (PD) relationship between siltuximab and CRP were used to support dose selection for multicentric Castleman's disease (CD).METHODS: PK/PD modeling was applied to explore the relationship between siltuximab PK and CRP suppression following intravenous siltuximab infusion in 47 patients with B cell non-Hodgkin's lymphoma (n = 17), multiple myeloma (n = 13), or CD (n = 17)., Currently, there are more effective therapeutic alternatives in multicentric Castleman disease: treatment with monotherapy of rituximab or in combination therapy with immunomodulatory drugs (thalidomide or lenalidomide, treatment with anti-IL-6 (siltuximab) or against its receptor (tocilizumab), Three (6%) of 53 patients had serious adverse events judged reasonably related to siltuximab (lower respiratory tract infection, anaphylactic reaction, sepsis).Siltuximab plus best supportive care was superior to best supportive care alone for patients with symptomatic multicentric Castlemans disease and well tolerated with prolonged exposure, Siltuximab, an anti-IL-6 monoclonal antibody, has demonstrated durable tumor and symptomatic responses in a multinational, randomized, placebo-controlled study of MCD.This preplanned safety analysis was conducted to evaluate the long-term safety of siltuximab treatment among 19 patients with MCD who had stable disease or better and were enrolled in a phase-1 study and subsequent ongoing, open-label, phase-2 extension study, Analysis of Inflammatory and Anemia-Related Biomarkers in a Randomized, Double-Blind, Placebo-Controlled Study of Siltuximab (Anti-IL6 Monoclonal Antibody) in Patients With Multicentric Castleman Disease, Siltuximab (IL6 antibody) is approved for the treatment of multicentric Castleman disease (MCD), Siltuximab for multicentric Castleman disease, FDA approval: siltuximab for the treatment of patients with multicentric Castleman disease, On April 22, 2014, the FDA granted full approval to siltuximab (SYLVANT for injection; Janssen Biotech, Inc.), a chimeric human-mouse monoclonal antibody to IL6, for the treatment of patients with multicentric Castleman disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative, Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial., EXPERIMENTAL DESIGN: In an open-label, dose-finding, 7 cohort, phase I study, patients with NHL, multiple myeloma, or symptomatic Castleman disease received siltuximab 3, 6, 9, or 12 mg/kg weekly, every 2 weeks, or every 3 weeks. , Currently, there are more effective therapeutic alternatives in multicentric Castleman disease: treatment with monotherapy of rituximab or in combination therapy with immunomodulatory drugs (thalidomide or lenalidomide, treatment with anti-IL-6 (siltuximab) or against its receptor (tocilizumab)., To evaluate the safety and pharmacokinetics of siltuximab, an anti-interleukin-6 chimeric monoclonal antibody (mAb) in patients with B-cell non-Hodgkin lymphoma (NHL), multiple myeloma, or Castleman disease.In an open-label, dose-finding, 7 cohort, phase I study, patients with NHL, multiple myeloma, or symptomatic Castleman disease received siltuximab 3, 6, 9, or 12 mg/kg weekly, every 2 weeks, or every 3 weeks., On April 22, 2014, the FDA granted full approval to siltuximab (SYLVANT for injection; Janssen Biotech, Inc.), a chimeric human-mouse monoclonal antibody to IL6, for the treatment of patients with multicentric Castleman disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative., Clinical benefit response (CBR; composite of hemoglobin, fatigue, anorexia, fever/night sweats, weight, largest lymph node size) was also evaluated in Castleman disease.Sixty-seven patients received a median of 16 siltuximab doses for a median of 8.5 (maximum 60.5) months; 29 were treated 1 year or longer., The recent approvals in North America, Europe and Brazil of siltuximab, a monoclonal antibody against IL-6, for iMCD now provide a safe and effective therapy that targets a key aspect of pathogenesis., Although much more work is needed to establish a standardized treatment approach, siltuximab appears to be a safe and effective treatment for patients with newly diagnosed and previously treated CD., No dose-limiting toxicity was reported, and only three patients had grade 3 or higher adverse events after a median exposure of 331 days (range, 1 to 1,148 days).These interim results strongly suggest that siltuximab is an effective treatment with favorable safety for the management of CD., Siltuximab is a new anti-IL-6, chimeric monoclonal antibody with potential therapeutic benefit in patients with CD.METHODS: We report interim results from an open-label, dose-finding, seven-cohort, phase I study in which patients with symptomatic, multicentric or unresectable, unicentric CD received siltuximab at 1-, 2-, or 3-week intervals., Siltuximab for multicentric Castleman disease., Siltuximab: a targeted therapy for idiopathic multicentric Castleman disease., Emerging treatments in Castleman disease - a critical appraisal of siltuximab., Siltuximab (Sylvant). Castleman's disease: good symptomatic efficacy in some patients., Siltuximab: a new option for the management of Castleman's disease., Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial., Siltuximab: A Review in Idiopathic (Human Herpesvirus-8-Negative) Multicentric Castleman Disease.[SEP]Relations: Siltuximab has relations: drug_drug with Sarilumab, drug_drug with Sarilumab, drug_drug with Afelimomab, drug_drug with Afelimomab, drug_drug with Fremanezumab, drug_drug with Fremanezumab, drug_drug with Sirukumab, drug_drug with Sirukumab, drug_drug with Intetumumab, drug_drug with Intetumumab.", "label": "yes"}
{"id": "converted_4489", "sentence1": "Is Mical an oxidoreductase?", "sentence2": "the MICALs, which are flavoprotein monooxygenase/hydroxylase enzymes that associate with flavin adenine dinucleotide (FAD) and use the co-enzyme nicotinamide adenine dinucleotide phosphate (NADPH) in Redox reactions, MICAL is an oxidoreductase, We have recently identified a new family of multidomain oxidoreductase (redox) enzymes, the MICALs,, the oxidoreductase MICAL[SEP]The oxidoreductase complex has relations: cellcomp_protein with CBR4, cellcomp protein with HSD17B8. Flavin adenine dinucleotide has relations with MAOB, MAOA, ACADM, and MAOA.", "label": "yes"}
{"id": "converted_3994", "sentence1": "Is there an association of alterations in ADCY7 and ulcerative colitis?", "sentence2": "To further resolve the genetic architecture of the inflammatory bowel diseases ulcerative colitis and Crohn's disease, we sequenced the whole genomes of 4,280 patients at low coverage and compared them to 3,652 previously sequenced population controls across 73.5 million variants. We then imputed from these sequences into new and existing genome-wide association study cohorts and tested for association at ∼12 million variants in a total of 16,432 cases and 18,843 controls. We discovered a 0.6% frequency missense variant in ADCY7 that doubles the risk of ulcerative colitis. Despite good statistical power, we did not identify any other new low-frequency risk variants and found that such variants explained little heritability. [SEP] ulcerative colitis (disease) has relations: disease_protein with ADCY7, disease_ proteins with IL7R and IL23R, and disease_proteins with CXCL8 and IL1R2.", "label": "yes"}
{"id": "converted_2755", "sentence1": "Is Baloxavir effective for influenza?", "sentence2": "Baloxavir marboxil (Xofluza™; baloxavir) is an oral cap-dependent endonuclease inhibitor that has been developed by Roche and Shionogi. The drug blocks influenza virus proliferation by inhibiting the initiation of mRNA synthesis. In February 2018, baloxavir received its first global approval in Japan for the treatment of influenza A or B virus infections. , This article summarized the milestones in the development of baloxavir leading to this first global approval for influenza A or B virus infections., Baloxavir acid (BXA), derived from the prodrug baloxavir marboxil (BXM), potently and selectively inhibits the cap-dependent endonuclease within the polymerase PA subunit of influenza A and B viruses., Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil., Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents., BACKGROUND: Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents., CONCLUSIONS: Single-dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza., A single oral dose of baloxavir is usually well tolerated; it hastens alleviation of influenza symptoms and shortens the duration of viral shedding., Japan was the first country to approve baloxavir marboxil as a treatment for influenza., This article summarized the milestones in the development of baloxavir leading to this first global approval for influenza A or B virus infections.<br>, In February 2018, baloxavir received its first global approval in Japan for the treatment of influenza A or B virus infections.[SEP]Oseltamivir has relations with Balsalazide, Ribavirin, Atazanavir, and Saquinavir. Rubella virus vaccine has relations: drug_drug with Baloxavir marboxil.", "label": "yes"}
{"id": "converted_3489", "sentence1": "Can radiation induced meningiomas be treated with radiosurgery?", "sentence2": "This is a case report of a patient treated with radiosurgery for radiation induced meningiomas, 30 years after childhood whole brain radiation. , This article reviews the unique characteristics and unusual response to the radiation induced meningiomas to radiosurgery. , Gamma knife stereotactic radiosurgery for radiation-induced meningiomas., RESULTS: We present our series of 12 patients with radiation-induced meningiomas treated with Gamma Knife stereotactic radiosurgery over a 12-year period at our institution. With a median follow-up of 35 months, local control was 100%., CONCLUSIONS: Gamma Knife radiosurgery is both a safe and effective treatment for radiation-induced meningiomas., Favorable outcomes of pediatric patients treated with radiotherapy to the central nervous system who develop radiation-induced meningiomas., All cases were managed with a single modality: resection alone (n = 7), fractionated radiotherapy (n = 2), and stereotactic radiosurgery (n = 1). , Stereotactic radiosurgery for radiation-induced meningiomas., The patients met criteria for a radiation-induced meningioma and underwent gamma knife radiosurgery. , CONCLUSION: SRS provides satisfactory control rates either after resection or as an alternative to resection. , This is a case report of a patient treated with radiosurgery for radiation induced meningiomas, 30 years after childhood whole brain radiation., This article reviews the unique characteristics and unusual response to the radiation induced meningiomas to radiosurgery., CONCLUSIONS\n\nGamma Knife radiosurgery is both a safe and effective treatment for radiation-induced meningiomas., RESULTS\n\nWe present our series of 12 patients with radiation-induced meningiomas treated with Gamma Knife stereotactic radiosurgery over a 12-year period at our institution., CONCLUSIONS Gamma Knife radiosurgery is both a safe and effective treatment for radiation-induced meningiomas., This article reviews the unique characteristics and unusual response to the radiation induced meningiomas to radiosurgery, Stereotactic radiosurgery for radiation-induced meningiomas, Also, LC rates with radiosurgery are at least comparable to those of surgical series for radiation-induced meningiomas, Gamma Knife radiosurgery for meningiomas: four cases of radiation-induced edema., This is a case report of a patient treated with radiosurgery for radiation induced meningiomas , 30 years after childhood whole brain radiation, Stereotactic radiosurgery ( SRS ) has become an important primary or adjuvant management for patients with intracranial meningiomas , but the value of this approach for radiation-induced tumors is unclear, This article reviews the unique characteristics and unusual response to the radiation induced meningiomas to radiosurgery, RESULTS\nWe present our series of 12 patients with radiation-induced meningiomas treated with Gamma Knife stereotactic radiosurgery over a 12-year period at our institution., OBJECTIVES\nTo ascertain the safety and efficacy of Gamma Knife radiosurgery as a treatment for radiation-induced meningiomas., As such, traditional radiotherapy is limited by lifetime tissue tolerances to radiation, leaving surgery and radiosurgery as attractive treatment options., CONCLUSIONS\nGamma Knife radiosurgery is both a safe and effective treatment for radiation-induced meningiomas., Stereotactic radiosurgery (SRS) has become an important primary or adjuvant management for patients with intracranial meningiomas, but the value of this approach for radiation-induced tumors is unclear., The patients met criteria for a radiation-induced meningioma and underwent gamma knife radiosurgery., OBJECTIVES: To ascertain the safety and efficacy of Gamma Knife radiosurgery as a treatment for radiation-induced meningiomas., RESULTS: We present our series of 12 patients with radiation-induced meningiomas treated with Gamma Knife stereotactic radiosurgery over a 12-year period at our institution., METHODS: A retrospective chart review was conducted to identify patients who received Gamma Knife radiosurgery for a meningioma and met the criteria for this being a radiation-induced tumor., We present our series of 12 patients with radiation-induced meningiomas treated with Gamma Knife stereotactic radiosurgery over a 12-year period at our institution., Stereotactic radiosurgery (SRS) has become an important primary or adjuvant management for patients with intracranial meningiomas, but the value of this approach for radiation-induced tumors is unclear.[SEP]Relations: skin meningioma has relations: disease_disease with malignant tumor of meninges, disease_disease with malignant tumor of meninges, disease_disease with meningioma (disease), disease_disease with meningioma (disease), disease_disease with malignant dermis tumor, disease_disease with malignant dermis tumor. benign meningioma has relations: disease_disease with meningioma (disease), disease_disease with meningioma (disease), disease_disease with benign neoplasm of meninges, disease_disease with benign neoplasm of meninges.", "label": "yes"}
{"id": "converted_415", "sentence1": "Can protein coding exons originate from ALU sequences?", "sentence2": "The Alu element has been a major source of new exons during primate evolution. Thousands of human genes contain spliced exons derived from Alu elements., More than 25% of Alu exons analyzed by RNA-Seq have estimated transcript inclusion levels of at least 50% in the human cerebellum, indicating widespread establishment of Alu exons in human genes., his study presents genomic evidence that a major functional consequence of Alu exonization is the lineage-specific evolution of translational regulation., Our data suggests that lineage-specific exonization events should be determined by the combination event of the formation of splicing sites and protection against site-specific mutation pressures. These evolutionary mechanisms could be major sources for primate diversification., Exonization of Alu elements creates primate-specific genomic diversity, Our data show that, once acquired, some exonizations were lost again in some lineages. In general, Alu exonization occurred at various time points over the evolutionary history of primate lineages, and protein-coding potential was acquired either relatively soon after integration or millions of years thereafter., Once integrated, they have the potential to become exapted as functional modules, e.g., as protein-coding domains via alternative splicing. This particular process is also termed exonization and increases protein versatility, alternative \"Alu-exons\" also carry the potential to greatly enhance genetic diversity by increasing the transcriptome of primates chiefly via alternative splicing., ere, we report a 5' exon generated from one of the two alternative transcripts in human tumor necrosis factor receptor gene type 2 (p75TNFR) that contains an ancient Alu-SINE, which provides an alternative N-terminal protein-coding domain.[SEP]Proteasome degradation has relations: pathway_protein with ELOC, pathway_ protein with UNKL. Antigen processing: Ubiquitination & Proteasomesome degradation have relations:  pathway_protein with UNKL, pathway protein with GLMN, pathway-protein with GLMN.", "label": "yes"}
{"id": "converted_3129", "sentence1": "Has Hesperidin any role as a Neuroprotective Agent?", "sentence2": "Neuroprotective effect of hesperetin and nano-hesperetin on recognition memory impairment and the elevated oxygen stress in rat model of Alzheimer's disease, Hesperidin attenuates depression-related symptoms in mice with mild traumatic brain injury, Neuroprotective Effects of Hesperidin on Cerebral Vasospasm, The neuroprotective effect of hesperidin in NMDA-induced retinal injury acts by suppressing oxidative stress and excessive calpain activation., This study suggests a potential neuroprotective role of hesperidin against 3-NP-induced Huntington's disease-like manifestations., Hesperidin potentiates the neuroprotective effects of diazepam and gabapentin against pentylenetetrazole-induced convulsions in mice: Possible behavioral, biochemical and mitochondrial alterations., Hesperidin, a flavanoglycone abundantly present in citrus fruits, is reported to have antioxidant, anti-inflammatory, and neuroprotective properties., PURPOSE\nHesperidin, a glycoside flavonoid, is thought to act as an anti-cancer agent, since it has been found to exhibit both pro-apoptotic and anti-proliferative effects in several cancer cell types., Hesperidin is a flavonone glycoside, belonging to the flavonoid family, which is widely found in Citrus species and acts as a potent antioxidant and anticancer agent., BACKGROUND\nHesperidin, a flavanone present in citrus fruits, has been identified as a potent anticancer agent because of its proapoptotic and antiproliferative characteristics in some tumor cells., Oxidative stress and cancer; the role of hesperidin, a citrus natural bioflavonoid, as a cancer chemoprotective agent., Our data suggests that hesperidin exerts its neuroprotective effect against rotenone due to its antioxidant, maintenance of mitochondrial function, and antiapoptotic properties in a neuroblastoma cell line., Taken together, these results demonstrate potent antioxidant and neuroprotective effects of hesperetin, implying its potential role in protecting neurons against various types of insults associated with many neurodegenerative diseases., The neuroprotective effect of hesperidin in NMDA-induced retinal injury acts by suppressing oxidative stress and excessive calpain activation.We found that hesperidin, a plant-derived bioflavonoid, may be a candidate agent for neuroprotective treatment in the retina, after screening 41 materials for anti-oxidative properties in a primary retinal cell culture under oxidative stress. , Neuroprotective effects of hesperidin, a plant flavanone, on rotenone-induced oxidative stress and apoptosis in a cellular model for Parkinson's disease.Rotenone a widely used pesticide that inhibits mitochondrial complex I has been used to investigate the pathobiology of PD both in vitro and in vivo. , Cytoprotective effects of hesperetin and hesperidin against amyloid β-induced impairment of glucose transport through downregulation of neuronal autophagy., Hesperidin potentiates the neuroprotective effects of diazepam and gabapentin against pentylenetetrazole-induced convulsions in mice: Possible behavioral, biochemical and mitochondrial alterations.Hesp possesses potent anticonvulsant activity which might be mediated through modulation of gamma-amino butyric acid/benzodiazepine receptor action., Antioxidant and neuroprotective effects of hesperidin and its aglycone hesperetin.The present study evaluated antioxidant and neuroprotective activities of hesperidin, a flavanone mainly isolated from citrus fruits, and its aglycone hesperetin using cell-free bioassay system and primary cultured rat cortical cells. , Potential neuroprotective effects of hesperidin on 3-nitropropionic acid-induced neurotoxicity in rats., Hesperidin inhibits glutamate release and exerts neuroprotection against excitotoxicity induced by kainic acid in the hippocampus of rats., Emerging evidences indicate hesperidin, a citrus flavanone, attenuates neurodegenerative processes and related complications., Potential anti-inflammatory effects of hesperidin from the genus Citrus., Antioxidant and neuroprotective effects of hesperidin and its aglycone hesperetin., Hesperidin is a flavonoid present in high concentration in citrus species and has numerous biological properties, principally antioxidant and anti-inflammatory.[SEP]Relations: Hesperetin has relations: drug_drug with Meperidine, drug_drug with Meperidine, drug_drug with Famotidine, drug_drug with Famotidine, drug_drug with Nevirapine, drug_drug with Nevirapine, drug_drug with Antipyrine, drug_drug with Antipyrine, drug_drug with Acenocoumarol, drug_drug with Acenocoumarol.", "label": "yes"}
{"id": "converted_464", "sentence1": "Are people with blood group O protected against severe Malaria?", "sentence2": "Differential carbonylation of cytoskeletal proteins in blood group O erythrocytes: potential role in protection against severe malaria., . Our findings indicate a possible correlation between the protection against severe malaria in blood group O individuals and a specific pattern of 4-HNE-carbonylation of cytoskeleton proteins., There is a predominance of blood group O in malaria-endemic regions, and several lines of evidence suggest that ABO blood groups may influence the outcome of P. falciparum infection, These data provide the first evidence that ABO blood group antigens influence macrophage clearance of P. falciparum-infected erythrocytes and suggest an additional mechanism by which blood group O may confer resistance to severe malaria., Blood group phenotypes A and B are risk factors for cerebral malaria in Odisha, India., type O is significantly associated with protection against CM, patients with type A and B group had increased risk for developing CM., Blood group O protects against severe Plasmodium falciparum malaria through the mechanism of reduced rosetting., Malaria has been a major selective force on the human population, and several erythrocyte polymorphisms have evolved that confer resistance to severe malaria. Plasmodium falciparum rosetting, a parasite virulence phenotype associated with severe malaria, is reduced in blood group O erythrocytes compared with groups A, B, and AB, but the contribution of the ABO blood group system to protection against severe malaria has received little attention, We hypothesized that blood group O may confer resistance to severe falciparum malaria through the mechanism of reduced rosetting., It appears that individuals who are of blood-group O are relatively resistant to the severe disease caused by P. falciparum infection.[SEP]Cerebral malaria has relations with disease_disease with malaria. Plasmodium falciparum malaria has Relations with disease diseases with malaria. It is contraindication with Betamethasone and Methylprednisolone, but not Prednisone.", "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]Relations: epidural spinal canal meningioma has relations: disease_disease with intraspinal meningioma, disease_disease with intraspinal meningioma. subarachnoid hemorrhage (disease) has relations: contraindication with Tranexamic acid, contraindication with Tranexamic acid, disease_disease with neurovascular disease, disease_disease with neurovascular disease, disease_disease with brain disease, disease_disease with brain disease, disease_protein with ADORA1, disease_protein with ADORA1.", "label": "yes"}
{"id": "converted_2008", "sentence1": "Is Meis1 implicated in microphthalmia?", "sentence2": "Meis1 coordinates a network of genes implicated in eye development and microphthalmia., Here we show that haploinsufficiency of Meis1, which encodes a transcription factor with evolutionarily conserved expression in the embryonic trunk, brain and sensory organs, including the eye, causes microphthalmic traits and visual impairment in adult mice., We propose that Meis1 is at the core of a genetic network implicated in eye patterning/microphthalmia, and represents an additional candidate for syndromic cases of these ocular malformations., We propose that Meis1 is at the core of a genetic network implicated in eye patterning/microphthalmia, and represents an additional candidate for syndromic cases of these ocular malformations., In the eye primordium, Meis1 coordinates, in a dose-dependent manner, retinal proliferation and differentiation by regulating genes responsible for human microphthalmia and components of the Notch signaling pathway., Meis1 coordinates a network of genes implicated in eye development and microphthalmia, We propose that Meis1 is at the core of a genetic network implicated in eye patterning/microphthalmia, and represents an additional candidate for syndromic cases of these ocular malformations. <CopyrightInformation>© 2015, In the eye primordium, Meis1 coordinates, in a dose-dependent manner, retinal proliferation and differentiation by regulating genes responsible for human microphthalmia and components of the Notch signaling pathway, We propose that Meis1 is at the core of a genetic network implicated in eye patterning/microphthalmia, and represents an additional candidate for syndromic cases of these ocular malformations. <CopyrightInformation>© 2015., In the eye primordium, Meis1 coordinates, in a dose-dependent manner, retinal proliferation and differentiation by regulating genes responsible for human microphthalmia and components of the Notch signaling pathway., Meis1 coordinates a network of genes implicated in eye development and microphthalmia.[SEP]Microphthalmia has relations with HMX1, TENM3, RBP4, CRB1, and BEST1. Microphthalmia can also have relations with CRB2 and RBP3.", "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] progressive supranuclear palsy has relations: disease_phenotype_positive with Parkinsonism with favorable response to dopaminergic medication, disease_disease with suprinuclear oculomotor palsy, disease-diseases with syndromic disease, and disease-phenotype-positive with Neuromuscular dysphagia. Relations: disease phenotype positive with Retrocollis.", "label": "yes"}
{"id": "converted_1519", "sentence1": "Does nifedipine inhibit L-type calcium channels?", "sentence2": "Nifedipine, an L-type calcium channel blocker, reduced the expression of synaptogamin and syntaxin and blocked the suppressive effect of vecuronium, suggesting that both agents inhibit presynaptic L-type calcium channels., Treatment with nifedipine to inhibit calcium influx via the L-type channel Cav1.2 (alpha(1C)) inhibited the TGFbeta stimulated increase in ANK expression at all phases of chondrogenesis., Finally, we found that PKCepsilon-induced stellation was significantly reduced by the specific L-type channel blocker nifedipine, indicating that calcium influx through VGCC mediates the change in astrocyte morphology induced by PKCepsilon., However, APV and nifedipine, an inhibitor of L-type calcium channels, failed to inhibit LTP when administered following the slow increase in ethanol., Both the metallic ions Cd2+ and Ni2+, known to inhibit voltage-gated calcium channels and T-type channels, respectively, and verapamil and nifedipine, typical blocker of L-type calcium channels completely prevented the hypoxic neuronal NO generation., Further, the L-type calcium channel blocker, nifedipine, was able to inhibit the initial increase in [Ca2+]i, suggesting that at least this phase of the TMT effect was mediated by calcium channels, although nifedipine had no significant effect on the time to reach the maximal [Ca2+]i level, Treatment with omega-conotoxin GVIA (3 microM) or nifedipine (10 microM) to inhibit Ca(2+) influx through N- or L-type voltage-dependent calcium channels (VDCCs), respectively, also decreased the rate of AP repolarization and increased AP duration, Concentrations of nifedipine (10 microM) and nimodipine (3 microM) that maximally inhibit L-type calcium channels reduced the sI(AHP) by 30 and 50%, respectively, Consequently, it was demonstrated in the present study that nimodipine and nitrendipine inhibit both L- and N-type calcium channels and thus seem to be unique among the dihydropyridines examined in their effects on calcium channels in dibutyryl cAMP-differentiated neuroblastoma x glioma hybrid NG 108-15 cells, whereas nifedipine and niguldipine appear to block mainly L-type calcium channels, However, APV and nifedipine, an inhibitor of L-type calcium channels, failed to inhibit LTP when administered following the slow increase in ethanol, Calcium-channel antagonists, omega-conotoxin GVIA (omega-CgTx GVIA; N-type), nifedipine (L-type), and omega-conotoxin MVIIC (omega-CmTx MVIIC; P/Q type), were used to characterize the voltage-operated Ca(2+) channels (VOCCs) involved in this release, The T- and L-type calcium channel blocker (CCB) mibefradil attenuates leg edema induced by the L-type CCB nifedipine in the spontaneously hypertensive rat: a novel differentiating assay., L-type calcium channel antagonist nifedipine reduces neurofilament restitution following traumatic optic nerve injury., Nifedipine, an L-type calcium channel blocker, restores the hypnotic response in rats made tolerant to the alpha-2 adrenergic agonist dexmedetomidine., Comparison of L-type calcium channel blockade by nifedipine and/or cadmium in guinea pig ventricular myocytes., Nifedipine inhibits picrotoxin-induced seizure activity: further evidence on the involvement of L-type calcium channel blockers in epilepsy.[SEP]Relations: Nifedipine has relations: drug_drug with Calcium, drug_drug with Calcium, drug_drug with Calcium chloride, drug_drug with Calcium chloride, drug_drug with Calcium cation, drug_drug with Calcium cation, drug_drug with Calcium levulinate, drug_drug with Calcium levulinate, drug_drug with Calcium acetate, drug_drug with Calcium acetate.", "label": "yes"}
{"id": "converted_3900", "sentence1": "Are Toll-like receptors (TLRs) induced by microbes?", "sentence2": "The C-type lectin receptor CLEC4E and Toll-like receptor TLR4 expressed by host cells are among the first line of defense in encountering pathogens., Gram-negative bacteria and endogenous molecules coordinate to trigger inflammatory cascades via Toll-like receptor 4 to induce excessive expression of cytokines such as tumor necrosis factor-α and to activate NLRP3 inflammasome, a multiprotein complex that processes pro-interleukin-1β into its mature form. , During viral infection, viral nucleic acids are detected by virus sensor proteins including toll-like receptor 3 or retinoic acid-inducible gene I-like receptors (RLRs) in mammalian cells. , Toll-like receptor 9 (TLR9) activation is attributed to delivery of bacterial DNA, We determine that HBCs have the capacity to play a defensive role, where they are responsive to Toll-like receptor stimulation and are microbicidal.[SEP]Toll-like receptor 2 protein complex has relations: cellcomp_protein with TLR1, cellcomp protein with TLR1 and cellcomp  protein with TTLR2. Toll-like receptor 1-Toll like receptor 2 protein complex also has relations with toll receptors 1 and 2.", "label": "yes"}
{"id": "converted_3965", "sentence1": "Is co-loss of BRCA2-RB1 associated with better prognosis for prostate cancer patients?", "sentence2": "In human prostate cancer cell lines (LNCaP and LAPC4), loss of BRCA2 leads to the castration-resistant phenotype. Co-loss of BRCA2-RB1 in human prostate cancer cells induces an epithelial-to-mesenchymal transition, which is associated with invasiveness and a more aggressive disease phenotype. Importantly, PARP inhibitors attenuate cell growth in human mCRPC-derived organoids and human CRPC cells harboring single-copy loss of both genes.CONCLUSIONS: Our findings suggest that early identification of this aggressive form of prostate cancer offers potential for improved outcomes with early introduction of PARP inhibitor-based therapy.[SEP] benign neoplasm of prostate has relations with prostatic adenoma, fibroma of prostate, prostate leiomyoma, and benign prostate phyllodes tumor. Disease_disease with prostate neoplasm has relations with prostatic adenoma, fibroma of prostate, and prostate leiomy oma.", "label": "no"}
{"id": "converted_711", "sentence1": "Do proton pump inhibitors affect thyroxine absorption?", "sentence2": "Proton-pump inhibitors, antacids and a long list of drugs may decrease thyroxine absorption, Many commonly used drugs, such as bile acid sequestrants, ferrous sulphate, sucralfate, calcium carbonate, aluminium-containing antacids, phosphate binders, raloxifene and proton-pump inhibitors, have also been shown to interfere with the absorption of levothyroxine., Pantoprazole did not influence endocrine function in healthy male volunteers during short-term treatment., PPIs should be added to the list of medications affecting the level of thyroid hormone in patients with hypothyroidism treated with LT4 replacement. Patients with hypothyroidism and normal TSH values during LT4 replacement therapy may need additional thyroid function testing after treatment with PPIs and may need adjustment of their LT4 dose.[SEP]Pantoprazole has relations: drug_effect with Thrombophlebitis, drug-effect with Nocturia. Raloxifene has relations with ThROMbocytopenia, drug effect with Albuminuria. Pantoprazol has relations with Thrombocy topenia and Alzheimer's disease.", "label": "yes"}
{"id": "converted_502", "sentence1": "Is Mycobacterium avium less susceptible to antibiotics than Mycobacterium tuberculosis?", "sentence2": "The prevalence of MAC lung infection in two inner city hospitals was four times higher than that of TB., Most patients with combined infection were clinically consistent with MTB and responded to anti MTB treatment alone., The triplex PCR developed by us could be used to detect and differentiate M. tuberculosis, M. avium and other mycobacteria in a single reaction tube., Twelve (15%) of the 80 blood cultures were positive for mycobacteria, with Mycobacterium avium being identified in 7 (8.8%) samples and M. tuberculosis in 5 (6.2%). , The antimycobacterial activities of RS-112997, RS-124922 and RS-118641, three capuramycin analogues that inhibit phospho-N-acetylmuramyl-pentapeptide translocase, were tested against clinical isolates of Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium intracellulare, The MIC50/90 (mg/L) results for RS-118641 were: M. tuberculosis, 1/2; multidrug-resistant (MDR) M. tuberculosis, 0.5/2; M. avium, 4/8; and M. intracellulare, 0.06/0.5, These results suggest that capuramycin analogues exhibit strong antimycobacterial potential and should be considered for further evaluation in the treatment of M. tuberculosis and M. avium-M. intracellulare complex infections in humans., Mycobacterium avium causes disseminated infection in patients with acquired immune deficiency syndrome., Overall incidences of Mycobacterium tuberculosis (TB) and Mycobacterium avium complex (MAC) were 0.8 and 1.4 cases/100 person-years of follow-up (PYF), decreasing from 1.8 (TB) and 3.5 cases/100 PYF (MAC) before September 1995 to 0.3 and 0.2 cases/100 PYF after March 1997., Because M tuberculosis disease is preventable and curable and yet communicable, physicians should maintain a high degree of suspicion for tuberculosis in HIV-infected adults. In comparison, the goal of treating M avium complex in patients with advanced HIV disease is to reduce constitutional symptoms and improve survival., MAC pulmonary disease should be considered in the differential diagnosis of SPNs, even when encountered in geographic regions with a high prevalence of pulmonary tuberculosis., From April 2001 to February 2002, 80 blood samples from patients who were suspected to have disseminated mycobacterial infection, presenting fever and (preferably) a CD4 T cell count<100.0 cell/mL were investigated, IL-10 underlies distinct susceptibility of BALB/c and C57BL/6 mice to Mycobacterium avium infection and influences efficacy of antibiotic therapy., Clinical utility of rifabutin 1 (RBT), a potent antibiotic used in multidrug regimens for tuberculosis (TB) as well as for infections caused by Mycobacterium avium complex (MAC), has been hampered due to dose-limiting toxicity. , Effective therapeutic regimens exist that are limited by the emergence of drug resistance and the inability of antibiotics to kill dormant organisms. , Clinical utility of rifabutin 1 (RBT), a potent antibiotic used in multidrug regimens for tuberculosis (TB) as well as for infections caused by Mycobacterium avium complex (MAC), has been hampered due to dose-limiting toxicity., a potent antibiotic used in multidrug regimens for tuberculosis (TB) as well as for infections caused by Mycobacterium avium complex (MAC),, Clinical utility of rifabutin 1 (RBT), a potent antibiotic used in multidrug regimens for tuberculosis (TB) as well as for infections caused by Mycobacterium avium complex (MAC), has been hampered due to dose-limiting toxicity., tuberculosis appear to have different genetic mechanisms for resisting the effects of these antibiotics, with pks12 playing a relatively more significant role in MAC.[SEP]Relations: tuberculosis has relations: disease_disease with mycobacterial infectious disease, disease_disease with mycobacterial infectious disease, disease_disease with tuberculosis, avian, disease_disease with tuberculosis, avian. mycobacterium avium complex disease has relations: disease_disease with mycobacterial infectious disease, disease_disease with mycobacterial infectious disease, disease_disease with primary bacterial infectious disease, disease_disease with primary bacterial infectious disease. Recurrent mycobacterium avium complex infections has relations: disease_phenotype_positive with monocytopenia with susceptibility to infections, disease_phenotype_positive with monocytopenia with susceptibility to infections.", "label": "yes"}
{"id": "converted_2602", "sentence1": "Is Rucaparib effective for ovarian cancer?", "sentence2": "INTERPRETATION: In patients with BRCA mutant or BRCA wild-type and LOH high platinum-sensitive ovarian carcinomas treated with rucaparib, progression-free survival was longer than in patients with BRCA wild-type LOH low carcinomas., High LOH is associated with response to the PARP inhibitor rucaparib in BRCA wild-type ovarian cancer., Rucaparib Approved for Ovarian Cancer., The FDA approved the PARP inhibitor rucaparib to treat women with advanced ovarian cancer who have already been treated with at least two chemotherapies and have a BRCA1 or BRCA2 gene mutation identified by an approved companion diagnostic test., Rucaparib (Rubraca™) is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor being developed by Clovis Oncology, Inc. (Boulder, CO, USA) for the treatment of solid tumours. It has been approved in the USA as monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies. , In 2016, the US Food and Drug Administration approved three novel drugs for the treatment of solid malignancies-olaratumab in selected patients with soft-tissue sarcoma, atezolizumab for the treatment of bladder cancer, and rucaparib for the treatment of ovarian cancer; also in 2016, the use of previously approved anticancer agents (including atezolizumab) was expanded into 11 new patient populations. , Conclusions:Rucaparib was tolerable and had activity in patients with platinum-sensitive germlineBRCA1/2-mutated HGOC., <b>OBJECTIVE</b>: To review the pharmacology, safety, efficacy, and the role of rucaparib in the treatment of relapsed, advanced ovarian cancer.<br><b>SUMMARY</b>: A total of 2 phase I/II trials and 1 phase II trial have evaluated the safety and efficacy of oral rucaparib in ovarian cancer., Rucaparib was found to be relatively well tolerated in clinical trials, with the most common adverse events being anemia, fatigue, and nausea.<br><b>CONCLUSION</b>: Rucaparib appears to be a safe and effective new option in the treatment of relapsed, advanced BRCA1/2 mutant ovarian cancer., In patients with deleterious BRCA1/2 mutation, an overall response rate of 80% was achieved in the phase II trial Assessment of Rucaparib in Ovarian CancEr Trial 2 (ARIEL2)., This article summarizes the milestones in the development of rucaparib leading to this first approval for ovarian cancer.<br>, These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer.<br>, Rucaparib: a Poly(ADP-Ribose) Polymerase Inhibitor for BRCA-Mutated Relapsed Ovarian Cancer., CONCLUSION Rucaparib appears to be a safe and effective new option in the treatment of relapsed, advanced BRCA1/2 mutant ovarian cancer., These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer., Rucaparib received US FDA Breakthrough Therapy designation for treatment of platinum-sensitive BRCA-mutated advanced ovarian cancer patients who received greater than two lines of platinum-based therapy., BACKGROUND Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity., Rucaparib appears to be a safe and effective new option in the treatment of relapsed, advanced BRCA1/2 mutant ovarian cancer., Rucaparib: A Poly(ADP-Ribose) Polymerase Inhibitor for BRCA-Mutated Relapsed Ovarian Cancer., Rucaparib: the past, present, and future of a newly approved PARP inhibitor for ovarian cancer., FDA Approval Summary: Rucaparib for the Treatment of Patients with Deleterious BRCA Mutation-Associated Advanced Ovarian Cancer., Olaparib and rucaparib have been approved by the US FDA as monotherapy for advanced recurrent ovarian cancer.[SEP]Relations: Rucaparib has relations: drug_drug with Lobucavir, drug_drug with Lobucavir, drug_drug with Estradiol, drug_drug with Estradiol, drug_drug with Capsaicin, drug_drug with Capsaicin, drug_drug with Olaparib, drug_drug with Olaparib, drug_drug with Lopinavir, drug_drug with Lopinavir.", "label": "yes"}
{"id": "converted_2140", "sentence1": "Is it feasible to obtain DNA read lengths that exceed 30 Kb?", "sentence2": "Single-molecule, real-time sequencing (SMRT) developed by Pacific BioSciences produces longer reads than secondary generation sequencing technologies such as Illumina. The long read length enables PacBio sequencing to close gaps in genome assembly, reveal structural variations, and identify gene isoforms with higher accuracy in transcriptomic sequencing.,  Third-generation sequencing, with read lengths>10 kb, will improve the assembly of complex genomes, but these techniques require high-molecular-weight genomic DNA (gDNA), and gDNA extraction protocols used for obtaining smaller fragments for short-read sequencing are not suitable for this purpose., The emergence and development of so called third generation sequencing platforms such as PacBio has permitted exceptionally long reads (over 20 kb) to be generated.[SEP]", "label": "no"}
{"id": "converted_1644", "sentence1": "Is Calcium/Calmodulin dependent protein kinase II (CaMKII) involved in cardiac arrhythmias and heart failure?", "sentence2": "In human hypertrophy, both CaMKII and PKA functionally regulate RyR2 and may induce SR Ca(2+) leak. In the transition from hypertrophy to HF, the diastolic Ca(2+) leak increases and disturbed Ca(2+) cycling occurs. This is associated with an increase in CaMKII- but not PKA-dependent RyR2 phosphorylation. CaMKII inhibition may thus reflect a promising therapeutic target for the treatment of arrhythmias and contractile dysfunction., Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is an enzyme with important regulatory functions in the heart and brain, and its chronic activation can be pathological. CaMKII activation is seen in heart failure, and can directly induce pathological changes in ion channels, Ca(2+) handling and gene transcription., In the recent years, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) was suggested to be associated with cardiac hypertrophy and heart failure but also with arrhythmias both in animal models as well as in the human heart., Calcium-calmodulin-dependent protein kinase II (CaMKII) has emerged as a central mediator of cardiac stress responses which may serve several critical roles in the regulation of cardiac rhythm, cardiac contractility and growth. Sustained and excessive activation of CaMKII during cardiac disease has, however, been linked to arrhythmias, and maladaptive cardiac remodeling, eventually leading to heart failure (HF) and sudden cardiac death. , Overexpression of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in transgenic mice results in heart failure and arrhythmias., From recent studies, it appears evident that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a central role in the arrhythmogenic processes in heart failure by sensing intracellular Ca(2+) and redox stress, affecting individual ion channels and thereby leading to electrical instability in the heart. , CaMKII activation is proarrhythmic in heart failure where myocardium is stretched., The Ca-calmodulin dependent kinase II (CaMKII) seems to be involved in the development of heart failure and arrhythmias and may therefore be a promising target for the development of antiarrhythmic therapies., Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is up-regulated in heart failure and has been shown to cause I(Na) gating changes that mimic those induced by a point mutation in humans that is associated with combined long QT and Brugada syndromes., CaMKII-dependent phosphorylation of Na(V)1.5 at multiple sites (including Thr-594 and Ser-516) appears to be required to evoke loss-of-function changes in gating that could contribute to acquired Brugada syndrome-like effects in heart failure., Because CaMKII expression and activity are increased in cardiac hypertrophy, heart failure, and during arrhythmias both in animal models as well as in the human heart a clinical significance of CaMKII is implied., The multifunctional Ca(2+)- and calmodulin-dependent protein kinase II (CaMKII) is now recognized to play a central role in pathological events in the cardiovascular system. CaMKII has diverse downstream targets that promote vascular disease, heart failure, and arrhythmias, so improved understanding of CaMKII signaling has the potential to lead to new therapies for cardiovascular disease., In our opinion, the multifunctional Ca and calmodulin-dependent protein kinase II (CaMKII) has emerged as a molecule to watch, in part because a solid body of accumulated data essentially satisfy Koch's postulates, showing that the CaMKII pathway is a core mechanism for promoting myocardial hypertrophy and heart failure. Multiple groups have now confirmed the following: (1) that CaMKII activity is increased in hypertrophied and failing myocardium from animal models and patients; (2) CaMKII overexpression causes myocardial hypertrophy and HF and (3) CaMKII inhibition (by drugs, inhibitory peptides and gene deletion) improves myocardial hypertrophy and HF,  In contrast, inhibiting the CaMKII pathway appears to reduce arrhythmias and improve myocardial responses to pathological stimuli. , In this review, we discuss the important role of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in the regulation of RyR2-mediated Ca(2+) release. In particular, we examine how pathological activation of CaMKII can lead to an increased risk of sudden arrhythmic death. Finally, we discuss how reduction of CaMKII-mediated RyR2 hyperactivity might reduce the risk of arrhythmias and may serve as a rationale for future pharmacotherapeutic approaches., Transgenic (TG) Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) δ(C) mice develop systolic heart failure (HF). CaMKII regulates intracellular Ca(2+) handling proteins as well as sarcolemmal Na(+) channels. We hypothesized that CaMKII also contributes to diastolic dysfunction and arrhythmias via augmentation of the late Na(+) current (late I(Na)) in early HF (8-week-old TG mice)., Thus, late I(Na) inhibition appears to be a promising option for diastolic dysfunction and arrhythmias in HF where CaMKII is found to be increased., We tested the hypothesis that increased RyR2 phosphorylation by Ca(2+)/calmodulin-dependent protein kinase II is both necessary and sufficient to promote lethal ventricular arrhythmias., CONCLUSIONS: our results suggest that Ca(2+)/calmodulin-dependent protein kinase II phosphorylation of RyR2 Ca(2+) release channels at S2814 plays an important role in arrhythmogenesis and sudden cardiac death in mice with heart failure., Excessive activation of calmodulin kinase II (CaMKII) causes arrhythmias and heart failure, but the cellular mechanisms for CaMKII-targeted proteins causing disordered cell membrane excitability and myocardial dysfunction remain uncertain., Transgenic (TG) Ca/calmodulin-dependent protein kinase II (CaMKII)delta(C) mice have heart failure and isoproterenol (ISO)-inducible arrhythmias. We hypothesized that CaMKII contributes to arrhythmias and underlying cellular events and that inhibition of CaMKII reduces cardiac arrhythmogenesis in vitro and in vivo., We conclude that CaMKII contributes to cardiac arrhythmogenesis in TG CaMKIIdelta(C) mice having heart failure and suggest the increased SR Ca leak as an important mechanism. Moreover, CaMKII inhibition reduces cardiac arrhythmias in vitro and in vivo and may therefore indicate a potential role for future antiarrhythmic therapies warranting further studies., Ca2+/calmodulin dependent protein kinase II (CaMKII) can phosphorylate RyR2 and modulate its activity. This phosphorylation positively modulates cardiac inotropic function but in extreme situations such as heart failure, elevated CaMKII activity can adversely increase Ca2+ release from the SR and lead to arrhythmogenesis. , Calcium/calmodulin-dependent kinase II (CaMKII) is a multifunctional serine/threonine kinase expressed abundantly in the heart. CaMKII targets numerous proteins involved in excitation-contraction coupling and excitability, and its activation may simultaneously contribute to heart failure and cardiac arrhythmias., Under stress conditions, excessive CaMKII activity promotes heart failure and arrhythmias, in part through actions at Ca(2+) homeostatic proteins., Ca-calmodulin-dependent protein kinase II (CaMKII) was recently shown to alter Na(+) channel gating and recapitulate a human Na(+) channel genetic mutation that causes an unusual combined arrhythmogenic phenotype in patients: simultaneous long QT syndrome and Brugada syndrome. CaMKII is upregulated in heart failure where arrhythmias are common, and CaMKII inhibition can reduce arrhythmias. Thus, CaMKII-dependent channel modulation may contribute to acquired arrhythmic disease. , In heart failure (HF), Ca(2+)/calmodulin kinase II (CaMKII) expression is increased. Altered Na(+) channel gating is linked to and may promote ventricular tachyarrhythmias (VTs) in HF. Calmodulin regulates Na(+) channel gating, in part perhaps via CaMKII., Thus, CaMKII-dependent regulation of Na(+) channel function may contribute to arrhythmogenesis in HF., Recent findings that CaMKII expression in the heart changes during hypertrophy, heart failure, myocardial ischemia, and infarction suggest that CaMKII may be a viable therapeutic target for patients suffering from common forms of heart disease.,  Overexpression of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in transgenic mice results in heart failure and arrhythmias., Transgenic (TG) Ca/calmodulin-dependent protein kinase II (CaMKII)delta(C) mice have heart failure and isoproterenol (ISO)-inducible arrhythmias., BACKGROUND: Transgenic (TG) Ca/calmodulin-dependent protein kinase II (CaMKII)delta(C) mice have heart failure and isoproterenol (ISO)-inducible arrhythmias., CaMKII targets numerous proteins involved in excitation-contraction coupling and excitability, and its activation may simultaneously contribute to heart failure and cardiac arrhythmias., Calcium/calmodulin-dependent protein kinase II contributes to cardiac arrhythmogenesis in heart failure., From recent studies, it appears evident that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a central role in the arrhythmogenic processes in heart failure by sensing intracellular Ca(2+) and redox stress, affecting individual ion channels and thereby leading to electrical instability in the heart., Ryanodine receptor phosphorylation, calcium/calmodulin-dependent protein kinase II, and life-threatening ventricular arrhythmias., CaMKII targets numerous proteins involved in excitation-contraction coupling and excitability, and its activation may simultaneously contribute to heart failure and cardiac arrhythmias, The Ca-calmodulin dependent kinase II (CaMKII) seems to be involved in the development of heart failure and arrhythmias and may therefore be a promising target for the development of antiarrhythmic therapies, Calcium-calmodulin kinase II mediates digitalis-induced arrhythmias., Transgenic (TG) Ca/calmodulin-dependent protein kinase II (CaMKII)delta(C) mice have heart failure and isoproterenol (ISO)-inducible arrhythmias[SEP]Relations: calcium- and calmodulin-dependent protein kinase complex has relations: cellcomp_protein with CAMK2A, cellcomp_protein with CAMK2A, cellcomp_protein with CAMK2D, cellcomp_protein with CAMK2D, cellcomp_protein with CAMK2B, cellcomp_protein with CAMK2B, cellcomp_protein with CAMK2G, cellcomp_protein with CAMK2G, cellcomp_protein with CAMK1G, cellcomp_protein with CAMK1G.", "label": "yes"}
{"id": "converted_1402", "sentence1": "Are there Conserved Noncoding Elements (CNEs) in plant genomes?", "sentence2": "Conservation and functional element discovery in 20 angiosperm plant genomes, The detailed view of conservation across angiosperms revealed not only high coding-sequence conservation but also a large set of previously uncharacterized intergenic conservation, Conserved noncoding sequences highlight shared components of regulatory networks in dicotyledonous plants, Using a comparative genomics approach with four dicotyledonous plant species (Arabidopsis thaliana, papaya [Carica papaya], poplar [Populus trichocarpa], and grape [Vitis vinifera]), we detected hundreds of CNSs upstream of Arabidopsis genes, Long identical multispecies elements in plant and animal genomes., Using an alignment-free information-retrieval approach, we have comprehensively identified all long identical multispecies elements (LIMEs), which include both syntenic and nonsyntenic regions, of at least 100 identical base pairs shared by at least two genomes, In contrast, among six plant genomes, we only found nonsyntenic LIMEs,  Although complex LIMEs were found in both animal and plant genomes, they differed significantly in their composition and copy number, Ultraconserved elements between the genomes of the plants Arabidopsis thaliana and rice, We consequently compared the genomes of Arabidopsis thaliana and rice, which diverged about 200 million years ago, and identified 25 ultraconserved elements that are longer than 100 bp, ultraconserved elements in plants tend to occur in clusters and locate at noncoding regions, the functions of these plant ultraconserved elements and the reasons why they are practically frozen during the evolution of millions of years remain a mystery, Conserved noncoding sequences in the grasses,  Using a local sequence alignment set to deliver only significant alignments, we found one or more CNSs in the noncoding regions of the majority of genes studied. Grass genes have dramatically fewer and much smaller CNSs than mammalian genes, Conserved noncoding sequences among cultivated cereal genomes identify candidate regulatory sequence elements and patterns of promoter evolution, Surveys for conserved noncoding sequences (CNS) among genes from monocot cereal species were conducted to assess the general properties of CNS in grass genomes and their correlation with known promoter regulatory elements, Comparisons of orthologous maize-rice and maize-sorghum gene pairs identified 20 bp as a minimal length criterion for a significant CNS among grass genes, with few such CNS found to be conserved across rice, maize, sorghum, and barley[SEP]Relations: central nervous system has relations: anatomy_protein_present with NONO, anatomy_protein_present with NONO, anatomy_protein_present with CNP, anatomy_protein_present with CNP, anatomy_protein_present with CNBP, anatomy_protein_present with CNBP, anatomy_protein_present with CNPPD1, anatomy_protein_present with CNPPD1, anatomy_protein_present with CNR1, anatomy_protein_present with CNR1.", "label": "yes"}
{"id": "converted_2801", "sentence1": "Is ibudilast effective for multiple sclerosis?", "sentence2": "Ibudilast slowed brain atrophy in PPMS and SPMS patients in a multicenter phase 2b study.,  Ibudilast inhibits several cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and toll-like receptor 4 and can cross the blood-brain barrier, with potential salutary effects in progressive multiple sclerosis., CONCLUSIONS: In a phase 2 trial involving patients with progressive multiple sclerosis, ibudilast was associated with slower progression of brain atrophy than placebo but was associated with higher rates of gastrointestinal side effects, headache, and depression., Specifically, the current evidence regarding treatment of progressive MS with ocrelizumab, simvastatin, ibudilast, alpha-lipoic acid, high-dose biotin, siponimod, and cell-based therapies are discussed., Based on our knowledge of pathophysiology, three therapeutic strategies are proposed: anti-inflammatory (ocrelizumab, siponimod…); remyelinating (opicinumab); and neuroprotective (high-dose biotin, ibudilast, simvastatin…). , Current article provides an overview of the pharmacology of IBD with a focus on preclinical and clinical data supporting its potential neuroprotective benefits for neurological conditions, including multiple sclerosis, neuropathic pain, medication overuse headache, stroke, opioid, alcohol and methamphetamine abuse., Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis., METHODS: SPRINT-MS is a randomized, placebo-controlled, phase II trial of ibudilast in patients with PMS., CONCLUSION: SPRINT-MS is designed to evaluate the safety and efficacy of ibudilast as a treatment for PMS while simultaneously validating five different imaging biomarkers as outcome metrics for use in future phase II proof-of-concept PMS trials., Ibudilast for the treatment of multiple sclerosis., AREAS COVERED: This article reviews various studies looking at ibudilast as a potential therapy for MS. It summarizes prior and current clinical trials of ibudilast in MS as well as its pharmacology.EXPERT OPINION: Although ibudilast has not been found to decrease the focal inflammatory activity in relapsing MS, it was shown to have an effect on preserving brain volume and disability progression. Ibudilast may have a role in the treatment of progressive MS phenotypes., Adverse events with ibudilast included gastrointestinal symptoms, headache, and depression.<br><b>CONCLUSIONS</b>: In a phase 2 trial involving patients with progressive multiple sclerosis, ibudilast was associated with slower progression of brain atrophy than placebo but was associated with higher rates of gastrointestinal side effects, headache, and depression., It summarizes prior and current clinical trials of ibudilast in MS as well as its pharmacology.<br><b>EXPERT OPINION</b>: Although ibudilast has not been found to decrease the focal inflammatory activity in relapsing MS, it was shown to have an effect on preserving brain volume and disability progression.[SEP]Relations: Ibudilast has relations: drug_drug with SC-236, drug_drug with SC-236, drug_drug with Iloprost, drug_drug with Iloprost, drug_drug with Pirlindole, drug_drug with Pirlindole, drug_drug with Metamizole, drug_drug with Metamizole, drug_drug with Epirizole, drug_drug with Epirizole.", "label": "yes"}
{"id": "converted_1167", "sentence1": "Is COL5A2 gene associated to ischemic heart disease?", "sentence2": "Analysis of a gene co-expression network establishes robust association between Col5a2 and ischemic heart disease, Col5a2, a gene previously not specifically linked to MI response but responsible for the classic type of Ehlers-Danlos syndrome, was found to have many and strong co-expression associations within this community, Col5a2 shows predictive potential in MI, and in principle may represent a novel candidate marker for the identification and treatment of ischemic cardiovascular disease, Analysis of a gene co-expression network establishes robust association between Col5a2 and ischemic heart disease.[SEP]Myocardial ischemia has relations with ADM2, ADRB2, TMED2, RAB5A, APLP2 and RABL2. Myocardial myocardial  ischemic syndrome is a type of heart failure. The disease is caused by a lack of oxygen to the heart.", "label": "yes"}
{"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]Relations: Autosomal dominant inheritance has relations: disease_phenotype_positive with osteogenesis imperfecta, disease_phenotype_positive with osteogenesis imperfecta, disease_phenotype_positive with osteogenesis imperfecta with opalescent teeth, blue sclerae and wormian bones but without fractures, disease_phenotype_positive with osteogenesis imperfecta with opalescent teeth, blue sclerae and wormian bones but without fractures, disease_phenotype_positive with combined osteogenesis imperfecta and Ehlers-Danlos syndrome, disease_phenotype_positive with combined osteogenesis imperfecta and Ehlers-Danlos syndrome. osteogenesis imperfecta has relations: disease_phenotype_positive with Autosomal dominant inheritance, disease_phenotype_positive with Autosomal dominant inheritance, disease_phenotype_positive with Autosomal dominant inheritance, disease_phenotype_positive with Autosomal dominant inheritance.", "label": "yes"}
{"id": "converted_3459", "sentence1": "Is the protein ABCG2 transmembrane?", "sentence2": "the transmembrane ATP-binding cassette transporter G2, ATP-binding cassette (ABC) transporters are transmembrane efflux transporters mediating the extrusion of an array of substrates ranging from amino acids and lipids to xenobiotics, and many therapeutic compounds, including anticancer drugs., The ATP-binding cassette (ABC) transporter family is a large class of ATP energy-dependent transmembrane proteins[SEP]Adenosine phosphate has relations with PRKAG2 and PRKAB2. It also relations with ACSS2, ACSS1 and ACSS3. It is also related to PRK AG1, PRAG1 and PRAG2.", "label": "yes"}
{"id": "converted_4263", "sentence1": "Is FTY720 FDA approved?", "sentence2": "FTY720 (Fingolimod) is a known sphingosine-1-phosphate (S1P) receptor agonist that exerts strong anti-inflammatory effects and was approved as the first oral drug for the treatment of multiple sclerosis by the US Food and Drug Administration (FDA) in 2010. [SEP]Fingolimod has relations with WIN 55212-2, G17DT, Octreotide, mRNA-1273 and S1PR5. It is not known if it has a relationship with the drug sildenafil.", "label": "yes"}
{"id": "converted_49", "sentence1": "Are ultraconserved elements often transcribed?", "sentence2": "Starting from a genome-wide expression profiling, we demonstrate for the first time a functional link between oxygen deprivation and the modulation of long noncoding transcripts from ultraconserved regions, termed transcribed-ultraconserved regions (T-UCRs), Our data gives a first glimpse of a novel functional hypoxic network comprising protein-coding transcripts and noncoding RNAs (ncRNAs) from the T-UCRs category, Highly conserved elements discovered in vertebrates are present in non-syntenic loci of tunicates, act as enhancers and can be transcribed during development, The majority of these regions map onto ultraconserved elements and we demonstrate that they can act as functional enhancers within the organism of origin, as well as in cross-transgenesis experiments, and that they are transcribed in extant species of Olfactores. We refer to the elements as 'Olfactores conserved non-coding elements', We used a custom microarray to assess the levels of UCE transcription during mouse development and integrated these data with published microarray and next-generation sequencing datasets as well as with newly produced PCR validation experiments. We show that a large fraction of non-exonic UCEs is transcribed across all developmental stages examined from only one DNA strand. Although the nature of these transcripts remains a mistery, our meta-analysis of RNA-Seq datasets indicates that they are unlikely to be short RNAs and that some of them might encode nuclear transcripts, Our data shows that the concurrent presence of enhancer and transcript function in non-exonic UCE elements is more widespread than previously shown. Moreover through our own experiments as well as the use of next-generation sequencing datasets, we were able to show that the RNAs encoded by non-exonic UCEs are likely to be long RNAs transcribed from only one DNA strand, Short ultraconserved promoter regions delineate a class of preferentially expressed alternatively spliced transcripts, The importance of other classes of non-coding RNAs, such as long intergenic ncRNAs (lincRNAs) and transcribed ultraconserved regions (T-UCRs) as altered elements in neoplasia, is also gaining recognition., Other ncRNAs, such as PIWI-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), transcribed ultraconserved regions (T-UCRs) and large intergenic non-coding RNAs (lincRNAs) are emerging as key elements of cellular homeostasis., The majority of these regions map onto ultraconserved elements and we demonstrate that they can act as functional enhancers within the organism of origin, as well as in cross-transgenesis experiments, and that they are transcribed in extant species of Olfactores., Transcribed ultraconserved regions (T-UCRs) are a subset of 481 sequences longer than 200 bp, which are absolutely conserved between orthologous regions of human, rat and mouse genomes, and are actively transcribed., Highly conserved elements discovered in vertebrates are present in non-syntenic loci of tunicates, act as enhancers and can be transcribed during development., The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator., In this report, we show that the Dlx-5/6 ultraconserved region is transcribed to generate an alternatively spliced form of Evf-1, the ncRNA Evf-2., These studies identify a critical role for TUC338 in regulation of transformed cell growth and of transcribed ultraconserved ncRNA as a unique class of genes involved in the pathobiology of HCC., Transcribed ultraconserved region (T-UCR) transcripts are a novel class of lncRNAs transcribed from ultraconserved regions (UCRs), The majority of these regions map onto ultraconserved elements and we demonstrate that they can act as functional enhancers within the organism of origin, as well as in cross-transgenesis experiments, and that they are transcribed in extant species of Olfactores, Transcribed ultraconserved regions (T-UCRs) are a subset of 481 sequences longer than 200 bp, which are absolutely conserved between orthologous regions of human, rat and mouse genomes, and are actively transcribed, Other ncRNAs, such as PIWI-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), transcribed ultraconserved regions (T-UCRs) and large intergenic non-coding RNAs (lincRNAs) are emerging as key elements of cellular homeostasis, Transcribed ultraconserved region in human cancers., We show that a large fraction of non-exonic UCEs is transcribed across all developmental stages examined from only one DNA strand, Although uc.338 is partially located within the poly(rC) binding protein 2 (PCBP2) gene, the transcribed ncRNA encoding uc.338 is expressed independently of PCBP2 and was cloned as a 590-bp RNA gene, termed TUC338, Moreover through our own experiments as well as the use of next-generation sequencing datasets, we were able to show that the RNAs encoded by non-exonic UCEs are likely to be long RNAs transcribed from only one DNA strand.[SEP]Relations: rRNA transcription has relations: bioprocess_protein with ANG, bioprocess_protein with ANG, bioprocess_bioprocess with plastid rRNA transcription, bioprocess_bioprocess with plastid rRNA transcription, bioprocess_bioprocess with mitochondrial rRNA transcription, bioprocess_bioprocess with mitochondrial rRNA transcription, bioprocess_bioprocess with ncRNA transcription, bioprocess_bioprocess with ncRNA transcription, bioprocess_bioprocess with nucleolar large rRNA transcription by RNA polymerase I, bioprocess_bioprocess with nucleolar large rRNA transcription by RNA polymerase I.", "label": "yes"}
{"id": "converted_1567", "sentence1": "Does low T3 negatively affect prognosis of patients after cardiac surgery?", "sentence2": "ur findings suggest that the development of LCOS after congenital heart surgery is associated with decreased total and free T3, and increased IL-8 levels at 48 hours, and preoperative tT4 level is an independent predictor of LCOS., Low basal fT3 concentration can reliably predict the occurrence of postoperative AF in CABG patients., A relevant finding was that the days of post-operative hospitalization (10+/-3 days, means+/-S.D.) was inversely correlated with the slope of the recovery of T3 concentration (P<0.001) or with the area under the plasma curves of T3 (P=0.024, time range 72-144 h) and the FT3/FT4 ratio (P=0.037, time range 72-144 h) during the post-operative period. [SEP]Interleukin-8 receptor activity has relations with molfunc_protein with CXCR2. Insect larval thoracic segments have relations with anatomy_anatomy with insect larval prothoracic segment, anatomy_Anatomy. with insect larvae metathoracics segment, and with insect mesothoracies segment. Insect larval mesothoraco segment has relations with insect larval prothoraco segment.", "label": "yes"}
{"id": "converted_4299", "sentence1": "Does αCGRP have amyloidogenic properties?", "sentence2": "αCGRP, another amyloidogenic member of the CGRP family., Therefore, in this work, we investigated the amyloidogenic profile of αCGRP, a 37-residue-long peptide hormone, utilizing both biophysical experimental techniques and Molecular Dynamics simulations. These efforts unravel a novel amyloidogenic member of the CGRP family and provide insights into the mechanism underlying the αCGRP polymerization.[SEP] neuropeptide hormone activity has relations with AVP, GRP, PRLH, NPPA, and GRP. Neuropeptic hormone activity can also have relations with PRH, PRP, and NPPA. The protein molfunc_protein can also be associated with the hormone AVP or AGRP. It can also associate with GRP or PRH.", "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]Bortezomib has relations with Protriptyline, Procarbazine, Progesterone, Probucol, and Hepatitis. It also has a negative effect on Hepatiti. It is not known if it has a positive effect on other drugs.", "label": "yes"}
{"id": "converted_673", "sentence1": "Does the protein mTOR regulate autophagy?", "sentence2": "autophagy is negatively regulated by the mammalian target of rapamycin receptor (mTOR), Subjecting cells to starvation or rapamycin efficiently induces autophagy by inhibiting the MTOR signaling pathway triggering increased autophagic flux. , Several pathways, including mTOR, have been shown to regulate autophagy., these results provide insights into the mechanism by which hyperactivation of mTORC1 promotes breast cancer progression through increasing autophagy and Akt activation in vivo.,  the canonical mTOR-controlled autophagy pathway, mTOR inhibition severely impairs liver regeneration and increases autophagy after PH, mTOR remains at a high level and inhibits autophagy., AKT is involved in granulosa cell autophagy regulation via mTOR signaling during rat follicular development and atresia., mammalian target of rapamycin (mTOR), a major negative regulator of autophagy., mTOR suppresses granulosa cell autophagy, Mammalian target of rapamycin (mTOR), a potent suppressor of autophagy,, The mTOR signaling pathway integrates inputs from a variety of upstream stimuli to regulate diverse cellular processes including proliferation, growth, survival, motility, autophagy, protein synthesis and metabolism, The activation of mammalian target of rapamycin (mTOR) signaling pathway blocks the effects of ghrelin-induced autophagy and apoptosis,,  inducing apoptosis and autophagy via the mTOR signaling pathway,  The mTOR gene regulates cell growth by controlling mRNA translation, ribosome biogenesis, autophagy, and metabolism.[SEP]Sirolimus has relations: drug_drug with Platelet Activating Factor, drug_ drug with Argatroban, drug-drug with Altrenogest. Protein S human has relations with drug_protein with MTOR and drug-protein withMTOR.", "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]Relations: adaptation to pheromone regulating conjugation with mutual genetic exchange has relations: bioprocess_bioprocess with negative adaptation of signaling pathway, bioprocess_bioprocess with negative adaptation of signaling pathway. Dexamethasone has relations: drug_effect with Poor appetite, drug_effect with Poor appetite, drug_effect with Growth delay, drug_effect with Growth delay, drug_effect with Anxiety, drug_effect with Anxiety. regulation of antisense RNA transcription has relations: bioprocess_bioprocess with negative regulation of antisense RNA transcription, bioprocess_bioprocess with negative regulation of antisense RNA transcription.", "label": "yes"}
{"id": "converted_909", "sentence1": "Does resveratrol reduce cardiac remodeling?", "sentence2": "In conclusion, resveratrol attenuated cardiac oxidative damage and left ventricular remodeling and enhanced the decreased expression of SIRT1 in hearts of old rats with emphysema and thus might be a therapeutic modality for cardiac injury complicated in chronic obstructive pulmonary disease (COPD)., In conclusion, resveratrol is a beneficial pharmacological tool that augments autophagy to bring about reverse remodeling in the postinfarction heart., Resveratrol administration reduced atrial CSPC loss, succeeded in preserving the functional abilities of CSPCs and mature cardiac cells, improved cardiac environment by reducing inflammatory state and decreased unfavorable ventricular remodeling of the diabetic heart, leading to a marked recovery of ventricular function. These findings indicate that RSV can constitute an adjuvant therapeutic option in DCM prevention.[SEP]Resveratrol has relations with Dipyridamole, Acenocoumarol, Tranilast, Antipyrine, Reteplase, and more. It is also in contact with the drug manufacturer, Bayer, which is responsible for the drug's development.", "label": "yes"}
{"id": "converted_1800", "sentence1": "Does Vitamin D induce  autophagy?", "sentence2": " 1,25(OH)2D treatment was accompanied by autophagy activation , Autophagy signaling pathway was regulated by vitamin D3, vitamin D induces autophagy, Vitamin D shows promise for the prevention and amelioration of pathologic responses in IBD, an effect that is mediated, at least in part, by the induction and modulation of autophagy.[SEP]Ergocalciferol has relations with drug_drug with Vitamin D and drug_protein with VDR. It is contraindication with familial isolated deficiency of vitamin E. It can also be used to treat vitamin D-deficiency. It's not recommended to use it to treat Vitamin E deficiency.", "label": "yes"}
{"id": "converted_46", "sentence1": "Are there web based self management strategies for chronic pain ?", "sentence2": "Fibromyalgia Symptom Reduction by Online Behavioral Self-monitoring, , This study aimed to evaluate effects of a web-based, self-monitoring and symptom management system (SMARTLog) that analyzes personal self-monitoring data and delivers data-based feedback over time., Moderate use (3 times weekly x 3 months) increased likelihood of clinically significant improvements in pain, memory, gastrointestinal problems, depression, fatigue, and concentration; heavy use (4.5 times weekly x five months) produced the above plus improvement in stiffness and sleep difficulties., Results suggest that the tailored online chronic pain management program showed promising effects on pain at 1 and 6 months posttreatment and quality of life at 6 months posttreatment in this naturalistic study., Results suggest the potential value of self-management for chronic pain patients and the potential acceptability of web-based delivery of intervention content., Patient involvement can be fostered by web-based applications combining health information with decision support or behaviour change support. These so-called Interactive Health Communication Applications (IHCAs) can reach great numbers of patients at low financial cost and provide information and support at the time, place and learning speed patients prefer., Web-based interventions may also be effective in enhancing self-management for individuals with chronic pain, but little is known about long-term effects. Research on Web-based interventions to support self-management following participation in pain management programs is limited. OBJECTIVE: The aim is to examine the long-term effects of a 4-week smartphone-intervention [SEP]Chronic pain has relations with Sjogren syndrome, Loeys-Dietz syndrome, Machado-Joseph disease, and glycogen storage disease. Disease_phenotype_positive with glycogen Storage Disease is a type of chronic pain. Chronic pain has Relations with Pain: phenotype with Pain and disease with Pain.", "label": "yes"}
{"id": "converted_1716", "sentence1": "Is the PTPN22 gene a biomarker for Rheumatoid Arthritis?", "sentence2": "Combined longitudinal analysis of the 2 cohorts suggests further association of several loci with Larsen score (KIF5A, PTPN22, AFF3, TAGAP) and therefore a significant accumulation of RA severity markers among RA susceptibility markers (p = 0.016), A non-intronic marker at TNFAIP3, GIN1/C5orf30, STAT4, ANKRD55/IL6ST, BLK and PTPN22 showed association with RA susceptibility, irrespective of the serological status, the latter three markers remaining significantly associated with anti-CCP negative RA, after correction for multiple testing, A C-to-T single nucleotide polymorphism (SNP) located at position 1858 of human PTPN22 cDNA and converting an arginine (R620) to tryptophan (W620) confers the highest risk of rheumatoid arthritis among non-HLA genetic variations that are known to be associated with this disease, TPN22 is a tyrosine phosphatase and functions as a damper of TCR signals. A C-to-T single nucleotide polymorphism (SNP) located at position 1858 of human PTPN22 cDNA and converting an arginine (R620) to tryptophan (W620) confers the highest risk of rheumatoid arthritis among non-HLA genetic variations that are known to be associated with this disease, In addition, how the overall activity of PTPN22 is regulated and how the R-to-W conversion contributes to rheumatoid arthritis is still poorly understood, Our data depict a model that can reconcile the conflicting observations on the functional impact of the C1858T SNP and also suggest that PTPN22.6 is a novel biomarker of rheumatoid arthritis., the level of PTPN22.6 in peripheral blood correlates with disease activity of rheumatoid arthritis, Lack of association of common variants in PTPN22 with RA in Han Chinese was confirmed, This study identifies MMEL1 and CTLA4 as RA susceptibility genes, provides suggestive evidence of association for a further six loci in the Han Chinese population and confirms lack of PTPN22 association in Asian populations, PTPN22 R620W genotype-phenotype correlation analysis and gene-environment interaction study in early rheumatoid arthritis: results from the ESPOIR cohort,  PTPN22 620W risk allele was associated with ACPA production [odds ratio (OR) = 2.21, 95% CI 1.4, 3.4, P < 0.0001], Hormonal treatment exposition and smoking were found to act with a protective effect against ACPA production (OR = 0.44, 95% CI 0.3, 0.7, P = 0.001) and early bone erosion (OR = 0.56, 95% CI 0.4-0.8, P = 0.003), respectively, and independently of HLADR and PTPN22 status,  RA patients (n=333) and controls (n=490) from the Cree/Ojibway NAN population in Central Canada were HLA-DRB1 typed and tested for 21 single-nucleotide polymorphisms (SNPs) that have previously been associated with RA, including PTPN22, TRAF1-C5, CTLA4, PADI4, STAT4, FCRL3, CCL21, MMEL1-TNFRSF14, CDK6, PRKCQ, KIF5A-PIP4K2C, IL2RB, TNFAIP3, IL10-1082G/A and REL, 21 single-nucleotide polymorphisms (SNPs) that have previously been associated with RA, including PTPN22, TRAF1-C5, CTLA4, PADI4, STAT4, FCRL3, CCL21, MMEL1-TNFRSF14, CDK6, PRKCQ, KIF5A-PIP4K2C, IL2RB, TNFAIP3, IL10-1082G/A and REL, Several other genes, including PTPN22 and PADI4, show modest association with RA, he HLA locus, particularly HLA-DRB1, is its strongest genetic risk determinant across ethnicities. Several other genes, including PTPN22 and PADI4, show modest association with RA. , Other variants in potentially pathogenic genes located in non-MHC regions have been implicated by recently performed genome wide analysis studies. These genes include PTPN22, TRAF1-C5, PADI4, STAT4, Several alleles in the epitope-recognition part of the HLA molecule that show the highest association with RA susceptibility, also share a common string of amminoacid residues (the so-called shared-epitope hypothesis). Other variants in potentially pathogenic genes located in non-MHC regions have been implicated by recently performed genome wide analysis studies. These genes include PTPN22, TRAF1-C5, PADI4, STAT4. , Among these genes, PTPN22 plays an outstanding role. CD40, STAT4, PRM1, and TNFAIP3 also seem to be of relevance., n particular, genome-wide association studies (GWAS) have provided supportive evidence that RA is a disease with a strong genetic background. Interestingly, a series of candidate genes have been identified outside of the classical major histocompatibility (MHC) locus, which had long been regarded as the major contributor to the pathogenesis of this disease. Among these genes, PTPN22 plays an outstanding role., HLA-DRB1 and the R620W single-nucleotide polymorphism of PTPN22 were genotyped, In addition, evidence of a significant interaction between the shared epitope and the risk allele of PTPN22 was observed only in these patients, Although SNPs in PADI4 had similar allele frequency among three groups [maximal difference 11%; (P >0.05)], the other three loci revealed statistically significant allele frequency differences (maximal difference 39% (P <0.00001), 13% (P <0.00001), and 8% (P <0.00001) in SLC22A4, PDCD1, and PTPN22, respectively), Several multiple, large-scale, genetic studies on autoimmune-disease-associated SNPs have been reported recently: peptidylarginine deiminase type 4 (PADI4) in rheumatoid arthritis (RA); solute carrier family 22 members 4 and 5 (SLC22A4 and 5) in RA and Crohn's disease (CD); programmed cell death 1 (PDCD1) in systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1D), and RA; and protein tyrosine phosphatase nonreceptor type 22 (PTPN22) in T1D, RA, and SLE,  Recently a number of convincing candidate genes have begun to emerge and an update has been provided for three of these: PTPN22, CTLA-4 and MIF., Recently a number of convincing candidate genes have begun to emerge and an update has been provided for three of these: PTPN22, challenges in identifying genetic polymorphisms that influence the susceptibility to rheumatoid arthritis are the same as those faced in most complex diseases, Association studies support a role for several genes, including TNFR2, PADI4, SLC22A4, RUNX1, and PTPN22, Although HLA-DRB1 is the main RA gene, it accounts for only part of the familial risk for RA. HLA-DRB1 alleles are neither necessary nor sufficient to cause the development of RA in a given individual. Several genome scans conducted in populations from France, Japan, North America and UK have confirmed the role of the HLA region and suggested several other susceptibility loci. Association studies support a role for several genes, including TNFR2, PADI4, SLC22A4, RUNX1, and PTPN22., Analyses of families with multiple autoimmune disorders have revealed a functional polymorphism, 620W, in the intracellular tyrosine phosphatase gene PTPN22 as a predisposing factor for type 1 diabetes, seropositive rheumatoid arthritis, systemic lupus erythematosus, and Hashimoto thyroiditis, and the presence of the PTPN22 protein appears to herald the development of autoantibodies in these disorders, Replication of putative candidate-gene associations with rheumatoid arthritis in >4,000 samples from North America and Sweden: association of susceptibility with PTPN22, CTLA4, and PADI4., We found strong evidence of an association of PTPN22 with the development of anti-citrulline antibody-positive RA (odds ratio [OR] 1.49; P=.00002), using previously untested EIRA samples.,  Exploration of our data set with clinically relevant subsets of RA reveals that PTPN22 is associated with an earlier age at disease onset (P=.004) and that PTPN22 has a stronger effect in males than in females (P=.03),  Given the strong statistical power to replicate a true-positive association in this study, our results provide support for PTPN22, CTLA4, and PADI4 as RA susceptibility genes and demonstrate novel associations with clinically relevant subsets of RA, In logistic regression analysis, ACPA predicted RA-development independent of PTPN22, while the PTPN22 polymorphism had no independent effect., In this Dutch cohort of UA-patients, the PTPN22 1858T allele does not markedly improve individual decision-making to predict RA-development, Risk of progression from undifferentiated arthritis to rheumatoid arthritis: the effect of the PTPN22 1858T-allele in anti-citrullinated peptide antibody positive patients, progression from undifferentiated arthritis to rheumatoid arthritis: the effect of the PTPN22 1858T-allele, Anti-citrullinated peptide antibodies (ACPA) and the C1858T missense single-nucleotide polymorphism (SNP) in the PTPN22 gene are both associated with the development of rheumatoid arthritis (RA), Associations between human leukocyte antigen, PTPN22, CTLA4 genotypes and rheumatoid arthritis phenotypes of autoantibody status, age at diagnosis and erosions in a large cohort study, HLA-DRB1 shared epitope (HLA-SE), PTPN22 and CTLA4 alleles are associated with cyclic citrullinated peptide (CCP) and rheumatoid arthritis (RA), Auto-antibodies, HLA and PTPN22: susceptibility markers for rheumatoid arthritis, The combination of the PTPN22 1858T variant and anti-CCP antibodies gave a high specificity for the disease, and was significantly associated with RA (P = 8.86 x 10(-5), OR 10.05, 95% CI 1.88-53.73), The combination of the T variant of the 1858 polymorphism of the PTPN22 gene in combination with the presence of anti-CCP antibodies, preferentially in a SE-positive individual, is associated with the development of RA, No association of the PTPN22 gene with mortality was detected, Cox proportional hazards regression models were used to assess the association of the HLA-DRB1 (including the shared epitope [SE]) and PTPN22 genes with the risk of death from all causes and from cardiovascular disease (CVD) and to assess the interactions between SE, smoking, and anti-cyclic citrullinated peptide (anti-CCP) status, adjusted by age at symptom onset and sex, The disease association of the common 1858C>T Arg620Trp (rs2476601) nonsynonymous single nucleotide polymorphism (SNP) of protein tyrosine phosphatase; nonreceptor type 22 (PTPN22) on chromosome 1p13 has been confirmed in type 1 diabetes and also in other autoimmune diseases, including rheumatoid arthritis and Graves' disease, To evaluate the predictive values for disease progression of various antibodies against citrullinated peptide proteins (ACPA) and their relation to PTPN22 1858C/T polymorphism and HLA-DRB1 alleles in early rheumatoid arthritis (RA), PTPN22, PADI-4, and CTLA-4 have been associated with risk for rheumatoid arthritis (RA), A significant multiplicative interaction between PTPN22 and smoking for more than 10 pack-years was observed (P = 0.04), No gene-gene interaction was observed between PTPN22 and HLA-SE, After adjusting for smoking and reproductive factors, PTPN22 was associated with RA risk among Caucasian women in these cohorts. We found both additive and multiplicative interactions between PTPN22 and heavy cigarette smoking., After adjusting for smoking and reproductive factors, PTPN22 was associated with RA risk among Caucasian women in these cohorts, Weak evidence for an effect at the PTPN22 locus was also observed, Association of the PTPN22 gene (-1123G > C) polymorphism with rheumatoid arthritis in Chinese patients, These data suggest, the CC genotype and C allele of the -1123G > C in the PTPN22 gene are associated with an increased risk for RA in Chinese population, Therefore, the CC genotype and C allele of the -1123G > C in the PTPN22 gene may be used as a genetic marker for the predisposition of RA in Chines, A longer duration of breastfeeding increased the risk of developing RA, especially among individuals seropositive for ACPA or IgM-RF or carrying the PTPN22 1858T variant, In a multiple logistic regression analysis, increasing time of breastfeeding (OR 9.5, 95% CI 2.14-42.43 for ≥ 17 months), seropositivity for ACPAs (OR 19.5, 95% CI 4.47-84.81), and carriage of the PTPN22 1858T variant (OR 3.2, 95% CI 1.36-7.54) remained significant predictors of RA, After quality control, 3209 patients and 3692 controls were included in the study. Eight markers (ie, rs1160542 (AFF3), rs1678542 (KIF5A), rs2476601 (PTPN22), rs3087243 (CTLA4), rs4810485 (CD40), rs5029937 (6q23), rs10760130 (TRAF1/C5) and rs7574865 (STAT4)) were significantly associated with RA by meta-analysis, Recent genome-wide association studies (GWAS) on RA identified known and novel susceptibility genes like HLA-DRB1, PTPN22, STAT4, TRAF1/C5, OLIG3/TNFAIP3, CD40, CCL21, MMEL1-TNFRSF14, CDK6, PRKCQ, IL2RB, and KIF5A-PIP4K2C, In the total RA inception cohort, the HLA-DRB1 shared epitope (per-allele odds ratio (OR) = 2.1, trend P < 0.0001), PTPN22 (per-allele OR = 1.5, trend P < 0.0001), OLIG3/TNFAIP3 locus (per-allele OR = 1.2, trend P = 0.009) and TRAF1/C5 locus (per-allele OR = 1.1, trend P = 0.04) were associated with RA, This study investigated five confirmed rheumatoid arthritis (RA) susceptibility genes/loci (HLA-DRB1, PTPN22, STAT4, OLIG3/TNFAIP3 and TRAF1/C5) for association with susceptibility and severity in an inception cohort, Progress has been made in determining the relative contributions and the interaction of the shared epitope, PTPN22 and smoking in conferring the risk of anticitrullinated protein antibodies-positive and negative RA, Homozygous and heterozygous carriers of the PTPN22 1858T allele had a decreased probability of remission, Our analyses have confirmed previous findings for genes PTPN22 and C5, Fifty-five percent of the FDRs had > or =1 copy of the shared epitope, 20% had > or =1 copy of the PTPN22 polymorphism, and approximately 16% were positive for rheumatoid factor (RF; including isotypes) and/or anti-cyclic citrullinated peptide antibody, As an effect several new genes have been recognized as an HLA-independent genetic risk factors of RA. PTPN22 gene polymorphism, C5/TRAF1 genes region polymorphism and TNFAIP3-OLIG3 genes region polymorphism(s) are among newly identified and already confirmed genetic risk factors, whereas STAT 4, CTLA4, PADI4 and IRF5 genes polymorphisms are listed among probable RA development genetic risk factors, After initial completion of the Human Genome Project on the 16th February 2001, significant progress has been made in identifying other than HLA genome regions linked to the increased RA susceptibility. As an effect several new genes have been recognized as an HLA-independent genetic risk factors of RA. PTPN22 gene polymorphism, C5/TRAF1 genes region polymorphism and TNFAIP3-OLIG3 genes region polymorphism(s) are among newly identified and already confirmed genetic risk factors, Patients were analysed for anti-MCV and anti-cyclic citrullinated peptide (CCP), and were genotyped for human leukocyte antigen (HLA)-DRB1 \"shared epitope\" (SE) and protein tyrosine phosphatase, non-receptor type 22 (PTPN22) 1858T, As well as the major susceptibility gene HLA-DRB1, recent genome-wide and candidate-gene studies reported additional evidence for association of single nucleotide polymorphism (SNP) markers in the PTPN22, STAT4, OLIG3/TNFAIP3 and TRAF1/C5 loci with RA., However, we were able to replicate the association signals between RA and HLA-DRB1 alleles, STAT4 (rs7574865), PTPN22 (rs2476601) and OLIG3/TNFAIP3 (rs10499194 and rs6920220), Additionally, SNPs rs7574865STAT4 (P = 9.2*10-6; OR = 1.71, 95% CI = 1.35 - 2.18) and rs2476601PTPN22 (P = 9.5*10-4; OR = 1.67, 95% CI = 1.23 - 2.26) were associated with susceptibility to RA, whereas after permutation testing OLIG3/TNFAIP3 SNPs rs10499194 and rs6920220 missed our criteria for significance (Pcorr = 0.114 and Pcorr = 0.180, respectively, In our Slovak population, HLA-DRB1 alleles as well as SNPs in STAT4 and PTPN22 genes showed a strong association with RA, Recent advances have led to novel identification of genetic polymorphisms that are associated with susceptibility to rheumatoid arthritis (RA). Currently, 5 loci (HLA, PTPN22, TRAF1/C5, TNFAIP3, and STAT4) have been consistently reported, whereas others have been observed less systematically, Genetic markers such as shared epitope alleles and PTPN22 1858T variant increase the relative risk for disease development, Particularly, ACPAs in combination with human leukocyte antigen-shared epitope alleles and PTPN22 1858T carriage increased the relative risks of developing RA compared with not having these factors, However, inconsistent results of the contributions of non-HLA susceptibility genes have been described, with the exception of a few genes repeatedly associated with RA-susceptibility, such as PTPN22 gene in populations of European ancestry and PADI4 gene in populations of Asian ancestry, revealing the presence of genetic heterogeneity in RA., Functional polymorphisms of PTPN22 and FcgR genes in Tunisian patients with rheumatoid arthritis, We found strong evidence of an association of PTPN22 620W allele and RA, In conclusion, we have confirmed that PTPN22 620W allele is associated with Tunisian RA but does not constitute a factor influencing clinical manifestations., The C1858T allele of the PTPN22 gene has been reported to confer risk for RA, Similarly, the presence or absence of the HLA-DRB1 shared epitope or the RA-associated PTPN22 allele had no influence on this association, Although some genetic risk factors for RA are well-established, most notably HLA-DRB1 and PTPN22, these markers do not fully account for the observed heritability, Lastly, in combination with the other two known genetic risk factors, HLA-DRB1 and PTPN22, the variants reported here generate more than a 45-fold RA-risk differential, Contribution of PTPN22 1858T, TNFRII 196R and HLA-shared epitope alleles with rheumatoid factor and anti-citrullinated protein antibodies to very early rheumatoid arthritis diagnosis, PTPN22 1858T, TNFRII 196R and HLA-SE alleles do not improve the predictive value of RF and ACPA for RA diagnosis in our cohort, and do not contribute to an earlier diagnosis in undifferentiated patients initially negative for RF and ACPA[SEP]Relations: PTPN22 has relations: disease_protein with rheumatoid arthritis, disease_protein with rheumatoid arthritis, disease_protein with juvenile idiopathic arthritis, disease_protein with juvenile idiopathic arthritis, disease_protein with type 1 diabetes mellitus, disease_protein with type 1 diabetes mellitus, disease_protein with IDDM 1, disease_protein with IDDM 1. MMEL1 has relations: disease_protein with rheumatoid arthritis, disease_protein with rheumatoid arthritis.", "label": "yes"}
{"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]Irinotecan has relations: drug_protein with UGT1A1, drug_ proteins with CYP3A7 and TOP1MT. The company also has relations with the FDA and the FDA-approved drug CYP1A9.", "label": "yes"}
{"id": "converted_147", "sentence1": "Has the protein TIEG1 been associated with apoptosis?", "sentence2": "TGF-beta) inducible early gene 1 (TIEG1) is known to induce apoptosis in TGF-beta sensitive pancreatic cancer cells, yet its effect on TGF-beta resistant cancer cells remains unclear, overexpression of TIEG1, protected ALL cells against chemotherapy-induced cell death,  TIEG1 might be involved in mediating this effect from the microenvironment onto the leukemia cells, We also demonstrate that TIEG-1 ectopic expression in CGNPs induces cell cycle arrest that can lead to apoptosis but fails to promote differentiation, TIEG1 acts as an inducer or repressor of gene transcription to enhance the TGFbeta/Smad pathway, as well at other signaling pathways, to regulate cell proliferation, differentiation, and apoptosis., TGFbeta inducible early gene (TIEG1) mimics TGFbeta action and induces apoptosis, the transforming growth factor-beta- (TGF-beta-) inducible early response 1 gene (TIEG1), which plays a pivotal role in TGF-beta-regulated cell growth control and apoptosis, Induction of mRNA for Smad4 and the TGF-beta1-regulated apoptosis-inducing transcription factor TGF-beta1-inducible early gene (TIEG1) was detected within the first 6 h of doxazosin treatmen, TIEG1 (TGF-beta inducible early gene) is a recently characterized transcription factor regulated by TGF-beta that induces apoptosis when overexpressed in pancreatic adenocarcinoma cell lines, Influence of TIEG1 on apoptosis, the influence of TIEG1 on apoptosis of HL-60 cells and the expression of Bcl-2/Bax, The expression of genes involved in insulin resistance (PDK4, AHSG) is increased, together with expression of TIEG1, a transcription factor that can induce apoptosis via the mitochondrial pathway, the overexpression of TIEG1 mediated growth inhibition and apoptosis in TGF-β1-resistant HCC cell lines,, On the other hand, KLF10 deficient keratinocytes showed increased proliferation and apoptosis, LF10, transforming growth factor-β-inducible early gene 1, IEG1 can induce apoptosis of cancer cells, TGF-β inducible early gene 1) plays a significant role in regulating cell proliferation and apoptosis, TIEG1) is a Krüppel-like transcription factor (KLF10) that was originally cloned from human osteoblasts as an early response gene to TGF-β treatment, Adenoviral delivery of TIEG1 (AdTIEG1) to TIEG1(-/-) cells reversed the RANKL-induced NFATc1 signaling defect in TIEG1(-/-) precursors and eliminated the differentiation and apoptosis defects, (TGF)-β inducible early gene (TIEG)-1 is implicated in the control of cell proliferation, differentiation, and apoptosis in some cell types, TIEG1 has been shown to mimic the effects of TGF-beta in various carcinoma cells and plays a critical role in the apoptotic cascade, (TIEG) is a family of primary response genes induced by TGF-beta, which are well recognized in regulating cellular proliferation and apoptosis, In human and murine tissues it has been shown that TIEG1 and TIEG2 induce apoptosis and inhibit cell growth, overexpression of TIEG1 in OLI-neu cells induced apoptosis, (TGF-beta(1))-inducible transcription factors have recently elicited interest because of their critical role in the regulation of cell proliferation, differentiation, and apoptosis, ectopic overexpression of TIEG is sufficient to trigger the apoptotic cell program in these cells[SEP]Relations: transcription factor binding has relations: molfunc_protein with DRG1, molfunc_protein with DRG1, molfunc_protein with ATG7, molfunc_protein with ATG7, molfunc_protein with APBB1, molfunc_protein with APBB1, molfunc_protein with TLE1, molfunc_protein with TLE1, molfunc_protein with KEAP1, molfunc_protein with KEAP1.", "label": "yes"}
{"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]Protein S human has relations with Trabectedin, Drotrecogin alfa, Floctafenine, Streptozocin and Floxuridine. Drug_drug has relations: drug_drug with DrotRecogin, drug_ drug with Floctacen, drug-drug with Streptocin.", "label": "yes"}
{"id": "converted_2570", "sentence1": "Is pregabalin effective for sciatica?", "sentence2": "CONCLUSIONS: Treatment with pregabalin did not significantly reduce the intensity of leg pain associated with sciatica and did not significantly improve other outcomes, as compared with placebo, over the course of 8 weeks. The incidence of adverse events was significantly higher in the pregabalin group than in the placebo group. , Whilst pregabalin (PGB) and gabapentin (GBP) are both used to treat neuropathic pain, their relative role in sciatica is unclear., GBP and PGB appeared to demonstrate comparable efficacy and SE. However, the amount and quality of evidence was low, and only indirect comparisons were available. [SEP]Pregabalin has relations with Pancreatitis, Menorrhagia, Pneumonia, Pain, and Pridinol. It also has a drug effect with Pain and an effect with Menor Rhagia.", "label": "no"}
{"id": "converted_682", "sentence1": "Is sumoylation implicated in myogenesis?", "sentence2": "Sentrin/small ubiquitin-like modifier (SUMO)-specific protease 2 (SENP2) has broad de-SUMOylation activities in vitro, which is essential for embryonic heart development., Silencing SENP2 can reduce myostatin expression and, therefore, promote myogenesis of skeletal muscle. These results reveal the important role of SENP2 in the regulation of myostatin expression and myogenesis., Overexpression of c-Ski/SnoN also induces skeletal muscle differentiation, but how c-Ski/SnoN function in myogenesis is largely unknown., Notably, loss of sumoylation in the Lys-50 site (via a Lys-to-Arg point mutation) potently activates muscle-specific gene expression and enhances myotube formation. Our study suggests a novel role for SUMO modification in the regulation of myogenic differentiation., Although this modification has little effect on SnoN repression of the plasminogen activator inhibitor-1 promoter and only modestly potentiates SnoN repression of the p21 promoter, SnoN sumoylation robustly augments the ability of SnoN to suppress transcription of the myogenesis master regulatory gene myogenin, Our study also points to a physiological role for SnoN sumoylation in the control of myogenin expression in differentiating muscle cells., Here, we biochemically characterize SnoN sumoylation in detail and report the physiological function of the modification. , An essential role of small ubiquitin-like modifier (SUMO)-specific Protease 2 in myostatin expression and myogenesis., These results reveal the important role of SENP2 in the regulation of myostatin expression and myogenesis., The E3 SUMO ligase Nse2 regulates sumoylation and nuclear-to-cytoplasmic translocation of skNAC-Smyd1 in myogenesis., Sumoylation of the basic helix-loop-helix transcription factor sharp-1 regulates recruitment of the histone methyltransferase G9a and function in myogenesis.,  We show that the overall load of sumoylated proteins present in myoblasts diminishes progressively throughout myogenesis, These novel results suggest that protein sumoylation plays a pivotal role in myoblast differentiation and is required to regulate the activity of key targets downstream of MyoD and myogenin., a composite sequence motif has recently been identified that couples phosphorylation, sumoylation, and perhaps also deacetylation to control transcriptional repression in stress response, mitogen and nuclear hormone signaling, myogenesis, and neuronal differentiation., Mutation of these SUMO acceptor sites in Sharp-1 does not impact its subcellular localization but attenuates its ability to act as a transcriptional repressor and inhibit myogenic differentiation. Consistently, co-expression of the SUMO protease SENP1 with wild type Sharp-1 abrogates Sharp-1-dependent inhibition of myogenesis. , Transforming growth factor-beta-independent regulation of myogenesis by SnoN sumoylation., Ubiquitin Specific Protease 25 (USP25), a member of the deubiquitinase family, is involved in several disease-related signal pathways including myogenesis, immunity and protein degradation. ,  In addition, we show that the skNAC interaction partner Smyd1 contains a putative sumoylation motif and is sumoylated in muscle cells, with depletion of Mms21/Nse2 leading to reduced concentrations of sumoylated Smyd1. Taken together, our data suggest that the function, specifically the balance between the nuclear and cytosolic roles, of the skNAC-Smyd1 complex might be regulated by sumoylation.[SEP]Relations: EHMT2 has relations: pathway_protein with Regulation of TP53 Activity through Methylation, pathway_protein with Regulation of TP53 Activity through Methylation, bioprocess_protein with regulation of histone H3-K4 methylation, bioprocess_protein with regulation of histone H3-K4 methylation, bioprocess_protein with regulation of histone H3-K9 methylation, bioprocess_protein with regulation of histone H3-K9 methylation. histone methyltransferase complex has relations: cellcomp_protein with PRDM4, cellcomp_protein with PRDM4. BHLHE41 has relations: bioprocess_protein with regulation of neurogenesis, bioprocess_protein with regulation of neurogenesis.", "label": "yes"}
{"id": "converted_278", "sentence1": "Is the tricarboxylic acid (TCA) cycle affected in inflammation?", "sentence2": "In this study, the levels of amino acids and trichloroacetic acid (TCA) cycle-related molecules in the colonic tissues and sera of patients with ulcerative colitis (UC) were profiled by gas chromatography/mass spectrometry (GC/MS), with the aim of evaluating whether the clinical state induced by UC leads to variations in the amino acid profile, Our study raises the possibility that GC/MS-based profiling of amino acids and TCA cycle-related molecules is a useful early diagnostic tool for UC., Succinate is an intermediate of the tricarboxylic acid (TCA) cycle, and plays a crucial role in adenosine triphosphate (ATP) generation in mitochondria., In plasma, most metabolites in the central metabolic pathway (glycolysis and TCA cycle) were significantly downregulated after zymosan administration, Thus, IL-1beta+TNFalpha treated astrocytes show a marked decrease in glycogen levels, a slight but not significant decrease in lactate release as well as a massive increase in both the pentose phosphate pathway and TCA cycle activities., A total of 77 and 92 metabolites were detected in serum and colon tissue, respectively, and among the metabolites the compositions of TCA cycle intermediates and amino acids changed depending on the degree of colitis, Extension of these findings identified a functional role for stretch-induced inhibition of succinate dehydrogenase (SDH) in mediating normoxic HIF1A stabilization, concomitant increases in glycolytic capacity, and improved tricarboxylic acid (TCA) cycle function, These studies reveal a surprising role for HIF1A in lung protection during ALI, where normoxic HIF1A stabilization and HIF-dependent control of alveolar-epithelial glucose metabolism function as an endogenous feedback loop to dampen lung inflammation, These results suggest a cataplerosis of the TCA cycle induced by phenobarbital, caused by the massive withdrawal of succinyl-CoA by ALAS induction, such that the TCA cycle is unable to supply the reduced cofactors to the RC, The mitochondrial respiratory chain (RC) and the tricarboxylic acid (TCA) cycle were explored in the Hmbs(-/-) mouse model. RC and TCA cycle were significantly affected in comparison to controls in mice treated with phenobarbital with decreased activities of RC complexes, Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. , Enhanced mitochondrial glucose oxidation was achieved by increased recruitment of the NOTCH1 intracellular domain (NICD1) to nuclear and mitochondrial genes that encode respiratory chain components and by NOTCH-dependent induction of pyruvate dehydrogenase phosphatase 1 (Pdp1) expression, pyruvate dehydrogenase activity, and glucose flux to the TCA cycle. , Metabolic reprogramming is implicated in macrophage activation,, BHB blocks the NLRP3 inflammasome without undergoing oxidation in the TCA cycle, and independently of uncoupling protein-2 (UCP2), sirtuin-2 (SIRT2), the G protein-coupled receptor GPR109A or hydrocaboxylic acid receptor 2 (HCAR2). , Our findings suggest that the anti-inflammatory effects of caloric restriction or ketogenic diets may be linked to BHB-mediated inhibition of the NLRP3 inflammasome., Succinate: a metabolic signal in inflammation.[SEP]Relations: acute tricyclic antidepressant poisoning has relations: disease_disease with poisoning, disease_disease with poisoning. ulcerative colitis (disease) has relations: contraindication with Trihexyphenidyl, contraindication with Trihexyphenidyl, disease_protein with HNF4A, disease_protein with HNF4A, disease_protein with HERC2, disease_protein with HERC2. Phenobarbital has relations: drug_drug with Tricaine, drug_drug with Tricaine.", "label": "yes"}
{"id": "converted_2430", "sentence1": "Are splicing speckles associated with transcription?", "sentence2": "We show here that RNA splicing speckled domains (splicing speckles) fluctuate in constrained nuclear volumes and remodel their shapes., We present a model where recycling splicing factors return as part of small sub-speckles from distal sites of RNA processing to larger splicing speckles by a directed ATP-driven mechanism through interchromatin spaces., Analysis of a HeLa cell line stably expressing EYFP-NHPX showed that the nucleolar accumulation of NHPX was preceded by its transient accumulation in splicing speckles., In vivo analysis of NHPX reveals a novel nucleolar localization pathway involving a transient accumulation in splicing speckles., \"Splicing speckles\" are major nuclear domains rich in components of the splicing machinery and polyA(+) RNA. Although speckles contain little detectable transcriptional activity, they are found preferentially associated with specific mRNA-coding genes and gene-rich R bands, and they accumulate some unspliced pre-mRNAs, RNA polymerase II transcribes mRNAs and is required for splicing, with some reports suggesting that the inactive complexes are stored in splicing speckle, In normal cell growth conditions GFPeIF4A-III was mainly nucleoplasmic, but in hypoxia stress conditions it moved to the nucleolus and splicing speckles., Localization of eIF4A-III in the nucleolus and splicing speckles is an indicator of plant stress.,  Using antibodies raised against mouse RBM6 to immunostain mammalian cell lines we found that the endogenous protein was both distributed diffusely in the nucleus and concentrated in a small number of nuclear foci that corresponded to splicing speckles/interchromatin granule clusters (IGCs, Subnuclear targeting of the RNA-binding motif protein RBM6 to splicing speckles and nascent transcripts.[SEP]Nuclear speck has relations with SPOP, SPRTN, MBD4, ERBIN, ILRUN, and ILNUN. Nuclear speck is a type of nucleus of the family of nuclear proteins.", "label": "no"}
{"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]Relations: RNA localization to chromatin has relations: bioprocess_protein with HNRNPU, bioprocess_protein with HNRNPU. promoter clearance from RNA polymerase I promoter has relations: bioprocess_bioprocess with promoter clearance during DNA-templated transcription, bioprocess_bioprocess with promoter clearance during DNA-templated transcription, bioprocess_bioprocess with promoter clearance from RNA polymerase I promoter for nuclear large rRNA transcript, bioprocess_bioprocess with promoter clearance from RNA polymerase I promoter for nuclear large rRNA transcript. testis has relations: anatomy_protein_present with PARP14, anatomy_protein_present with PARP14, anatomy_protein_present with CGGBP1, anatomy_protein_present with CGGBP1.", "label": "yes"}
{"id": "converted_3503", "sentence1": "Are stretch enhancers transcribed more than super-enhancers?", "sentence2": "Super-enhancers are transcriptionally more active and cell type-specific than stretch enhancers., We found that stretch enhancers are more abundant, more distal to transcription start sites, cover twice as much the genome, and are significantly less conserved than super-enhancers. In contrast, super-enhancers are significantly more enriched for active chromatin marks and cohesin complex, and more transcriptionally active than stretch enhancers. Importantly, a vast majority of super-enhancers (85%) overlap with only a small subset of stretch enhancers (13%), which are enriched for cell type-specific biological functions, and control cell identity genes. These results suggest that super-enhancers are transcriptionally more active and cell type-specific than stretch enhancers, and importantly, most of the stretch enhancers that are distinct from super-enhancers do not show an association with cell identity genes, are less active, and more likely to be poised enhancers., These results suggest that super-enhancers are transcriptionally more active and cell type-specific than stretch enhancers, and importantly, most of the stretch enhancers that are distinct from super-enhancers do not show an association with cell identity genes, are less active, and more likely to be poised enhancers.[SEP]Cohesin complex has relations with STAG2, RAD21 and SMC1A. Cohesin Complex is a protein-protein complex. It is the most complex protein complex in the world. It has more than 1,000 protein-like proteins.", "label": "no"}
{"id": "converted_4628", "sentence1": "Is tirabrutinib effective for lymphoma?", "sentence2": "In March 2020, oral tirabrutinib was approved in Japan for the treatment of recurrent or refractory primary central nervous system lymphoma. Tirabrutinib is also under regulatory review in Japan for the treatment of Waldenström's macroglobulinemia and lymphoplasmacytic lymphoma. Clinical development is underway in the USA, Europe and Japan for autoimmune disorders, chronic lymphocytic leukaemia, B cell lymphoma, Sjogren's syndrome, pemphigus and rheumatoid arthritis. This article summarizes the milestones in the development of tirabrutinib leading to the first approval of tirabrutinib for the treatment of recurrent or refractory primary central nervous system lymphoma in Japan., CONCLUSION: These data indicate favorable efficacy of tirabrutinib in patients with relapsed/refractory PCNSL., Tirabrutinib was well tolerated and showed promising efficacy for B-cell NHL/CLL., rabrutinib was approved in Japan for the treatment of recurrent or refractory primary central nervous system lymphoma. Tirabrutinib is also , Here, we provide a comprehensive review of the preclinical and clinical activity of tirabrutinib, a drug approved in Japan for relapsed or refractory primary central nervous system lymphoma and all lines of Waldenström macroglobulinemia/lymphoplasmacytic lymphoma., Tirabrutinib (ONO/GS-4059; Ono Pharmaceutical) is a newly developed drug that selectively and irreversibly inhibits Bruton's tyrosine kinase (BTK) and has been approved in Japan for treating relapsed/refractory primary central nervous system lymphoma (PCNSL)., A 64-year-old patient with recurrent PCNSL enrolled in the phase I/II clinical trial of tirabrutinib, a second-generation BTK inhibitor designed for treating relapsed/refractory PCNSL., BACKGROUND: The safety, tolerability, efficacy, and pharmacokinetics of tirabrutinib, a second-generation, highly selective oral Bruton's tyrosine kinase inhibitor were evaluated for relapsed/refractory primary central nervous system lymphoma (PCNSL).M,  2020, oral tirabrutinib was approved in Japan for the treatment of recurrent or refractory primary central nervous system lymphoma. Tirabru, ine kinase inhibitor tirabrutinib (for relapsed and refractory PCNSL) and high-dose chemotherapy with autologous stem cell transplantation support using thiotepa and busulfan (BuTT) were approved by the Japanese Ministry of Health and Welfare in March 2020 and has recently become available for clinical practice. While these novel, BACKGROUND: The safety, tolerability, efficacy, and pharmacokinetics of tirabrutinib, a second-generation, highly selective oral Bruton's tyrosine kinase inhibitor were evaluated for relapsed/refractory primary central nervous system lymphoma (PCNSL).METHODS: Patients with relapsed/refractory PCNSL, Karnofsky performance status ≥70, and normal end-organ function received tirabrutinib 320 and 480 , Histological verification of the treatment effect of tirabrutinib for relapsed/refractory primary central nervous system lymphoma., In March 2020, oral tirabrutinib was approved in Japan for the treatment of recurrent or refractory primary central nervous system lymphoma.[SEP]Relations: Ibrutinib has relations: drug_drug with Ibritumomab tiuxetan, drug_drug with Ibritumomab tiuxetan, drug_drug with Acalabrutinib, drug_drug with Acalabrutinib, drug_drug with Tixocortol, drug_drug with Tixocortol. Thiotepa has relations: drug_drug with Ibritumomab tiuxetan, drug_drug with Ibritumomab tiuxetan, drug_drug with Acalabrutinib, drug_drug with Acalabrutinib.", "label": "yes"}
{"id": "converted_2231", "sentence1": "Is apremilast effective for psoriatic arthritis?", "sentence2": "Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3)., OBJECTIVE: To evaluate apremilast treatment in patients with active psoriatic arthritis, including current skin involvement, despite prior therapy with conventional disease-modifying antirheumatic drugs and/or biologic agents., CONCLUSIONS: Apremilast demonstrated clinically meaningful improvements in psoriatic arthritis and psoriasis at week 16; sustained improvements were seen with continued treatment through 52 weeks. , Apremilast: A Novel Drug for Treatment of Psoriasis and Psoriatic Arthritis., OBJECTIVE: To review the pharmacology, efficacy, and safety of apremilast and determine its role relative to other agents in the treatment of psoriasis and psoriatic arthritis., CONCLUSIONS: Apremilast has a novel mechanism of action and is safe and effective for the management of psoriasis and psoriatic arthritis. ,  In particular, apremilast has been recently approved for the treatment of psoriasis and psoriatic arthritis., Apremilast, an oral phosphodiesterase 4 inhibitor, has an acceptable safety profile and is effective for treatment of plaque psoriasis and psoriatic arthritis., As part of the National Institute for Health and Clinical Excellence (NICE) single technology appraisal (STA) process, the manufacturer of apremilast was invited to submit evidence for its clinical and cost effectiveness for the treatment of active psoriatic arthritis (PsA) for whom disease-modifying anti-rheumatic drugs (DMARDs) have been inadequately effective, not tolerated or contraindicated., Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 (PALACE 1) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug (DMARD) and/or biologic therapy., In patients with psoriatic arthritis, there are no clinical trials comparing apremilast with TNF alpha antagonists, and no interpretable trials of apremilast after failure of a TNF alpha antagonist., Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 (PALACE 1) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug (DMARD) and/or biologic therapy.In the 24-week, placebo-controlled phase of PALACE 1, patients (N=504) were randomised (1:1:1) to placebo, apremilast 20 mg twice a day (BID) or apremilast 30 mg BID, No imbalance in major adverse cardiac events, serious or opportunistic infections, malignancies or laboratory abnormalities was observed.Apremilast was effective in the treatment of psoriatic arthritis, improving signs and symptoms and physical function, Apremilast is a novel oral PDE4 enzyme inhibitor capable of blocking leukocyte production of IL-12, IL-23, TNF-a, INF- with subsequent suppression of Th1 and Th17-mediated immune responses, and proven clinical efficacy for psoriasis as well as rheumatoid and psoriatic arthritis.Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) showed a significant (P&lt;0.05) decrease after 85 days of treatment with apremilast 20 mg twice daily in 8 patients with active discoid lupus, The purpose of this study is to give an overview of the new treatments approved by the U.S. Food and Drug Administration (FDA) for use in psoriatic arthritis (PsA).FDA has approved three new drugs for PsA: Certolizumab-pegol: a PEGylated Fc-free tumour necrosis factor inhibitor (TNFi); ustekinumab: an anti interleukin (IL)-12 and IL-23 mAb; and apremilast and oral phosphodiesterase 4 inhibitor., In all trials, the drug had an acceptable safety profile, with the most common adverse effects of diarrhea, nausea, and headache.Apremilast has a novel mechanism of action and is safe and effective for the management of psoriasis and psoriatic arthritis., Apremilast is a well-tolerated and effective phosphodiesterase type 4 inhibitor that is indicated for the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis., Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 (PALACE 1) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug (DMARD) and/or biologic therapy.In the 24-week, placebo-controlled phase of PALACE 1, patients (N=504) were randomised (1:1:1) to placebo, apremilast 20 mg twice a day (BID) or apremilast 30 mg BID., Newer drugs in the treatment armamentarium that have shown efficacy for both psoriasis and psoriatic arthritis consist of the anti-IL-17 agent, secukinumab, and a phosphodiesterase-4 inhibitor, apremilast., To review the pharmacology, efficacy, and safety of apremilast and determine its role relative to other agents in the treatment of psoriasis and psoriatic arthritis.A PubMed search (1946 to December 2015) using the terms apremilast and CC-10004 was conducted to identify relevant articles.In vitro or in vivo evaluations of apremilast published in the English language were eligible for inclusion., In patients with psoriatic arthritis, there are no clinical trials comparing apremilast with TNF alpha antagonists, and no interpretable trials of apremilast after failure of a TNF alpha antagonist., No imbalance in major adverse cardiac events, serious or opportunistic infections, malignancies or laboratory abnormalities was observed.Apremilast was effective in the treatment of psoriatic arthritis, improving signs and symptoms and physical function., Apremilast is a novel oral PDE4 enzyme inhibitor capable of blocking leukocyte production of IL-12, IL-23, TNF-a, INF- with subsequent suppression of Th1 and Th17-mediated immune responses, and proven clinical efficacy for psoriasis as well as rheumatoid and psoriatic arthritis.Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) showed a significant (P<0.05) decrease after 85 days of treatment with apremilast 20 mg twice daily in 8 patients with active discoid lupus., Apremilast was effective in the treatment of psoriatic arthritis, improving signs and symptoms and physical function., Apremilast has a novel mechanism of action and is safe and effective for the management of psoriasis and psoriatic arthritis., Apremilast, an oral phosphodiesterase 4 inhibitor, demonstrated effectiveness (versus placebo) for treatment of active psoriatic arthritis in the psoriatic arthritis long-term assessment of clinical efficacy (PALACE) phase III clinical trial program., Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 (PALACE 1) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug (DMARD) and/or biologic therapy., Apremilast: A Review in Psoriasis and Psoriatic Arthritis., Drug safety evaluation of apremilast for treating psoriatic arthritis., Apremilast for the treatment of psoriatic arthritis., Apremilast mechanism of action and application to psoriasis and psoriatic arthritis., Apremilast: A Phosphodiesterase 4 Inhibitor for the Treatment of Psoriatic Arthritis.[SEP]Relations: Apremilast has relations: drug_drug with Aprepitant, drug_drug with Aprepitant, drug_drug with Ampicillin, drug_drug with Ampicillin, drug_drug with Antipyrine, drug_drug with Antipyrine, drug_drug with Apramycin, drug_drug with Apramycin, drug_drug with Methadone, drug_drug with Methadone.", "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]Relations: Axitinib has relations: drug_drug with Panobinostat, drug_drug with Panobinostat, drug_drug with Proguanil, drug_drug with Proguanil, drug_drug with Afelimomab, drug_drug with Afelimomab, drug_drug with Entrectinib, drug_drug with Entrectinib, drug_drug with Dolutegravir, drug_drug with Dolutegravir.", "label": "no"}
{"id": "converted_525", "sentence1": "Are BBS mutations involved in syndromic Hirschsprung disease?", "sentence2": "Epistasis between RET and BBS mutations modulates enteric innervation and causes syndromic Hirschsprung disease, Here, we report 3 families with BBS and HSCR with concomitant mutations in BBS genes and regulatory RET elements, whose functionality is tested in physiologically relevant assays. Our data suggest that BBS mutations can potentiate HSCR predisposing RET alleles, which by themselves are insufficient to cause disease, Epistasis between RET and BBS mutations modulates enteric innervation and causes syndromic Hirschsprung disease., Our data suggest that BBS mutations can potentiate HSCR predisposing RET alleles, which by themselves are insufficient to cause disease., Here, we report 3 families with BBS and HSCR with concomitant mutations in BBS genes and regulatory RET elements, whose functionality is tested in physiologically relevant assays, Our data suggest that BBS mutations can potentiate HSCR predisposing RET alleles, which by themselves are insufficient to cause disease, Here, we report 3 families with BBS and HSCR with concomitant mutations in BBS genes and regulatory RET elements, whose functionality is tested in physiologically relevant assays[SEP]Disease_phenotype_positive has relations with Autosomal dominant inheritance. Disease_protein with MED12, disease_ proteins with EDNRB and GDNF have relations with hirschsprung disease. Disease phenotype positive has relations with Autosomal dominant inheritance.", "label": "yes"}
{"id": "converted_926", "sentence1": "Is there a role for transcription factories in genome organization?", "sentence2": "The mammalian nucleus is a highly complex structure that carries out a diverse range of functions such as DNA replication, cell division, RNA processing, and nuclear export/import. Many of these activities occur at discrete subcompartments that intersect with specific regions of the genome. Over the past few decades, evidence has accumulated to suggest that RNA transcription also occurs in specialized sites, called transcription factories, that may influence how the genome is organized. There may be certain efficiency benefits to cluster transcriptional activity in this way. However, the clustering of genes at transcription factories may have consequences for genome stability, and increase the susceptibility to recurrent chromosomal translocations that lead to cancer, In the eukaryotic nucleus, genes are transcribed in transcription factories, Based on this analysis, we propose that transcription factories result from the aggregation of RNA polymerase II-containing pre-initiation complexes assembled next to each other in the nuclear space. Such an aggregation can be triggered by the phosphorylation of the C-terminal domain of RNA polymerase II molecules and their interaction with various transcription factors. Individual transcription factories would thus incorporate tissue-specific, co-regulated as well as housekeeping genes based only on their initial proximity to each other in the nuclear space, active polymerases cluster into replication and transcription \"factories\" in both pro- and eukaryotes. We conclude that the second law of thermodynamics acts through nonspecific entropic forces between engaged polymerases to drive the self-organization of genomes into loops containing several thousands (and sometimes millions) of basepairs, Since the advent of FISH (fluorescence in situ hybridization), there have been major advances in our understanding of how the genome is organized in interphase nuclei. Indeed, this organization is found to be non-random and individual chromosomes occupy discrete regions known as territories,  in proliferating cells, there is evidently a correlation between radial positioning and gene density. Indeed, gene-poor chromosomes tend to be located towards the nuclear edge, while those that are more gene-rich are positioned more internally, Recently described active chromatin hubs and transcription factories also involve long-range interactions, The transcription factory model has implications for the regulation of transcription initiation and elongation, for the organization of genes in the genome, for the co-regulation of genes and for genome instability.[SEP]Relations: HIV Transcription Initiation has relations: pathway_protein with CCNH, pathway_protein with CCNH. transcription factor binding has relations: molfunc_protein with JUN, molfunc_protein with JUN, molfunc_protein with JUNB, molfunc_protein with JUNB, molfunc_protein with JUND, molfunc_protein with JUND, molfunc_protein with SAP18, molfunc_protein with SAP18.", "label": "yes"}
{"id": "converted_2349", "sentence1": "Do chromatin features predict genes associated with eQTLs?", "sentence2": "Using the random forest classifier, we found that genomic proximity plus five TF and chromatin features are able to predict>90% of target genes within 1 megabase of eQTLs, Using the random forest classifier, we found that genomic proximity plus five TF and chromatin features are able to predict >90% of target genes within 1 megabase of eQTLs., Cell type-specific gene expression in humans involves complex interactions between regulatory factors and DNA at enhancers and promoters. Mapping studies for expression quantitative trait loci (eQTLs), transcription factors (TFs) and chromatin markers have become widely used tools for identifying gene regulatory elements, but prediction of target genes remains a major challenge. Here, we integrate genome-wide data on TF-binding sites, chromatin markers and functional annotations to predict genes associated with human eQTLs. Using the random forest classifier, we found that genomic proximity plus five TF and chromatin features are able to predict >90% of target genes within 1 megabase of eQTLs. Despite being regularly used to map target genes, proximity is not a good indicator of eQTL targets for genes 150 kilobases away, but insulators, TF co-occurrence, open chromatin and functional similarities between TFs and genes are better indicators. Using all six features in the classifier achieved an area under the specificity and sensitivity curve of 0.91, much better compared with at most 0.75 for using any single feature. We hope this study will not only provide validation of eQTL-mapping studies, but also provide insight into the molecular mechanisms explaining how genetic variation can influence gene expression.[SEP] transcription factor binding has relations with C1QBP, METTL23, ETS1, CENPF, AHR, and AHR. Molfunc_protein with CenPF is related to the transcription factor CENFBP. molfunc-protein with AHR is also related to AHR as is molfunc-protein.", "label": "yes"}
{"id": "converted_1513", "sentence1": "Is thrombophilia related to increased risk of miscarriage?", "sentence2": "Thrombophilia does hardly increase the risk of IUGR/PMPC or if so, it can be prevented by LMWH, for illustrative purposes, a patient presenting with combined thrombophilia--both genetic and acquired--will be discussed. This patient had suffered severe gestational complications that led to devastating obstetrical outcome, Thrombophilias have been implicated in complications related to ischemic placental disease including recurrent pregnancy loss, intrauterine fetal demise, preeclampsia, fetal growth restriction, placental abruption, and preterm delivery, Further information about the combined risk of aPC resistance and pregnancy is needed before guidance on the management of affected women can be formulated., Thrombotic risk during pregnancy and the puerperium is higher in asymptomatic women with than without thrombophilia, Further studies are required to assess the thrombotic risk in women with preeclampsia as well as early or late recurrent pregnancy loss., Risk of pregnancy-related venous thrombosis in carriers of severe inherited thrombophilia, In conclusion, homozygous carriers of factor V Leiden and, to a lesser extent, double heterozygous carriers of factor V Leiden and of the prothrombin mutation have an increased risk of venous thrombosis during pregnancy, particularly high during the postpartum period, Careful diagnosis, observation and monitoring can add significant benefit to LMWH therapy during pregnancy, Pregnancy in healthy women is accompanied by hypercoagulable changes that may interact with thrombophilia risk factors and threaten pregnancy., Fifty-three (13 %) women had antiphospholipid antibodies (lupus anticoagulant and/or anti-beta2-glycoprotein 1 antibodies) mainly associated with the risk of spontaneous abortion during the first trimester, thrombophilia was found to be considerably more common in women with pregnancy-associated complications in comparison with the general population, and most frequently in conjunction with venous thromboembolism during pregnancy and the postpartum period, When counseling white women with a history of preeclampsia, screening for thrombophilia can be useful for preconceptional counseling and pregnancy management., knowledge combined with the appropriate use of thromboprophylaxis and treatment in women who have objectively confirmed VTE continue to improve maternal and perinatal outcomes, The risk of having thrombophilia is doubled in men who have fathered pregnancies which ended in perinatal death as well as in the mothers of such pregnancies., The prevalence of thrombophilic variants is of possible public health significance for other morbidity; but perhaps not in relation to preeclampsia, This study suggests that thrombophilia \"mediates\" in lowering of cardiovascular risk factors in women with a history of preeclampsia[SEP]Relations: thrombophilia has relations: disease_disease with inherited thrombophilia, disease_disease with inherited thrombophilia, disease_phenotype_positive with Recurrent thrombophlebitis, disease_phenotype_positive with Recurrent thrombophlebitis, disease_phenotype_positive with Preeclampsia, disease_phenotype_positive with Preeclampsia, disease_phenotype_positive with Hypercoagulability, disease_phenotype_positive with Hypercoagulability, disease_phenotype_positive with Thromboembolism, disease_phenotype_positive with Thromboembolism.", "label": "yes"}
{"id": "converted_4161", "sentence1": "Does Curare function by stimulating the acetylcholine receptor?", "sentence2": "Usual clinical concentrations of curare cause competitive inhibition of muscle nicotinic acetylcholine receptors while higher concentrations may induce open channel blockade., nicotinic acetylcholine receptor (nAChR)-blocking agents [e.g., curare or alpha-bungarotoxin (alpha-BTX), The short neurotoxins to which erabutoxins belong act by blocking the nicotinic acetylcholine receptor, Both EFS- and carbachol-evoked contractions of the UES were blocked by curare at a lower concentration than by atropine or hexamethonium, suggesting that the acetylcholine receptor is nicotinic., We applied ACh alone; the nicotinic acetylcholine receptor (nAChR) antagonist curare, either alone or in the presence of ACh; and the muscarinic acetylcholine receptor (mAChR) antagonist atropine, either alone or in the presence of ACh., The EFS-induced contraction of the UES was completely blocked by tetrodotoxin and curare, and abolished in Ca2+ -free Ringer solution., Curare binding and the curare-induced subconductance state of the acetylcholine receptor channel., We have further investigated this particular mutation by examining the interaction of the competitive antagonist d-tubocurarine (curare) with the receptor., d-Tubocurarine (curare) is a well-characterized competitive antagonist of nicotinic acetylcholine receptors (AChRs), and it is usually assumed that curare and agonists share a common binding site., Curare action on nicotinic acetylcholine receptors has a number of facets, of which the best known is competitive antagonism., The mode of action of curare, a well-known competitive antagonist of acetylcholine at the nicotinic receptor, was examined with the single channel recording technique. , ently, however, it has been shown that curare can also block the channels opened by ACh at the frog neuromuscular junction as well as on rat and Aplysia neurones; moreover, curare is able to depolarize rat myotubes and thus behaves as an agonist for the cholinergic receptor of this preparation (see ref. 6). U, One site, competitively blocked by bungarotoxin and by curare, is presumably the acetylcholine receptor., In neuromuscular junction (NMJ) preparations, movements of the muscle must be inhibited if imaging during stimulation is desired (e.g., by application of curare, a potent acetylcholine receptor inhibitor)., Curare has long been regarded as a typical competitive antagonist of acetylcholine (ACh) at the vertebrate neuromuscular junction., Curare inhibition of wild-type receptors is consistent with curare binding to a single high-affinity binding site [inhibitor constant (Ki) = 20 nM]., Phenylalanine substitution for alpha Y198 [alpha Y198F (notation used here: subunit/amino acid in wild-type/residue number/substitution)] causes a 10-fold increase in curare affinity (Ki = 3.1 nM), and measurement of the recovery from curare inhibition indicates that this increase in affinity is due to a reduction in the rate of curare dissociation from the receptor., rthermore, sudden increases of research activity are ascribable to historic events, like the first use of curare as muscle relaxant during surgery.DIS, Recently, however, it has been shown that curare can also block the channels opened by ACh at the frog neuromuscular junction as well as on rat and Aplysia neurones; moreover, curare is able to depolarize rat myotubes and thus behaves as an agonist for the cholinergic receptor of this preparation (see ref., In Aplysia nervous tissue, curare appears not to be a specific antagonist for the nicotinic ACh receptor, but rather to be a specific blocking agent for a class of receptor-activated Na+ and Cl- responses., The mode of action of curare, a well-known competitive antagonist of acetylcholine at the nicotinic receptor, was examined with the single channel recording technique.[SEP]Relations: Muscarinic acetylcholine receptors has relations: pathway_protein with CHRM5, pathway_protein with CHRM5, pathway_protein with CHRM5, pathway_protein with CHRM5, pathway_protein with CHRM1, pathway_protein with CHRM1, pathway_protein with CHRM1, pathway_protein with CHRM1, pathway_protein with CHRM4, pathway_protein with CHRM4.", "label": "no"}
{"id": "converted_3383", "sentence1": "AhR ligands are attractive drug targets for pharmaceutical development due to their induction of Cyp1a1, yes or no?", "sentence2": " Based on our review of the data, there is little evidence to support the indiscriminate exclusion of AhR activators/Cyp1a1 inducers from early drug developmental pipelines. We also found no evidence that short-term treatment with RMAhRLs produce \"dioxin-like toxicity\", However, recent discoveries of new AhR ligands with potential therapeutic applications have been reported, inviting reconsideration of this policy., Based on our review of the data, there is little evidence to support the indiscriminate exclusion of AhR activators/Cyp1a1 inducers from early drug developmental pipelines., Based on our review of the data , there is little evidence to support the indiscriminate exclusion of AhR activators/Cyp1a1 inducers from early drug developmental pipelines, However , recent discoveries of new AhR ligands with potential therapeutic applications have been reported , inviting reconsideration of this policy, Based on our review of the data, there is little evidence to support the indiscriminate exclusion of AhR activators/Cyp1a1 inducers from early drug developmental pipelines., However, recent discoveries of new AhR ligands with potential therapeutic applications have been reported, inviting reconsideration of this policy., Combining in vivo and in vitro findings, we identified nine AhR agonists, six of which are marketed therapeutics and have been approved by the U.S. Food and Drug Administration, including leflunomide, flutamide, and nimodipine.[SEP]Nimodipine has relations: drug_protein with AHR, drug_ protein with A HR. aryl hydrocarbon receptor complex has relations with cellcomp_protein and AHRR. Leflunomide has Relations with Drug_protein With AHR. Flutamide has Relations With Drug_ protein With Ahr.", "label": "yes"}
{"id": "converted_3749", "sentence1": "Is the TFR1 gene dispensable for erythropoiesis?", "sentence2": "These studies describe how point mutations of the transferrin receptor can cause a microcytic anemia that does not respond to iron therapy and would not be detected by routine iron studies, such as serum ferritin., Ret-He was the only red cell marker affected prior to the onset of brain ID. The clinical practice of using anemia as the preferred biomarker for diagnosis of iron deficiency may need reconsidering., The restoration of EPO production and EPOR mRNA expression with ASP treatment activated EPOR downstream JAK2/STAT5 and PI3K/Akt signaling, induced their target genes, such as Bcl-xL, Fam132b and Tfrc, and increased Bcl-2/Bax ratio in bone marrow-derived mononuclear cells of CKD rats., Transferrin-bound iron binding to transferrin receptor 1 (TfR1) is essential for cellular iron delivery during erythropoiesis. , aken together, decreasing TfR1 expression during β-thalassemic erythropoiesis, either directly via induced haploinsufficiency or via exogenous apotransferrin, decreases ineffective erythropoiesis and provides an endogenous mechanism to upregulate hepcidin, leading to sustained iron-restricted erythropoiesis and preventing systemic iron overload in β-thalassemic mice., The type 1 transferrin receptor (TfR1) is well known as a key player in erythroid differentiation through its role in iron uptake. , The signaling functions of both TfR1 and TfR2 in erythroid cells were unexpected and these recent findings open a new field of research regarding the last steps of erythroid differentiation and their regulation., Erythropoiesis requires large amounts of iron for hemoglobin synthesis, which is mainly provided by macrophages and the intestines in a transferrin (Tf)-bound form.,  In humans, hematopoietic erythroid precursor cells express high levels of TFR1 and specifically take up the FTH homopolymer (H-ferritin)., We found decreased expression of hepcidin and TfR2 and increased expression of TfR1 and NGAL in the beta-thalassemia mouse models, compared with the control mice., Soluble transferrin receptor-1 (sTfR1) concentrations are increased in the plasma under two conditions that are associated with increased iron absorption, i.e. iron deficiency and increased erythropoiesis., Hemochromatosis is caused by mutations in HFE, a protein that competes with transferrin (TF) for binding to transferrin receptor 1 (TFR1)., Here we report that sorting nexin 3 (Snx3) facilitates the recycling of transferrin receptor (Tfrc) and thus is required for the proper delivery of iron to erythroid progenitors., These findings provide direct evidence that Tfr1 is essential for hematopoiesis through binding diferric transferrin to supply iron to cells.[SEP]Relations: hemochromatosis has relations: disease_protein with TFR2, disease_protein with TFR2. hemopoiesis has relations: bioprocess_protein with TWSG1, bioprocess_protein with TWSG1, bioprocess_protein with L3MBTL1, bioprocess_protein with L3MBTL1, bioprocess_protein with GFI1, bioprocess_protein with GFI1. Erythropoietin has relations: drug_protein with EPOR, drug_protein with EPOR.", "label": "no"}
{"id": "converted_2866", "sentence1": "Does simvastatin improve outcomes of aneurysmal subarachnoid hemorrhage?", "sentence2": "Randomized controlled trials have shown that simvastatin and intravenous magnesium do not prevent DCI or improve functional outcomes after aneurysmal subarachnoid hemorrhage (aSAH)., Conclusions Simvastatin showed no benefits in decreasing the incidence of vasospasm, DCI, or all-cause mortality after aneurysmal SAH. We conclude that patients with SAH should not be treated routinely with simvastatin during the acute stage., We found no statistically significant effects on vasospasm detected by transcranial cerebral Doppler (relative risk [RR], 0.91; 95% confidence interval [CI], 0.55-1.49), delayed cerebral ischemia (DCI) (RR, 0.85; 95% CI, 0.63-1.14), or all-cause mortality (RR, 1.02; 95% CI, 0.67-1.54)., BACKGROUND: Simvastatin might be beneficial to the patients with aneurysmal subarachnoid hemorrhage. However, the results remained controversial. , CONCLUSIONS: Compared to control intervention, simvastatin intervention was found to have no influence on delayed ischaemic deficit, delayed cerebral infarction, mRS≤2, vasospasm, ICU stay, hospital stay, and mortality in patients with acute aneurysmal subarachnoid hemorrhage., Current evidence does not support prophylactic use of clazosentan, magnesium, or simvastatin. , Recently, acute simvastatin treatment was not shown to be beneficial in neurological outcome using modified Rankin Scale., CONCLUSIONS: The current study does not support that acute simvastatin treatment improves cognitive outcome after aneurysmal subarachnoid hemorrhage., CONCLUSION: This study demonstrated that 80 mg simvastatin treatment was effective in preventing cerebral vasospasm after aneurysmal SAH, but did not improve the clinical outcome in Korean patients., High-Dose Simvastatin Is Effective in Preventing Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study in Korean Patients., CONCLUSIONS\nThe current study does not support that acute simvastatin treatment improves cognitive outcome after aneurysmal subarachnoid hemorrhage., CONCLUSIONS\nHigh-dose simvastatin treatment should not be prescribed routinely for aneurysmal subarachnoid hemorrhage., Randomized controlled trials have shown that simvastatin and intravenous magnesium do not prevent DCI or improve functional outcomes after aneurysmal subarachnoid hemorrhage (aSAH)., CONCLUSIONS\nCompared to control intervention, simvastatin intervention was found to have no influence on delayed ischaemic deficit, delayed cerebral infarction, mRS≤2, vasospasm, ICU stay, hospital stay, and mortality in patients with acute aneurysmal subarachnoid hemorrhage., CONCLUSIONS The current study does not support that acute simvastatin treatment improves cognitive outcome after aneurysmal subarachnoid hemorrhage., CONCLUSIONS High-dose simvastatin treatment should not be prescribed routinely for aneurysmal subarachnoid hemorrhage., CONCLUSIONS Compared to control intervention, simvastatin intervention was found to have no influence on delayed ischaemic deficit, delayed cerebral infarction, mRS≤2, vasospasm, ICU stay, hospital stay, and mortality in patients with acute aneurysmal subarachnoid hemorrhage., There were also no differences in DID, delayed cerebral infarction, favorable mRS outcome, and MMSE scores, and MMSE-assessed cognitive impairment between both groups.<br><b>CONCLUSIONS</b>: The current study does not support that acute simvastatin treatment improves cognitive outcome after aneurysmal subarachnoid hemorrhage.<br>[SEP]Relations: Simvastatin has relations: drug_effect with Hemolytic anemia, drug_effect with Hemolytic anemia, drug_effect with Dyspnea, drug_effect with Dyspnea, drug_effect with Arthritis, drug_effect with Arthritis, drug_effect with Erythema, drug_effect with Erythema, drug_effect with Ophthalmoplegia, drug_effect with Ophthalmoplegia.", "label": "no"}
{"id": "converted_370", "sentence1": "Is intense physical activity associated with longevity?", "sentence2": "Our major finding is that repeated very intense exercise prolongs life span in well trained practitioners., Death rates declined with increased levels of total activity (estimated in kilocalories), and declined also with increased intensity of effort measured as from none, to light, to moderately vigorous or vigorous sports play. Death rates at any given quantity of physical exercise were lower for men playing moderately intense sports than for less vigorous men., he purpose of this study was to investigate if jogging, which can be very vigorous, is associated with increased all-cause mortality in men and women., This long-term study of joggers showed that jogging was associated with significantly lower all-cause mortality and a substantial increase in survival for both men and women., Light activities (<4 multiples of resting metabolic rate (METs)) were not associated with reduced mortality rates, moderate activities (4-<6 METs) appeared somewhat beneficial, and vigorous activities (> or =6 METs) clearly predicted lower mortality rates (p, trend = 0.72, 0.07, and <0.001, respectively)., These data demonstrate a graded inverse relationship between total physical activity and mortality. Furthermore, vigorous activities but not nonvigorous activities were associated with longevity., The capacity for prolonged and vigorous physical exercise, particularly if the exercise is recreational, is a strong indicator of longevity.[SEP]Cessation of head growth has relations: disease_phenotype_positive with Angelman syndrome due to a point mutation, phenotype_phenotypes with Secondary microcephaly, and neurodevelopmental disorder with progressive microce PHaly, spasticity, and brain anomalies. Cessation has relations with maternal 15q11q13 deletion, paternal uniparental disomy of chromosome 15, and Angelman Syndrome due to paternal 15q12q13 deletions. It also has relations with recessive head growth, which can be caused by a number of factors.", "label": "yes"}
{"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]Relations: Ocrelizumab has relations: drug_drug with Otelixizumab, drug_drug with Otelixizumab, drug_drug with Afelimomab, drug_drug with Afelimomab, drug_drug with Crenezumab, drug_drug with Crenezumab, drug_drug with Nemolizumab, drug_drug with Nemolizumab, drug_drug with Pexelizumab, drug_drug with Pexelizumab.", "label": "yes"}
{"id": "converted_2210", "sentence1": "Is dupilumab an antibody targeting the IL-1 receptor?", "sentence2": "Atopic dermatitis (AD) is characterized by type 2 helper T (Th2) cell-driven inflammation. Dupilumab is a fully human monoclonal antibody directed against the IL-4 receptor α subunit that blocks the signaling of IL-4 and IL-13, both key cytokines in Th2-mediated pathways., Dupilumab, a humanized monoclonal antibody to the interteukin-4R is the first antibody (i.e. 'biological') with published efficacy shown in controlled prospective studies in atopic dermatitis. , Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis., Best evidence of the clinical efficacy of novel immunologic approaches using biological agents in patients with AD is available for the anti-IL-4 receptor α-chain antibody dupilumab, but a number of studies are currently ongoing with other specific antagonists to immune system players.,  Dupilumab, a fully human anti-interleukin-4 receptor α monoclonal antibody, inhibits interleukin-4 and interleukin-13 signalling, key drivers of type-2-mediated inflammation. , Dupilumab was also introduced as a possible treatment for patients with severe pemphigus. It can directly inhibit IL-4 by targeting IL-4 α-chain receptor., We evaluated the efficacy and safety of dupilumab (SAR231893/REGN668), a fully human monoclonal antibody to the alpha subunit of the interleukin-4 receptor[SEP]Dupilumab has relations: drug_protein with IL4R, drug_drug with Avelumab, and drug_ drug with IGN311. It also has relations with Olaratumab, which is in development with Pfizer.", "label": "no"}
{"id": "converted_2092", "sentence1": "Can valproic acid prolong survival of glioblastoma patients?", "sentence2": "For patients who presented with epilepsy, the use of the antiepileptic drug VPA did not associate with survival when compared with patients who did not receive VPA treatment., This prognostic effect is not solely explained by early diagnosis, and survival is not associated with VPA treatment., Several in vivo and in vitro studies have indicated that VPA has radiosensitizing effects for gliomas and radioprotective influence on normal brain tissue or hippocampal neurons. The results of several retrospective studies have also indicated potential benefit to improve survival of patients with GBM. Moreover, the promising treatment results of a phase 2 trial of concurrent radiation therapy, temozolomide, and VPA for patients with GBM have been recently reported. , While there have not been any novel anti-GBM therapeutics approved for many years, there has been the gradual accumulation of clinical data suggesting that the widely used anti-convulsant agent, valproic acid (VPA) may significantly prolong survival in GBM patients.,  Additionally, VPA may result in improved outcomes compared to historical data and merits further study., Several retrospective studies in seizure patients with glioblastoma treated with chemotherapy have provided evidence for a moderately improved survival with the use of valproic acid, possibly due to inhibition of histone deacetylase, Several clinical studies have reported that valproic acid could prolong survival of GBM patients, While there have not been any novel anti-GBM therapeutics approved for many years, there has been the gradual accumulation of clinical data suggesting that the widely used anti-convulsant agent, valproic acid (VPA) may significantly prolong survival in GBM patients, Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma, Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma., Valproic acid use during radiation therapy for glioblastoma associated with improved survival., Patients receiving VPA alone (97 [16.9%]) appeared to derive more survival benefit from TMZ/RT (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.24-0.63) than patients receiving an EIAED only (252 [44%]) (HR 0.69, 95% CI 0.53-0.90) or patients not receiving any AED (HR 0.67, 95% CI 0.49-0.93). , Several retrospective studies in seizure patients with glioblastoma treated with chemotherapy have provided evidence for a moderately improved survival with the use of valproic acid, possibly due to inhibition of histone deacetylase., Several uncontrolled retrospective case series and a post hoc analysis of the registration trial for temozolomide indicated an association between valproic acid (VPA) use and improved survival outcomes in patients with newly diagnosed glioblastoma.To confirm the hypothesis suggested above, a combined analysis of survival association of antiepileptic drug use at the start of chemoradiotherapy with temozolomide was performed in the pooled patient cohort (n = 1,869) of four contemporary randomized clinical trials in newly diagnosed glioblastoma: AVAGlio (Avastin in Glioblastoma; NCT00943826), CENTRIC (Cilengitide, Temozolomide, and Radiation T, Several clinical studies have reported that valproic acid could prolong survival of GBM patients., Patients receiving VPA alone (97 [16.9%]) appeared to derive more survival benefit from TMZ/RT (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.24-0.63) than patients receiving an EIAED only (252 [44%]) (HR 0.69, 95% CI 0.53-0.90) or patients not receiving any AED (HR 0.67, 95% CI 0.49-0.93).VPA may be preferred over an EIAED in patients with glioblastoma who require an AED during TMZ-based chemoradiotherapy., The combination of radiotherapy, temozolomide and valproic acid (VPA) has shown some promise in retrospective analyses of patients with glioblastoma, although their mechanisms of action remain unknown.We investigated the in vitro and in vivo effects of pretreating glioma cells with temozolomide and VPA as an immunization strategy to boost an adaptive immune response in a syngeneic mouse model.Temozolomide and VPA induced autophagy in GL261 glioma cells, and caused tumor antigen-specific T-cells to become activated effector T-cells., Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma.[SEP]Relations: Valproic acid has relations: contraindication with gallbladder disease, contraindication with gallbladder disease, contraindication with hematologic disease, contraindication with hematologic disease, contraindication with kidney disease, contraindication with kidney disease, contraindication with neurotic disorder, contraindication with neurotic disorder, contraindication with liver disease, contraindication with liver disease.", "label": "yes"}
{"id": "converted_3146", "sentence1": "Is L-4F an apoE mimetic peptide?", "sentence2": "Apolipoprotein A-I mimetic peptide 4F suppresses tumor-associated macrophages and pancreatic cancer progression., L-4F, an Apolipoprotein A-I (ApoA-I) mimetic peptide, is engineered to mimic the anti-inflammatory and anti-oxidative functionalities of ApoA-I.[SEP] apolipoprotein A-I binding has relations with ABCA1, TREM2, LCAT, SCARB1 and HSPD1. Molfunc_protein with T REM2 has relations: molfunc-TREM2-ABCA1-LCAT-SCARB-HSPD.", "label": "no"}
{"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]Relations: Protein S human has relations: drug_drug with Coagulation Factor IX (Recombinant), drug_drug with Coagulation Factor IX (Recombinant), drug_drug with Ceftobiprole, drug_drug with Ceftobiprole, drug_drug with Ceftazidime, drug_drug with Ceftazidime, drug_drug with Cimicoxib, drug_drug with Cimicoxib, drug_drug with Potassium citrate, drug_drug with Potassium citrate.", "label": "no"}
{"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] histone H3 acetylation has relations with TAF5L, TAF6L, LEF1, IRF4 and IRF5. Bioprocess_protein with Taf5L has relations: bioprocession_protein with TAF 5L, biop rocess_ protein with T AF5L and T AF6L.", "label": "yes"}
{"id": "converted_1260", "sentence1": "Was tamoxifen tested for treatment of glioma patients?", "sentence2": "Tamoxifen might have a role in the initial treatment of high-grade gliomas and should be studied in future Phase II trials building on the newly established platform of concurrent chemoradiotherapy., The addition of high-dose tamoxifen to standard radiotherapy does not improve the survival of patients with diffuse intrinsic pontine glioma., In this study, in which tamoxifen was used in conjunction with radiotherapy, progression free survival was shown to be less good when compared with historical data HR = 3.1 (CI: 1.7-5.7)., The addition of high-dose tamoxifen, although well tolerated, confers no clinical benefit to patients treated with diffuse intrinsic pontine glioma treated with standard radiotherapy., CONCLUSIONS: Carboplatin and high dose tamoxifen has similar response rates to other regimens for recurrent malignant gliomas and are probably equivalent to those found using tamoxifen as monotherapy. , CONCLUSIONS: Pegylated liposomal doxorubicin administered alone or in combination with tamoxifen is safe and moderately effective in patients with recurrent high-grade glioma., Protein kinase C (PKC) inhibitors such as high-dose tamoxifen and hypericin also have been used in the treatment of malignant gliomas. , Considering these facts, polyethylene-glycol-liposomal doxorubicin with and without tamoxifen was evaluated within two sequential Phase II trials performed at our institution. , In a parallel phase-II-study investigating post-operative treatment with tamoxifen (TAM), carboplatin and radiation therapy for glioblastomas, 16 of 49 patients (33%) showed multifocal recurrence, which developed after a mean of 46 weeks, raising the question of an association with therapy., Radiation therapy and high-dose tamoxifen in the treatment of patients with diffuse brainstem gliomas: results of a Brazilian cooperative study. Brainstem Glioma Cooperative Group., PURPOSE: The efficacy of radiation therapy (RT) combined with tamoxifen (TX) was tested in patients diagnosed with diffuse brainstem gliomas in a multicenter trial., CONCLUSION: This treatment combination produced no significant change in the overall poor prognosis of these patients. Most tumors responded initially to treatment but recurred as the study progressed. A minority of patients seemed to benefit from the extended use of TX. , Tamoxifen, a protein kinase C inhibitor when administered in high dosages, is currently being used as an adjuvant in the treatment of patients with malignant gliomas., We present a patient with a recurrent malignant glioma who was continued on high dose tamoxifen despite radiologic documented doubling of the tumor size and who eventually showed a delayed response to this agent nine months after initiation of treatment., The combination of oral tamoxifen (120 to 240 mg/m2/day) and subcutaneous interferon-alpha [6 x 10(6) U three times per week] was associated with significant neurotoxicity in this group of recurrent glioma patients, resulting in early study closure., A phase I study of high-dose tamoxifen for the treatment of refractory malignant gliomas of childhood., Phase I clinical trial assessing temozolomide and tamoxifen with concomitant radiotherapy for treatment of high-grade glioma., Prolonged treatment with biologic agents for malignant glioma: a case study with high dose tamoxifen., Tamoxifen as a potential treatment of glioma., We tested the efficacy and toxicity of the combination of high-dose tamoxifen and interferon alpha in adults with recurrent glioma in a phase II trial. , PURPOSE: The efficacy of radiation therapy (RT) combined with tamoxifen (TX) was tested in patients diagnosed with diffuse brainstem gliomas in a multicenter trial. , We tested the efficacy and toxicity of the combination of high-dose tamoxifen and interferon alpha in adults with recurrent glioma in a phase II trial., The efficacy of radiation therapy (RT) combined with tamoxifen (TX) was tested in patients diagnosed with diffuse brainstem gliomas in a multicenter trial., The efficacy of radiation therapy (RT) combined with tamoxifen (TX) was tested in patients diagnosed with diffuse brainstem gliomas in a multicenter trial., We tested the efficacy and toxicity of the combination of high-dose tamoxifen and interferon alpha in adults with recurrent glioma in a phase II trial. Eligible patients had radiographically measurable recurrent gliomas of any grade after initial radiation therapy., Thyroid function was suppressed to reduce IGF-1 levels in glioma patients and high-dose tamoxifen administered.  Propylthiouracil was used to induce chemical hypothyroidism in 22 patients with recurrent glioma., Activity against recurrent gliomas has been reported for both tamoxifen and interferon alpha, agents that have more acceptable toxicity profiles and that can be administered in an outpatient setting. We tested the efficacy and toxicity of the combination of high-dose tamoxifen and interferon alpha in adults with recurrent glioma in a phase II trial., Thyroid function was suppressed to reduce IGF-1 levels in glioma patients and high-dose tamoxifen administered., Radiation therapy and high-dose tamoxifen in the treatment of patients with diffuse brainstem gliomas: results of a Brazilian cooperative study., We tested the efficacy and toxicity of the combination of high-dose tamoxifen and interferon alpha in adults with recurrent glioma in a phase II trial., The subsequent in vitro testing of the tumor that was removed after the recurrence of tumor (22 months after the initiation of tamoxifen) revealed loss of sensitivity to tamoxifen., The combination of oral tamoxifen (120 to 240 mg/m2/day) and subcutaneous interferon-alpha [6 x 10(6) U three times per week] was associated with significant neurotoxicity in this group of recurrent glioma patients, resulting in early study closure.[SEP]Relations: Tamoxifen has relations: drug_effect with Lymphedema, drug_effect with Lymphedema, drug_drug with Glisoxepide, drug_drug with Glisoxepide, drug_drug with Glyburide, drug_drug with Glyburide, drug_effect with Erythema, drug_effect with Erythema, drug_effect with Edema, drug_effect with Edema.", "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] ER-associated misfolded protein catabolic process has relations with RNF5, RNF185, DERL1, UFD1 and SDF2L1. Bioprocess_protein with R NF5 is a type of misfolding protein. It is a form of protein catabolism.", "label": "yes"}
{"id": "converted_3321", "sentence1": "Is there a vaccine for rotavirus?", "sentence2": "Safety and Immunogenicity of Pentavalent Rotavirus Vaccine (RV5), This study compares the safety and immunogenicity of pentavalent rotavirus vaccine (RV5), Effectiveness of rotavirus pentavalent vaccine,  rotavirus pentavalent vaccine (RotaTeq®) as a sole vaccine, We describe rotavirus vaccine coverage and missed opportunities for rotavirus vaccination., CONCLUSIONS\n\nAddressing missed opportunities for rotavirus vaccination is essential to achieving the 80% rotavirus vaccine coverage target outlined by Healthy People 2020., Complete rotavirus vaccine coverage could be improved to 81% if all missed opportunities within the ACIP-recommended schedule were addressed., RESULTS\n\nThe national coverage for rotavirus vaccine achieved a year after the introduction was 89% for one dose and 82% for two doses, respectively., CONCLUSIONS\n\nNorway achieved a high national coverage and excellent adherence with the strict age limits for rotavirus vaccine administration during the first year of introduction, indicating robustness of the national immunisation programme., Upper age limit recommendations for rotavirus vaccine administration contributed to suboptimal vaccination coverage., Catching-up with pentavalent vaccine: Exploring reasons behind lower rotavirus vaccine coverage in El Salvador., US Rotavirus Vaccine Efficacy Group., We describe rotavirus vaccine coverage and missed opportunities for rotavirus vaccination., Rotavirus vaccines: a story of success., Clinical and immunological studies of rotavirus vaccines., Impact of rotavirus vaccine on rotavirus diarrhoea in countries of East and Southern Africa., Rotavirus diarrheal episodes were identified by ELISA., The decrease in rotavirus positivity was inversely related to increase in rotavirus vaccine coverage showing impact of rotavirus vaccines., We described trends in rotavirus positivity among tested stool samples before and after rotavirus vaccine introduction., The RIT 4237 bovine rotavirus vaccine has served as a useful model for rotavirus vaccination, but the vaccine will not be further developed or tested., Only the RRV vaccine induced a low level of protection against rotavirus diarrhea mainly of serotype G1 specificity., It is recommended that new rotavirus vaccine candidates be developed at cheaper price to speed up the introduction of rotavirus immunization in the developing world in general., Review of rotavirus vaccine trials in Finland., Risk of intussusception after monovalent rotavirus vaccination., Rotavirus vaccines are underused compared with other routine vaccines., With rotavirus vaccines now available globally , it will be useful to assemble the available evidence on the epidemiology and burden of rotavirus gastroenteritis in India , in order to weigh the urgency of introducing a vaccine to help control rotavirus disease, Is there evidence that rotavirus vaccines are effective in preventing acute gastroenteritis complications such as dehydration and hospitalization, With the introduction of new rotavirus vaccines in sight , rotavirus gastroenteritis may be regarded as the single most frequent vaccine-preventable disease among children in the EU, With the recent introduction of the two rotavirus vaccines , RotaTeq and Rotarix , in many countries , it appears that the total number of hospitalizations due to rotavirus infections is being reduced , at least in developed countries that implemented a universal immunization program, Change in rotavirus epidemiology in northeast Florida after the introduction of rotavirus vaccine, With the recent postlicensure identification of an increased risk of intussusception with rotavirus vaccine , the 14 Latin American countries currently using rotavirus vaccine must now weigh the health benefits versus risks to assess whether to continue vaccination, Impact of rotavirus vaccines on rotavirus disease, With safe and efficacious rotavirus vaccines now on the verge of widespread adoption , researchers can be vital advocates for their uptake into routine immunization programs, Rotavirus vaccine RIX4414 (Rotarix™): a pharmacoeconomic review of its use in the prevention of rotavirus gastroenteritis in developed countries., In addition, various naturalistic studies have demonstrated 'real-world' effectiveness after the introduction of widespread rotavirus vaccination programmes in the community setting., The monovalent rotavirus vaccine RIX4414 (Rotarix™) is administered as a two-dose oral series in infants and has demonstrated protective efficacy against RVGE in clinical trials conducted in developed countries., Numerous cost-effectiveness analyses have been conducted in developed countries in which a universal rotavirus vaccination programme using RIX4414 was compared with no universal rotavirus vaccination programme., It is also difficult to draw conclusions regarding the cost effectiveness of rotavirus vaccine RIX4414 relative to that of the pentavalent rotavirus vaccine, which is administered as a three-dose oral series., Although indirect comparisons in cost-effectiveness analyses indicate that RIX4414 provided more favourable incremental cost-effectiveness ratios when each vaccine was compared with no universal rotavirus vaccination programme, results were generally sensitive to vaccine costs., A rotavirus vaccine for prophylaxis of infants against rotavirus gastroenteritis., A live attenuated monovalent rotavirus vaccine (Rotarix) containing human rotavirus strain RIX4414 of G1P1A P[8] specificity is being developed to meet the global need., Rotarix significantly reduced rotavirus gastroenteritis episodes and rotavirus-related hospitalizations in vaccinated infants compared with placebo recipients (P < 0.05)., We describe the intussusception epidemiology prior to rotavirus vaccine, temporal association of intussusception cases to administration of rotavirus vaccine, and estimate the additional number of intussusception cases that may be associated with rotavirus vaccine., Epidemiology of intussusception before and after rotavirus vaccine introduction in Fiji., In 2012, Fiji introduced rotavirus vaccine (Rotarix, GSK) into the national immunisation schedule., Four trials of RIT 4237 bovine rotavirus vaccine, one trial of group A RRV-1 rhesus rotavirus vaccine, and one trial of rhesus-human reassortant rotavirus vaccines D x RRV and DS1 x RRV were carried out between 1983-1989., Problems associated with the use of any oral rotavirus vaccine include acid lability of the vaccine virus, which requires buffering, and a slight but significant interference of oral poliovirus vaccine with the uptake of rotavirus vaccine., In the near future, oral heterologous rotavirus vaccines may be available for prevention of severe rotavirus gastroenteritis., There was no apparent difference between bovine and rhesus-based rotavirus vaccines in the protective efficacy against severe rotavirus gastroenteritis., Efficacy studies of this vaccine in 6-12 month-old children gave results characteristic of the performance of oral rotavirus vaccines in general: 58% protective efficacy against any rotavirus gastroenteritis and 82% against \"clinically significant\" gastroenteritis., Live oral rotavirus vaccine strain RIT 4237, derived from group A bovine rotavirus NCDV, was given to human volunteers in Tampere, Finland in 1982., Targeted efforts to evaluate indirect effects of rotavirus vaccine in low income countries are required to understand the total impact of rotavirus vaccine on the global burden of rotavirus disease., Widespread introduction of rotavirus vaccines has led to major reductions in the burden of rotavirus gastroenteritis worldwide., While rotavirus vaccine indirect effects have been demonstrated in high and middle income countries, there are very little data from low income countries where force of infection, population structures and vaccine schedules differ., Measuring indirect effects of rotavirus vaccine in low income countries., Intussusception among recipients of rotavirus vaccine: reports to the vaccine adverse event reporting system., Rotavirus vaccine was licensed on August 31, 1998, and subsequently recommended for routine use among infants., To describe the cases of intussusception among rotavirus vaccine recipients reported to the Vaccine Adverse Event Reporting System from October 1998 through December 1999., Infants vaccinated with rotavirus vaccine in the United States., There were 98 confirmed cases of intussusception after vaccination with rotavirus vaccine reported to the Vaccine Adverse Event Reporting System; 60 of these developed intussusception within 1 week after vaccination., Using a passive surveillance system for vaccine adverse events, we observed at least a fourfold increase over the expected number of intussusception cases occurring within 1 week of receipt of rotavirus vaccine., Other studies were initiated to further define the relationship between rotavirus vaccine and intussusception., In light of these and other data, the rotavirus vaccine manufacturer voluntarily removed its product from the market, and the recommendation for routine use of rotavirus vaccine among US infants has been withdrawn., To review the biology, immunology, and virology of rotavirus infections and describe the efforts towards the construction of vaccines using human and animal rotaviruses., In August 1998 the Food and Drug Administration in the United States approved the licensure of a rotavirus vaccine.[SEP]Relations: Rotavirus vaccine has relations: drug_drug with Sirolimus, drug_drug with Sirolimus, drug_drug with Sirolimus, drug_drug with Sirolimus, drug_drug with Mitomycin, drug_drug with Mitomycin, drug_drug with Mitomycin, drug_drug with Mitomycin, drug_drug with Flunisolide, drug_drug with Flunisolide.", "label": "yes"}
{"id": "converted_520", "sentence1": "Does ziconotide bind to N-type calcium channels?", "sentence2": "Since this region partially overlaps with residues previously implicated in block of the channel by omega-conotoxin GVIA, we assessed the effects of mutations in the putative EF hand domain on channel block by omega-conotoxin GVIA and the structurally related omega-conotoxin MVIIA. Both of the toxins irreversibly block the activity of wild type alpha(1B) N-type channels. , Despite their high sequence homology, the peptide neurotoxins omega-conotoxin MVIIA and MVIIC selectively block N- and P/Q-type calcium channels, respectively. ,  Binding assay for both N- and P/Q-type calcium channels showed that amino acid residues restricted to the N-terminal half are important for the recognition of N-type channels, whereas essential residues for P/Q-type channel recognition are widely spread over the whole omega-conotoxin molecule., Ziconotide is a novel peptide that blocks the entry of calcium into neuronal N-type voltage-sensitive calcium channels, preventing the conduction of nerve signals., Ziconotide is a selective, potent and reversible blocker of neuronal N-type voltage-sensitive calcium channels (VSCCs)., The therapeutic benefit of ziconotide derives from its potent and selective blockade of neuronal N-type voltage-sensitive calcium channels., Interactions of intrathecally administered ziconotide, a selective blocker of neuronal N-type voltage-sensitive calcium channels, with morphine on nociception in rats., Ziconotide, a new N-type calcium channel blocker, administered intrathecally for acute postoperative pain., Ziconotide, an intrathecally administered N-type calcium channel antagonist for the treatment of chronic pain., Thus, ziconotide is the first of a new class of agents--N-type calcium channel blockers, or NCCBs., Ziconotide, formerly known also as SNX- 111, represents a new class of agents, the N-type calcium channel blockers., The selective N-type calcium channel blocker ziconotide ameliorates severe chronic pain but has a narrow therapeutic window and requires intrathecal administration., A selective N-type calcium channel inhibitor, ziconotide (Prialt), is a neuroactive peptide recently marketed as a novel nonopioid treatment for severe chronic pain., As the clinically available analgesics, pregabalin (alpha2delta-subunit calcium channel ligand), ziconotide (N-type calcium channel blocker), mexiletine (sodium channel blocker), and duloxetine (serotonin and norepinephrine reuptake inhibitors) were evaluated in these neurochemically-induced allodynia models., The present investigation was designed to assess the safety and analgesic efficacy of ziconotide, a new N-type calcium channel blocker, when administered intrathecally to patients with acute postoperative pain., Inhibition of the N-type calcium channel by intrathecal administration of the channel-specific blocker omega-conotoxin MVIIA (ziconotide) is efficacious in the treatment of severe chronic pain., Ziconotide is a powerful analgesic drug that has a unique mechanism of action involving potent and selective block of N-type calcium channels, which control neurotransmission at many synapses., In conclusion, present findings provide implication that the spinal anti-nociceptive mechanistic site of pregabalin is different from that of ziconotide, mexiletine, and duloxetine, and pregabalin could have a broader anti-nociceptive mechanism other than N-type calcium channel blockade., Ziconotide (SNX-111), a selective blocker of neuronal N-type voltage-sensitive calcium channels, is antinociceptive when it is administered intrathecally., Effects of intrathecal administration of ziconotide, a selective neuronal N-type calcium channel blocker, on mechanical allodynia and heat hyperalgesia in a rat model of postoperative pain., A state-dependent Ca(V)2.2 inhibitor may provide an improved therapeutic window over ziconotide, the peptidyl Ca(V)2.2 inhibitor used clinically. , There is also human validation data from ziconotide, the CaV2.2-selective peptidyl inhibitor used clinically to treat refractory pain. , A selective N-type calcium channel inhibitor, ziconotide (Prialt), is a neuroactive peptide recently marketed as a novel nonopioid treatment for severe chronic pain. , The neuroprotective effects of intrathecal administration of the selective N-type calcium channel blocker ziconotide in a rat model of spinal ischemia.[SEP]Relations: Ziconotide has relations: drug_drug with Calcium, drug_drug with Calcium, drug_drug with Calcium cation, drug_drug with Calcium cation, drug_drug with Calcium acetate, drug_drug with Calcium acetate, drug_drug with Calcium chloride, drug_drug with Calcium chloride, drug_drug with Calcium gluconate, drug_drug with Calcium gluconate.", "label": "yes"}
{"id": "converted_724", "sentence1": "Are there any clinical trials of the effect of evening primrose oil on postmenopausal symptoms ?", "sentence2": "To analyze whether the time (morning/evening) of administration of a compound containing 60 mg of dry soy seed extract (glycine max) with 40% of total isoflavones, primrose oil and α-tocopherol modifies the effect on the climacteric syndrome., The object of this study was to evaluate the effect of different doses of a compound containing isoflavones 60 mg, primrose oil 440 mg and vitamin E 10 mg. (IOVE) on menopausal complaints. This was an open, multicentre, randomised, group comparative, efficacy and safety trial., Emphasis was placed on randomized, double-blind, placebo-controlled clinical trials, as these provide the best efficacy and safety data, Nonprescription therapies reviewed include black cohosh, dong quai, evening primrose oil, physical activity, phytoestrogens, and red clover, The effect of oral evening primrose oil on menopausal hot flashes: a randomized clinical trial., The aim of this study was to compare the efficacy of evening primrose with placebo in improvement of menopausal hot flashes. ,  The application of oral evening primrose oil compared with placebo for controlling hot flashes may decrease more the intensity of attacks , Our search identified 58 randomised controlled trials of which 11 involved the use of clonidine, six for SSRIs, four for gabapentin, seven for black cohosh, seven for red clover, 18 for phytoestrogens, two for ginseng, one for evening primrose,, Single clinical trials have found no benefit for dong quai, evening primrose oil,, Single clinical trials have found that dong quai, evening primrose oil,, To evaluate the efficacy of gamolenic acid provided by evening primrose oil in treating hot flushes and sweating associated with the menopause. DESIGN: Randomised, double blind, placebo controlled study.[SEP] Evening primrose oil has relations with Primidone, Estradiol, Acetaminophen, Prednisone, Antipyrine, and more. It is also used as an ingredient in some household cleaning products.", "label": "yes"}
{"id": "converted_4418", "sentence1": "Do SETD1A mutations predispose to schizophrenia?", "sentence2": "Recapitulation and Reversal of Schizophrenia-Related Phenotypes in Setd1a-Deficient Mice., SETD1A, a lysine-methyltransferase, is a key schizophrenia susceptibility gene. Mice carrying a heterozygous loss-of-function mutation of the orthologous gene exhibit alterations in axonal branching and cortical synaptic dynamics accompanied by working memory deficits. We show that Setd1a binds both promoters and enhancers with a striking overlap between Setd1a and Mef2 on enhancers. Setd1a targets are highly expressed in pyramidal neurons and display a complex pattern of transcriptional up- and downregulations shaped by presumed opposing functions of Setd1a on promoters and Mef2-bound enhancers. Notably, evolutionarily conserved Setd1a targets are associated with neuropsychiatric genetic risk burden. Reinstating Setd1a expression in adulthood rescues cognitive deficits. Finally, we identify LSD1 as a major counteracting demethylase for Setd1a and show that its pharmacological antagonism results in a full rescue of the behavioral and morphological deficits in Setd1a-deficient mice. Our findings advance understanding of how SETD1A mutations predispose to schizophrenia (SCZ) and point to novel therapeutic interventions.[SEP]SETD1A has relations: disease_protein with schizophrenia, disease_ protein with epilepsy, and protein_protein. SETD1B has relations with BOD1L1, E2F1, and SETD2B.", "label": "yes"}
{"id": "converted_63", "sentence1": "Are long non coding RNAs as conserved in sequence as protein coding genes?", "sentence2": "Most lncRNAs are under lower sequence constraints than protein-coding genes and lack conserved secondary structures, making it hard to predict them computationally., hey are under stronger selective pressure than neutrally evolving sequences-particularly in their promoter regions, which display levels of selection comparable to protein-coding genes., bout one-third seem to have arisen within the primate lineage.[SEP]GLI proteins bind promoters of Hh responsive genes to promote transcription. GLI proteins have relations with GLI1, GLI2, and GLI3.", "label": "no"}
{"id": "converted_2592", "sentence1": "Are there sex differences in the transcriptome of the mouse hippocampus?", "sentence2": "To better understand the possible molecular basis for the sex-biased nature of neurological disorders, we used a developmental series of female and male mice at 1, 2, and 4 months of age to assess both mRNA and protein in the hippocampus with RNA-sequencing and mass-spectrometry, respectively., The bulk of these differentially expressed genes are changed in both sexes at one or more ages, but a total of 198 transcripts are differentially expressed between females and males at one or more ages. The number of transcripts that are differentially expressed between females and males is greater in adult animals than in younger animals. Additionally, we identify 69 transcripts that show complex and sex-specific patterns of temporal regulation through postnatal development, 8 of which are heat-shock proteins. , Additionally, this analysis reveals sex differences in the transcriptome of the developing mouse hippocampus, and further clarifies the need to include both female and male mice in longitudinal studies involving molecular changes in the hippocampus.[SEP]Bioprocess_bioprocess with plastid rRNA transcription has relations with NPM3, MARS1, NIFK, SPIN1, and N PM3. RRNA transcription can also be used to make other proteins, such as n-methyl-D-methyltransferase (NMDT) or n-methyl-transcription (NMT)", "label": "yes"}
{"id": "converted_2782", "sentence1": "Can breastfeeding confer protection from type I diabetes?", "sentence2": "In the neonate and infant, among other benefits, lactation confers protection from future both type 1 and type 2 diabetes.[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]Relations: salivary gland type cancer of the breast has relations: disease_disease with breast cancer, disease_disease with breast cancer.", "label": "yes"}
{"id": "converted_2661", "sentence1": "Has rituximab been considered as a treatment for chronic fatigues syndrome? (November 2017)", "sentence2": " The use of rintatolimod and rituximab as well as counselling, behavioural and rehabilitation therapy programs may be of benefit for CFS/ME, but the evidence of their effectiveness is still limited. [SEP]Rituximab has relations with Rilotumumab, Fremanezumab and Seribantumab. It also has a relationship with Parsatuzumab as well as Alemtuzumb. It is not known if it has arelationship with Zytumab or Zyrtec.", "label": "yes"}
{"id": "converted_4223", "sentence1": "Has the companion diagnostic HercepTest received FDA approval?", "sentence2": "The FDA-Approved Breast Cancer HER2 Evaluation Kit (HercepTest; Dako) May Miss Some HER2-Positive Breast Cancers., HER2 fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) tests were performed on 52 cases using a US Food and Drug Administration (FDA)-approved kit (HercepTest, FDA kit) and a laboratory-developed test (LDT) with the HercepTest antibody and a Leica Bond automated stainer.[SEP]", "label": "yes"}
{"id": "converted_2916", "sentence1": "Is there any role for HUWE1 in MYC signalling?", "sentence2": "HUWE1 is a critical colonic tumour suppressor gene that prevents MYC signalling, DNA damage accumulation and tumour initiation., To determine the importance of HUWE1, we chose to examine its function in colorectal cancer, where it is mutated in up to 15 per cent of tumours. Modelling of identified mutations showed that they inactivate the E3 ubiquitin ligase activity of HUWE1. Genetic deletion of Huwe1 rapidly accelerated tumourigenic in mice carrying loss of the intestinal tumour suppressor gene Apc, with a dramatic increase in tumour initiation. Mechanistically, this phenotype was driven by increased MYC and rapid DNA damage accumulation leading to loss of the second copy of Apc The increased levels of DNA damage sensitised Huwe1-deficient tumours to DNA-damaging agents and to deletion of the anti-apoptotic protein MCL1. Taken together, these data identify HUWE1 as a bona fide tumour suppressor gene in the intestinal epithelium and suggest a potential vulnerability of HUWE1-mutated tumours to DNA-damaging agents and inhibitors of anti-apoptotic proteins.[SEP]Protein S human has relations: drug_drug with Peginterferon beta-1a. Regulation of intestinal epithelial structure maintenance has relations with NEUROD1. Disease_protein with IFNB1. anus neoplasm has relations. with IF NB1. protein tyrosine kinase inhibitor activity has. relations: molfunc_ protein with HYAL2.", "label": "yes"}
{"id": "converted_694", "sentence1": "Is there a phylogenetic analysis for HIV?", "sentence2": "The results of Burst and phylogenetic analysis suggested that the C. neoformans var. grubii strains could be separated into three nonredundant evolutionary groups (Burst group 1 to group 3). , Phylogenetic trees were constructed to evaluate the relationships between the variants, We analyzed pol (protease/reverse transcriptase) sequences from 135 newly diagnosed HIV-1-infected patients during the years 2009-2011. For phylogenetic relationships, sequences were aligned to the most recent reference data set from the Los Alamos database using BioEdit (version 7.1.3). The resulting alignment was analyzed with the Phylip package (version 3.67) building a neighbor-joining tree based on the Kimura two-parameter substitution model, . Phylogenetic analysis of gag gene were then performed using the MEGA 3.1 software, the gene distances were calculated by Distance program. There were three different HIV-1 subtypes including B, CRF01-AE and CRF07-BC present among twenty four MSMs in Zhengzhou, Phylogenetic analysis showed interpatient and intrapatient clustering of LTR nucleotide sequences.,  We evaluated the risk factors for intrafamilial transmission of HIV-1 infection through qualitative epidemiology following pol and env gene sequencing and phylogenetic analysis, Phylogenetic analysis has shown that the Siberian 10.RU.6637 isolate displays the highest sequence identity to the HIV-1 subtype AG forms circulating in Uzbekistan, Phylogenetic analysis showed that the evolutionary relationship of Env between HIV and SIV was the closest and they appeared to descend from a common ancestor, and the relationship of HIV and EIAV was the furthest, DI was confirmed when maximum sequence divergence was excessive and supported by phylogenetic analysis,  (HIV-1) dual infection (DI) has been associated with decreased CD4 T-cell counts and increased viral loads; however, the frequency of intrasubtype DI is poorly understood., The aim of this study was to investigate the phylogenetic relationships of HIV-1 subtype C strains from Bangladesh and related strains from other countries, and thereby clarify when and from where subtype C was introduced in the country and how it subsequently spread within Bangladesh,  This study characterized HCV genotype 5 sequences from South Africa, including six near full-length genomes, as well as the E1 region from an additional 12 genotype 5 samples. Phylogenetic analysis of these near full-length genome sequences revealed that all genotype 5 sequences formed a close cluster with high bootstrap support,  The evolutionary history of the B subregion was not as clear as the C subregion, as the short length of this region yielded poor phylogenetic results,  Finally, a phylogenetic tree was constructed to elucidate the observed pattern of HIV TDR[SEP]Relations: dentinogenesis imperfecta has relations: disease_phenotype_positive with Abnormality of the dental root, disease_phenotype_positive with Abnormality of the dental root, disease_phenotype_positive with Short dental roots, disease_phenotype_positive with Short dental roots, disease_phenotype_positive with Autosomal dominant inheritance, disease_phenotype_positive with Autosomal dominant inheritance, disease_protein with DSPP, disease_protein with DSPP, disease_phenotype_positive with Persistence of primary teeth, disease_phenotype_positive with Persistence of primary teeth.", "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]Relations: inflammatory bowel disease has relations: disease_phenotype_positive with Abnormal intestine morphology, disease_phenotype_positive with Abnormal intestine morphology, disease_phenotype_positive with Abnormal intestine morphology, disease_phenotype_positive with Abnormal intestine morphology, contraindication with Phenobarbital, contraindication with Phenobarbital, contraindication with Phenobarbital, contraindication with Phenobarbital, disease_protein with GHRL, disease_protein with GHRL.", "label": "yes"}
{"id": "converted_4699", "sentence1": "Are there roles for cohesin mutations in AML?", "sentence2": "Several landmark studies have shown that cohesin mutations perturb the balance between self-renewal and differentiation of hematopoietic stem and progenitor cells (HSPC). Emerging data now begin to uncover the molecular mechanisms that underpin this phenotype. Among these mechanisms is a role for cohesin in the control of inflammatory responses in HSPCs and myeloid cells. Inflammatory signals limit HSPC self-renewal and drive HSPC differentiation. Consistent with this, cohesin mutations promote resistance to inflammatory signals, and may provide a selective advantage for AML progression. [SEP] acute promyelocytic leukemia has relations with PML, GLI2, ASXL1, and Gingival bleeding. Disease_phenotype_positive with Somatic mutation, disease_phenotypes with Gingival mutation, and disease_protein withGLI2.", "label": "yes"}
{"id": "converted_550", "sentence1": "Does d-tubocurarine (d-TC) induces irreversible inhibition of nicotinic acetylcholine receptor (nAChR) at the neuromuscular junction?", "sentence2": "An integrated model describing the interaction of nondepolarizing neuromuscular blocking agents with reversible anticholinesterase agents is derived and compared with a naive model using experimental data obtained from four anesthetized dogs. Three consecutive but separate steady-state d-tubocurarine blocks (approximately 50, 70, and 90%) were induced in each of the four dogs and reversed by short edrophonium infusions., The ability of hexamethonium (C6) to reverse the neuromuscular blocking action of tubocurarine (Tc), Volatile anesthetics enhance the neuromuscular blockade produced by nondepolarizing muscle relaxants (NDMRs). The neuromuscular junction is a postulated site of this interaction. We tested the hypothesis that volatile anesthetic enhancement of muscle relaxation is the result of combined drug effects on the nicotinic acetylcholine receptor., Concentration-effect curves for the inhibition of acetylcholine-induced currents were established for vecuronium, d-tubocurarine, isoflurane, and sevoflurane. Subsequently, inhibitory effects of NDMRs were studied in the presence of the volatile anesthetics at a concentration equivalent to half the concentration producing a 50% inhibition alone. All individually tested compounds produced rapid and readily reversible concentration-dependent inhibition., The pharmacological diversity of the different isoforms of the nicotinic acetylcholine receptor arises from the diversity of the subunits that assemble to form the native receptors. The aim of this study was to investigate the actions of the muscle relaxants d-tubocurarine, pancuronium and vecuronium on different isoforms of nicotinic acetylcholine receptors, At all three receptor types, d-tubocurarine and pancuronium blocked the responses elicited by acetylcholine in a reversible manner. , As further evidence of anticholinesterase activity, methamidophos (1-100 microM) was able to reverse the blockade by d-tubocurarine, There was an initial partial reversal of the neuromuscular inhibition caused by tubocurarine, Isoflurane and sevoflurane enhance the receptor blocking effects of nondepolarizing muscle relaxants on nicotinic acetylcholine receptors., Because other purinergic 2X (P2X) receptor antagonists, NF023 and NF279, do not have the reverse effects on the neuromuscular blockade of d-TC, the effect of NF449 seems irrelevant to inhibition of P2X receptors., The association rate constant for Tc binding to sites on the nicotinic acetylcholine receptor appears to be very fast (k+D = 8.9 x 10(8) M-1 s-1) and comparable to that for acetylcholine (ACh)., The aim of this study was to investigate the mechanism for the reversal effect of NF449 (a suramin analogue) on the neuromuscular block induced by d-tubocurarine (d-TC)., Study of the reversal effect of NF449 on neuromuscular blockade induced by d-tubocurarine.[SEP]Relations: Tubocurarine has relations: drug_drug with Acetylcholine, drug_drug with Acetylcholine, drug_drug with Succinylcholine, drug_drug with Succinylcholine, drug_drug with Naltrexone, drug_drug with Naltrexone, drug_drug with Acetyldigoxin, drug_drug with Acetyldigoxin. Acetylcholine has relations: drug_drug with Tubocurarine, drug_drug with Tubocurarine.", "label": "no"}
{"id": "converted_4351", "sentence1": "Are circRNAs susceptible to degradation by RNase R?", "sentence2": "Currently, an increasing body of evidence has demonstrated that 1) majority of circRNAs are evolutionarily conserved across species, stable, and resistant to RNase R degradation, , Circular RNA (circRNA) has a closed-loop structure, and its 3' and 5' ends are directly covalently connected by reverse splicing, which is more stable than linear RNA., CircRNAs are a kind of closed circular RNA molecule widely existing in transcriptomes. Due to lack of free ends, they are not easily cleaved by RNase R, thus avoiding degradation. , Circular RNAs (circRNAs) are a class of newly-identified non-coding RNA that lack 5' (cap) and 3' (polyadenylation) ends and are linked by a covalent bond to form a closed loop structure. In comparison to linear RNAs, circRNAs are more resistant to exonuclease RNase R-mediated degradation with a much stronger stability due to the absence of 3' terminals, Circular RNAs (circRNAs) own unique capabilities to communicate with nucleic acids and ribonucleoproteins and are emerging as indispensable compositions of the regulatory messages encoded in the genome. Due to lack of 3' termini, circRNAs are more resistant to degradation by exonuclease RNase R and possess greater stability than linear RNAs. , RNase R is a strong 3' to 5' exoribonuclease, which efficiently degrades linear RNAs, such as mRNAs and rRNAs; therefore, the circular parts of lariat RNAs and the circRNAs can be segregated from eukaryotic total RNAs by their RNase R resistance., Lariat RNAs and circRNAs are both RNase R resistant RNAs., In comparison to linear RNAs, circRNAs are more resistant to exonuclease RNase R-mediated degradation with a much stronger stability due to the absence of 3' terminals., Due to lack of 3' termini, circRNAs are more resistant to degradation by exonuclease RNase R and possess greater stability than linear RNAs., Because circRNAs are not easily degraded by exonuclease RNase R, they can exist more stably in body fluids than linear RNAs., Therefore, it is essential to perform the RT-qPCR validation step only after linear RNAs have been degraded using an exonuclease such as ribonuclease R (RNase R)., is a strong 3' to 5' exoribonuclease, which efficiently degrades linear RNAs, such as mRNAs and rRNAs; therefore, the circular parts of lariat RNAs and the circRNAs can be segregated from eukaryotic total RNAs by their RNase R resistance. Thus, RNase, sion of circRNAs is prevalent in tissues and body fluids,and their abnormal expression is related to tumor progression.circRNAs are stable even under the treatment of RNase R because of their circular conformation.As circRNAs, e to lack of 3' termini, circRNAs are more resistant to degradation by exonuclease RNase R and possess greater stability than linear RNAs. Mo, e circRNAs are not easily degraded by exonuclease RNase R, they can exist more stably in body fluids than linear RNAs. Based,  is stable, difficult to cleave and resistant to RNA exonuclease or RNase R degradation. circRN, the unique structures, circRNAs are resistant to exonuclease RNase R and maintain stability more easily than linear RNAs. Rece, rison to linear RNAs, circRNAs are more resistant to exonuclease RNase R-mediated degradation with a much stronger stability due to the absence of 3' terminals. Conseque,  RT-PCR analysis showed that sheep circRNAs are resistant to RNase R digestion and are expressed in prenatal and postnatal pituitary glands. GO and , Currently, an increasing body of evidence has demonstrated that 1) majority of circRNAs are evolutionarily conserved across species, stable, and resistant to RNase R degradation, and often exhibit cell-specific, and tissue-specific/developmental-stage-specific expression and can be largely independent of the expression levels of the linear host gene-encoded linear RNAs; 2) the biogenesis of circRNAs via back-splicing is different from the canonical splicing of linear RNAs; 3) circRNA biogenesis is regulated by specific cis-acting elements and trans-acting factors; 4) circRNAs regulate biological and pathological processes by sponging miRNAs, binding to RNA-binding protein (RBP), regulators of splicing and transcription, modifiers of parental gene expression, and regulators of protein translation or being translated into peptides in various diseases; 5) circRNAs have been identified for their enrichment and stability in exosomes and detected in body fluids such as human blood, saliva, and cerebrospinal fluids, suggesting that these exo-circRNAs have potential applications as disease biomarkers and novel therapeutic targets; 6) several circRNAs are regulated by oxidative stress and mediate reactive oxygen species (ROS) production as well as promote ROS-induced cellular death, cell apoptosis, and inflammation; 7) circRNAs have also emerged as important regulators in atherosclerotic cardiovascular disease, metabolic disease, and cancers; 8) the potential mechanisms of several circRNAs have been described in diseases, hinting at their potential applications as novel therapeutic targets., To prove their circularity as well as biochemically enrich these transcripts, it has become standard in the field to use the 3'-5' exonuclease RNase R. Here, we demonstrate that standard protocols involving RNase R can fail to digest >20% of all highly expressed linear RNAs, but these shortcomings can largely be overcome., We propose that such an R-loop dependent ciRNA degradation likely represents a mechanism that on one hand limits ciRNA accumulation by recruiting RNase H1 and on the other hand resolves R-loops for transcriptional elongation at some GC-rich ciRNA-producing loci., As circular RNAs (circRNAs) are resistant to degradation by exonucleases, their abundance relative to linear RNAs can be used as a surrogate marker for mRNA stability in the absence of transcription., The synthetic circular sponge was resistant to digestion with RNase R. Luciferase assays and functional experiments showed that the circular multi-miR sponge was more stable than its linear counterpart., RNAs with highly structured 3' ends, including snRNAs and histone mRNAs, are naturally resistant to RNase R, but can be efficiently degraded once a poly(A) tail has been added to their ends., Thousands of eukaryotic protein-coding genes generate circular RNAs that have covalently linked ends and are resistant to degradation by exonucleases.[SEP]Relations: rRNA transcription has relations: bioprocess_bioprocess with 5S class rRNA transcription by RNA polymerase III, bioprocess_bioprocess with 5S class rRNA transcription by RNA polymerase III, bioprocess_bioprocess with ncRNA transcription, bioprocess_bioprocess with ncRNA transcription, bioprocess_protein with SIRT7, bioprocess_protein with SIRT7. protein binding has relations: molfunc_protein with RNASE10, molfunc_protein with RNASE10, molfunc_protein with RNASE1, molfunc_protein with RNASE1.", "label": "no"}
{"id": "converted_2501", "sentence1": "Down's syndrome occurs when an individual has an extra copy or part of a copy of chromosome 21, yes or no?", "sentence2": "Down syndrome (DS; trisomy 21) is the most common survivable disorder due to aneuploidy., Down syndrome (DS), trisomy 21, is caused by increased dose of genes present on human chromosome 21 (HSA21), Down syndrome, or Trisomy 21, is the most frequently occurring chromosomal abnormality in live-born children. , Down syndrome (DS), caused by trisomy of chromosome 21,, Submicroscopic duplication of chromosome 21 and trisomy 21 phenotype (Down syndrome)., Trisomy 21 or Down syndrome is a chromosomal disorder resulting from the presence of all or part of an extra Chromosome 21., Down syndrome is a genetic disorder, occurring when an individual has all or part of an extra copy of chromosome 21., Downs syndrome (DS) occurs due to an extra copy of chromosome 21., Down syndrome, which arises in individuals carrying an extra copy of chromosome 21, is associated with a greatly increased risk of early-onset Alzheimer disease., Aneuploidy refers to the presence of an extra copy of a specific chromosome, or trisomy, as seen in Down's syndrome (trisomy 21), or the absence of a single chromosome, or monosomy, as seen in Turner syndrome (a single X chromosome in females: 45, X)., Down syndrome (DS) or Trisomy 21 (Ts21) is caused by the presence of an extra copy of all or part of human chromosome 21 (Hsa21) and is the most frequent survivable congenital chromosomal abnormality., Down syndrome (DS) is a major cause of mental retardation and heart disease. Although it is usually caused by the presence of an extra chromosome 21, a subset of the diagnostic features may be caused by the presence of only band 21q22., Down syndrome is usually caused by complete trisomy 21., Down syndrome, the most frequent genetic disorder, is characterized by an extra copy of all or part of chromosome 21., Down syndrome (DS), caused by an extra copy of chromosome 21, affects 1 in 750 live births and is characterized by cognitive impairment and a constellation of congenital defects., Down syndrome (DS) results from one extra copy of human chromosome 21 and leads to several alterations including intellectual disabilities and locomotor defects., Down's syndrome results from the production of three copies of chromosome 21 within a cell. , Downs syndrome (DS) occurs due to an extra copy of chromosome 21., Trisomy 21 (Ts21) is the most common live-born human aneuploidy; it results in a constellation of features known as Down's syndrome (DS)., Down syndrome comprises multiple malformations and is due to trisomy of chromosome 21., n 1959, J. Lejeune, M. Gautier, and R. Turpin demonstrated that the children with Down syndrome had an extra copy of chromosome 21., To develop a reliable and specific method for rapid prenatal diagnosis of Trisomy 21 (Down syndrome)., Trisomy 21 Down syndrome is the most common genetic cause for congenital malformations and intellectual disability, Down syndrome, characterized by an extra chromosome 21 is the most common genetic cause for congenital malformations and learning disability. [SEP]Relations: Down syndrome has relations: disease_protein with S100B, disease_protein with S100B, disease_phenotype_positive with Sporadic, disease_phenotype_positive with Sporadic, disease_protein with RAD21, disease_protein with RAD21, disease_phenotype_positive with Abnormality of the lymphatic system, disease_phenotype_positive with Abnormality of the lymphatic system, disease_protein with NRAS, disease_protein with NRAS.", "label": "yes"}
{"id": "converted_3070", "sentence1": "Are recessive coding variants responsible for the majority of undiagnosed nonconsanguineous individuals?", "sentence2": "Our results suggest that recessive coding variants account for a small fraction of currently undiagnosed nonconsanguineous individuals, and that the role of noncoding variants, incomplete penetrance, and polygenic mechanisms need further exploration.[SEP]", "label": "no"}
{"id": "converted_124", "sentence1": "Is DITPA a thyroid hormone analog utilized in experimental and clinical studies", "sentence2": "DITPA normalized the elevated serum T(3) and TSH when the dose reached 1 mg/kg · d and T(4) and rT(3) increased to the lower normal range., The identification of 3,5-diiodothyropropionic acid (DITPA) that binds to both α- and β-type TRs with relatively low affinity was unique in that this analog improves left ventricular function in heart failure as well as lowers cholesterol., Treatment with DITPA attenuates the acute inflammatory response and reduces myocardial infarct size., Thus DITPA administration impairs baseline cardiac parameters in mice and can be fatal during in vivo acute myocardial I/R., DITPA improved some hemodynamic and metabolic parameters, but there was no evidence for symptomatic benefit in congestive heart failure, The results suggested that DITPA can promote a healthy vasculature independently from its thyroid-related metabolic effects. ,  Moreover, DITPA and T(4) were efficacious in preventing effects of hypothyroidism on cardiac function and BVD, Both T4 and DITPA had beneficial effects on chamber remodeling, which was most likely due to beneficial changes in cell shape and improved vascular supply., The thyroid analog DITPA enhances endothelial nitric oxide and beta-adrenergic-mediated vasorelaxation by increasing nitric oxide in the vasculature.[SEP]3,5-diiodothyropropionic acid has relations with Ethionamide, Motesanib, Ritonavir, Escitalopram, Flumatinib, and Moteinib. It is also related with Moteinsanib and Roteinavir. It can also be used as a drug by itself.", "label": "yes"}
{"id": "converted_1964", "sentence1": "Is there any involvement of the long non-coding RNA Gomafu in schizophrenia?", "sentence2": "The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing., Here, we profile these transcriptomic responses and show that long non-coding RNAs (lncRNAs) are dynamically regulated by neuronal activation, including acute downregulation of the lncRNA Gomafu, previously implicated in brain and retinal development. Moreover, we demonstrate that Gomafu binds directly to the splicing factors QKI and SRSF1 (serine/arginine-rich splicing factor 1) and dysregulation of Gomafu leads to alternative splicing patterns that resemble those observed in SZ for the archetypal SZ-associated genes DISC1 and ERBB4. Finally, we show that Gomafu is downregulated in post-mortem cortical gray matter from the superior temporal gyrus in SZ. These results functionally link activity-regulated lncRNAs and alternative splicing in neuronal function and suggest that their dysregulation may contribute to neurological disorders., Gomafu/MIAT/Rncr2 is a long noncoding RNA that has been proposed to control retinal cell specification, stem cell differentiation and alternative splicing of schizophrenia-related genes., The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing, Moreover, we demonstrate that Gomafu binds directly to the splicing factors QKI and SRSF1 (serine/arginine-rich splicing factor 1) and dysregulation of Gomafu leads to alternative splicing patterns that resemble those observed in SZ for the archetypal SZ-associated genes DISC1 and ERBB4. , Finally, we show that Gomafu is downregulated in post-mortem cortical gray matter from the superior temporal gyrus in SZ. , The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing.[SEP]Regulation of neural retina development has relations with PTF1A, SIX3, DLL4 and DLL5. Bioprocess has negative and positive regulation of neighborly retina development.", "label": "yes"}
{"id": "converted_3776", "sentence1": "Is MAGE-A3 immunotherapeutic effective for non-small-cell lung cancer?", "sentence2": "INTERPRETATION: Adjuvant treatment with the MAGE-A3 immunotherapeutic did not increase disease-free survival compared with placebo in patients with MAGE-A3-positive surgically resected NSCLC. Based on our results, further development of the MAGE-A3 immunotherapeutic for use in NSCLC has been stopped., In the overall population, median disease-free survival was 60·5 months (95% CI 57·2-not reached) for the MAGE-A3 immunotherapeutic group and 57·9 months (55·7-not reached) for the placebo group (hazard ratio [HR] 1·02, 95% CI 0·89-1·18; p=0·74). Of the patients who did not receive chemotherapy, median disease-free survival was 58·0 months (95% CI 56·6-not reached) in those in the MAGE-A3 group and 56·9 months (44·4-not reached) in the placebo group (HR 0·97, 95% CI 0·80-1·18; p=0·76). Because of the absence of treatment effect, we could not identify a gene signature predictive of clinical benefit to MAGE-A3 immunotherapeutic. , uvant treatment with the MAGE-A3 immunotherapeutic did not increase disease-free survival compared with placebo in patients with MAGE-A3-positive surgically resected NSCLC. Ba[SEP]Small cell lung carcinoma has relations with GRIK3, CSF3, TP73, EPHB3, TAOK3, and TP73. It is also associated with TP73 and E PHB3.", "label": "no"}
{"id": "converted_1409", "sentence1": "Does Apolipoprotein E (ApoE) have anti-inflammatory activity?", "sentence2": " have previously reported that apolipoprotein E (apoE), a protein component of very-low-density lipoproteins (VLDL) and high-density lipoproteins and a potent plasma-borne atheroprotective factor, exerts anti-inflammatory activity in macrophages by switching the activation profile from M1 (\"classic\") to M2 (\"alternative\") in a process involving signaling via low-density lipoprotein receptor , anti-inflammatory activity in macrophages , Small peptides corresponding to the receptor-binding region of apoE mimic the anti-inflammatory activity of the apoE , Apolipoprotein (apo) E-containing high-density lipoprotein (HDL) has antioxidant, anti-inflammatory and anti-atherogenic properties[SEP]APOE has relations: molfunc_protein with antioxidant activity, bioprocess_ protein with negative regulation of inflammatory response. APOE also has relations with hyperlipoproteinemia, cellcomp_protein, and lipoprotein particle. The APOE gene is responsible for the development of the human papillomavirus (HPV), a virus that can cause cancer.", "label": "yes"}
{"id": "converted_2407", "sentence1": "Has the proteome of mice hippocampus been analysed?", "sentence2": "We employed a discovery-based proteomic approach in subcellular fractions of hippocampal tissue from chronic intermittent alcohol (CIE)-exposed C57Bl/6J mice to gain insight into alcohol-induced changes in GluN2B signaling complexes. ,  We employed shotgun liquid chromatography-mass spectrometry (LC-MS) proteomic and metabonomic profiling approaches on prefrontal cortex (PFC) and hippocampal (HPC) tissue from Df(16)A+/-mice, a model of the 22q11.2 deletion syndrome. ,  Molecular alterations in the frontal cortex and hippocampus ofTsc1+/-and control mice, with or without rapamycin treatment, were investigated. A quantitative mass spectrometry-based shotgun proteomic approach (LC-MSE) was employed as an unbiased method to detect changes in protein levels., This dataset reports on the analysis of mouse hippocampus by LC-MS/MS, from mice fed a diet that was either deficient in n-3 FA (n-3 Def) or sufficient in n-3 FA (n-3 Adq). , Using isobaric tags for relative and absolute quantitation (iTRAQ) and proteomic methods, here we identified learning-induced changes in the hippocampal proteome of non-transgenic (NonTg) and 3 × Tg-AD mice, a widely used animal model of AD. [SEP]Hippocampus fimbria has relations: anatomy_anatomy with central nervous system cell part cluster. frontal cortex has relations with HIPK3, anatomy_protein_present with HIPk3, and anatomy_ protein_present with HIPHK4, and HIPK2, among others.", "label": "yes"}
{"id": "converted_4037", "sentence1": "Is Tocilizumab (Actemra) used to block/antagonize the  IL-6 receptor?", "sentence2": "Preliminary clinical results have indicated that antagonism of the IL-6 receptor (IL-6R), including with the FDA-approved humanized monoclonal antibody tocilizumab, can improve the outcomes of patients with severe or critical COVID-19 while maintaining a good safety profile., Tocilizumab, an anti-IL-6 receptor antibody, and corticosteroids were initially used to treat the increase in acute inflammatory proteins and the anasarca, resulting in decreased cytokine levels. , Tocilizumab, a monoclonal antibody against the IL-6 receptor, was initiated at a dose of 8 mg/kg every 4 weeks., we randomly assigned patients with type 2 diabetes or obesity to intravenous tocilizumab (an IL-6 receptor antagonist) ,  Clinical studies are investigating whether tocilizumab (anti-IL-6 receptor) can help preserve beta cell function in patients recently diagnosed with T1D, Tocilizumab (RoActemra or Actemra) is a recombinant humanized monoclonal antibody that acts as an interleukin (IL)-6 receptor antagonist., To increase the number of cycles of antigen binding and lysosomal degradation, we engineered tocilizumab (Actemra), an antibody against the IL-6 receptor (IL-6R), to rapidly dissociate from IL-6R within the acidic environment of the endosome (pH 6.0) while maintaining its binding affinity to IL-6R in plasma (pH 7.4)., Tocilizumab (Actemra; Genentech, Inc) is the first biologic therapy targeting the cytokine interleukin 6 (IL-6)., over, our findings showed that combination of tocilizumab (Actemra; Roche), an anti-IL-6R monoclonal antibody, with carboplatin synergistically inhibited growth and proliferation of the EOC cells and the most direct axis for IL-6 gene expression was NF-κB pathway.CONC, Roche is co-developing tocilizumab (Actemra, RoActemra), a humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody, with Chugai Pharmaceutical., Tocilizumab (TCZ) is a compound that inhibits the IL-6 receptor., Tocilizumab (TCZ), is a recombinant humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody which has a main use in the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis (sJIA) and polyarticular juvenile idiopathic arthritis (pJIA)., the US Food and Drug Administration accepted a complete-response submission for the use of Actemra (tocilizumab), the first humanized IL-6 receptor-inhibiting monoclonal antibody, for the treatment of RA. Although thi, increase the number of cycles of antigen binding and lysosomal degradation, we engineered tocilizumab (Actemra), an antibody against the IL-6 receptor (IL-6R), to rapidly dissociate from IL-6R within the acidic environment of the endosome (pH 6.0) while maintaining its binding affinity to IL-6R in plasma (pH 7.4). Studies usin,  present study, we have shown that the humanized anti-IL-6 receptor tocilizumab (Actemra) is also a potent inhibitor of IL-8 in TNBC cells. Similar ef, Roche is co-developing tocilizumab (Actemra, RoActemra), a humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody, with Chugai Pharmaceutical. Tocili, tory gene activation is inhibited in vitro by tocilizumab, a humanized antibody to IL6 receptor (IL6R). Tocilizumab, These lines of evidence indicate that tocilizumab is able to bind to both sIL-6R and mIL-6R and to inhibit IL-6 binding to its receptors, leading to the blockade of the IL-6 signaling through both sIL-6R and mIL-6R, but not block the signaling of other IL-6 family cytokines., Tocilizumab inhibits signal transduction mediated by both mIL-6R and sIL-6R, but not by the receptors of other members of IL-6 cytokine family., In addition, tocilizumab had the ability to bind to human IL-6R expressing COS-7 cells and to suppress the growth of the IL-6-dependent myeloma cell line, KPMM2., To characterize the biological activity of tocilizumab, a humanized anti-human interleukin-6 receptor (IL-6R) monoclonal antibody, we examined its binding activity to both soluble IL-6R (sIL-6R) and membrane bound IL-6R (mIL-6R) and its neutralizing activity to other IL-6 family cytokines., Tocilizumab inhibited the proliferation of BaF/IL-6R induced by IL-6, but did not inhibit the proliferation of BaF/IL-11R, BaF/OSMR, BaF/LIFR and BaF/CNTFR cells induced by their corresponding cytokines., Moreover, tocilizumab suppressed the IL-6/sIL-6R complex-induced proliferation of human gp130-transfected cell, BAF-h130., In addition, tocilizumab had the ability to dissociate IL-6 and sIL-6R from their preformed complex., ELISA assay demonstrated that tocilizumab bound to sIL-6R and inhibited IL-6 binding to sIL-6R in a dose-dependent manner., Tocilizumab recognizes both the membrane-bound and the soluble form IL-6R and specifically blocks IL-6 actions., Humanized antihuman IL-6 receptor antibody, tocilizumab., Tocilizumab is a humanized antihuman IL-6 receptor antibody designed using genetic engineering technology., Tocilizumab is expected to ameliorate the autoimmune inflammatory diseases with IL-6 overproduction and has been clinically developed as a therapeutic agent for RA, systemic-onset and articular types of JIA, Crohn's disease, etc., Tocilizumab/Actemra is an anti-IL-6R antibody, which can competitively block IL-6 binding to the IL-6R., Tocilizumab (TCZ; RoActemra® or Actemra®) is a recombinant humanized monoclonal antibody that acts as an interleukin 6 (IL-6) receptor antagonist., In 2009 the US Food and Drug Administration accepted a complete-response submission for the use of Actemra (tocilizumab), the first humanized IL-6 receptor-inhibiting monoclonal antibody, for the treatment of RA., Tocilizumab binds to the interleukin-6 receptor (IL-6R) and thereby blocks signaling of the pro-inflammatory cytokine IL-6., Tocilizumab (RoActemra(®); Actemra(®)) is a recombinant humanized monoclonal antibody that acts as an interleukin-6 receptor antagonist.[SEP]Relations: Tocilizumab has relations: drug_protein with IL6R, drug_protein with IL6R, drug_drug with Elagolix, drug_drug with Elagolix, drug_drug with Acteoside, drug_drug with Acteoside, drug_drug with Metronidazole, drug_drug with Metronidazole, drug_drug with Atezolizumab, drug_drug with Atezolizumab.", "label": "yes"}
{"id": "converted_2327", "sentence1": "Is ACI-35 a passive vaccine?", "sentence2": "Two active vaccines targeting either nonphosphorylated (AAD-vac1) and phosphorylated tau (ACI-35) have entered Phase I testing.[SEP]", "label": "no"}
{"id": "converted_1032", "sentence1": "Is there association of matrix metalloproteinases with behaviour of pituitary adenomas?", "sentence2": "While detailed histological subtyping remains the best independent predictor of aggressive behavior in the majority of cases, evidence suggests that the additional analyses of FGFR4, MMP, PTTG, Ki-67, p53, and deletions in chromosome 11 may contribute to decisions concerning management of aggressive pituitary adenomas., We observed elevation of MMP-2 and -9 expression and consequent 3-D cell invasion in cells under-expressing RECK. ,  Based on the significance of matrix metalloproteinases (MMPs) for tumor growth and angiogenesis, we have studied the effect of batimastat (BB-94), a synthetic MMPs inhibitor (MMPI) on the progression of prolactin-secreting pituitary adenoma in rats. , Inhibition of estrogen-induced pituitary tumor growth and angiogenesis in Fischer 344 rats by the matrix metalloproteinase inhibitor batimastat., The results of our study provide evidence for an inhibitory effect of batimastat, a synthetic MMPI, on the growth and angiogenesis in an experimental model of human prolactinoma., In summary, the differential expression of extracellular matrix components, integrins and matrix metalloproteinase contributes to the control of pituitary hormone production and cell proliferation during tumorigenesis., Data on the dural invasiveness of pituitary adenomas have been correlated to the expression of matrix metalloproteinases (e.g. MMP-9). , We found no correlation of MMP-9 expression and tumour invasion., The matrix metalloproteinases (MMPs) and their nature inhibitors-the tissue inhibitors of metalloproteinases (TIMPs) may play a central role in these processes., CONCLUSIONS: TIMP-1 and TIMP-2 may play a key role in invasive pituitary adenomas to biological behavior., The matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases that are able to degrade the extracellular matrix and allow angiogenesis and tumor invasion. , MMP-9 expression did not differ between noninvasive tumors and normal pituitary gland, or between different sized prolactinomas. MMP-9 expression was related to aggressive tumor behavior. It was higher in invasive macroprolactinomas (P = 0.003) when compared with noninvasive macroprolactinomas or the normal anterior pituitary gland. In addition, although there was no difference in whether MMP-9 was present or not when nonfunctioning adenomas that recurred were compared with those that did not, samples of recurrent tumor at the second presentation were more likely to express MMP-9 (P = 0.01). Pituitary carcinomas were significantly more likely to be MMP-9 positive compared with normal anterior pituitary gland (P = 0.05), but there was no difference from invasive adenomas. Angiogenesis assessed by vascular density was related to MMP-9 expression (P<0.05). In summary, we have shown the presence of MMP-9 expression in some invasive and recurrent pituitary adenomas, and in the majority of pituitary carcinoma. The mechanisms whereby MMP-9 expression influences tumor recurrence and invasiveness, and its association with angiogenesis, remains to be elucidated. , Beside the digestion of the extracellular matrix during tumor invasion and metastasis, more recently, new functions for matrix metalloproteinases (MMPs) have been proposed. , CONCLUSION: No correlation could be established between the invasive potential of tumors and MMP-1, -2, and -3 expression levels. , Matrix metalloproteinase 2 and 9 expression correlated with cavernous sinus invasion of pituitary adenomas., Data on the dural invasiveness of pituitary adenomas have been correlated to the expression of matrix metalloproteinases (e.g., We found surprisingly high levels of MMP activity and low levels of tissue inhibitor of metalloproteinases, indicating a high level of extracellular matrix-degrading activity in pituitary adenomas., The matrix metalloproteinases (MMPs) and their nature inhibitors-the tissue inhibitors of metalloproteinases (TIMPs) may play a central role in these processes. , We found surprisingly high levels of MMP activity and low levels of tissue inhibitor of metalloproteinases, indicating a high level of extracellular matrix-degrading activity in pituitary adenomas., There was an association between the invasion of pituitary adenomas and Ki-67 LI (P = 0.039) or the expression of VEGF (P &lt; 0.001) and MMP-9 (P &lt; 0.001). But c-myc LI and bcl-2 expression have no association with invasiveness of pituitary adenomas (P = 0.061 vs., nm23 and MMP-9 have associations with invasiveness of pituitary adenomas,, Matrix metalloproteinase secreted by pituitary cells can release growth factors from the extracellular matrix that, in turn, control pituitary cell proliferation and hormone secretion. In summary, the differential expression of extracellular matrix components, integrins and matrix metalloproteinase contributes to the control of pituitary hormone production and cell proliferation during tumorigenesis., There was an association between the invasion of pituitary adenomas and Ki-67 LI (P = 0.039) or the expression of VEGF (P &lt; 0.001) and MMP-9 (P &lt; 0.001)., Although our study has shown that MVD and the expression of VEGF, Ki-67, nm23 and MMP-9 have associations with invasiveness of pituitary adenomas, they are lack of specificity.[SEP]Relations: Pituitary adenoma has relations: disease_phenotype_positive with pituitary adenoma, disease_phenotype_positive with pituitary adenoma. Activation of Matrix Metalloproteinases has relations: pathway_protein with TIMP2, pathway_protein with TIMP2, pathway_protein with TIMP2, pathway_protein with TIMP2, pathway_protein with TIMP2, pathway_protein with TIMP2, pathway_protein with MMP7, pathway_protein with MMP7.", "label": "yes"}
{"id": "converted_3938", "sentence1": "Is carpal tunnel syndrome a type of nerve entrapment?", "sentence2": " Carpal tunnel syndrome (CTS) is a common entrapment neuropathy, often requiring carpal tunnel release (CTR) surgery., Carpal tunnel syndrome (CTS) is an entrapment neuropathy accounting for up to 90% of nerve compression syndromes,  Carpal tunnel syndrome (CTS) is the most frequent entrapment neuropathy in humans. , Carpal tunnel syndrome (CTS) is the most common focal entrapment mononeuropathy, comprising medium nerve chronic inflammation and fibrosis., Carpal tunnel syndrome (CTS) is the most common nerve entrapment neuropathy which is the result of the compression of the median nerve in the wrist. , Dear sir, one of the most common entrapment neuropathy syndromes in clinical practice is \"Entrapment of median nerve in carpal tunnel\" also called \"Carpal tunnel syndrome (CTS)\" (Aydin et al., 2007; Huisstede et al., 2010)., BACKGROUND: Carpal tunnel syndrome (CTS) is the most common type of peripheral nerve entrapment and is a significant cause of morbidity., BACKGROUND: Carpal tunnel syndrome and ulnar nerve entrapment at the elbow are the most common entrapment neuropathies seen in adults., Entrapment neuropathies are of various types, but the most common type is carpal tunnel syndrome., Carpal Tunnel Syndrome and Other Entrapment Neuropathies., Unlike Guyon's canal syndrome, carpal tunnel syndrome (CTS) is the most common nerve entrapment of the upper extremity.,  chronic renal failure tend to develop peripheral nerve entrapment and carpal tunnel syndrome is the best-known peripheral entrapment neuropathy among them. Contrary to ca, Carpal tunnel syndrome (CTS) is a common form of peripheral nerve entrapment, which is observed due to compression of the median nerve at the level of the carpal tunnel in the wrist. Bifi, INTRODUCTION: Carpal tunnel syndrome (CTS) is considered a simple entrapment of the median nerve at the carp, Compressive neuropathy of the median nerve at the level of the carpal tunnel, known as carpal tunnel syndrome, is the most common entrapment neuropathy, affecting about 0.1-1% of the general population. Magne, BACKGROUND: Carpal tunnel syndrome (CTS) is entrapment of median nerve in carpal tunnel of th, Dear sir, one of the most common entrapment neuropathy syndromes in clinical practice is \"Entrapment of median nerve in carpal tunnel\" also called \"Carpal tunnel syndrome (CTS)\" (Aydin et al., 2007; Huisstede et al., 2010). This syndr, OBJECTIVE: Carpal tunnel syndrome (CTS) is a common median nerve entrapment neuropathy characterized by pain, paresthesias, diminished peripheral nerve conduction velocity (NCV) and maladaptive functional brain neuroplastici, Carpal tunnel syndrome (CTS), caused by entrapment of the median nerve in the carpal tunnel, impairs hand function including dexterous manipulation. The , This review focuses on three of the most common entrapment neuropathies in the upper limbs: carpal tunnel syndrome (median nerve entrapment at the wrist), cubital tunnel syndrome (ulnar nerve entrapment at the elbow), and radial tunnel syndrome (posterior interosseous nerve entrapment)., Electrodiagnostic (EDX) testing is usually an essential part of the evaluation of entrapment neuropathies, and examinations for the most common entrapment neuropathies, carpal tunnel syndrome and ulnar neuropathy at the elbow, constitute a significant part of the daily work in EDX laboratories., This study reviews the existing, more or less, detailed EDX criteria or practice parameters that are suggested by consensus groups in peer-reviewed journals for the most common entrapment neuropathies: carpal tunnel syndrome, ulnar neuropathy at the elbow, common peroneal (fibular) neuropathy at the fibular head, and tibial neuropathy at the tarsal tunnel., This report demonstrates that the Semmes-Weinstein monofilament test and nerve conduction studies can identify entrapment of the palmar cutaneous branch of the median nerve concomitant with carpal tunnel syndrome., Entrapment neuropathy of the palmar cutaneous branch of the median nerve concomitant with carpal tunnel syndrome: a case report., A case of the entrapment neuropathy of the palmar cutaneous branch of the median nerve, concomitant with carpal tunnel syndrome is presented., The entrapment syndromes discussed are suprascapular nerve entrapment, carpal tunnel syndrome, cubital tunnel syndrome, meralgia paraesthetica, thoracic outlet syndrome and anterior interosseous nerve syndrome., Carpal tunnel syndrome is a neuropathy resulting from compression of the median nerve as it passes through a narrow tunnel in the wrist on its way to the hand., More typically, carpal tunnel syndrome is the most common peripheral entrapment neuropathy encountered in industry., Carpal tunnel syndrome is the most frequently encountered peripheral nerve entrapment., Carpal tunnel syndrome, an entrapment neuropathy of the median nerve, is rarely seen in childhood., Carpal tunnel syndrome (CTS) is the most common type of peripheral nerve entrapment and is a significant cause of morbidity., Carpal tunnel syndrome (CTS) is a nerve entrapment disorder, involving the median nerve when it passes the carpal tunnel at the wrist., The carpal tunnel syndrome is the most frequent entrapment syndrome of peripheral nerves., BACKGROUND: Compression of the median nerve at the wrist, or carpal tunnel syndrome, is the most commonly recognized nerve entrapme, Carpal tunnel syndrome is the most common of the median nerve entrapments., BACKGROUND: Carpal tunnel syndrome (CTS) is by far the most common entrapment neuropathy (, Introduction: Carpal tunnel syndrome, entrapment of median nerve at the wrist, is one of the most commonly encountered peripheral neuropathies in the up, Carpal tunnel syndrome, a median nerve entrapment neuropathy, is characterized by sensorimotor deficits., Carpal tunnel syndrome (CTS) is a common form of peripheral nerve entrapment, which is observed due to compression of the median nerve at the level of the carpal tunnel in the wrist., [Carpal tunnel syndrome and other nerve entrapment syndromes].[SEP]Relations: carpal tunnel syndrome has relations: disease_disease with nerve compression syndrome, disease_disease with nerve compression syndrome, disease_disease with nerve compression syndrome, disease_disease with nerve compression syndrome, disease_disease with genetic peripheral neuropathy, disease_disease with genetic peripheral neuropathy, disease_disease with genetic peripheral neuropathy, disease_disease with genetic peripheral neuropathy, disease_phenotype_positive with Constrictive median neuropathy, disease_phenotype_positive with Constrictive median neuropathy.", "label": "yes"}
{"id": "converted_1139", "sentence1": "Are ACTA1 (alpha actin) and NEB (nebulin) genes related to nemaline myopathy?", "sentence2": "Nemaline myopathy (NM) is a group of congenital myopathies, characterized by the presence of distinct rod-like inclusions \"nemaline bodies\" in the sarcoplasm of skeletal muscle fibers. To date, ACTA1, NEB, TPM3, TPM2, TNNT1, and CFL2 have been found to cause NM., Nemaline myopathy (NM) is the most common congenital myopathy and is caused by mutations in various genes including NEB (nebulin), TPM2 (beta-tropomyosin), TPM3 (gamma-tropomyosin), and ACTA1 (skeletal alpha-actin). 20-25% of NM cases carry ACTA1 defects and these particular mutations usually induce substitutions of single residues in the actin protein. , Nemaline myopathy (NM) is a genetically and clinically heterogenous muscle disorder, which is myopathologically characterized by nemaline bodies. Mutations in six genes have been reported to cause NM: Nebulin (NEB Pelin 1999), alpha-skeletal muscle actin (ACTA1 Nowak 1999), alpha-slow tropomyosin (TPM3 Laing 1995), beta-tropomyosin (TPM2 Donner 2002), slow troponin T (TNNT1 Johnston 2000) and cofilin 2 (CFL2 Agrawal 2007). The majority of cases are due to mutation in NEB and ACTA1. , Nemaline myopathy is a heterogenous form of congenital myopathy characterised by a variable spectrum of clinical features, predominated in the severe form by profound muscle hypotonia and weakness accompanied by respiratory insufficiency. The clinical variability, with differing age of onset and severity of symptoms makes the diagnosis of nemaline myopathy difficult in some cases. Severe forms of nemaline myopathy may be caused by mutation of a number of different genes: skeletal muscle actin (ACTA1), nebulin (NEB) and alpha-tropomyosin (TPM3), all of which encode components of the sarcomeric thin filaments of skeletal muscle. , Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes. , We report muscle MRI findings of 10 patients from 8 families with nemaline myopathy. Patients with involvement of the nebulin (NEB) gene showed a consistent pattern of selective muscle involvement corresponding to clinical severity., Patients with nemaline myopathy secondary to mutations in the skeletal muscle alpha-actin (ACTA1) gene showed diffuse involvement of thigh and leg muscles with relative sparing of the gastrocnemii., Congenital myopathies are clinical and genetic heterogeneous disorders characterized by skeletal muscle weakness ranging in severity. Three major forms have been identified: actin myopathy, intranuclear rod myopathy, and nemaline myopathy. Nemaline myopathy is the most common of these myopathies and is further subdivided into seven groups according to severity, progressiveness, and age of onset. At present, five genes have been linked to congenital myopathies. These include alpha-actin (ACTA1), alpha- and beta-tropomyosin (TPM3 and TPM2), troponin T (TNNT1), and nebulin (NEB). , Nemaline myopathy is a structural congenital myopathy which may show both autosomal dominant and autosomal recessive inheritance patterns. Mutations in three different genes have been identified as the cause of nemaline myopathy: the gene for slow alpha-tropomyosin 3 (TPM3) at 1q22-23, the nebulin gene (NEB) at 2q21.1-q22, and the actin gene (ACTA1) at 1q42., Nemaline myopathy is a clinically and genetically heterogeneous condition. The clinical spectrum ranges from severe cases with antenatal or neonatal onset and early death to late onset cases with only slow progression. Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42. , Nemaline myopathy (NM) is the most common congenital myopathy and is caused by mutations in various genes including NEB (nebulin), TPM2 (beta-tropomyosin), TPM3 (gamma-tropomyosin), and ACTA1 (skeletal alpha-actin)., Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42., Five genes have now been associated with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1)., Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes., Severe forms of nemaline myopathy may be caused by mutation of a number of different genes: skeletal muscle actin (ACTA1), nebulin (NEB) and alpha-tropomyosin (TPM3), all of which encode components of the sarcomeric thin filaments of skeletal muscle., Five genes have now been associated with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1)., Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42., Mutations in three different genes have been identified as the cause of nemaline myopathy: the gene for slow alpha-tropomyosin 3 (TPM3) at 1q22-23, the nebulin gene (NEB) at 2q21.1-q22, and the actin gene (ACTA1) at 1q42., Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes, Five genes have now been associated with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1), Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42, Nemaline myopathy (NM) is the most common congenital myopathy and is caused by mutations in various genes including NEB (nebulin), TPM2 (beta-tropomyosin), TPM3 (gamma-tropomyosin), and ACTA1 (skeletal alpha-actin), Five genes have now been associated with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1), Nemaline myopathy (NM) is the most common congenital myopathy and is caused by mutations in various genes including NEB (nebulin), TPM2 (beta-tropomyosin), TPM3 (gamma-tropomyosin), and ACTA1 (skeletal alpha-actin), Mutations in three different genes have been identified as the cause of nemaline myopathy: the gene for slow alpha-tropomyosin 3 (TPM3) at 1q22-23, the nebulin gene (NEB) at 2q21.1-q22, and the actin gene (ACTA1) at 1q42, Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42, Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes, Severe forms of nemaline myopathy may be caused by mutation of a number of different genes: skeletal muscle actin (ACTA1), nebulin (NEB) and alpha-tropomyosin (TPM3), all of which encode components of the sarcomeric thin filaments of skeletal muscle[SEP]Relations: nemaline myopathy has relations: disease_protein with ACTA1, disease_protein with ACTA1, disease_disease with alpha-actinopathy, disease_disease with alpha-actinopathy, disease_protein with NEB, disease_protein with NEB, disease_disease with qualitative or quantitative defects of alpha-actin, disease_disease with qualitative or quantitative defects of alpha-actin. alpha-actinopathy has relations: disease_disease with nemaline myopathy, disease_disease with nemaline myopathy.", "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]Relations: Nivolumab has relations: drug_drug with Avelumab, drug_drug with Avelumab, drug_drug with Urelumab, drug_drug with Urelumab, drug_drug with Cemiplimab, drug_drug with Cemiplimab. urothelial carcinoma has relations: disease_disease with urothelial neoplasm, disease_disease with urothelial neoplasm, disease_protein with HRAS, disease_protein with HRAS.", "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]Relations: coronary artery disease has relations: disease_disease with arterial disorder, disease_disease with arterial disorder, disease_disease with heart disease, disease_disease with heart disease, disease_disease with coronary heart disease, susceptibility to, disease_disease with coronary heart disease, susceptibility to, disease_disease with congenital coronary artery anomaly, disease_disease with congenital coronary artery anomaly, disease_disease with intermediate coronary syndrome, disease_disease with intermediate coronary syndrome.", "label": "yes"}
{"id": "converted_1501", "sentence1": "Have germline variants been associated to colorectal cancer?", "sentence2": "Overall, we identified aberrant transcripts in 8% of the patients (familial cases 30%; early-onset manifestation 21%). In eight of them, two different out-of-frame pseudoexons were found consisting of a 167-bp insertion from intron 4 in five families with a shared founder haplotype and a 83-bp insertion from intron 10 in three patients. The pseudoexon formation was caused by three different heterozygous germline mutations, which are supposed to activate cryptic splice sites, We apply OS-Seq to resequence the exons of either 10 or 344 cancer genes from human DNA samples. In our assessment of capture performance, >87% of the captured sequence originated from the intended target region with sequencing coverage falling within a tenfold range for a majority of all targets. Single nucleotide variants (SNVs) called from OS-Seq data agreed with >95% of variants obtained from whole-genome sequencing of the same individual., The minor alleles of CD44 rs8193 C>T, ALCAM rs1157 G>A, and LGR5 rs17109924 T>C were significantly associated with increased TTR (9.4 vs. 5.4 years; HR, 0.51; 95% CI: 0.35-0.93; P = 0.022; 11.3 vs. 5.7 years; HR, 0.56; 95% CI: 0.33-0.94; P = 0.024, and 10.7 vs. 5.7 years; HR, 0.33; 95% CI: 0.12-0.90; P = 0.023, respectively) and remained significant in the multivariate analysis stratified by ethnicity. In recursive partitioning, a specific gene variant profile including LGR5 rs17109924, CD44 rs8193, and ALDH1A1 rs1342024 represented a high-risk subgroup with a median TTR of 1.7 years (HR, 6.71, 95% CI: 2.71-16.63, P < 0.001)., In this study, we identified common germline variants in VEGF-dependent and -independent angiogenesis genes predicting clinical outcome and tumor response in patients with mCRC receiving first-line bevacizumab and oxaliplatin-based chemotherapy., We identified 22 nonsynonymous somatic mutations of which the majority was of missense type. In germline, three novel nonsynonymous variants were identified in the following genes: CSMD3, EPHB6 and C10orf137, and none of the variants were present in 890 population-matched healthy controls. It is possible that the identified germline variants modulate predisposition to CRC., One patient proved to carry an APC whole-gene deletion; 4 of 25 (16%) patients showed biallelic and 3 of 25 (12%) monoallelic MUTYH mutations. In the three heterozygous subjects no pathogenetic variants were found in OGG1, MTH1, APE1, MSH2, and MSH6 genes. Frequency assessment of MUTYH mutations in healthy subjects showed that only Y165C and G382D reach a subpolymorphic frequency., Scrutinizing the molecular genetic results and family data of 242 index patients with pathogenic APC mutations led to the identification of 10 mosaic cases (4%). C>T transitions were observed in CGA sites in four of the 10 cases with somatic mosaicism, which is significantly more than 26 of the 232 non-mosaic cases (p = 0.02). Phenotypes of patients with somatic mosaicism ranged from an attenuated form of polyposis coli to florid polyposis with major extracolonic manifestations., Altogether 12 previously reported changes and four novel genetic alterations, mostly in intronic sequences, were identified. The results revealed the presence of biallelic germline MYH mutations in two patients. These patients were compound heterozygotes for two of the most common germline mutations c.494 A>G (p.Y165C); c.1,145 G>A (p.G382D). These variants are established to be associated with adenomatous polyposis and colorectal cancer.[SEP]Relations: EDRF1 has relations: disease_protein with colorectal cancer, disease_protein with colorectal cancer, disease_protein with colorectal carcinoma, disease_protein with colorectal carcinoma. Somatic mutation has relations: disease_phenotype_positive with colorectal cancer, disease_phenotype_positive with colorectal cancer, disease_phenotype_positive with esophageal cancer, disease_phenotype_positive with esophageal cancer. malignant colon neoplasm has relations: disease_disease with colorectal cancer, disease_disease with colorectal cancer.", "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]Relations: postsynaptic membrane has relations: cellcomp_protein with GABRG2, cellcomp_protein with GABRG2, cellcomp_protein with GABRB3, cellcomp_protein with GABRB3, cellcomp_protein with TMUB1, cellcomp_protein with TMUB1, cellcomp_protein with GABRB1, cellcomp_protein with GABRB1, cellcomp_protein with SRGAP2, cellcomp_protein with SRGAP2.", "label": "no"}
{"id": "converted_3375", "sentence1": "Are breaks in double stranded DNA associated with ionizing radiation?", "sentence2": "DNA double-strand breaks (DSBs) are major DNA lesions that are constantly formed during physiological processes such as DNA replication, transcription, and recombination, or as a result of exogenous agents such as ionizing radiation, radiomimetic drugs, and genome editing nucleases, Whereas most endogenous and exogenous DNA damaging agents typically generate lesions that are relatively isolated and can be repaired easily, ionizing radiation (IR) also induces clustered lesions causing DNA double strand breaks (DSBs), The induction of DNA interstrand cross-links by ionizing radiation has been largely ignored in favour of studies on double-strand break formation and repair., While much is known about radiation-induced DNA double-strand breaks (DSBs) and their repair, , Exposure of cells to ionizing radiation induces DNA double-strand breaks., DNA double-strand breaks are considered to be the most deleterious lesion induced by ionizing radiation., Influence of chromatin structure on the induction of DNA double strand breaks by ionizing radiation., Ionizing radiation and radiomimetic drugs such as bleomycin, calichieamycin, neocarzinostatin chromophore, and other synthetic agents can produce both single and double strand breaks in DNA., RESULTS BRCA2-defective cells were unable to repair the double-strand DNA breaks induced by ionizing radiation., BACKGROUND Induction of DNA double strand breaks and alterations in the repair of these breaks is implicated in breast carcinogenesis., Double-stranded breaks ( DSBs ) are the most injurious type of DNA damage , being induced by ionizing radiation ( IR ) and cytotoxic agents used in cancer treatment, Double-stranded breaks ( DSBs ) are cytotoxic DNA lesions caused by oxygen radicals , ionizing radiation , and radiomimetic chemicals, Gamma-ray irradiation introduces single and/or double strand breaks into the DNA molecule of the cells.[SEP] Bleomycin has relations with Arsenic trioxide, Isosulfan blue, Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated), Tetradecyl hydrogen sulfate (ester), and Tetradesulfonate.", "label": "yes"}
{"id": "converted_1900", "sentence1": "Has \"RNA interference\" been awarded Nobel prize?", "sentence2": "Since the first unequivocal description of RNA interference (RNAi) in 1998, it has remained one of the hottest topics under investigation, culminating in the award of a Nobel Prize to its discoverers in 2006., RNA interference (RNAi) is considered one of the most powerful genomic tools which allows the study of drug discovery and understanding of the complex cellular processes by high-content screens. This field of study, which was the subject of 2006 Nobel Prize of medicine, has drastically changed the conventional methods of analysis of genes.,  Almost 10 years after Fire and Mello received the Nobel Prize for the discovery of this mechanism in flat worms, RNA interference is on the edge of becoming a new class of therapeutics.[SEP]", "label": "yes"}
{"id": "converted_3", "sentence1": "Are long non coding RNAs spliced?", "sentence2": "Our analyses indicate that lncRNAs are generated through pathways similar to that of protein-coding genes, with similar histone-modification profiles, splicing signals, and exon/intron lengths., For alternative exons and long noncoding RNAs, splicing tends to occur later, and the latter might remain unspliced in some cases., bosome-mapping data to identify lncRNAs of Caenorhabditis elegans. We found 170 long intervening ncRNAs (lincRNAs), which had single- or multiexonic structures that did not overlap protein-coding transcripts, and about sixty antisense lncRNAs (ancRNAs), which were complementary to protein-coding transcripts, We introduce an approach to predict spliced lncRNAs in vertebrate genomes combining comparative genomics and machine learning., Owing to similar alternative splicing pattern to mRNAs, the concept of lncRNA genes was put forward to help systematic understanding of lncRNAs. , Our synthesis of recent studies suggests that neither size, presence of a poly-A tail, splicing, direction of transcription, nor strand specificity are of importance to lncRNA function.[SEP]Relations: long noncoding RNA binding has relations: molfunc_protein with MIR384, molfunc_protein with MIR384.", "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]Relations: Portal inflammation has relations: disease_phenotype_positive with FADD-related immunodeficiency, disease_phenotype_positive with FADD-related immunodeficiency. Respiratory distress has relations: disease_phenotype_positive with progressive supranuclear palsy-corticobasal syndrome, disease_phenotype_positive with progressive supranuclear palsy-corticobasal syndrome, disease_phenotype_positive with cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency, disease_phenotype_positive with cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency. colitis (disease) has relations: disease_protein with MIF, disease_protein with MIF. Ascites has relations: disease_phenotype_positive with fetal parvovirus syndrome, disease_phenotype_positive with fetal parvovirus syndrome.", "label": "yes"}
{"id": "converted_1416", "sentence1": "Is c-myc subject to regulation by the circadian clock?", "sentence2": "The current study encompasses the investigation of simultaneous expression of four circadian clock genes (Bmal1, Clock, Per1 and Per2) and three clock-controlled cell cycle genes (Myc, Cyclin D1 and Wee1), Our results suggest that aberrant expression of circadian clock genes can lead to aberrant expression of their downstream targets that are involved in cell proliferation and apoptosis and hence may result in manifestation of CLL., Loss of Bmal1 reduced the expression of per1, per2, per3, wee1 and p53. The expression of p21 and c-myc was also altered in certain cell lines., In particular, the proto-oncogene c-Myc has been documented to be under circadian regulation., The circadian expression of c-MYC is modulated by the histone deacetylase inhibitor trichostatin A in synchronized murine neuroblastoma cells., Our results, using the murine neuroblastoma cell line N2A, show that Per1 and c-Myc steady-state mRNA levels oscillate with the same phase., These experiments demonstrate for the first time that a significant decrease in c-Myc transcript and protein levels can be achieved after a short TSA treatment applied only at specific circadian times. This is also followed by a reduction in the proliferation rate of the cell population., Among the circadian output pathways, the rhythmic sympathetic signaling plays a key role in the central-peripheral timing mechanism that simultaneously activates the cell cycle clock via AP1-controlled Myc induction and p53 via peripheral clock-controlled ATM activation., Jet-lag promptly desynchronizes the central clock-SNS-peripheral clock axis, abolishes the peripheral clock-dependent ATM activation, and activates myc oncogenic potential, leading to tumor development in the same organ systems in wild-type and circadian gene-mutant mice., The results showed that over-expression of Per2 induced not only cell cycle arrest at G2/M phase but also an increase in apoptosis, which was confirmed by characteristic morphological changes, FCM and evident DNA fragmentation. Further experiments confirmed both up-regulation of P53 and down-regulation of CylinB1and C-myc., On the other hand, while P53 was found to be down-regulated. CylinB1 and C-myc were up-regulated. after Per2 knockdown., We also show that BMAL1 epigenetic inactivation impairs the characteristic circadian clock expression pattern of genes such as C-MYC, catalase, and p300 in association with a loss of BMAL1 occupancy in their respective promoters., Per2 mutant (Per2(m/m)) mice show an increase in lymphomas and deregulated expression of cyclin D and c-Myc genes that are key to proliferation control., The expression of cell cycle genes such as Wee1, Cyclins, and c-Myc are under circadian control and could be directly under the regulation of the circadian transcriptional complex., Overexpressed mPER2 also altered the expression of apoptosis-related genes. The mRNA and protein levels of c-Myc, Bcl-X(L) and Bcl-2 were downregulated,, Temporal expression of genes involved in cell cycle regulation and tumor suppression, such as c-Myc, Cyclin D1, Cyclin A, Mdm-2 and Gadd45alpha is deregulated in mPer2 mutant mice., The temporal expression of genes involved in cell cycle regulation and tumor suppression, such as c-Myc, Cyclin D1, Cyclin A, Mdm-2, and Gadd45alpha, is deregulated in mPer2 mutant mice.[SEP]Relations: PER2 has relations: bioprocess_protein with regulation of circadian rhythm, bioprocess_protein with regulation of circadian rhythm, bioprocess_protein with negative regulation of circadian rhythm, bioprocess_protein with negative regulation of circadian rhythm. entrainment of circadian clock by photoperiod has relations: bioprocess_protein with RBM4, bioprocess_protein with RBM4, bioprocess_protein with FBXL6, bioprocess_protein with FBXL6, bioprocess_protein with RBM4B, bioprocess_protein with RBM4B.", "label": "yes"}
{"id": "converted_4165", "sentence1": "Is belimumab effective for the lupus nephritis?", "sentence2": "Long-term effects of combined B-cell immunomodulation with rituximab and belimumab in severe, refractory systemic lupus erythematosus: 2-year results., CONCLUSIONS: Combined B-cell targeted therapy with RTX and BLM prevented full B-cell repopulation including DN B cells, with concomitant specific reduction of SLE-relevant autoantibodies. , Clinical Efficacy of Routinely Administered Belimumab on Proteinuria and Neuropsychiatric Lupus., Conclusions: In our series, BEL led to a decrease of proteinuria in patients with proteinuria of more than 1,000 mg/g creatinine despite standard of care treatment, and led to a marked clinical improvement in one patient with NPSLE. No adverse events were observed. Routinely administered BEL shows clinical efficacy on non-approved manifestations, but careful patient selection is warranted., Phase II Randomized Trial of Rituximab Plus Cyclophosphamide Followed by Belimumab for the Treatment of Lupus Nephritis., OBJECTIVE: To assess the safety, mechanism of action, and preliminary efficacy of rituximab followed by belimumab in the treatment of refractory lupus nephritis (LN)., CONCLUSION: The addition of belimumab to a treatment regimen with rituximab and CYC was safe in patients with refractory LN., RECENT FINDINGS: Recently, the Belimumab in Subjects with Systemic Lupus Erythematosus - Lupus Nephritis trial tested belimumab, an inhibitor of B-cell activating factor, as an add-on therapy to steroids and either mycophenolate mofetil (MMF) or cyclophosphamide when given IV monthly over a period of 104 weeks at an effect size of 11% for a Primary Efficacy Renal Response. , Case report: successful treatment of membranous lupus nephritis with belimumab in an African female immigrant., Recently introduced into the market, belimumab (Benlysta) is a monoclonal antibody that has potential clinically efficacious applications for the treatment of lupus nephritis., Successful treatment of a mycophenolate mofetil-refractory proliferative lupus nephritis with Belimumab in a 19-year-old woman., Following treatment with belimumab, proteinuria rapidly improved to almost normal levels and clinical remission lasted. Belimumab might hold promise for this indication.[SEP]Relations: Belimumab has relations: drug_drug with Lumiliximab, drug_drug with Lumiliximab, drug_drug with Luspatercept, drug_drug with Luspatercept, drug_drug with Tremelimumab, drug_drug with Tremelimumab, drug_drug with Dupilumab, drug_drug with Dupilumab, drug_drug with Rituximab, drug_drug with Rituximab.", "label": "yes"}
{"id": "converted_1695", "sentence1": "Is calcium overload involved in the development of diabetic cardiomyopathy?", "sentence2": "High-glucose treatment resulted in increased intracellular calcium ([Ca2+]i) which was mobilized to the mitochondria. Concomitant intra-mitochondrial calcium ([Ca2+]m) increase resulted in enhanced reactive oxygen and nitrogen species generation. These events led to mitochondrial dysfunction and apoptosis., The novel findings of the study reveal that high glucose induces apoptosis by both mitochondria-dependent and independent pathways via concomitant rise in intracellular calcium., Diabetes-induced myocardial dysfunction has been attributed, in part, to calcium overload within individual myocytes., It seems that intracellular calcium overload is intimately involved in the development of diabetic cardiomyopathy;, BACKGROUND: It has been suggested that intracellular Ca2+ overload in cardiac myocytes leads to the development of diabetic cardiomyopathy., The results from the alloxan-rat model of diabetes support the view that membrane abnormalities with respect to Ca2+ handling may lead to the occurrence of intracellular Ca2+ overload and the development of diabetic cardiomyopathy., It seems that intracellular calcium overload is intimately involved in the development of diabetic cardiomyopathy; however, a concentrated research effort is required to understand the primary biochemical lesion in the pathogenesis of cardiac dysfunction in diabetes., It has been suggested that the occurrence of an intracellular Ca2+ overload may result in the development of diabetic cardiomyopathy, which is associated with depletion of high-energy phosphate stores and a derangement of ultrastructure and cardiac dysfunction.[SEP]Disease_phenotype_positive with reticular dysgenesis. Abnormality of mitochondrial metabolism has relations. Type I diabetes mellitus has relations with sclerosing cholangitis, multicentric osteolysis-nodulosis-arthropathy spectrum. Cardiomyopathy diabetes deafness has relations: disease_disease with syndromic disease, disease-diseases-with-syndromic-disorders-in-common.", "label": "yes"}
{"id": "converted_390", "sentence1": "Does PU.1 (SPI1) affect NF-kB binding?", "sentence2": "Recent data demonstrate that developmental transcription factors like the macrophage fate-determining Pu.1 set the stage for the activity of ubiquitous transcription factors activated by inflammatory stimuli, like NF-kB, AP-1, and interferon regulatory factors (IRFs)., Within 1217 bp of upstream sequence, 3 sites for NF-kB, 10 sites for NF-IL6, 15 sites for AP1, 6 sites for AP4, 2 sites for CHOP/CEBP alpha and 1 site for SP1 and PU.1 were identified., As little as 82 bp of upstream sequence gave relatively strong luciferase activity, a region containing both a PU.1 and NF-kB site., Potential transcription regulatory elements, AP1, AP2, AP3, NF-kB and GATA recognition sequences, are located within 523 bp upstream of the p35 gene; however, no TATA box was identified. The p40 subunit gene consists of eight exons. A TATA box is located 30 bp upstream from the transcription start site, and AP1, AP3, GATA, and Pu.1 recognition sequences are located within 690 bp upstream of the p40 gene., Several putative binding sequences for ubiquitous (Sp1, AP-1, AP-2, and NF-kB) and leukocyte-specific (PU.1) transcription factors have been identified in the proximal region of the CD11c promoter which may participate in the regulation of the expression of p150,95., PU.1 is regulated by NF-kappaB through a novel binding site in a 17 kb upstream enhancer element.[SEP] transcription factor binding has relations with SPI1, SP1, NAB1, ZFPM1 and TFDP1. Molfunc_protein with ZFPm1 is related to the transcription factor ZFP, which binds to SPI1. molfunc-protein with TFDP is also related to TFDP, which binding to SP1.", "label": "yes"}
{"id": "converted_1354", "sentence1": "Has the presence of delayed enhancement been documented in athletes performing strenuous exercise?", "sentence2": "Atypical findings such as marked cardiac dilation, reduced deformation, or small patches of delayed gadolinium enhancement may be commonly encountered in well-trained athletes, but, at present, the prognostic significance of such findings is unknown. , On CMR, DGE localized to the interventricular septum was identified in 5 of 39 athletes who had greater cumulative exercise exposure and lower RVEF (47.1 ± 5.9 vs. 51.1 ± 3.7%, P = 0.042) than those with normal CMR., Post-event cardiac MRI demonstrated the interval appearance of delayed enhancement of gadolinium at the inferior insertion of the right ventricle and in the interventricular septum-a novel finding that may represent subtle inflammation secondary to a combined exercise and altitude effect., No evidence of delayed enhancement of the left ventricular myocardium was found on CMR imaging, suggesting that the increase in cardiac biomarkers after the marathon may not have be due to myocardial necrosis., Of the 102 runners, five had a CAD pattern of LGE, and seven had a non-CAD pattern of LGE. The CAD pattern of LGE was located in the territory of the left anterior descending coronary artery more frequently than was the non-CAD pattern (P = .0027, Fisher exact test). The prevalence of LGE in runners was higher than that in age-matched control subjects (12% vs 4%; P = .077, McNemar exact test).[SEP]Myocardial infarction has relations with Nylidrin, Fosamprenavir, Lansoprazole, Drospirenone, Modafinil, and Fosaprenavirs. Myocardialinfarction can be prevented with the use of these drugs. For more information, visit the National Institutes of Health.", "label": "yes"}
{"id": "converted_1005", "sentence1": "Is amoxicillin used for treatment of malnutrition in children?", "sentence2": " Another RCT did not show superiority of ceftriaxone over amoxicilllin for these same outcomes, but adressed SAM children with and without complications (p = 0.27). Another RCT showed no difference between amoxicillin and cotrimoxazole efficacies for pneumonia in underweight, but not SAM. Our meta-analysis of 12 pooled susceptibility-studies for all types of bacterial isolates, including 2767 stricly SAM children, favoured amoxicillin over cotrimoxazole for susceptibility medians: 42% (IQR 27-55%) vs 22% (IQR 17-23%) and population-weighted-means 52.9% (range 23-57%) vs 35.4% (range 6.7-42%).,  Susceptibility-studies favour amoxicillin over cotrimoxazole. , Oral amoxicillin for 5 days was as effective as intramuscular ceftriaxone for 2 days (1 RCT). For uncomplicated SAM, amoxicillin showed no benefit over placebo (1 retrospective study). , Children who took amoxicillin and de-worming had 95% (HR = 1.95, 95%-CI = 1.17, 3.23) and 74% (HR = 1.74, 95%-CI = 1.07, 2.83) more probability to recover from SAM as compared to those who didn't take them., METHODS: In this randomized, double-blind, placebo-controlled trial, we randomly assigned Malawian children, 6 to 59 months of age, with severe acute malnutrition to receive amoxicillin, cefdinir, or placebo for 7 days in addition to ready-to-use therapeutic food for the outpatient treatment of uncomplicated severe acute malnutrition. , In the amoxicillin, cefdinir, and placebo groups, 88.7%, 90.9%, and 85.1% of the children recovered, respectively (relative risk of treatment failure with placebo vs. amoxicillin, 1.32; 95% confidence interval [CI], 1.04 to 1.68; relative risk with placebo vs. cefdinir, 1.64; 95% CI, 1.27 to 2.11). The mortality rates for the three groups were 4.8%, 4.1%, and 7.4%, respectively (relative risk of death with placebo vs. amoxicillin, 1.55; 95% CI, 1.07 to 2.24; relative risk with placebo vs. cefdinir, 1.80; 95% CI, 1.22 to 2.64)., Evaluation of the routine use of amoxicillin as part of the home-based treatment of severe acute malnutrition., OBJECTIVE: To determine whether the inclusion of amoxicillin correlates with better recovery rates in the home-based treatment of severe acute malnutrition with ready-to-use therapeutic food., The standard protocol group received a 7-day course of amoxicillin at the onset of treatment., RESULTS: Four hundred and ninety-eight children were treated according to the standard protocol with amoxicillin, and 1955 were treated under the alternate protocol without antibiotics. , The recovery rate for children who received amoxicillin was worse at 4 weeks (40%vs. 71%) but similar after up to 12 weeks of therapy (84%vs. 86%), compared to the children treated without antibiotics., CONCLUSIONS: This review of two therapeutic feeding programmes suggests that children with severe acute malnutrition who were treated without amoxicillin did not have an inferior rate of recovery., Treatment of severe malnutrition with 2-day intramuscular ceftriaxone vs 5-day amoxicillin., To determine whether the inclusion of amoxicillin correlates with better recovery rates in the home-based treatment of severe acute malnutrition with ready-to-use therapeutic food., Evaluation of the routine use of amoxicillin as part of the home-based treatment of severe acute malnutrition, OBJECTIVE: To determine whether the inclusion of amoxicillin correlates with better recovery rates in the home-based treatment of severe acute malnutrition with ready-to-use therapeutic food. METHODS: This retrospective cohort study compared data from the treatment of two groups of children in Malawi aged 6-59 months with uncomplicated severe acute malnutrition. , The recovery rate for children who received amoxicillin was worse at 4 weeks (40%vs. 71%) but similar after up to 12 weeks of therapy (84%vs. 86%), compared to the children treated without antibiotics. Regression modelling indicated that this difference at 4 weeks was most strongly associated with the receipt of amoxicillin. CONCLUSIONS: This review of two therapeutic feeding programmes suggests that children with severe acute malnutrition who were treated without amoxicillin did not have an inferior rate of recovery. , CONCLUSIONS: This review of two therapeutic feeding programmes suggests that children with severe acute malnutrition who were treated without amoxicillin did not have an inferior rate of recovery. [SEP]Relations: Amoxicillin has relations: contraindication with bone fracture, contraindication with bone fracture, contraindication with liver disease, contraindication with liver disease, contraindication with osteoporosis, contraindication with osteoporosis, drug_drug with Ampicillin, drug_drug with Ampicillin, contraindication with kidney disease, contraindication with kidney disease.", "label": "yes"}
{"id": "converted_1369", "sentence1": "Are microRNA (miR) regulated through DNA methylation of their promoters?", "sentence2": "We found that Tcf3 down-regulation in the context of constitutively active Wnt signaling does not result from promoter DNA methylation but is likely to be caused by a plethora of mechanisms at both the RNA and protein level as shown by the observed decrease in activating histone marks (H3K4me3 and H3-acetylation) and the upregulation of miR-211, a novel Wnt-regulated microRNA that targets Tcf3 and attenuates early neural differentiation in mouse ESCs, ene silencing of MIR22 in acute lymphoblastic leukaemia involves histone modifications independent of promoter DNA methylation, Whereas a CpG island was identified within the promoter element of MIR22, no promoter DNA methylation was detected in these cells, xtensive promoter DNA hypermethylation and hypomethylation is associated with aberrant microRNA expression in chronic lymphocytic leukemia, Integration of DNA methylation and miRNA promoter data led to the identification of 128 recurrent miRNA targets for aberrant promoter DNA methylation, Together, our findings characterize the role of epigenetic changes in the regulation of miRNA transcription and create a repository of disease-specific promoter regions that may provide additional insights into the pathogenesis of CLL, NA methylation of microRNA genes in multiple myeloma, Recently, epigenetic dysregulation of tumor-suppressor miRNA genes by promoter DNA methylation has been implicated in human cancers, including multiple myeloma (MM), ethylation of tumor suppressor microRNAs, Dysregulation of miRNA expression involved in cancer can be triggered by multiple mechanisms including aberrant DNA methylation of the miRNA gene promoter, Of note, DNA methylation of tumor suppressor miRNAs has been implicated in various human cancers, Moreover, miRNA silencing mediated by aberrant promoter DNA methylation can potentially be reversed by hypomethylating agents, and hence may pose a new therapeutic target in cancer,  In this review, the authors will focus on the aberrant methylation of miRNAs in the pathogenesis of lymphoid malignancies including chronic lymphocytic leukemia, multiple myeloma and acute lymphoblastic leukemia, Here, we review those miRNAs implicated in AD that are regulated by promoter DNA methylation and/or chromatin modifications and, which frequently direct the expression of constituents of the epigenetic machinery, concluding with the delineation of a complex epigenetic-miRNA regulatory network and its alterations in AD, Furthermore, we also discuss epigenetic dysregulation of tumor-suppressor miRNA genes by promoter DNA methylation and the interaction of DNA methylation with miRNAs involved in the regulation of HSC activation and liver fibrosi, Instead, the cell type-specific silencing of these genes is due to enhanced p21 mRNA degradation, 14-3-3sigma promoter DNA methylation and reduced processing of the miR-34a primary transcript, Some tumor-suppressive miRNAs are known to be epigenetically silenced by promoter DNA methylation in cancer, In the present study, we aimed to identify miRNA genes that are silenced by DNA hypermethylation in hepatocellular carcinoma (HCC), It was found that miR-335, which is harbored within an intron of its protein-coding host gene, MEST, was downregulated by aberrant promoter hypermethylation via further methylation assays, including methylation-specific PCR, combined bisulfite and restriction analysis, bisulfite sequencing analysis and 5-aza-2'-deoxycytidine treatment, he levels of miR-335/MEST methylation were significantly higher in 18 (90%) out of 20 primary HCC tumors, compared to their non-tumor tissue counterparts (P<0.001), In conclusion, our results indicate that expression of miR-335 is reduced by aberrant DNA methylation in HCC.[SEP]Relations: promoter clearance from RNA polymerase I promoter has relations: bioprocess_bioprocess with promoter clearance during DNA-templated transcription, bioprocess_bioprocess with promoter clearance during DNA-templated transcription, bioprocess_bioprocess with promoter clearance from RNA polymerase I promoter for nuclear large rRNA transcript, bioprocess_bioprocess with promoter clearance from RNA polymerase I promoter for nuclear large rRNA transcript. histone modification has relations: bioprocess_bioprocess with histone methylation, bioprocess_bioprocess with histone methylation, bioprocess_bioprocess with histone biotinylation, bioprocess_bioprocess with histone biotinylation. MEST has relations: bioprocess_protein with regulation of lipid storage, bioprocess_protein with regulation of lipid storage.", "label": "yes"}
{"id": "converted_1523", "sentence1": "Can siRNA affect response to afatinib treatment?", "sentence2": "On the other hand, miR-146a enhanced the inhibition of cell proliferation by drugs targeting EGFR, including both TKIs (gefitinib, erlotinib, and afatinib) and a monoclonal antibody (cetuximab), These effects were independent of the EGFR mutation status (wild type, sensitizing mutation or resistance mutation), but were less potent compared to the effects of siRNA targeting of EGFR, Among the anti-EGFR agents tested, the strongest biological effect was observed when afatinib was combined with T790M-specific-siRNAs, The combination of a potent, irreversible kinase inhibitor such as afatinib, with T790M-specific-siRNAs should be further investigated as a new strategy in the treatment of lung cancer containing the resistant T790M mutation., The strongest biological effect was observed when afatinib was combined with an EGFR-specific siRNA, The addition of EGFR siRNA to either TKIs or cetuximab additively enhanced growth inhibition and induction of apoptosis in all five cell lines, independent of the EGFR mutation status (wild-type or sensitizing mutation or resistant mutation)., The combination of a potent, irreversible kinase inhibitor such as afatinib, with EGFR-specific siRNAs should be further investigated as a new strategy in the treatment of lung cancer and other EGFR dependent cancers, including those with downstream resistance mutations.[SEP]Afatinib has relations with Sirolimus, Cannabidiol, Lapatinib, Binimetinib, Dovitinib and more. Afatinib is a synthetic form of the anti-depressant and anti-psychotic drug doxorubicin.", "label": "yes"}
{"id": "converted_3707", "sentence1": "Has MLE4901 been tested in phase III clinical trials?", "sentence2": "METHODS\n\nThis phase 2, randomised, double-blind, placebo-controlled, single-centre, crossover trial assessed the effectiveness of an oral neurokinin 3 receptor antagonist (MLE4901) on menopausal hot flushes., Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled trial.[SEP]", "label": "no"}
{"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]Relations: Schistosoma japonicum infectious disease has relations: disease_disease with schistosomiasis, disease_disease with schistosomiasis. schistosomiasis has relations: disease_disease with Schistosoma japonicum infectious disease, disease_disease with Schistosoma japonicum infectious disease, disease_disease with Schistosoma japonicum infectious disease, disease_disease with Schistosoma japonicum infectious disease, disease_disease with Schistosoma intercalatum infectious disease, disease_disease with Schistosoma intercalatum infectious disease, disease_disease with Schistosoma intercalatum infectious disease, disease_disease with Schistosoma intercalatum infectious disease.", "label": "yes"}
{"id": "converted_3309", "sentence1": "Is induction of interferon by TLR7 higher in males?", "sentence2": "ur results suggest that variations of TLR7 impair the immune response to HCV and imply a gender-specific effect of this X-chromosomal variation., The c.32A>T variation was over-represented in female patients with chronic HCV-infection compared to patients with other chronic liver diseases and to healthy controls (P < 0.05). In contrast, c.2403 G>A was less prevalent in male patients with chronic HCV-infection (P < 0.05). No association was observed for the third variant, c.1-120T>G. Haplotype analysis confirmed the differential distribution of TLR7 variants between the groups. Within the group of female patients with chronic HCV-infection, c.32T was predictive of an unfavourable outcome of interferon-alpha therapy (P < 0.05)[SEP]Chronic lung disease has relations: disease_phenotype_positive with midline interhemispheric variant of holoprosencephaly. Chronic lung disease also has relations with neonatal acute respiratory distress due to SP-B deficiency, combined immunodeficiency due to LRBA deficiency, and familial papillary or follicular thyroid carcinoma. For more information on chronic lung disease, visit www.lungdiseaselifeline.org or call the National Institutes of Health at 1-800-273-8255.", "label": "yes"}
{"id": "converted_3340", "sentence1": "Is MLL3 part of the ASCOM complex?", "sentence2": "MLL3 as part of ASCOM complex, MLL3 as part of activating signal cointegrator-2 -containing complex (ASCOM)[SEP]", "label": "yes"}
{"id": "converted_3245", "sentence1": "Is the Fluzone intradermal and the Fluzone intradermal quadrivalent vaccine produced by different companies?", "sentence2": "An intradermal version of Fluzone® split-virion inactivated trivalent influenza vaccine, containing 9 µg hemagglutinin per strain of A/H1N1, A/H3N2, and one B lineage virus (Fluzone Intradermal, Sanofi Pasteur), became available in the US during the 2011-2012 influenza season for adults 18-64 years of age. In advance of the 2015-2016 season, Fluzone Intradermal was replaced with Fluzone Intradermal Quadrivalent vaccine, which contains 9 µg hemagglutinin per strain of the two A-strain viruses and both B-strain lineage viruses (Victoria and Yamagata).[SEP]", "label": "no"}
{"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]LADD syndrome has relations: disease_disease with EEC syndrome and related syndrome. LADD syndrome also has relations with autosomal dominant disease, genetic otorhinolaryngological malformation, genetic multiple congenital anomalies/dysmorphic syndrome without intellectual disability, disease_phenotype_positive with Autosomal dominant inheritance, and disease-phenotype-with-autosomal-dominant inheritance.", "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]Down syndrome has relations with RAD21, PRDX6, S100B, SLC19A1 and PRDX2. Down syndrome has also relations with SLC100B and SLC20A1.", "label": "yes"}
{"id": "converted_3855", "sentence1": "Does IL18 signaling have a role in thymus?", "sentence2": "IL18 signaling promotes homing of mature Tregs into the thymus., Collectively, this study provides a detailed characterization of the mature Treg subsets in the mouse thymus and identifies a key role of IL18 signaling in controlling the CCR6-CCL20-dependent migration of Tregs into the thymus., er, we show that IL18R+ Tregs are endowed with higher capacity to populate the thymus than their IL18R- or IL18R-/- counterparts, highlighting the key role of IL18R in this process, IL18 signaling promotes homing of mature Tregs into the thymus, inally, we demonstrate that IL18 signaling is critical for the induction of the key thymus-homing chemokine receptor - CCR6 on Tregs. , Moreover, we show that IL18R+ Tregs are endowed with higher capacity to populate the thymus than their IL18R- or IL18R-/- counterparts, highlighting the key role of IL18R in this process.[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]Lymph node has relations with ATRX, PRX, APTX, PRDX6, and PRDX3. Lymph node can also have relations with PRX and APTX. lymph node can be seen by looking at the lymph node's lymph nodes.", "label": "yes"}
{"id": "converted_876", "sentence1": "Can fetal aneuploidy be detected with non-invasive prenatal testing?", "sentence2": "Non-invasive prenatal testing with cell-free DNA: US physician attitudes toward implementation in clinical practice., The aim of this study was to assess awareness, potential adoption, and current utilization of non-invasive prenatal testing (NIPT) analysis for common fetal aneuploidies among obstetricians, Cell-free DNA has been used for fetal rhesus factor and sex determination, fetal aneuploidy screening, cancer diagnostics and monitoring, and other applications., The recent release of new, non-invasive prenatal tests for fetal aneuploidy using cell-free fetal DNA (cffDNA) has been hailed as a revolution in prenatal testing and has triggered significant commercial interest in the field., Non-invasive prenatal testing (NIPT) for aneuploidy using cell-free DNA in maternal plasma is revolutionizing prenatal screening and diagnosis., SNP-based non-invasive prenatal testing detects sex chromosome aneuploidies with high accuracy., Non-invasive prenatal testing (NIPT) of cell-free fetal DNA in maternal plasma is a novel approach, designed for detecting common aneuploidies in the fetus., This study aimed to develop a single-nucleotide polymorphism-based and informatics-based non-invasive prenatal test that detects sex chromosome aneuploidies early in pregnancy., RAPIDR: an analysis package for non-invasive prenatal testing of aneuploidy., Non-invasive prenatal testing for aneuploidy: current status and future prospects., Non-invasive prenatal testing of fetal whole chromosome aneuploidy by massively parallel sequencing., Attitudes towards non-invasive prenatal testing for aneuploidy among US adults of reproductive age., [Non-invasive prenatal test in the diagnosis of aneuploidy 13, 18 and 21--theoretical and practical aspects]., To track and analyze two false positive cases from non-invasive prenatal testing for potential fetal aneuploidy., Non-invasive prenatal testing (NIPT) of fetal aneuploidy using cell-free fetal DNA is becoming part of routine clinical practice., To report secondary or additional findings arising from introduction of non-invasive prenatal testing (NIPT) for aneuploidy by whole genome sequencing as a clinical service., Israeli Society of Medical Genetics NIPT Committee Opinion 072013: Non-invasive prenatal testing of cell-free DNA in maternal plasma for detection of fetal aneuploidy., In recent years, technical advances in the molecular analysis of fetal DNA (e.g., digital PCR and massively parallel sequencing (MPS)) has enabled the successful implementation of noninvasive testing into clinical practice, such as fetal sex assessment, RhD genotyping, and fetal chromosomal aneuploidy detection.With the ability to decipher the entire fetal genome from maternal plasma DNA, we foresee that an increased number of non-invasive prenatal tests will be available for detecting many single-gene disorders in the near future, First identified in 1997, cell-free fetal DNA (cffDNA) has just recently been used to detect fetal aneuploidy of chromosomes 13, 18, and 21, showing its potential to revolutionize prenatal genetic testing as a non-invasive screening tool, Non-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma has been developed for the detection of fetal aneuploidy, Israeli Society of Medical Genetics NIPT Committee Opinion 072013: Non-invasive prenatal testing of cell-free DNA in maternal plasma for detection of fetal aneuploidy, Non-invasive prenatal testing for fetal aneuploidies in the first trimester of pregnancy, To explore the value of next-generation sequencing for the non-invasive prenatal testing of fetal chromosomal aneuploidies, Secondary findings from non-invasive prenatal testing for common fetal aneuploidies by whole genome sequencing as a clinical service, To report secondary or additional findings arising from introduction of non-invasive prenatal testing (NIPT) for aneuploidy by whole genome sequencing as a clinical service, Secondary findings from non-invasive prenatal testing for common fetal aneuploidies by whole genome sequencing as a clinical service., Motivations for undertaking DNA sequencing-based non-invasive prenatal testing for fetal aneuploidy: a qualitative study with early adopter patients in Hong Kong., OBJECTIVE: To determine whether non-invasive prenatal testing by maternal plasma DNA sequencing can uncover all fetal chromosome aneuploidies in one simple sequencing event. , Non-invasive prenatal diagnosis of fetal aneuploidies using massively parallel sequencing-by-ligation and evidence that cell-free fetal DNA in the maternal plasma originates from cytotrophoblastic cells., Non-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma has been developed for the detection of fetal aneuploidy., Non-invasive prenatal testing (NIPT) of cell-free fetal DNA in maternal plasma is a novel approach, designed for detecting common aneuploidies in the fetus., non-invasive prenatal tests for fetal aneuploidy using cell-free fetal DNA (cffDNA) has been hailed as a revolution in prenatal testing and has triggered significant commercial interest in the field.,  Non-invasive prenatal testing (NIPT) of fetal aneuploidy using cell-free fetal DNA is becoming part of routine clinical practice. RAPIDR (Reliable Accurate Prenatal non-Invasive Diagnosis R package) is an easy-to-use open-source R package that implements several published NIPT analysis methods., The clinical data collected thus far indicate that NIPT is highly sensitive in detecting trisomies 21 and 18, and fairly sensitive in detecting trisomy 13 and sex chromosome aneuploidies. Because false-positive results may occur, an abnormal result must be validated by invasive prenatal testing., When non-invasive prenatal screening for aneuploidy is available, maternal age alone should not be an indication for invasive prenatal diagnosis in a twin pregnancy. (II-2A) If non-invasive prenatal screening is not available, invasive prenatal diagnosis in twins should be offered to women aged 35 and over., Therefore, methods with high sensitivity and precision are required to detect and differentiate fetal DNA from the large background of maternal DNA. In recent years, technical advances in the molecular analysis of fetal DNA (e.g., digital PCR and massively parallel sequencing (MPS)) has enabled the successful implementation of noninvasive testing into clinical practice, such as fetal sex assessment, RhD genotyping, and fetal chromosomal aneuploidy detection.With the ability to decipher the entire fetal genome from maternal plasma DNA, we foresee that an increased number of non-invasive prenatal tests will be available for detecting many single-gene disorders in the near future., Non-invasive prenatal testing for fetal aneuploidies in the first trimester of pregnancy., Secondary findings from non-invasive prenatal testing for common fetal aneuploidies by whole genome sequencing as a clinical service., To explore the value of next-generation sequencing for the non-invasive prenatal testing of fetal chromosomal aneuploidies., [Cell-free nucleic acid-based non-invasive prenatal diagnosis of fetal aneuploidies]., Maternal age alone is a poor minimum standard for prenatal screening for aneuploidy, and it should not be used a basis for recommending invasive testing when non-invasive prenatal screening for aneuploidy is available., Israeli Society of Medical Genetics NIPT Committee Opinion 072013: Non-invasive prenatal testing of cell-free DNA in maternal plasma for detection of fetal aneuploidy., Attitudes towards non-invasive prenatal testing for aneuploidy among US adults of reproductive age., The recent release of new, non-invasive prenatal tests for fetal aneuploidy using cell-free fetal DNA (cffDNA) has been hailed as a revolution in prenatal testing and has triggered significant commercial interest in the field., Non-invasive prenatal testing (NIPT) of fetal aneuploidy using cell-free fetal DNA is becoming part of routine clinical practice., Non-invasive prenatal testing (NIPT) by massively parallel sequencing is a useful clinical test for the detection of common fetal aneuploidies., The clinical data collected thus far indicate that NIPT is highly sensitive in detecting trisomies 21 and 18, and fairly sensitive in detecting trisomy 13 and sex chromosome aneuploidies.[SEP]Relations: sex chromosome has relations: cellcomp_protein with SMC6, cellcomp_protein with SMC6, cellcomp_protein with SMC5, cellcomp_protein with SMC5. somatic recombination of T cell receptor gene segments has relations: bioprocess_bioprocess with T cell receptor V(D)J recombination, bioprocess_bioprocess with T cell receptor V(D)J recombination, bioprocess_bioprocess with somatic diversification of T cell receptor genes, bioprocess_bioprocess with somatic diversification of T cell receptor genes, bioprocess_bioprocess with somatic diversification of immune receptors via germline recombination within a single locus, bioprocess_bioprocess with somatic diversification of immune receptors via germline recombination within a single locus.", "label": "yes"}
{"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]Relations: thymoma has relations: disease_protein with CD274, disease_protein with CD274. colorectal carcinoma has relations: disease_protein with CD93, disease_protein with CD93, disease_protein with CD46, disease_protein with CD46. carcinoma has relations: disease_protein with CDS1, disease_protein with CDS1, disease_protein with CDK4, disease_protein with CDK4.", "label": "yes"}
{"id": "converted_2663", "sentence1": "Is the petrous bone used in ancient DNA sampling?", "sentence2": "Large-scale genomic analyses of ancient human populations have become feasible partly due to refined sampling methods. The inner part of petrous bones and the cementum layer in teeth roots are currently recognized as the best substrates for such research., Ancient DNA (aDNA) research involves invasive and destructive sampling procedures that are often incompatible with anthropological, anatomical, and bioarcheological analyses requiring intact skeletal remains. The osseous labyrinth inside the petrous bone has been shown to yield higher amounts of endogenous DNA than any other skeletal element; however, accessing this labyrinth in cases of a complete or reconstructed skull involves causing major structural damage to the cranial vault or base., first genome-wide ancient DNA from Anatolian Neolithic farmers, whose genetic material we obtained by extracting from petrous bones,[SEP]Petrous part of temporal bone has relations: anatomy_anatomy with zone of bone organ. acalvaria has relations with disease_protein with NAT2 and disease_phenotype_positive with Abnormal skull morphology. It also has Relations with MTHFR and MTHFD1.", "label": "yes"}
{"id": "converted_1302", "sentence1": "Does thyroid hormone signaling affect microRNAs expression in the heart?", "sentence2": "e show that the heart regulates systemic energy homeostasis via MED13, a subunit of the Mediator complex, which controls transcription by thyroid hormone and other nuclear hormone receptors. MED13, in turn, is negatively regulated by a heart-specific microRNA, miR-208a., On the other hand, T₃ treatment increased miR-350 expression., Through a bioinformatics screening using TargetScan, we identified thyroid hormone receptor β1 (TRβ1), which negatively regulates β-MHC transcription, as a target of miR-27a, hese findings suggested that miR-27a regulates β-MHC gene expression by targeting TRβ1 in cardiomyocytes., We found that a cardiac-specific microRNA (miR-208) encoded by an intron of the alphaMHC gene is required for cardiomyocyte hypertrophy, fibrosis, and expression of betaMHC in response to stress and hypothyroidism., Moreover, miR-27a was demonstrated to modulate β-MHC gene regulation via thyroid hormone signaling and to be upregulated during the differentiation of mouse embryonic stem (ES) cells or in hypertrophic hearts in association with β-MHC gene upregulation.[SEP]Response to thyroid hormone has relations with CAB39 and ANXA2. thyroid hormone receptor binding has relations: molfunc_protein with MED17 and MED17. response to hormone is related to response to the thyroid hormone hormone receptor, which binds to the pituitary gland. Response to hormone can also be related to the adrenal gland, which is responsible for the production of testosterone.", "label": "yes"}
{"id": "converted_4011", "sentence1": "Are there small molecule CGRPs under development for the treatment of migraine?", "sentence2": "Meanwhile, 1 small-molecule CGRP receptor antagonist (ubrogepant, MK-1602) is currently in phase 3 studies for the acute treatment of migraine., Several other small-molecular CGRP receptor antagonists are in earlier stages of development for acute migraine treatment or prevention. [SEP]Migraine disorder has relations with PRDM16, LRP1, TRPM8, TGFBR2, HTR2A and HTR3A. Migraine disorder is a type of migraine.", "label": "yes"}
{"id": "converted_3284", "sentence1": "Do de novo truncating mutations in WASF1 cause cancer?", "sentence2": "De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures., Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling. This study provides evidence that de novo heterozygous mutations in WASF1 cause a rare form of intellectual disability.[SEP]Disease_phenotype_positive with neurofibromatosis type 1 due to NF1 mutation or intragenic deletion. Seizure has relations with hyperinsulinism due to HNF1A deficiency. SCAR complex has relations: cellcomp_protein with WASF1, cellcomp protein with WASF2, and cellcomp  with WASF1. Disease phenotype positive with lissencephaly due to LIS1 mutation, disease_phenotypes_positive with hyperinsulin due to UCP2 deficiency.", "label": "no"}
{"id": "converted_1699", "sentence1": "Is RIP1 (RIP-1) part of the necrosome?", "sentence2": "formation of a different necrosome whose components, besides RIP1 and RIP3, are still unknown, necrosome complex consisting of RIP1, RIP3, FADD, caspase-8 and cFLIP(L)., assembly of a supramolecular complex containing the receptor-interacting protein kinases 1 and 3 (RIP1 and RIP3) that delivers a pronecrotic signal. Such complex has recently been dubbed necrosome, Receptor interacting protein kinase 1 (RIPK1/RIP1) and RIP3 are key components of the necrosome. , The phosphorylation of RIP1 and RIP3 is critical for assembly of the necrosome,, RIP1-RIP3 \"necrosome\" complex , RIP1 and RIP3 mediate necrosome aggregation leading to the formation of amyloid-like signaling complexes., Formation of the RIP1/RIP3 complex (called necrosome) , The RIP1/RIP3 necrosome , Rip1-Rip3 death complex (necrosome), he 'necrosome', that includes receptor-interacting protein (RIP)1, RIP3 and caspase-8. , RIP-1 kinase activity triggers formation of the necrosome (in complex with RIP-3) leading to programmed necrosis. [SEP]Protein S human has relations: drug_drug with Cefpirome, drug_ drug with Interferon alfa-n1, and drug_ Drug with Ceferpirome. Protein S human also has relations with the Protein S Human gene for protein-coding.", "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]Relations: DDX11 has relations: bioprocess_protein with establishment of sister chromatid cohesion, bioprocess_protein with establishment of sister chromatid cohesion, bioprocess_protein with positive regulation of sister chromatid cohesion, bioprocess_protein with positive regulation of sister chromatid cohesion, bioprocess_protein with sister chromatid cohesion, bioprocess_protein with sister chromatid cohesion, molfunc_protein with chromatin binding, molfunc_protein with chromatin binding, bioprocess_protein with positive regulation of chromatin binding, bioprocess_protein with positive regulation of chromatin binding.", "label": "yes"}
{"id": "converted_1937", "sentence1": "Does NADPH oxidase 5 require any subunit for function?", "sentence2": "Nox5 forms a functional oligomer mediated by self-association of its dehydrogenase domain.,  While Nox1-4 require regulatory subunits, including p22phox, Nox5 activity does not depend on any subunits. ,  Thus, Nox5 forms a catalytically active oligomer in the membrane that is mediated by its dehydrogenase domain. , Coexpression of specific Nox catalytic subunits (Nox1, Nox2, Nox3, Nox4, or Nox5) along with their corresponding regulatory subunits (NOXO1/NOXA1 for Nox1; p47phox/p67phox/Rac for Nox2; NOXO1 for Nox3; no subunits for Nox4 or Nox5) resulted in marked production of reactive oxygen. [SEP]NOXO1 has relations: cellcomp_protein with NADPH oxidase complex. membrane has relations with CHD5, cellcomp protein with CDH5, and pathway_ protein with RHO GTPases activate NADPH Oxidases. NoxO1 can also be used as a basis for the development of the NOXO2 protein.", "label": "no"}
{"id": "converted_700", "sentence1": "Can FOXOs modulate longevity?", "sentence2": "Forkhead box O (FOXO) transcription factors have a conserved function in regulating metazoan lifespan., In contrast to FoxO1, FoxO3a and FoxO6 were specifically diminished in the CNS of HFD animals possibly contributing to the reduced lifespan observed in these animals., Interestingly, many target proteins of AMPK are so-called longevity factors, e.g., SIRT1, p53, and FoxOs, which not only can increase the stress resistance and extend the lifespan of many organisms but also inhibit the inflammatory responses. , Components of anti-ageing and autophagy include SirTs and FoxOs., Since Sirts and FoxOs are reliable markers of longevity, the results appear to suggest that Longevinex induces longevity after prolonged feeding via induction of autophagy, while it converts death signals into survival signals and provides cardioprotection within a relatively shorter period of time., Forkhead box O (FOXO) transcription factors are involved in various cellular processes, including cell proliferation, stress resistance, metabolism, and longevity, In this respect, members of the mammalian forkhead transcription factors of the O class (FoxOs) that include FoxO1, FoxO3, FoxO4 and FoxO6 are increasingly being recognized as exciting prospects for multiple disorders. These transcription factors govern development, proliferation, survival and longevity during multiple cellular environments that can involve oxidative stress. , Here we discuss the fascinating but complex role of FoxOs during cellular injury and oxidative stress, progenitor cell development, fertility, angiogenesis, cardiovascular function, cellular metabolism and diabetes, cell longevity, immune surveillance and cancer., Many longevity genes, e.g. FoxOs and SIRT1, are inhibitors of NF-kappaB signaling. , Interestingly, several longevity genes such as SIRT1, SIRT6, and FoxOs can clearly suppress NF-kappaB signaling and in this way delay the aging process and extend lifespan., Yet, FoxOs also can significantly affect normal cell survival and longevity, requiring new treatments for neoplastic growth to modulate novel pathways that integrate cell proliferation, metabolism, inflammation and survival., These observations link FoxO function in mammalian systems with the evolutionarily conserved role of FoxO in promotion of stress resistance and longevity in lower phylogenetic systems. Furthermore, these findings have implications for aging in higher organisms and in malignant stem cell biology, and suggest that FoxOs may play an important role in the maintenance and integrity of stem cell compartments in a broad spectrum of tissues., Forkhead box O (FoxO) transcription factors are important downstream targets of the PI3K/Akt signaling pathway and crucial regulators of cell fate. This function of FoxOs relies on their ability to control diverse cellular functions, including proliferation, differentiation, apoptosis, DNA repair, defense against oxidative stress and ageing., This brief review focuses on the molecular mechanisms, cellular effects and resulting organismal phenotypes generated by differentially regulated FoxO proteins and discusses our current understanding of the role of FoxOs in disease and ageing processes., In this review, we focus on the several interactions of aging-associated signaling cascades regulated either by Sirtuins and FoxOs or NF-kappaB signaling pathways. We provide evidence that signaling via the longevity factors of FoxOs and SIRT1 can inhibit NF-kappaB signaling and simultaneously protect against inflamm-aging process., In diverse species transcription factors belonging to the forkhead/winged helix box gene, group O (FOXO) subfamily have been found to be crucial in downstream suppression of the life-shortening effects of insulin/insulin-like growth factor-I receptor signalling pathways that, when upregulated, accelerate ageing by suppression of FOXO. , In humans, FOXO3a, as well as FOXO1 and -4, and their downstream effectors, could hold the key to counteracting ageing and common diseases., FOXO transcription factors have important roles in metabolism, cellular proliferation, stress tolerance, and aging. [SEP]Relations: central nervous system has relations: anatomy_protein_present with FOXO4, anatomy_protein_present with FOXO4, anatomy_protein_present with FOXO1, anatomy_protein_present with FOXO1, anatomy_protein_present with FOXN3, anatomy_protein_present with FOXN3, anatomy_protein_present with FOXK2, anatomy_protein_present with FOXK2. transcription factor binding has relations: molfunc_protein with FOXC1, molfunc_protein with FOXC1.", "label": "yes"}
{"id": "converted_220", "sentence1": "Has depression been shown to be a predictor of frailty?", "sentence2": "significant role of frailty as a predictor of depression in a relatively younger old Chinese population, significant relationships between frailty and depressive symptoms and mortality at 1 year, These findings suggest that malnutrition is a major predictor of frailty or the \"failure to thrive\" syndrome in older persons. Depression is a major cause of poor nutritional status in older persons., Depressed mood was associated with increased risk of steep strength decline, in particular in older men with low body weight. Low body weight in combination with depressed mood may be an indicator of frailty or severe disease status that leads to accelerated strength loss and disability., Longitudinally, depressed mood was the only independent predictor of decline in cognition, functional ability, physician-rated health, and mortality;[SEP]Disease_phenotype_positive with lysinuric protein intolerance. Malnutrition has relations with Ganciclovir, Primidone, and fructose intolerance. Disease_phenotypes with secondary short bowel syndrome have relations with Primidones. Disease-phenotype-positive with fructose intolerance, disease-phenotypes-with-secondary-short-bowel-syndrome.", "label": "yes"}
{"id": "converted_419", "sentence1": "Are there transposon-free regions in mammalian genomes?", "sentence2": "Transposon-free regions in mammalian genomes., Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length. The majority of human TFRs correlate with orthologous TFRs in the mouse, despite the fact that most transposons are lineage specific. Many human TFRs also overlap with orthologous TFRs in the marsupial opossum, indicating that these regions have remained refractory to transposon insertion for long evolutionary periods. Over 90% of the bases covered by TFRs are noncoding, much of which is not highly conserved. Most TFRs are not associated with unusual nucleotide composition, but are significantly associated with genes encoding developmental regulators, suggesting that they represent extended regions of regulatory information that are largely unable to tolerate insertions, a conclusion difficult to reconcile with current conceptions of gene regulation., All three elements insert only rarely within many Polycomb-regulated regions, a property that may contribute to the origin of \"transposon-free regions\" (TFRs) in metazoan genomes., Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length., RESULTS: Here we report that transposon-free regions (TFRs) are prominent genomic features of amphibian and fish lineages, and that many have been maintained throughout vertebrate evolution, although most transposon-derived sequences have entered these lineages after their divergence. , Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length. , All three elements insert only rarely within many Polycomb-regulated regions, a property that may contribute to the origin of \"transposon-free regions\" (TFRs) in metazoan genomes. , Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length., Here we report that transposon-free regions (TFRs) are prominent genomic features of amphibian and fish lineages, and that many have been maintained throughout vertebrate evolution, although most transposon-derived sequences have entered these lineages after their divergence.[SEP]Relations: regulation of establishment of actomyosin contractile ring localization involved in mitotic cell cycle has relations: bioprocess_bioprocess with regulation of mitotic actomyosin contractile ring localization, bioprocess_bioprocess with regulation of mitotic actomyosin contractile ring localization, bioprocess_bioprocess with regulation of establishment of actomyosin contractile ring localization, bioprocess_bioprocess with regulation of establishment of actomyosin contractile ring localization. vertebra has relations: anatomy_anatomy with non-transverse process-bearing vertebra, anatomy_anatomy with non-transverse process-bearing vertebra, anatomy_anatomy with transverse process-bearing vertebra, anatomy_anatomy with transverse process-bearing vertebra, anatomy_anatomy with predorsal vertebra, anatomy_anatomy with predorsal vertebra.", "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]Neuronal tumor has relations: disease_disease with extraventricular neurocytoma. Neuronal synapse has relations with cellcomp_protein with ATP1B2. Neuron to neuron synapse is a synapse between a neuron and a synapses. The synapse connects the neurons to the rest of the nervous system. It also connects the synapses to the other neurons.", "label": "yes"}
{"id": "converted_3248", "sentence1": "Is endotrophin derived from collagen?", "sentence2": "endotrophin production from type IV collagen, High levels of COL6A3 and its cleaved product, endotrophin (ETP), Endotrophin is released from COL VI[SEP]Collagen type IV trimer has relations with OTOL1, COL4A1,COL4A2, COL5, COL6, COL7, COL8, COL9, COL10, COL11, COL12, COL13, COL14, COL15.", "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]Relations: urinary bladder neoplasm has relations: disease_disease with urinary bladder cancer, disease_disease with urinary bladder cancer. benign neoplasm of prostate has relations: disease_disease with prostatic adenoma, disease_disease with prostatic adenoma, disease_disease with fibroma of prostate, disease_disease with fibroma of prostate, disease_disease with prostate leiomyoma, disease_disease with prostate leiomyoma, disease_disease with prostate neoplasm, disease_disease with prostate neoplasm.", "label": "yes"}
{"id": "converted_1835", "sentence1": "Do statins cause diabetes?", "sentence2": "Statin use has been associated with increased risk of developing type 2 diabetes (T2DM), and with impaired glycemic control in T2DM patients, The relationship between T2DM and statins is further complicated since these drugs can cause new onset diabetes (NOD) although there is an overall benefit in terms of preventing vascular events , It has been repeatedly reported that statins may cause new-onset diabetes mellitus (DM)., However, a small, but significant risk of new-onset diabetes has been reported in patients treated with statins., The National Lipid Association (NLA) Statin Diabetes Safety Task Force concluded that the cardiovascular benefit of statin therapy outweighs the risk for developing diabetes, It has been repeatedly reported that statins may cause new-onset diabetes mellitus (DM), It has been repeatedly reported that statins may cause new-onset diabetes mellitus (DM). However, limited evidence exists from direct head to head comparisons of statins on whether the risk of DM differs among statins., Short-term statin exposure is associated with reduced all-cause mortality in persons with diabetes., Despite the fact that higher statin doses are more likely to lead to new-onset diabetes, for every case of diabetes caused, there are approximately three cardiovascular events reduced with high dose versus moderate dose statin therapy., It has been repeatedly reported that statins may cause new-onset diabetes mellitus (DM).,  Statins are evidence-based drugs to prevent cardiovascular (CV) disease. However, their benefits have been disputed by a statin-related increased risk of new onset diabetes,  Compared with pravastatin, treatment with higher potency statins, especially atorvastatin and simvastatin, might be associated with an increased risk of new onset diabetes,  statins are associated with a small increase in incidence of diabetes in patients predisposed to glycemic alteration,  Higher potency statin use is associated with a moderate increase in the risk of new onset diabetes compared with lower potency statins in patients treated for secondary prevention of cardiovascular disease, An increased risk of new onset treated diabetes was found in those treated with statins showing significant duration and dose effect, Although most of the clinical studies suggest a worsening of insulin resistance and secretion, the cardiovascular benefits of statin therapy outweigh the risk of developing insulin resistance, thus the data suggest the need to treat dyslipidemia and to make patients aware of the possible risk of developing type 2 diabetes or, if they already are diabetic, of worsening their metabolic control, Statin therapy can slightly increase risk of incident diabetes in subjects with hypercholesterolemia.[SEP]Relations: Simvastatin has relations: contraindication with diabetes mellitus (disease), contraindication with diabetes mellitus (disease), drug_effect with Arthritis, drug_effect with Arthritis, contraindication with diabetic ketoacidosis, contraindication with diabetic ketoacidosis, drug_effect with Edema, drug_effect with Edema. Atorvastatin has relations: drug_effect with Dysphagia, drug_effect with Dysphagia.", "label": "yes"}
{"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]Relations: SLC22A3 has relations: anatomy_protein_present with heart, anatomy_protein_present with heart, anatomy_protein_present with colon, anatomy_protein_present with colon, cellcomp_protein with membrane, cellcomp_protein with membrane, anatomy_protein_present with kidney, anatomy_protein_present with kidney, anatomy_protein_present with intestine, anatomy_protein_present with intestine.", "label": "yes"}
{"id": "converted_3711", "sentence1": "Was vivotif licensed in Europe and the US at the same time?", "sentence2": "Vivotif® is an oral live attenuated vaccine which contains a mutated strain of Salmonella (Ty21a) and reproduces the natural infection. The vaccine was first licensed in Europe in 1983 and in the US in 1989, and over the years it has proved efficacious and safe.[SEP]Salmonellosis has relations: disease_protein with HLA-DRB1. Disease_disease with invasive non-typhoidal salmonellotes. Disease-diseases with paratyphoid fever and typhoid fever have relations with salmonella infections. Salmonella is the most common cause of foodborne illness.", "label": "no"}
{"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]Relations: Selumetinib has relations: drug_drug with Gliquidone, drug_drug with Gliquidone, drug_drug with Glasdegib, drug_drug with Glasdegib, drug_drug with Bortezomib, drug_drug with Bortezomib, drug_drug with Afelimomab, drug_drug with Afelimomab, drug_drug with Glipizide, drug_drug with Glipizide.", "label": "yes"}
{"id": "converted_4243", "sentence1": "Is RUNX1T1 associate with obesity?", "sentence2": "RUNX1T1 rs34269950 is associated with obesity and metabolic syndrome., Of these SNPs only rs34269950 located in the 'RRACH' motif, the most common N6-methyladenosine (m6A) methylation modification site (recognized by FTO), was significantly associated with obesity risk and metabolic abnormalities. Specifically, compared to AA genotype, rs34269950 del/del genotype was associated with a 1.47 [95% confidence interval (CI): 1.01-2.14, P = 0.042] fold higher rate of obesity risk. , Our study demonstrates that RUNX1T1 rs34269950, located in a potential FTO recognition motif, is significantly associated with waist circumference. T[SEP]Metabolic syndrome X has relations with SIRT1 and INPPL1. METTL3 has relations: protein_protein with YY1 and disease_proteinwith NR1I2. Metabolic syndrome Y has Relations with HMGA1 and SIRT2.", "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_5", "sentence1": "Does metformin interfere thyroxine absorption?", "sentence2": "LT4 absorption is unchanged by concomitant metformin ingestion., It has been hypothesized that metformin may suppress serum thyrotropin (TSH) concentrations by enhancing LT4 absorption or by directly affecting the hypothalamic-pituitary axis.[SEP]Metformin has relations with Thrombocytopenia, Sensory impairment, and Pyridoxine. Metformin is contraindication with thymus gland disease, injury, and other conditions. It is not recommended for use in people suffering from any of these conditions. For confidential support call the Samaritans on 08457 90 90 90, visit a local Samaritans branch or click here for details.", "label": "no"}
{"id": "converted_1270", "sentence1": "Can administration of the thyrotropin releasing hormone reduce fatigue in cancer patients?", "sentence2": "TRH administration was associated with significant improvement (p < 0.05) in fatigue levels as measured by the Visual Analog Scale-Energy (VAS-E), was associated with significant (p < 0.05) improvement in sleep disturbances and improved quality of life. , This decrease in CRP level with TRH administration was associated with improvement in energy levels as measured by the VAS-E. , In the present pilot, randomized, placebo-controlled, crossover study, we investigated the efficacy and safety of TRH as a treatment for CF., TRH administration was associated with significant improvement in fatigue level as measured by the VAS-E, the fatigue and vigor subscales of the POMS, and the fatigue subscale of FACIT-F (p < 0.05). , TRH administration was efficacious, safe, and tolerable in the treatment of CF with a positive impact on quality of life. These results provide a crucial impetus for pursuing TRH therapeutics to treat CF., Thyrotropin-releasing hormone can relieve cancer-related fatigue: hypothesis and preliminary observations., Global assessment using both subjective and objective parameters showed that TRH exerted clear anti-fatigue effects in four of the six TRH treatments. , These initial findings support the proposal that TRH can ameliorate cancer-related fatigue.[SEP]Fatigue has relations with Atropine, Urofollitropin, Parathyroid hormone, Mitoxantrone, Levothyroxine, and more. Fatigue has a drug_effect with Uropine and a drug-effect with Parathyroxine.", "label": "yes"}
{"id": "converted_4530", "sentence1": "Are functional tests a good biomarker for Duchenne Muscular Dystrophy?", "sentence2": "North Star Ambulatory Assessment is practical and reliable., allow assessment of high-functioning boys with Duchenne muscular dystrophy., agnosis and tracking of symptom progression of DMD usually relies on creatine kinase tests, evaluation of patient performance in various ambulatory assessments, and detection of dystrophin from muscle biopsies, which are invasive and painful for the patient. While the, Aim: Using baseline data from a clinical trial of domagrozumab in Duchenne muscular dystrophy, we evaluated the correlation between functional measures and quantitative MRI assessments of thigh muscle. Patients & methods: Analysis included timed functional tests, knee extension/strength and North St, A New Functional Scale and Ambulatory Functional Classification of Duchenne Muscular Dystrophy: Scale Development and Preliminary Analyses of Reliability and Validity., his preliminary investigation describes the relationship between community ambulation measured by the StepWatch activity monitor and the current standard of functional assessment, the 6-minute walk test, in ambulatory boys with Duchenne muscular dystrophy (n = 16) and healthy controls (n = 13). All, ith strength assessments. MV index, fat fraction and T2-mapping measures had moderate correlations (r ∼ 0.5) to all functional tests, North Star Ambulatory Assessment and age. Conclusion: The moderate correlation between functional tests, age and baseline MRI measures supports MRI as a biomarker in Duchenn, on with clinically meaningful outcome measures such as North Star Ambulatory Assessment (NSAA) and 6 minute walk test (6MWT) is paramount for biomarker qualification. In this stu, Quantitative muscle strength assessment in duchenne muscular dystrophy: longitudinal study and correlation with functional measures., The 6-minute walk test, timed 10-meter walk/run test, and supine-up time are commonly used timed functional tests that also sufficiently monitor changes in muscle function; however, they strongly depend on patient collaboration, Conclusion: The moderate correlation between functional tests, age and baseline MRI measures supports MRI as a biomarker in Duchenne muscular dystrophy clinical trials., Currently, functional measures continue to serve as the primary outcome for the majority of DMD clinical trials., Patients & methods: Analysis included timed functional tests, knee extension/strength and North Star Ambulatory Assessment., The 6-minute walk test, timed 10-meter walk/run test, and supine-up time are commonly used timed functional tests that also sufficiently monitor changes in muscle function; however, they strongly depend on patient collaboration., We have developed a new scale and the associated classification system, to assess the functional ability of children diagnosed with DMD. Preliminary evaluation of the psychometric properties of the functional scale and classification systems indicate sufficient reliability and concurrent validity., Quantitative MRI is an objective and sensitive biomarker to detect subclinical changes, though the examination costs may be a reason for its limited use. In this study, a high correlation between all clinical assessments and quantitative MRI scans was found. The combinational use of these methods provides a better understanding about disease progression; however, longitudinal studies are needed to validate their reliability., The children's functional performance was assessed using 6-minute walk tests and timed performance tests. The correlations between the flexibilities of the lower limb muscles and the performance tests were examined., The flexibilities of the lower extremity muscles were found to be correlated to the 6-minute walk tests and the timed performance tests. The flexibility of the hamstrings (r = -.825), the gastrocnemius muscles (r = .545), the hip flexors (r = .481), and the tensor fascia latae (r = .445) were found to be correlated with functional performance as measured by the 6-minute walk tests (P < .05), Nine biomarkers have been identified that correlate with disease milestones, functional tests and respiratory capacity. Together these biomarkers recapitulate different stages of the disorder that, if validated can improve disease progression monitoring.,  In conclusion, the motor function measure and timed function tests measure disease severity in a highly comparable fashion and all tests correlated with quantitative muscle MRI values quantifying fatty muscle degeneration.,  This study is to date the most thorough long-term evaluation of QMT in a cohort of DMD patients correlated with other measures, such as the North Star Ambulatory Assessment (NSAA) or three 6-min walk test (6MWT)., The MFM scale was a useful instrument in the follow up of patients with DMD. Moreover, it is a more comprehensive scale to assess patients and very good for conducting trials to evaluate treatment., MD subjects were evaluated using the Vignos lower extremity functional rating, and tests including 6 min walk test (6MWT) and 10 m walk., TFTs appear to be slightly more responsive and predictive of disease progression than the 6MWT in 7-12.9 year olds., herefore, in our group of ambulant patients with DMD, timed functional testing was the most sensitive parameter to determine the extent of disease progression. Timed functional testing may therefore be considered as an additional outcome measure in drug trials to evaluate the effects of therapy in ambulant patients with DMD and possibly in other neuromuscular disorders., Time to rise is a useful and simple tool in the screening of neuromuscular disorders such as Duchenne muscular dystrophy,, he muscle strength of the wrist extensors and the radial deviation range of motion at the wrist were found to be strongly correlated with six of the seven tasks assessed. These two clinical assessments appear to be good indicators of overall wrist and hand function.[SEP]Relations: Duchenne muscular dystrophy has relations: disease_phenotype_positive with Muscular dystrophy, disease_phenotype_positive with Muscular dystrophy, disease_phenotype_positive with Skeletal muscle atrophy, disease_phenotype_positive with Skeletal muscle atrophy, disease_protein with BCHE, disease_protein with BCHE, disease_protein with DMD, disease_protein with DMD, disease_protein with ACHE, disease_protein with ACHE.", "label": "yes"}
{"id": "converted_3531", "sentence1": "Is Huntington's disease is caused by expansion of a CTG repeat in the HTT gene on Chromosome 4?", "sentence2": "Huntington's disease (HD) is caused by a CAG repeat expansion that encodes a polyglutamine (polyQ) expansion in the HD disease protein, huntingtin (HTT)., Huntington disease (HD) is a dominantly inherited disorder caused by a CAG expansion mutation in the huntingtin (HTT) gene, which results in the HTT protein that contains an expanded polyglutamine tract., In Huntington's disease (HD), expansion of CAG codons in the huntingtin gene (HTT) leads to the aberrant formation of protein aggregates and the differential degeneration of striatal medium spiny neurons (MSNs)., Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline, and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p., Huntington's disease (HD) is a polyglutamine disorder caused by a CAG expansion in the Huntingtin (HTT) gene exon 1., IMPORTANCE\n\nHuntington disease (HD), a prototypic monogenic disease, is caused by an expanded CAG repeat in the HTT gene exceeding 35 units., Huntington's disease (HD) is an autosomal dominantly inherited disorder caused by the expansion of CAG repeats in the Huntingtin (HTT) gene., Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin (HTT) gene., BACKGROUND Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT., Huntington's disease (HD) is an inherited neurodegenerative disease caused by an expanded CAG repeat in the HTT gene., IMPORTANCE Huntington disease (HD), a prototypic monogenic disease, is caused by an expanded CAG repeat in the HTT gene exceeding 35 units., Huntington 's disease ( HD ) is an inherited neurodegenerative disorder caused by a CAG repeat expansion within exon 1 of the huntingtin ( HTT ) gene. , Huntington 's disease ( HD) , a dominantly inherited neurodegenerative disease , is defined by its genetic cause , a CAG-repeat expansion in the HTT gene , its motor and psychiatric symptomology and primary loss of striatal medium spiny neurons ( MSNs) . , Huntington 's disease ( HD ) is an incurable neurodegenerative disorder caused by a CAG repeat expansion in exon 1 of the Huntingtin ( HTT ) gene. , Huntington 's disease ( HD ) is a progressive neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin ( HTT ) gene , which encodes a polyglutamine tract in the HTT protein . , Huntington 's disease ( HD ) is an autosomal progressive neurodegenerative disorder caused by the expansion of CAG repeats in the HTT gene. , Huntington 's disease ( HD ) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat in exon 1 of the huntingtin ( htt ) gene. , Huntington 's disease ( HD) , caused by a CAG repeat expansion in the huntingtin ( HTT ) gene , is characterized by abnormal protein aggregates and motor and cognitive dysfunction . , Huntington 's disease ( HD ) is a neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat in exon 1 of the huntingtin ( HTT ) gene. , Huntington 's disease ( HD ) is an autosomal disease caused by a CAG repeat expansion in the huntingtin ( HTT ) gene. , BACKGROUND\nHuntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT., Huntington's disease (HD) is an autosomal dominant disorder caused by an expansion in the trinucleotide CAG repeat in exon-1 in the huntingtin gene, located on chromosome 4., HD is caused by expansion of the CAG trinucleotide repeat region in exon 1 of the Huntingtin gene (HTT), leading to the formation of mutant HTT transcripts (muHTT)., Huntington's disease (HD) is a neurodegenerative disorder characterized by involuntary choreic movements, cognitive impairment, and behavioral changes, caused by the expansion of an unstable CAG repeat in HTT., Huntington disease (HD), the most common inherited cause of chorea, is an autosomal dominant disorder, caused by an expanded trinucleotide CAG repeat (>39) in the HTT gene on chromosome 4p16.3., Huntington's disease (HD) is an inherited neurodegenerative disease caused by an expanded CAG repeat in the huntingtin (HTT) gene.[SEP]Relations: Huntington disease has relations: disease_protein with HTT, disease_protein with HTT, disease_protein with OGG1, disease_protein with OGG1, disease_disease with Huntington disease and related disorders, disease_disease with Huntington disease and related disorders, disease_protein with GDNF, disease_protein with GDNF, disease_protein with CNR1, disease_protein with CNR1.", "label": "no"}
{"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] response to thyroid hormone has relations with response to thyroxine. Bioprocess_protein with HPN, biop rocess_ protein with CAB39, and bioprocession_protein with HPN. Response to thyroid hormone has relations with response to thyroid  hormone. response to thyroxine has relations with response to thyroid Hormone.response to thyroxine has relationships with the response to hormone.", "label": "yes"}
{"id": "converted_4601", "sentence1": "Is Epistaxis associated with dental implant placement?", "sentence2": " The overall survival rate of the implants into the sinus cavity was 95.6%, without statistical differences according to the level of penetration. The clinical and radiological complications were 3.4% and 14.8% respectively. The most frequent clinical complication was the epistaxis, , implant placement and protrusion of the implant up to 3mm beyond the sinus floor does not alter the stability and outcome of dental implants, one year post-restoration. This could be associated with minor complications ranging from epistaxis to sinusitis, which are manageable.[SEP] Epistaxis has relations with Nicotine, Topotecan, Estradiol, Montelukast, Thiotepa, and Monteluks. It also has a relationship with the drug_effect with Nicotine.", "label": "yes"}
{"id": "converted_1982", "sentence1": "Is lenvatinib effective for renal cell carcinoma?", "sentence2": "However, the combination of lenvatinib, a multitargeted agent that inhibits VEGF as well as FGF receptors, and everolimus demonstrated promising results in a randomized phase II trial. , The FDA has approved the combination of lenvatinib and everolimus to treat advanced or metastatic renal cell carcinoma., Moreover, a recent Phase II study demonstrated a significant benefit for the second-line combination treatment with everolimus plus lenvatinib (a novel TKI) in terms of progression-free survival and overall survival compared to the single-agent everolimus., We then discuss two recently approved growth factor receptor antagonists i.e. cabozantinib and lenvatinib, and a recently approved checkpoint inhibitor, nivolumab, and issues pertaining to drug development, and future directions in treatment of metastatic RCC. , INTERPRETATION: Lenvatinib plus everolimus and lenvatinib alone resulted in a progression-free survival benefit for patients with metastatic renal cell carcinoma who have progressed after one previous VEGF-targeted therapy. , Lenvatinib therapy for the treatment of patients with advanced renal cell carcinoma., Lenvatinib therapy for the treatment of patients with advanced renal cell carcinoma.[SEP]Lenvatinib has relations with Carbamazepine, Carbimazole, Carbinoxamine, Carbutamide, Carfilzomib, and Carbutamide. It is also related to CarfilZomib.", "label": "yes"}
{"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]Malignant ear neoplasm has relations with inner ear cancer, middle ear cancer and head and neck cancer. Glioma has relations: disease_phenotype_positive with glioma susceptibility, disease phenotype positive withglioma potential. Disease_disease with sensory system cancer is related to sensory system cancer. Disease diseases with sensory systems cancer are related to head and neck cancers.", "label": "yes"}
{"id": "converted_2487", "sentence1": "Is there any role of Dlx1 and Dlx2 transcription factors in cortical interneurons?", "sentence2": "The postnatal functions of the Dlx1&2 transcription factors in cortical interneurons (CINs) are unknown. Here, using conditional Dlx1, Dlx2, and Dlx1&2 knockouts (CKOs), we defined their roles in specific CINs. The CKOs had dendritic, synaptic, and survival defects, affecting even PV+ CINs. We provide evidence that DLX2 directly drives Gad1, Gad2, and Vgat expression, and show that mutants had reduced mIPSC amplitude. In addition, the mutants formed fewer GABAergic synapses on excitatory neurons and had reduced mIPSC frequency. Furthermore, Dlx1/2 CKO had hypoplastic dendrites, fewer excitatory synapses, and reduced excitatory input. We provide evidence that some of these phenotypes were due to reduced expression of GRIN2B (a subunit of the NMDA receptor), a high confidence Autism gene. Thus, Dlx1&2 coordinate key components of CIN postnatal development by promoting their excitability, inhibitory output, and survival., Furthermore, Dlx1/2 CKO had hypoplastic dendrites, fewer excitatory synapses, and reduced excitatory input.[SEP]GAD2 has relations: pathway_protein with MECP2 regulates transcription of genes involved in GABA signaling. SLC32A1 has Relations: anatomy_protein_present with dorsolateral prefrontal cortex, anatomy_ protein_ present with dorsolateral prefrontal cortex. protein_protein with CPLX4, protein_ protein with RHEX, protein protein with RHEX.", "label": "yes"}
{"id": "converted_4399", "sentence1": "Is gabapentin effective for chronic pelvic pain?", "sentence2": "There were no significant between-group differences in both worst and average numerical rating scale (NRS) pain scores at 13-16 weeks after randomisation. The mean worst NRS pain score was 7·1 (standard deviation [SD] 2·6) in the gabapentin group and 7·4 (SD 2·2) in the placebo group. Mean change from baseline was -1·4 (SD 2·3) in the gabapentin group and -1·2 (SD 2·1) in the placebo group (adjusted mean difference -0·20 [97·5% CI -0·81 to 0·42]; p=0·47). The mean average NRS pain score was 4·3 (SD 2·3) in the gabapentin group and 4·5 (SD 2·2) in the placebo group. Mean change from baseline was -1·1 (SD 2·0) in the gabapentin group and -0·9 (SD 1·8) in the placebo group (adjusted mean difference -0·18 [97·5% CI -0·71 to 0·35]; p=0·45)., INTERPRETATION: This study was adequately powered, but treatment with gabapentin did not result in significantly lower pain scores in women with chronic pelvic pain, and was associated with higher rates of side-effects than placebo. Given the increasing reports of abuse and evidence of potential harms associated with gabapentin use, it is important that clinicians consider alternative treatment options to off-label gabapentin for the management of chronic pelvic pain and no obvious pelvic pathology., Gabapentin not effective for chronic pelvic pain in women., Gabapentin not effective for chronic pelvic pain in women[SEP]Gabapentin has relations with Bone pain, Pain, Abdominal pain, Chest pain, Back pain and Chest pain. Gabapentin can also be used to treat back pain. The drug is available in the U.S. and Europe.", "label": "no"}
{"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]Hydrocephalus has relations with isotretinoin-like syndrome, Noonan syndrome-like disorder with loose anagen hair, and methylmalonic aciduria/acidemia and homocystinuria. Hydrocephalus can also have relations with Glatiramer, which is used in the treatment of the disease. The disease can also be treated with the drug  GlatIRamer. The drug is used to treat hydrocephalus and other brain disorders.", "label": "yes"}
{"id": "converted_2016", "sentence1": "Is ocular melanosis a risk factor for uveal melanoma?", "sentence2": "Ocular/oculodermal (oculo[dermal]) melanocytosis is a congenital periocular pigmentary condition that can lead to the development of uveal melanoma, estimated at 1 in 400 affected patients., Melanosis oculi is often underestimated as a risk factor for uveal melanoma and glaucoma. Ophthalmic surveillance, every 6 or 12 months is important, in patients with ocular melanocytosis for early detection of high risk diseases.,  One of about 400 patients with ODM followed for life is estimated to develop uveal melanoma. Excessive melanocytes in the uveal tract in ODM may provide the biologic basis for susceptibility to the development of uveal melanoma. Patients with ODM should be monitored ophthalmoscopically, especially during the susceptible period, for the development of uveal melanoma. The authors suggest that a national registry of ODM patients be created and prospective data collected to better assess the risk of developing uveal melanoma., In the white population, an association between oculo(dermal) melanocytosis (ODM) and uveal melanoma is well recognized. , Malignant melanomas may arise in the uveal tract, the conjunctiva, the skin of the eyelid, or the orbit. Risk factors so far identified include pre-existing choroidal naevi for uveal melanomas, primary acquired melanosis (PAM) for conjunctival tumours, and ocular and oculodermal melanocytosis for uveal and orbital lesions. , Risk factors so far identified include pre-existing choroidal naevi for uveal melanomas, primary acquired melanosis (PAM) for conjunctival tumours, and ocular and oculodermal melanocytosis for uveal and orbital lesions., Phacomatosis pigmentovascularis of cesioflammea type in 7 patients: combination of ocular pigmentation (melanocytosis or melanosis) and nevus flammeus with risk for melanoma., In the fourth case the melanoma was detected in a routine examination and we were able to apply a preserving treatment with I125 brachytherapy.DISCUSSION: Melanosis oculi is often underestimated as a risk factor for uveal melanoma and glaucoma., Association of ocular and oculodermal melanocytosis with the rate of uveal melanoma metastasis: analysis of 7872 consecutive eyes., Risk factors so far identified include pre-existing choroidal naevi for uveal melanomas, primary acquired melanosis (PAM) for conjunctival tumours, and ocular and oculodermal melanocytosis for uveal and orbital lesions, In the fourth case the melanoma was detected in a routine examination and we were able to apply a preserving treatment with I125 brachytherapy.Melanosis oculi is often underestimated as a risk factor for uveal melanoma and glaucoma, In this study, patients with melanocytosis who developed uveal melanoma were found to have double the risk for metastasis compared with those without melanocytosis.To determine the relationship of oculo(dermal) melanocytosis to the prognosis of patients with uveal melanoma.Retrospective chart review of 7872 patients with uveal melanoma treated at the Ocular Oncology Service, Wills Eye Institute, from August 25, 1970, through August 27, 2008.Enucleation, plaque radiotherapy, local resection, or thermotherapy.Metastasis and death.Of 7872 patients with uveal melanoma, oculo(dermal) melanocytosis was present in 230 (3%), By multivariable analysis, the factors predictive of metastasis in patients harboring uveal melanoma associated with oculo(dermal) melanocytosis were increased tumor thickness (P = .001) and the presence of subretinal fluid (P = .05), and the only factor predictive of death was increased tumor thickness (P = .009). , In the fourth case the melanoma was detected in a routine examination and we were able to apply a preserving treatment with I125 brachytherapy.Melanosis oculi is often underestimated as a risk factor for uveal melanoma and glaucoma., Risk factors so far identified include pre-existing choroidal naevi for uveal melanomas, primary acquired melanosis (PAM) for conjunctival tumours, and ocular and oculodermal melanocytosis for uveal and orbital lesions., CONCLUSIONS AND RELEVANCE Patients with uveal melanoma associated with oculo(dermal) melanocytosis have double the risk for metastasis compared with those with no melanocytosis., By multivariable analysis, the factors predictive of metastasis in patients harboring uveal melanoma associated with oculo(dermal) melanocytosis were increased tumor thickness (P = .001) and the presence of subretinal fluid (P = .05), and the only factor predictive of death was increased tumor thickness (P = .009)., CONCLUSIONS AND RELEVANCE Patients with uveal melanoma associated with oculo(dermal) melanocytosis have double the risk for metastasis compared with those with no melanocytosis.[SEP]Relations: melanoma has relations: disease_disease with ocular melanoma, disease_disease with ocular melanoma, disease_phenotype_positive with Uveal melanoma, disease_phenotype_positive with Uveal melanoma, disease_disease with eyelid melanoma, disease_disease with eyelid melanoma, disease_disease with skin cancer, disease_disease with skin cancer, disease_disease with amelanotic skin melanoma, disease_disease with amelanotic skin melanoma.", "label": "yes"}
{"id": "converted_1226", "sentence1": "Are there interactomes available for POU5F1 and SOX2?", "sentence2": "The interactomes of POU5F1 and SOX2 enhancers in human embryonic stem cells., We assayed long-range chromosomal interactions on putative enhancers of POU5F1 and SOX2 genes in human embryonic stem cells (hESCs) using 4C-Seq technique. We discovered that their frequent interacting regions mainly overlap with early DNA replication domains. The interactomes are associated with active histone marks and enriched with 5-hydroxymethylcytosine sites. In hESCs, genes within the interactomes have elevated expression. Additionally, some genes associated with the POU5F1 enhancer contribute to pluripotency. Binding sites for multiple DNA binding proteins, including ATF3, CTCF, GABPA, JUND, NANOG, RAD21 and YY1, are enriched in both interactomes.[SEP]NANOG repress genes related to differentiation, pathway_protein with POU5F1 (OCT4), SOX2, NANOG activate genes relatedto proliferation, protein_ protein with PSORS1C3. N ANOG has relations: protein_ proteins with SOX1, SOX3, and SOX4, and protein_ protein with POU5f1, POU4, Pou5F2, and POU3.", "label": "yes"}
{"id": "converted_3493", "sentence1": "Is there a BRCA mutation analysis in the Greek population?", "sentence2": "Comprehensive BRCA mutation analysis in the Greek population. Experience from a single clinical diagnostic center., Germline mutations in the BRCA1 and BRCA2 genes are associated with hereditary predisposition to breast and ovarian cancer. Sensitive and accurate detection of BRCA1 and BRCA2 mutations is crucial for personalized clinical management of individuals affected by breast or ovarian cancer, and for the identification of at-risk healthy relatives. We performed molecular analysis of the BRCA1 and BRCA2 genes in 898 Greek families, using Sanger sequencing or Next Generation Sequencing for the detection of small insertion/deletion frameshift, nonsynonymous, truncating and splice-site alterations and MLPA for the detection of large genomic rearrangements. In total, a pathogenic mutation was identified in 12.9% of 898 families analyzed. Of the 116 mutations identified in total 9% were novel and 14.7% were large genomic rearrangements. Our results indicate that different types of mutational events in the BRCA1 and BRCA2 genes are responsible for the hereditary component of breast/ovarian cancer in the Greek population. Therefore the methodology used in the analysis of Greek patients must be able to detect both point and small frameshift mutations in addition to large genomic rearrangements across the entire coding region of the two genes.[SEP]Breast has relations: anatomy_protein_present with RIMKLB, anatomy_ protein_ present with GCSAM. adaptation to pheromone regulating conjugation with mutual genetic exchange has relations. bioprocess_bioprocession with negative adaptation of signaling pathway has relations with breast. breast has relations to other parts of the body, such as the stomach, bowel, and bladder. breast can also have relations with other organs, including the heart, liver and kidney.", "label": "yes"}
{"id": "converted_2792", "sentence1": "Is celecoxib effective for treatment of amyotrophic lateral sclerosis?", "sentence2": "NTERPRETATION: At the dosage studied, celecoxib did not have a beneficial effect on research subjects with ALS, and it was safe. A biological effect of celecoxib was not demonstrated in the cerebrospinal fluid. Further studies of celecoxib at a dosage of 800 mg/day in ALS are not warranted., Prostaglandin E(2) levels in cerebrospinal fluid were not elevated at baseline and did not decline with treatment.<br><b>INTERPRETATION</b>: At the dosage studied, celecoxib did not have a beneficial effect on research subjects with ALS, and it was safe.[SEP] Celecoxib has relations with Arthropathy, Coronary artery atherosclerosis, Corticotropin and Citalopram. It is contraindication with stroke disorder and is not approved for use in the United States.", "label": "no"}
{"id": "converted_3936", "sentence1": "Is cabergoline used for treatment of the Nelson's syndrome ?", "sentence2": "Due to a rapid regrowth of the tumour, the patient did not receive gamma-knife therapy and was treated with cabergoline and somatostatin analogue for some time. , Identification of D(2) receptors in corticotroph tumors led to clinical trials of cabergoline therapy in limited cases of Nelson's syndrome, ectopic ACTH-secreting tumors, and recently Cushing's disease (CD).,  In our observation cabergoline at 2 mg per week seems to be efficient after a 3 and a half years follow-up, in accordance with some recent publications. , Clinical and biochemical stabilization of Nelson's syndrome with long-term low-dose cabergoline treatment., We report the results of long-term (6-year) treatment of Nelson's syndrome with the long-acting dopamine agonist, cabergoline, in a 55-year-old woman., This case demonstrates that long-term cabergoline treatment may be efficient in patients with Nelson's syndrome., Therefore, in addition to prolactinomas, targets of dopamine agonist therapy are somatotroph tumors, nonfunctioning pituitary tumors, corticotroph pituitary tumors, Nelson's syndrome, gonadotropinomas, and thyrotropin-secreting pituitary tumors., Nelson's syndrome: complete remission with cabergoline but not with bromocriptine or cyproheptadine treatment., The results obtained show for the first time that a long-term treatment with cabergoline also brings about a complete remission of Nelson's syndrome in the presence of a pituitary macroadenoma., Complete remission of Nelson's syndrome after 1-year treatment with cabergoline., In this case report we demonstrated that treatment with the long-acting D2 receptor agonist cabergoline for 1 year induced normalization of plasma ACTH levels and disappearance of the pituitary tumor in a patient with Nelson's syndrome. , This case demonstrated that cabergoline treatment is able to induce the remission of Nelson's syndrome and may be a valid therapeutic alternative in this syndrome., However, some preliminary data suggest a potential use of cabergoline in combination with ketoconazole, or alone, in selected cases of Cushing's disease or Nelson's syndrome., We report the results of long-term (6-year) treatment of Nelson's syndrome with the long-acting dopamine agonist, cabergoline, in a 55-year-old woman. The, actinomas. Identification of D(2) receptors in corticotroph tumors led to clinical trials of cabergoline therapy in limited cases of Nelson's syndrome, ectopic ACTH-secreting tumors, and recently Cushing's diseas, In order to investigate on the direct effect played by cabergoline treatment on the remission of Nelson's syndrome, the treatment was withdrawn., lactinomas. Identification of D(2) receptors in corticotroph tumors led to clinical trials of cabergoline therapy in limited cases of Nelson's syndrome, ectopic ACTH-secreting tumors, and recently Cushing's disease (CD).OBJECTIVE: To evaluate the long-term efficacy of cabergoline monotherapy in patients with CD.METHODS: Retrospective analysis of non-randomized clinical therapy with cabergoline in 30 patients with CD treated in academic cente[SEP]Relations: Cabergoline has relations: drug_drug with Norepinephrine, drug_drug with Norepinephrine, drug_drug with Antipyrine, drug_drug with Antipyrine, contraindication with gallbladder disease, contraindication with gallbladder disease, drug_effect with Headache, drug_effect with Headache, drug_effect with Vertigo, drug_effect with Vertigo.", "label": "yes"}
{"id": "converted_4514", "sentence1": "Do angiotensin-converting-enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) increase the likelihood of severe COVID-19?", "sentence2": "These findings suggest that the use of ACE-I and ARB is not associated with adverse outcomes and may be associated with improved outcomes in COVID-19, which is immediately relevant to care of the many patients on these medications., There are theoretical concerns that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) could increase the risk of severe Covid-19., ACEIs and ARBs were associated with a slight reduction in Covid-19 hospitalization risk compared with treatment with other first-line antihypertensives (OR for ACEIs 0.95, 95% CI 0.92-0.98; OR for ARBs 0.94, 95% CI 0.90-0.97)., There were no meaningful differences in risk for ACEIs compared with ARBs., ACEIs and ARBs were not associated with an increased risk of Covid-19 hospitalization or with hospitalization involving ICU admission, invasive mechanical ventilation, or death., In patients with HTN and COVID-19, neither ACEi nor ARBs were independently associated with mortality., Our data confirm Specialty Societal recommendations, suggesting that treatment with ACEIs or ARBs should not be discontinued because of COVID-19., Random-effects meta-analysis showed ACEI/ARB treatment was significantly associated with a lower risk of mortality in hypertensive COVID-19 patients (odds ratio [OR] = 0.624, 95% confidence interval [CI] = 0.457-0.852, p = .003, I2  = 74.3%)., In addition, the ACEI/ARB treatment was associated with a lower risk of ventilatory support (OR = 0.682, 95% CI = 0.475-1.978, p = .037, I2  = 0.0%). In conclusion, these results suggest that ACEI/ARB medications should not be discontinued for hypertensive patients in the context of COVID-19 pandemic., Use of ACE-I or ARB medications was not associated with increased risk of hospitalization, intensive care unit admission, or death. Compared to patients with charted past medical history, there was a lower risk of hospitalization for patients on ACE-I (odds ratio (OR) 0.43; 95% confidence interval (CI) 0.19-0.97; P = 0.0426) and ARB (OR 0.39; 95% CI 0.17-0.90; P = 0.0270)., The second analysis showed that the use of ACEI and/or ARB did not affect in-hospital mortality (risk ratio [RR] 95% [CI]] = 0.88 [0.64-1.20], p = 0.42). The subgroup analysis by limiting studies of patients with hypertension showed ACEI and/or ARB use was associated with a significant reduction of in-hospital mortality compared with no ACEI or ARB use (RR [CI] = 0.66 [0.49-0.89], p = 0.004). Our analysis demonstrated that ACEI and/or ARB use was associated neither with testing positive rates of COVID-19 nor with mortality of COVID-19 patients., ACEIs/ARBs are protective factors against mortality in COVID-19 patients with HTN, and these agents can be considered potential therapeutic options in this disease., There has been a lot of speculation that patients with coronavirus disease 2019 (COVID-19) who are receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) may be at increased risk for adverse outcomes., Although further research on the influence of blood-pressure-lowering drugs, including those not targeting the renin-angiotensin system, is warranted, there are presently no compelling clinical data showing that ACEIs and ARBs increase the likelihood of contracting COVID-19 or worsen the outcome of SARS-CoV‑2 infections, There has been a lot of speculation that patients with coronavirus disease 2019 (COVID-19) who are receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) may be at increased risk for adverse outcomes, ACEIs and ARBs do not promote a more severe outcome of COVID-19., Meta-analysis showed no significant increase in the risk of COVID-19 infection (odds ratio [OR]: 0.95, 95%CI: 0.89-1.05) in patients receiving ACEI/ARB therapy, and ACEI/ARB therapy was associated with a decreased risk of severe COVID-19 (OR: 0.75, 95%CI: 0.59-0.96) and mortality (OR: 0.52, 95%CI: 0.35-0.79)., Subgroup analyses showed among the general population, ACEI/ARB therapy was associated with reduced severe COVID-19 infection (OR: 0.79, 95%CI: 0.60-1.05) and all-cause mortality (OR: 0.31, 95%CI: 0.13-0.75), and COVID-19 infection (OR: 0.85, 95% CI: 0.66-1.08) were not increased., On the basis of the available evidence, ACEI/ARB therapy should be continued in patients who are at risk for, or have COVID-19, either in general population or hypertension patients., Some studies of hospitalized patients suggested that the risk of death and/or severe illness due to COVID-19 is not associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin II receptor type 1 blockers (ARBs), Available evidence, in particular, data from human studies, does not support the hypothesis that ACEI/ARB use increases ACE2 expression and the risk of complications from COVID-19. We conclude that patients being treated with ACEIs and ARBs should continue their use for approved indications.[SEP]Relations: type 2 angiotensin receptor binding has relations: molfunc_protein with AGT, molfunc_protein with AGT. Protein S human has relations: drug_drug with Anti-inhibitor coagulant complex, drug_drug with Anti-inhibitor coagulant complex, drug_drug with Ardeparin, drug_drug with Ardeparin, drug_drug with Peginterferon alfa-2b, drug_drug with Peginterferon alfa-2b, drug_drug with Coagulation Factor IX (Recombinant), drug_drug with Coagulation Factor IX (Recombinant).", "label": "no"}
{"id": "converted_604", "sentence1": "Has the fungus Ashbya gossypii got many nuclei that share cytoplasm?", "sentence2": "multinucleated Ashbya gossypii cells., multinucleated Ashbya gossypii fungal cells, Nuclei in the filamentous, multinucleated fungus Ashbya gossypii divide asynchronously. , multinucleated Ashbya gossypii cells, We analyzed a unique asynchronous nuclear division cycle in a multinucleated filamentous fungus, Ashbya gossypii.,  multinucleated hyphae in Ashbya gossypii., We have followed the migration of GFP-labelled nuclei in multinucleate hyphae of Ashbya gossypii, multinucleate fungus Ashbya gossypii, Ashbya gossypii grows as multinucleated and constantly elongating hyphae, multinucleated hyphae of Ashbya gossypii., We report the mechanistic basis guiding the migration pattern of multiple nuclei in hyphae of Ashbya gossypii. , multinucleate fungal cells, multinucleate Ashbya gossypii cells relies on a minimal network of genes, Clustering of nuclei in multinucleated hyphae is prevented by dynein-driven bidirectional nuclear movements and microtubule growth control in Ashbya gossypii., In the multinucleate fungus Ashbya gossypii, cytoplasmic microtubules (cMTs) emerge from the spindle pole body outer plaque (OP) in perpendicular and tangential directions., multinucleated hyphae of Ashbya gossypii., multiple nuclei in Ashbya gossypii hyphae, Ashbya gossypii has a budding yeast-like genome but grows exclusively as multinucleated hyphae.[SEP] cytoplasmic microtubule has relations with SPACA9, TOGARAM1, C4orf47, ARHGAP18, SYBU, and SYBU. Cellcomp_protein with TOGarAM1 is related to cellcomp_ protein with C 4orf47. cellcomp-protein with SYBU is related with cellcomp protein with SY BU.", "label": "yes"}
{"id": "converted_1108", "sentence1": "Is PLK2 involved in alpha-synuclein phosphorylation in Parkinson disease?", "sentence2": "An increase in α-synuclein levels due to gene duplications/triplications or impaired degradation is sufficient to trigger its aggregation and cause familial Parkinson disease , Here, we report that Polo-like kinase 2 (PLK2), an enzyme up-regulated in synucleinopathy-diseased brains, interacts with, phosphorylates and enhances α-synuclein autophagic degradation in a kinase activity-dependent manner., Polo-like kinase 2 regulates selective autophagic α-synuclein clearance and suppresses its toxicity in vivo, Collectively, our findings demonstrate that PLK2 is a previously undescribed regulator of α-synuclein turnover and that modulating its kinase activity could be a viable target for the treatment of synucleinopathies.,  α-Synuclein increased PLK2 levels and GSK-3β activity and increased the levels of phosphorylated α-Synuclein and Tau, Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system, Several neurological diseases, including Parkinson disease and dementia with Lewy bodies, are characterized by the accumulation of alpha-synuclein phosphorylated at Ser-129 (p-Ser-129), Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons., PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay, These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system.[SEP] synucleinopathy has relations with Parkinson disease. autosomal recessive Parkinson disease has relations: disease_disease with PLA2G6-associated neurodegeneration. disease_protein with LRRK2, disease_ protein with L RRK2 and disease_ proteins with PRKN.", "label": "yes"}
{"id": "converted_1941", "sentence1": "Is NSD-1015 an inhibitor of Aromatic L-Amino Acid Decarboxylase?", "sentence2": "When pretreated with a central AADC inhibitor (NSD-1015), further application of l-dopa failed to increase the motoneuron activity although the expression of DA in the AADC cells was not completely inhibited. , Inhibition of Ddc by AADC inhibitor NSD-1015 or anti-sense morpholino oligonucleotides (MO) reduced brain volume and body length. , We evaluated this in vivo by reverse dialysis of the aromatic-l-amino-acid decarboxylase (EC 4.1.1.28) inhibitor NSD-1015 (20μM) and selected concentrations of l- or d-tyrosine. , Neurochemical study of effects of the new anxiolytic drugs afobazol and ladasten on the synthesis and metabolism of monoamines and their metabolites in the brain structures of Wistar rat on the model of monoamine synthesis blockade induced by aromatic amino acid decarboxylase inhibitor NSD-1015, To establish the neurotransmitter role(s) of L-3,4-dihydroxyphenylalanine (DOPA) in its own right, we attempted to clarify whether i.p. injection of a DOPA antagonist, DOPA cyclohexyl ester (CHE), would antagonize the behavioral responses of conscious rats to DOPA in the presence of 3-hydroxybenzylhydrazine (NSD-1015) (100 mg/kg i.p.), a central aromatic L-amino acid decarboxylase (AADC) inhibitor., TH and TPH activities were determined in tissue extracts by measuring the accumulation of L-Dopa and 5-HTP respectively, following the administration of the aromatic L-amino acid decarboxylase inhibitor, NSD-1015. , Results of a neurochemical study of the effects of the new anxiolytic drugs afobazole and ladasten on the synthesis and metabolism of monoamines and their metabolites determined by HPLC on the model of monoamine synthesis blockade induced by NSD-1015 (aromatic L-amino acid decarboxylase) in the brain structures of Wistar rats are reported. , . When pretreated with a central AADC inhibitor (NSD-1015), NSD 1015 (general AADC inhibitor), monoamine synthesis blockade induced by NSD-1015 (aromatic L-amino acid decarboxylase) , the aromatic-l-amino-acid decarboxylase (EC 4.1.1.28) inhibitor NSD-1015, An accumulation of L-dihydroxyphenylalanine (DOPA) in the median eminence of female rats treated with 3-hydroxybenzylhydrazine (NSD 1015), and inhibitor of aromatic L-amino acid decarboxylase (DOPA decarboxylase) activity, was associated with a decreased concentration of dopamine in the median eminence and pronounced reduction in the release of dopamine into hypophysial portal blood., 6S-BH4 increased extracellular DOPA levels in the presence of NSD 1015, an inhibitor of aromatic L-amino acid decarboxylase (an index of in vivo tyrosine hydroxylase activity), to an extent similar to the increase induced by 6R-BH4., 5-HT synthesis was estimated by measuring the accumulation of the 5-HT precursor, 5-hydroxytryptophan (5-HTP), in the neurointermediate lobe of male Long-Evans rats following the administration of NSD 1015, an inhibitor of aromatic L-amino acid decarboxylase., Monoamine synthesis was studied in different parts of the brain by measuring the accumulated dopa and 5-hydroxytryptophan (5-HTP), 30 min after NSD 1015 (3-hydroxybenzylhydrazine HCl, 100 mg/kg) an inhibitor of aromatic L-amino-acid decarboxylase, given i.p., HPLC coupled with electrochemical detection was used to make concurrent measurements of the rate of accumulation of 5-hydroxytryptophan and 3,4-dihydroxyphenylalanine in selected brain regions (striatum, nucleus accumbens, septum, medial periventricular hypothalamus) and thoracic spinal cords of rats treated with NSD 1015, an inhibitor of aromatic-L-amino-acid decarboxylase., The activity of 5-hydroxytryptaminergic neurons has been estimated from measurements of: concentrations of 5-hydroxyindoleacetic acid; the ratio of the concentrations of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine; the rate of accumulation of 5-hydroxytryptophan following the administration of an aromatic L-amino acid decarboxylase inhibitor (e.g., NSD 1015); the rate of accumulation of 5-hydroxytryptamine, and the rate of decline of 5-hydroxyindoleacetic acid following the administration of a monoamine oxidase inhibitor (e.g., pargyline)., The accumulation of dopa (3,4-dihydroxyphenylalanine) after administration of NSD 1015 to inhibit aromatic l-amino acid decarboxylase was determined as an index of NE synthesis., The central aromatic amino acid DOPA decarboxylase inhibitor, NSD-1015, does not inhibit L-DOPA-induced circling in unilateral 6-OHDA-lesioned-rats., The centrally acting aromatic amino acid dopa decarboxylase (AADC) inhibitor, 3-hydroxybenzyl hydrazine (NSD-1015), is widely used to study the neurotransmitter-like actions of L-DOPA., The aromatic amino acid decarboxylase inhibitor, NSD-1015, increases release of dopamine: response characteristics., The aromatic amino acid decarboxylase inhibitor NSD 1015 markedly increased the dopa concentration., Using a microdialysis technique, the rat striatum was perfused with NSD-1015, an inhibitor of aromatic L-amino acid decarboxylase, and the amount of L-3,4-dihydroxyphenylalanine (L-DOPA) and 5-hydroxytryptophan (5-HTP) accumulating in dialysate was measured as an index of in vivo activities of tyrosine hydroxylase and tryptophan hydroxylase., Also, we studied the effect of MnCl2 on extracellular levels of l-Dopa in the presence of aromatic amino acid decarboxylase (AADC) inhibitor 3-hydroxybencilhydracine-HCl (NSD 1015)., The role of L-DOPA itself was investigated by administering several doses of an aromatic L-amino acid decarboxylase inhibitor, NSD 1015, prior to 100 mg/kg L-DOPA to 5-day-old rats., An accumulation of L-dihydroxyphenylalanine (DOPA) in the median eminence of female rats treated with 3-hydroxybenzylhydrazine (NSD 1015), and inhibitor of aromatic L-amino acid decarboxylase (DOPA decarboxylase) activity, was associated with a decreased concentration of dopamine in the median eminence and pronounced reduction in the release of dopamine into hypophysial portal blood. , [Neurochemical study of effects of the new anxiolytic drugs afobazol and ladasten on the synthesis and metabolism of monoamines and their metabolites in the brain structures of Wistar rat on the model of monoamine synthesis blockade induced by aromatic amino acid decarboxylase inhibitor NSD-1015]., DOPA was measured in the anterior pituitary and hypothalamic-hypophysial portal blood after treatment with NSD-1015, a DOPA decarboxylase inhibitor. , Central action of an inhibitor of brain dopa-decarboxylase, NSD-1015, on cyanamide-induced alcohol drinking in rats., The role of L-DOPA itself was investigated by administering several doses of an aromatic L-amino acid decarboxylase inhibitor, NSD 1015, prior to 100 mg/kg L-DOPA to 5-day-old rats. , The centrally acting aromatic amino acid dopa decarboxylase (AADC) inhibitor, 3-hydroxybenzyl hydrazine (NSD-1015), is widely used to study the neurotransmitter-like actions of L-DOPA. , Furthermore, the ethanol-induced enhancement of 3,4-dihydroxyphenylalanine accumulation in the mesolimbic dopamine terminal area after NSD 1015 (an inhibitor of l-aromatic amino acid decarboxylase) was completely antagonized by mecamylamine in doses (3.0 and 6.0 mg/kg) that exerted no effects per se., The acetylcholinesterase inhibitor physostigmine (0.5 mg/kg s.c.) enhanced L-dihydroxyphenylalanine (DOPA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in both the corpus striatum and limbic areas (nucleus accumbens) after inhibition of aromatic amino acid decarboxylase with NSD-1015, indicating an enhanced synthesis of dopamine in these brain regions., Estradiol benzoate-treated rats had significantly lower anterior pituitary DOPA accumulation after intraperitoneal administration of 3,4-hydroxybenzyl-hydrazine dihydrochloride (NSD-1015), an irreversible inhibitor of L-aromatic amino acid decarboxylase whereas methylene blue did not affect anterior pituitary DOPA accumulation when compared to controls., The accumulation of dihydroxyphenylalanine (DOPA) following administration of the L-aromatic amino acid decarboxylase inhibitor, NSD 1015, was used to estimate DA synthesis., Inhibition of PE synthesis by i.p. injection of the aromatic L-amino acid decarboxylase inhibitor, NSD 1015, produced a reversal of the effects of MDL 72,145 and Ro 19-6327., After 42 hr of abstinence, rats were challenged with either cocaine (15 mg/kg, ip) or saline, followed by the aromatic L-amino acid decarboxylase inhibitor 3-hydroxybenzylhydrazine (NSD-1015; 100 mg/kg, ip)., Following motor activity observations, the cerebral aromatic L-amino acid decarboxylase inhibitor NSD-1015 (100 mg kg-1 intraperitoneally) was administered and 30 min. later the animals were decapitated for subsequent analysis of the accumulated forebrain DOPA and 5-HTP levels, as an estimate of the rate of monoamine synthesis., The utility of this technique was demonstrated by comparing the effects on the scans of halothane and pentobarbital anesthesia and by the administration of NSD 1015, a peripheral and central inhibitor of L-aromatic amino-acid decarboxylase, between back-to-back scans., Addition of the aromatic amino acid decarboxylase inhibitor, 3-hydroxybenzylhydrazine (NSD 1015), prevented the formation of N-acetylcompounds from L-[3H]tyrosine, without resulting in an accumulation of label in L-DOPA., The effects of the peripheral aromatic amino acid decarboxylase (AADC) inhibitors, carbidopa and benserazide, and the central AADC inhibitor, 3-hydroxybenzylhydrazine (NSD-1015) on peripheral and brain monoamine oxidase (MAO) A and B activity were investigated in the rat., Although the putative role of NSD-1015 is as an aromatic amino acid decarboxylase inhibitor, the present results demonstrate that, either as a result of this function and/or in addition to this role, NSD-1015 is a potent activator of the release of dopamine., The aromatic amino acid decarboxylase inhibitor, NSD-1015, increases release of dopamine: response characteristics., The central aromatic amino acid DOPA decarboxylase inhibitor, NSD-1015, does not inhibit L-DOPA-induced circling in unilateral 6-OHDA-lesioned-rats., The L-aromatic amino acid decarboxylase inhibitor, NSD-1015 (3-hydroxybenzylhydrazine dihydrochloride) was then given ICV twice daily in a volume of 5.0 microliters in the following doses: 0.005, 0.01, 0.1 and 1.0 micrograms., Although the putative role of NSD-1015 is as an aromatic amino acid decarboxylase inhibitor, the present results demonstrate that, either as a result of this function and/or in addition to this role, NSD-1015 is a potent activator of the release of dopamine..[SEP]Relations: aromatic L-amino acid decarboxylase deficiency has relations: disease_protein with DDC, disease_protein with DDC, disease_disease with neurometabolic disease, disease_disease with neurometabolic disease, disease_phenotype_positive with Nasal obstruction, disease_phenotype_positive with Nasal obstruction, disease_phenotype_positive with Gastroesophageal reflux, disease_phenotype_positive with Gastroesophageal reflux. aromatic-L-amino-acid decarboxylase activity has relations: molfunc_protein with DDC, molfunc_protein with DDC.", "label": "yes"}
{"id": "converted_2184", "sentence1": "Is hydroxyurea usually used to treated infectious disease?", "sentence2": "Hydroxyurea represents the only available disease-modifying therapy for SCA, and has proven safety and efficacy in high-resource countries, In conclusion, the data here presented suggests that hydroxyurea may prevent priapism attacks in sickle cell disease, probably at higher doses than usually prescribed for painful crisis prevention.., Clinical follow-up of hydroxyurea-treated adults with sickle cell disease., t may also attenuate optimal response to hydroxyurea therapy, the only effective and practical treatment option for SCD in sub-Saharan Africa, Hydroxyurea is one of the most successfully used therapies for sickle cell disease, Clinical experience with hydroxyurea for patients with sickle cell disease (SCD) has been accumulating for the past 25 years. The bulk of the current evidence suggests that hydroxyurea is well-tolerated, safe, and efficacious for most patients with SCD[SEP]Hydroxyurea is contraindication with anemia (disease) and kidney disease. The drug is also not approved for use in people with Hepatitis A or Fever. HydroxyureA is not approved to be used in people who have HIV or AIDS.", "label": "no"}
{"id": "converted_3760", "sentence1": "Are bacteria in the genus Clostridium facultative anaerobes?", "sentence2": "strict anaerobe Clostridium acetobutylicum, Clostridia belong to those bacteria which are considered as obligate anaerobe, e.g. oxygen is harmful or lethal to these bacteria., We report here the closed genome of Clostridium pasteurianum ATCC 6013, a saccharolytic, nitrogen-fixing, and spore-forming Gram-positive obligate anaerobe, Clostridium pasteurianum BB, a saccharolytic and spore-forming obligate anaerobe, Clostridium difficile is a spore-forming obligate anaerobe that is a leading cause of healthcare-associated infections, However, the discovery of antimicrobials has been biased towards aerobes and facultative anaerobes, and strict anaerobes such as Clostridium spp., Clostridium is a large genus of obligate anaerobes belonging to the Firmicutes phylum of bacteria, most of which have a Gram-positive cell wall structure., Such bacteria are either obligate anaerobic bacteria like Clostridium or Bifidobacterium or facultative anaerobic like Escherichia coli or Salmonella., Antimicrobial production by strictly anaerobic Clostridium spp.[SEP]Clostridium difficile colitis has relations: phenotype_phenotype with Unusual gastrointestinal infection, phenotype_ phenotype with unusual gastrointestinal infection. Bifidobacterium has relations with infection caused by Bacteroides infectious disease. Fusobacteria has relations to Clostridia infectious disease, and Bactrocera with Bacto-infectious disease. Bacteriophthalmia has Relations with Bacterium infectious Disease.", "label": "no"}
{"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]Relations: Propranolol has relations: contraindication with muscular disease, contraindication with muscular disease, contraindication with bronchial disease, contraindication with bronchial disease, drug_drug with Propiomazine, drug_drug with Propiomazine, contraindication with neonatal jaundice, contraindication with neonatal jaundice, contraindication with myopathy, contraindication with myopathy.", "label": "yes"}
{"id": "converted_4600", "sentence1": "Is NfL (neurofilament light chain) a biomarker of neurodegeneration?", "sentence2": "Neurofilament light chain (NfL) has recently been proposed as a promising biomarker in frontotemporal dementia (FTD). , Neurofilament light chain (NfL) is a new, non-disease specific, widely studied biomarker indicative of axonal injury and degeneration, the neurodegeneration biomarker neurofilament light chain (NfL) , bNfL can be used as a potential biomarker to predict disease onset, severity, and progression of genetic ataxia., Neurofilament light chain protein (NfL) is a promising biomarker of neurodegeneration.[SEP]Frontotemporal dementia has relations: disease_phenotype_positive with PRKAR1B-related neurodegenerative dementia with intermediate filaments. Frontotem temporal dementia with motor neuron disease. Protein S human has relations with Nefazodone, Phenylbutazone, Flurbiprofen axetil and Phenyl butazone. Back to Mail Online home. back to the page you came from.", "label": "yes"}
{"id": "converted_1536", "sentence1": "Are OATP1B1 and OATP1B3 associated with bilirubin transport?", "sentence2": "OATP1B1 and OATP1B3-mediated transport of bilirubin was confirmed and inhibition was determined for atazanavir, rifampicin, indinavir, amprenavir, cyclosporine, rifamycin SV and saquinavir. , Examples of adaptive nontoxic changes in liver function, which may elevate direct (conjugated) and/or indirect (unconjugated) bilirubin above baseline levels, include reversible inhibition of UGT1A1-mediated bilirubin metabolism and OATP1B1-, OATP1B3-, or MRP2-mediated transport (Keogh., Due to limited solubility and poor ionization of bilirubin and its glucuronide, the formation of estradiol 3-glucuronide was used as a surrogate to assess UGT1A1 activity, while the transport of pitavastatin, CDCF, and taurocholate were used as surrogate probe substrates to monitor the function of OATP1B1/OATP1B3, MRP2, and BSEP, respectively., OATP1B1 and OATP1B3-mediated transport of bilirubin was confirmed and inhibition was determined for atazanavir, rifampicin, indinavir, amprenavir, cyclosporine, rifamycin SV and saquinavir., However, because drug transporters also contribute to bilirubin elimination, the purpose of this work was to investigate the in vitro inhibition of OATP1B1, OATP1B3, MRP2, and BSEP of select test drugs known to elicit hyperbilirubinemia., Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia.Moreover, OATP1B1 and OATP1B3 null mutations may confer substantial drug toxicity risks., Bilirubin elimination is a multifaceted process consisting of uptake of bilirubin into the hepatocytes facilitated by OATP1B1 and OATP1B3., Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver., Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia., The data show that a substantial fraction of bilirubin conjugates is primarily secreted by MRP3 at the sinusoidal membrane into the blood, from where they are subsequently reuptaken by sinusoidal membrane-bound organic anion transporting polypeptides OATP1B1 and OATP1B3., Evaluating the in vitro inhibition of UGT1A1, OATP1B1, OATP1B3, MRP2, and BSEP in predicting drug-induced hyperbilirubinemia., OATP1B1 and OATP1B3-mediated transport of bilirubin was confirmed and inhibition was determined for atazanavir, rifampicin, indinavir, amprenavir, cyclosporine, rifamycin SV and saquinavir, Bilirubin elimination is a multifaceted process consisting of uptake of bilirubin into the hepatocytes facilitated by OATP1B1 and OATP1B3, Due to limited solubility and poor ionization of bilirubin and its glucuronide, the formation of estradiol 3-glucuronide was used as a surrogate to assess UGT1A1 activity, while the transport of pitavastatin, CDCF, and taurocholate were used as surrogate probe substrates to monitor the function of OATP1B1/OATP1B3, MRP2, and BSEP, respectively, Examples of adaptive nontoxic changes in liver function, which may elevate direct (conjugated) and/or indirect (unconjugated) bilirubin above baseline levels, include reversible inhibition of UGT1A1-mediated bilirubin metabolism and OATP1B1-, OATP1B3-, or MRP2-mediated transport (Keogh, In vitro, faldaprevir inhibited key processes involved in bilirubin clearance: UDP glucuronosyltransferase (UGT) 1A1 (UGT1A1) (IC50 0.45 µM), which conjugates bilirubin, and hepatic uptake and efflux transporters, organic anion-transporting polypeptide (OATP) 1B1 (IC50 0.57 µM), OATP1B3 (IC50 0.18 µM), and multidrug resistance-associated protein (MRP) 2 (IC50 6.2 µM), which transport bilirubin and its conjugates, Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia, Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia.Moreover, OATP1B1 and OATP1B3 null mutations may confer substantial drug toxicity risks, OATP1B1 (a.k.a. OATP-C, OATP2, LST-1, or SLC21A6) is a liver-specific organic anion uptake transporter and has been shown to be a higher affinity bilirubin uptake transporter than OATP1B3, In vitro OATP1B1 and OATP1B3 inhibition is associated with observations of benign clinical unconjugated hyperbilirubinemia., Examples of adaptive nontoxic changes in liver function, which may elevate direct (conjugated) and/or indirect (unconjugated) bilirubin above baseline levels, include reversible inhibition of UGT1A1-mediated bilirubin metabolism and OATP1B1-, OATP1B3-, or MRP2-mediated transport (Keogh. Adv Pharmacol 63:1-42, 2012). , Using mice deficient in Oatp1a/1b and in the multispecific sinusoidal export pump Abcc3, we found that Abcc3 secretes bilirubin conjugates into the blood, while Oatp1a/1b transporters mediate their hepatic reuptake. , Bilirubin elimination is a multifaceted process consisting of uptake of bilirubin into the hepatocytes facilitated by OATP1B1 and OATP1B3. , OATP1B1 polymorphism is a major determinant of serum bilirubin level but not associated with rifampicin-mediated bilirubin elevation., Unconjugated bilirubin (UCB) is taken up into hepatocytes by human organic anion transporting polypeptide 1B1 (OATP1B1; encoded for by the SLCO1B1 gene)., However, because drug transporters also contribute to bilirubin elimination, the purpose of this work was to investigate the in vitro inhibition of OATP1B1, OATP1B3, MRP2, and BSEP of select test drugs known to elicit hyperbilirubinemia. Test drugs investigated in this study were atazanavir and indinavir, which are associated with hyperbilirubinemia and elevations in serum transaminase; ritonavir and nelfinavir, which are not associated with hyperbilirubinemia; and bromfenac, troglitazone, and trovafloxacin, which are associated with severe idiosyncratic hepatotoxicity exhibiting elevations in serum bilirubin and transaminase., Test drugs investigated in this study were atazanavir and indinavir, which are associated with hyperbilirubinemia and elevations in serum transaminase; ritonavir and nelfinavir, which are not associated with hyperbilirubinemia; and bromfenac, troglitazone, and trovafloxacin, which are associated with severe idiosyncratic hepatotoxicity exhibiting elevations in serum bilirubin and transaminase. Due to limited solubility and poor ionization of bilirubin and its glucuronide, the formation of estradiol 3-glucuronide was used as a surrogate to assess UGT1A1 activity, while the transport of pitavastatin, CDCF, and taurocholate were used as surrogate probe substrates to monitor the function of OATP1B1/OATP1B3, MRP2, and BSEP, respectively., In vitro, faldaprevir inhibited key processes involved in bilirubin clearance: UDP glucuronosyltransferase (UGT) 1A1 (UGT1A1) (IC50 0.45 µM), which conjugates bilirubin, and hepatic uptake and efflux transporters, organic anion-transporting polypeptide (OATP) 1B1 (IC50 0.57 µM), OATP1B3 (IC50 0.18 µM), and multidrug resistance-associated protein (MRP) 2 (IC50 6.2 µM), which transport bilirubin and its conjugates., In vitro OATP1B1 and OATP1B3 inhibition is associated with observations of benign clinical unconjugated hyperbilirubinemia., 3.  The results indicated that in vivo Fi values >0.2 or R-values >1.5 for OATP1B1 or OATP1B3, but not UGT1A1, are associated with previously reported clinical cases of drug-induced unconjugated hyperbilirubinemia., OATP1B1 and OATP1B3-mediated transport of bilirubin was confirmed and inhibition was determined for atazanavir, rifampicin, indinavir, amprenavir, cyclosporine, rifamycin SV and saquinavir.[SEP]Relations: UGT1A1 has relations: disease_protein with bilirubin encephalopathy, disease_protein with bilirubin encephalopathy, bioprocess_protein with bilirubin conjugation, bioprocess_protein with bilirubin conjugation, protein_protein with B3GALT1, protein_protein with B3GALT1, drug_protein with Alvocidib, drug_protein with Alvocidib. SLCO1B1 has relations: molfunc_protein with bile acid transmembrane transporter activity, molfunc_protein with bile acid transmembrane transporter activity.", "label": "yes"}
{"id": "converted_3323", "sentence1": "Is BNN20 involved in Parkinson's disease?", "sentence2": "Neurotrophic factors are among the most promising treatments aiming at slowing or stopping and even reversing Parkinson's disease (PD). However, in most cases, they cannot readily cross the human blood-brain-barrier (BBB). Herein, we propose as a therapeutic for PD the small molecule 17-beta-spiro-[5-androsten-17,2'-oxiran]-3beta-ol (BNN-20), a synthetic analogue of DHEA, which crosses the BBB and is deprived of endocrine side-effects. Using the \"weaver\" mouse, a genetic model of PD, which exhibits progressive dopaminergic neurodegeneration in the Substantia Nigra (SN), we have shown that long-term administration (P1-P21) of BNN-20 almost fully protected the dopaminergic neurons and their terminals, via i) a strong anti-apoptotic effect, probably mediated through the Tropomyosin receptor kinase B (TrkB) neurotrophin receptor's PI3K-Akt-NF-κB signaling pathway, ii) by exerting an efficient antioxidant effect, iii) by inducing significant anti-inflammatory activity and iv) by restoring Brain-Derived Neurotrophic Factor (BDNF) levels. By intercrossing \"weaver\" with NGL mice (dual GFP/luciferase-NF-κΒ reporter mice, NF-κΒ.GFP.Luc), we obtained Weaver/NGL mice that express the NF-κB reporter in all somatic cells. Acute BNN-20 administration to Weaver/NGL mice induced a strong NF-κB-dependent transcriptional response in the brain as detected by bioluminescence imaging, which was abolished by co-administration of the TrkB inhibitor ANA-12. This indicates that BNN-20 exerts its beneficial action (at least in part) through the TrkB-PI3K-Akt-NF-κB signaling pathway. These results could be of clinical relevance, as they suggest BNN-20 as an important neuroprotective agent acting through the TrkB neurotrophin receptor pathway, mimicking the action of the endogenous neurotrophin BDNF. Thus BNN-20 could be proposed for treatment of PD.[SEP]Relations: Parkinson disease has relations: disease_protein with BST1, disease_protein with BST1, disease_protein with BDNF, disease_protein with BDNF, disease_protein with FBP1, disease_protein with FBP1, disease_protein with CNTNAP2, disease_protein with CNTNAP2, disease_protein with TBP, disease_protein with TBP.", "label": "yes"}
{"id": "converted_2072", "sentence1": "Is vemurafenib used for thyroid cancer?", "sentence2": "Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial., Vemurafenib, an oncogenic BRAF kinase inhibitor approved for BRAF-positive melanoma, showed clinical benefit in three patients with BRAF(V600E)-positive papillary thyroid cancer in a phase 1 trial., INTERPRETATION: Vemurafenib showed antitumour activity in patients with progressive, BRAF(V600E)-positive papillary thyroid cancer refractory to radioactive iodine who had never been treated with a multikinase inhibitor. , CONTEXT: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation., Efficacy and tolerability of vemurafenib in patients with BRAF(V600E) -positive papillary thyroid cancer: M.D. Anderson Cancer Center off label experience., CONCLUSIONS: Vemurafenib is a potentially effective and well-tolerated treatment strategy in patients with advanced PTC harboring the BRAF(V600E) mutation., The US Food and Drug Administration-approved BRAF inhibitors, vemurafenib and dabrafenib, have demonstrated superior efficacy in patients with BRAF-mutant melanomas but have limited efficacy in BRAF-mutant colorectal cancer. Little is known at this time regarding BRAF inhibitors in thyroid cancer. Initial reports in patients with progressive, radioactive iodine-refractory BRAF-mutant papillary thyroid cancer suggest response rates of approximately 30-40%., Use of vemurafenib in anaplastic thyroid carcinoma: a case report., Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib., CONTEXT: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.OBJECTIVE: To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.DESIGN: A retrospective review at MD Anderson Cancer Center.METHODS: The best responses were evaluated using RECIST v1.1., Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.A retrospective review at MD Anderson Cancer Center.The best responses were evaluated using RECIST v1.1, CONTEXT: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.OBJECTIVE: To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.DESIGN: A retrospective review at MD Anderson Cancer Center.METHODS: The best responses were evaluated using RECIST v1.1. , Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib., Metformin or rapamycin adjuvant treatment may provide clinical benefits with minimal side effects to BRAFV600E-positive advanced thyroid cancer patients treated with vemurafenib., Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.A retrospective review at MD Anderson Cancer Center.The best responses were evaluated using RECIST v1.1., Our data demonstrate that vemurafenib induces ER stress response-mediated autophagy in thyroid cancer and autophagy inhibition may be a beneficial strategy to sensitize BRAF-mutant thyroid cancer to vemurafenib.., Combination of vemurafenib and metformin decreased cell viability and increased apoptosis in both BCPAP papillary thyroid cancer cells and 8505c anaplastic thyroid cancer cells., Targeting autophagy sensitizes BRAF-mutant thyroid cancer to vemurafenib., Propranolol sensitizes thyroid cancer cells to cytotoxic effect of vemurafenib., mTOR inhibitors sensitize thyroid cancer cells to cytotoxic effect of vemurafenib., Vemurafenib induced a high level of autophagy in BRAF-mutant thyroid cancer cells.[SEP]Relations: Vemurafenib has relations: drug_drug with Parathyroid hormone, drug_drug with Parathyroid hormone, contraindication with iris disease, contraindication with iris disease, drug_drug with Antipyrine, drug_drug with Antipyrine, drug_drug with Thyroid, porcine, drug_drug with Thyroid, porcine, drug_drug with Testosterone, drug_drug with Testosterone.", "label": "yes"}
{"id": "converted_1444", "sentence1": "Is arimoclomol a co-inducer of the heat shock response?", "sentence2": "Arimoclomol is a hydroxylamine derivative, a group of compounds which have unique properties as co-inducers of heat shock protein expression, but only under conditions of cellular stress. , In this review we summarize the evidence for the neuroprotective effects of enhanced heat shock protein expression by Arimoclomol and other inducers of the Heat Shock Response. , arimoclomol, a co-inducer of the heat shock stress response,, The heat-shock response (HSR) was activated in P23H retinae, and this was enhanced with arimoclomol treatment. ,  We also assessed these functions in mice treated with a known heat shock protein inducer, arimoclomol.,  Under conditions of excessive stress, arimoclomol induces amplification of the cytoprotective heat shock response in order to protect motor neurons from death. , Although both arimoclomol and celastrol induced the expression of Hsp70, Arimoclomol, an amplifier of heat shock protein expression involved in cellular stress response, has emerged as a potential therapeutic candidate in amyotrophic lateral sclerosis (ALS) in recent years., The mechanism of action of arimoclomol involves potentiation of the heat shock response, and treatment with arimoclomol increased Hsp70 expression. , Arimoclomol is an investigational drug for amyotrophic lateral sclerosis (ALS) that amplifies heat shock protein gene expression during cell stress., Arimoclomol, a coinducer of heat shock proteins, delayed progression of amyotrophic lateral sclerosis (ALS) in a mouse model in which motor neurons in the spinal cord and motor cortex degenerate.[SEP]Arimoclomol has relations with SOD1, heat shock protein binding, IRAK1 and LMAN2. ArimoclomOL has relations: drug_protein with S OD1, drug_ protein with L MAN2, molfunc_ proteins with LMAN1 and IRAK proteins with IRAK.", "label": "yes"}
{"id": "converted_366", "sentence1": "Is there an association between TERT promoter mutation and survival of glioblastoma patients?", "sentence2": "Glioblastoma patients with TERT mutations showed a shorter survival than those without TERT mutations in univariate analysis (median, 9.3 vs. 10.5 months; P = 0.015) and multivariate analysis after adjusting for age and gender (HR 1.38, 95 % CI 1.01-1.88, P = 0.041). However, TERT mutations had no significant impact on patients' survival in multivariate analysis after further adjusting for other genetic alterations, or when primary and secondary glioblastomas were separately analysed. These results suggest that the prognostic value of TERT mutations for poor survival is largely due to their inverse correlation with IDH1 mutations, which are a significant prognostic marker of better survival in patients with secondary glioblastomas., Patients with tumors lacking hTERT expression/TA showed a significant survival benefit (Kaplan-Meier test, both P < .01), which, however, was based exclusively on the younger patient subgroup (≤60 y, both P < .005; >60 y, both ns). , Glioblastoma patients with TERT mutations showed a shorter survival than those without TERT mutations in univariate analysis (median, 9.3 vs[SEP]Adult glioblastoma has relations with disease_disease with glioma (diseases) and disease with adult infiltrating astrocytic neoplasm. Somatic mutation has relations: disease_phenotype_positive withglioma susceptibility, disease phenotype positive with retinoblastomas, and disease_ phenotype_ positive with gl ioma susceptibility. Adult spinal cord gliobeasts have relations with adult gliOBlastoma.", "label": "yes"}
{"id": "converted_3413", "sentence1": "Is celecoxib effective for amyotrophic lateral sclerosis?", "sentence2": "In conclusion, the celecoxib-creatine combination was selected as preferable to the minocycline-creatine combination for further evaluation. , ESULTS: Celecoxib did not slow the decline in muscle strength, vital capacity, motor unit number estimates, ALS Functional Rating Scale-Revised, or affect survival. , INTERPRETATION: At the dosage studied, celecoxib did not have a beneficial effect on research subjects with ALS, and it was safe. , INTERPRETATION\n\nAt the dosage studied, celecoxib did not have a beneficial effect on research subjects with ALS, and it was safe., RESULTS\n\nCelecoxib did not slow the decline in muscle strength, vital capacity, motor unit number estimates, ALS Functional Rating Scale-Revised, or affect survival., RESULTS\nCelecoxib did not slow the decline in muscle strength, vital capacity, motor unit number estimates, ALS Functional Rating Scale-Revised, or affect survival., INTERPRETATION: At the dosage studied, celecoxib did not have a beneficial effect on research subjects with ALS, and it was safe., RESULTS: Celecoxib did not slow the decline in muscle strength, vital capacity, motor unit number estimates, ALS Functional Rating Scale-Revised, or affect survival., At the dosage studied, celecoxib did not have a beneficial effect on research subjects with ALS, and it was safe., Celecoxib did not slow the decline in muscle strength, vital capacity, motor unit number estimates, ALS Functional Rating Scale-Revised, or affect survival.[SEP] Celecoxib has relations with Arthropathy, Coronary artery atherosclerosis, Cholelithiasis, Epistaxis, and Corticotropin. It also has a relationship with the drug_drug with Corticotropicin.", "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_298", "sentence1": "Can a given genotype exhibit opposite fitness effects (beneficial and detrimental) within the same environment?", "sentence2": "Mutations beneficial in one environment may cause costs in different environments, resulting in antagonistic pleiotropy. Here, we describe a novel form of antagonistic pleiotropy that operates even within the same environment, where benefits and deleterious effects exhibit themselves at different growth rates., The hfq mutations were beneficial, deleterious or neutral at an intermediate growth rate (0.5 h(-1)) and one changed from beneficial to deleterious within a 36 min difference in doubling time., Two genetic models exist to explain the evolution of ageing - mutation accumulation (MA) and antagonistic pleiotropy (AP)., Under AP, late-acting deleterious mutations accumulate because they confer beneficial effects early in life., Many marker loci responded in opposite directions to selection for late- and early-life fitness, indicating negative genetic correlations or trade-offs between those traits. Indirect evidence suggested that some negative genetic correlations were due to antagonistic pleiotropy., Here, we describe a novel form of antagonistic pleiotropy that operates even within the same environment, where benefits and deleterious effects exhibit themselves at different growth rates., The basis of antagonistic pleiotropy in hfq mutations that have opposite effects on fitness at slow and fast growth rates., Here, we describe a novel form of antagonistic pleiotropy that operates even within the same environment, where benefits and deleterious effects exhibit themselves at different growth rates[SEP]Adaptation to pheromone regulating conjugation with mutual genetic exchange has relations. Migraine with or without aura has relations with Photophobia. Lacrimation abnormality has relations: disease_phenotype_positive with EEC syndrome, disease-phenotype-positive with Hemiparesis. Bioprocess with negative adaptation of signaling pathway, bioprocession_biopro cess with response to phersomone-conjugation with genetic exchange.", "label": "yes"}
{"id": "converted_908", "sentence1": "Is miR-126 involved in heart failure?", "sentence2": "he miRNAs miR-126 and miR-508-5p are associated with the outcome of ICM and NICM patients with CHF. These two miRNAs could be useful in the diagnosis of CHF patients, and might provide novel targets for prevention and treatment of CHF., The plasma concentration of miR-126 was negatively correlated with age and NYHA class, and could be a useful biomarker for heart failure., In 10 patients with heart failure, plasma concentrations of miR-126 were up-regulated with improvement of the NYHA class from IV to III.[SEP]Congestive heart failure has relations with Rimantadine, Metoprolol, Ibutilide, Iopromide, Bisoprolols, and I butilide. The drug effect of RimantAdine is the same as that of Metoprorolol. The effect of Ibutillide is similar to that of Bisoprosol.", "label": "yes"}
{"id": "converted_3037", "sentence1": "Are there graph kernel libraries available implemented in JAVA?", "sentence2": "graphkernels: R and Python packages for graph comparison., Measuring the similarity of graphs is a fundamental step in the analysis of graph-structured data, which is omnipresent in computational biology. Graph kernels have been proposed as a powerful and efficient approach to this problem of graph comparison. Here we provide graphkernels, the first R and Python graph kernel libraries including baseline kernels such as label histogram based kernels, classic graph kernels such as random walk based kernels, and the state-of-the-art Weisfeiler-Lehman graph kernel. The core of all graph kernels is implemented in C ++ for efficiency. Using the kernel matrices computed by the package, we can easily perform tasks such as classification, regression and clustering on graph-structured samples.[SEP]", "label": "no"}
{"id": "converted_3046", "sentence1": "Does Rhamnose have any effect on aging?", "sentence2": "The monosaccharide analysis showed that rhamnose (Rha) and glucose (Glu) may play vital roles in maintaining the antioxidant and anti-aging activities. , Some of these mechanisms will be reviewed as well as the capacity of fucose- and rhamnose-rich oligo- and polysaccharides (FROP and RROP) to counteract several of the mechanisms involved in skin aging.[SEP] increased groin pigmentation with raindrop depigmentation has relations: phenotype_phenotype with Mixed hypo- and hyperpigmentation of the skin. disease_phenotypes with thumb deformity-alopecia-pigmented anomaly syndrome. response to rhamnose has relations with response to hexose, bioprocess_bioprocession with response to hexose and cellular response to rhamnosed stimulus. Response to hexose has relations with cellular response  to rhnose stimulus.", "label": "yes"}
{"id": "converted_3114", "sentence1": "Is there any association between suicide and autism in adolescents, yes or no?", "sentence2": ": In all subjects from our research on PubMed, 21.3% of subjects with autism spectrum disorder reported suicidal ideation, have attempted suicide or died by suicide (115 out of 539 subjects) and 7.7% of subjects supported for suicidal thoughts or attempted suicide exhibited an autism spectrum disorder (62 out of 806 subjects), all ages combined. , Suicide attempts are accompanied by a willingness for death and can lead to suicide. They are more common in high-functioning autism and Asperger subjects.,  A total sample of 10 adolescents and young adults diagnosed with AS was obtained. The high proportion of respondents with scores above the cutoff point on the overt victimization and relational victimization scales suggests that these adolescents and young adults experienced high levels of victimization. Of the sample, 20 percent met criteria for a diagnosis of Major Depressive Disorder, 30 percent met criteria for Generalized Anxiety Disorder and 50 percent had clinically significant level of suicidal ideation., Previous studies reported a high prevalence of depression among patients with autism spectrum disorder (ASD) and suggested a relationship between ASD and suicidality, Patients with ASD had an increased risk of suicide attempts compared with those without ASD., The suicidal behaviors are frequently observed in the adolescents and adults with an ASD without intellectual deficience. , Suicide is a major problem in Western society. However we have very little understanding of suicidal behaviour among individuals with autism spectrum disorders. , The available research provides little empirical evidence for the processes underlying suicidal behaviour in adolescents and young adults with autism,  The present study aims to assess the rate of suicidality (suicidal ideation, behaviors and attempts) and associated risk factors for suicidality in high functioning ASD, here is a lack of clinical awareness on suicidal behaviors of children and adolescents with autism spectrum disorder (ASD), suicidality in children and adolescents with diagnosis of high functioning autism spectrum disorder , Consistent with the previous findings, rate of suicidality is higher in individuals with ASD, Detection of Suicidality in Adolescents with Autism Spectrum Disorders, Over 15% of young people with autism spectrum disorders (ASD) will contemplate or attempt suicide during adolescence. Yet,, Until recently, suicidality in autism spectrum disorder (ASD) was rarely discussed. , Suicidality in Autism Spectrum Disorder., highlighted not only that suicidal thoughts and suicide attempts can occur in adolescents and young adults with ASD, but also that suicidality is likely more common in ASD than in the general population. , The emerging studies indicate that the increased risk of self-injurious behavior in younger and less cognitively able children with ASD3,4 is matched by an increased risk of suicidality in those at a more advanced developmental level., RESULTS\nIn all subjects from our research on PubMed, 21.3% of subjects with autism spectrum disorder reported suicidal ideation, have attempted suicide or died by suicide (115 out of 539 subjects) and 7.7% of subjects supported for suicidal thoughts or attempted suicide exhibited an autism spectrum disorder (62 out of 806 subjects), all ages combined., Risk of Suicide Attempts Among Adolescents and Young Adults With Autism Spectrum Disorder: A Nationwide Longitudinal Follow-Up Study., Although the suicide risk of autism spectrum disorder (ASD) has been suggested to be higher than previously recognized, there are few case reports focusing on the process for preventing suicide reattempts.[SEP]Relations: autism spectrum disorder has relations: disease_disease with autism (disease), disease_disease with autism (disease), disease_protein with MTNR1A, disease_protein with MTNR1A, disease_protein with MAOA, disease_protein with MAOA, disease_protein with ADA, disease_protein with ADA, disease_protein with AVP, disease_protein with AVP.", "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]Relations: Ipilimumab has relations: drug_drug with Durvalumab, drug_drug with Durvalumab, drug_drug with Dusigitumab, drug_drug with Dusigitumab, drug_drug with Lerdelimumab, drug_drug with Lerdelimumab. Nivolumab has relations: drug_drug with Durvalumab, drug_drug with Durvalumab, drug_drug with Dusigitumab, drug_drug with Dusigitumab.", "label": "yes"}
{"id": "converted_4390", "sentence1": "Can IFNg induce the expression of IDO?", "sentence2": "IFNG inducible IDO/GTPCH inflammation cascade, IFNG-induced up-regulation of indoleamine 2,3-dioxygenase (IDO), IFN-γ-induced indoleamine-2,3-dioxgenase (IDO) , strong and positive correlation between IDO1 and IFNG mRNA expression levels ,  The tryptophan-degrading activity of IDO1 was not induced significantly by Chlamydia infection alone, but the addition of IFNG greatly increased its activity. [SEP]Indoleamine 2,3-dioxygenase activity has relations with IDO2 and IDO1. Response to type III interferon has relations: bioprocess_protein with IFNLR1, biopracess_ protein with IF NLR1. response to type IV interferons has relations to IFNL R1,IFNLR2.", "label": "yes"}
{"id": "converted_4214", "sentence1": "Are there antimicrobial proteins in royal jelly?", "sentence2": "Jellein, a peptide derived from royal jelly of honeybee has been shown to have promising effect against several bacterial and fungal species. , It is also the most studied bee product, aimed at unravelling its bioactivities, such as antimicrobial, antioxidant, anti-aging, immunomodulatory, and general tonic action against laboratory animals, microbial organisms, farm animals, and clinical trials, Jelleines, isolated as novel antibacterial peptides from the Royal Jelly (RJ) of bees, exhibit broad-spectrum protection against microbial infections., The study showed significant antimicrobial activity from several proteins present in the honey of M. beecheii.[SEP]Bacterial arthritis has relations: disease_protein with IFNG, disease_ protein with TNF. Disease_disease with gonococcal infection of joint has relations with bacterial arthritis. Disease diseases with infectious disease have relations with infective arthritis.", "label": "yes"}
{"id": "converted_2656", "sentence1": "Is Enlimomab effective for stroke treatment?", "sentence2": "However, this treatment failed to show benefit in the Enlimomab Acute Stroke Trial., There was no increase in the frequency of adverse events with increasing doses of enlimomab.CONCLUSIONS: Doses of enlimomab between 140 and 480 mg administered over 5 days did not increase the risk of adverse events in patients with ischaemic or haemorrhagic stroke during an observation period of 30 +/- 10 days., Examination of several potential mechanisms for the negative outcome in a clinical stroke trial of enlimomab, a murine anti-human intercellular adhesion molecule-1 antibody: a bedside-to-bench study., BACKGROUND AND PURPOSE: Enlimomab, a murine monoclonal anti-human intercellular adhesion molecule (ICAM)-1 antibody, had a negative outcome in a multicenter acute-stroke trial. , These observations provide several possible mechanisms for central nervous system-related clinical deterioration that occurred when Enlimomab was given in acute ischemic stroke., Fewer patients had symptom-free recovery on enlimomab than placebo (p = 0.004), and more died (22.2 versus 16.2%). The negative effect of enlimomab was apparent on days 5, 30, and 90 of treatment (p = 0.005). There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever. , CONCLUSIONS: The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome., Patients experiencing fever were more likely to have a poor outcome or die.The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome., The negative effect of enlimomab was apparent on days 5, 30, and 90 of treatment (p = 0.005)., Patients experiencing fever were more likely to have a poor outcome or die.<br><b>CONCLUSIONS</b>: The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome.<br>, Unfortunately, the case fatality rate in this trial was significantly higher in the enlimomab patient group than in the placebo group., CONCLUSIONS The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome., BACKGROUND AND PURPOSE Enlimomab, a murine monoclonal anti-human intercellular adhesion molecule (ICAM)-1 antibody, had a negative outcome in a multicenter acute-stroke trial., The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome..[SEP]Relations: Ischemic stroke has relations: drug_effect with Celecoxib, drug_effect with Celecoxib, drug_effect with Celecoxib, drug_effect with Celecoxib, drug_effect with Ramipril, drug_effect with Ramipril, drug_effect with Ramipril, drug_effect with Ramipril, drug_effect with Pazopanib, drug_effect with Pazopanib.", "label": "no"}
{"id": "converted_1520", "sentence1": "Is there any data to suggest that TRH (thyrotropin releasing hormone) administration can improve symptom severity of amyotrophic lateral sclerosis patients?", "sentence2": "These central nervous system (CNS)-mediated effects provide the rationale for use of TRH and its analogs in the treatment of brain and spinal injury, and CNS disorders like schizophrenia, Alzheimer's disease, epilepsy, amyotrophic lateral sclerosis, Parkinson's disease, depression, shock and ischemia., The Effect of TRH to correct the abnormal F responses in SSP might be consistent with effects of TRH to reduce spasticity in amyotrophic lateral sclerosis described previously, Agents undergoing therapeutic trials at present include CNTF, IGF1 glutamate antagonists, branched-chain amino acids and TRH analogue., Evidence that thyrotropin-releasing hormone (TRH) has prominent trophic effects on the motor system led to several negative therapeutic trials in amyotrophic lateral sclerosis, a disease of the motor system., The results of the clinical evaluation at the beginning and end of the treatment as well as after patient follow up demonstrated that beneficial effects do not occur equally in all patients but rather are transitory and do not improve the natural evolution of the disease., The neurological evaluation after acute TRH-T treatment showed an objective improvement in 3 of the 8., The outcome of the study, in agreement with some and at variance with other studies, was that TRH induced a statistically significant neurological improvement in 17 of the 23 ALS patients but little or none in the other ALS patients and in patients with other neurological diseases., [A case of amyotrophic lateral sclerosis with disturbance of vertical ocular movement responding to thyrotropin releasing hormone (TRH)]., TRH injections resulted in improvement of disturbance of vertical ocular movement, but no effect was seen on the weakness of the limb., 13 patients with amyotrophic lateral sclerosis (ALS) were treated with intravenous infusion of thyrotropin-releasing hormone (TRH). , Similar improvements in speech, swallowing and in tongue and jaw movements were seen after iv and oral administration in nine, five and eight patients respectively. , No clinical improvement was detected. , A trial of Thyrotropin Releasing Hormone (TRH) 5.0 mg/kg body weight subcutaneously every other day for two weeks produced transient increased tone in muscles, along with other (side-) effects in patients with Amyotrophic Lateral Sclerosis (ALS)., Although the mechanism is not known, several reports of the effectiveness of thyrotropin releasing hormone (TRH) in ALS were recently published., Protirelin (thyrotropin-releasing hormone) appears to be a neuromodulator in the extrahypothalamic nervous system and has been suggested as an adjunct in the treatment of amyotrophic lateral sclerosis (ALS). , Clinical studies have shown that response to TRH is state dependent, that is, it depends on whether the patient has bulbar or nonbulbar signs and is male or female. Future studies must take into consideration this state dependence as a specific feature of the pharmacological action of TRH and its analogues., Three of the studies showed a transient, statistically significant effect in at least some muscles. The two studies that demonstrated no such effect both used TRH in very small doses. It therefore seems reasonable to conclude that the effect of TRH in ALS is a definite, acute, and transient response. , It was found that in only 3 out of 14 patients with moderately progressed disease no improvement was achieved, while in 11 cases the improvement was from 10 to 20%. However, the improvement was transient, and TRH treatment failed to stop the progression of the disease., Only 3 patients noted subjective improvement of strength., In 6 of the 9, TRH induced a significant increase in vibratory inhibition. This suggests that the TRH-induced reduction of spasticity might be due to an increase in presynaptic inhibition acting on Ia fibres., However, 2 mg DN-1417, IM twice a day for 1 month in an open-label trial, produced no objective improvement of strength in nine patients with ALS. , Our experience suggests that this approach is safe, has high patient acceptance, and is worthy of more careful evaluation., Focal, small-to-moderate and transient improvement occurred in the muscle strength and function of patients with ALS who received TRH in dose-response and screening studies. In a small pilot study of 12 patients, 3 months administration of TRH at 10 mg per kg on alternate days resulted in localized increased strength of jaw muscles as well as significant improvement in lower extremity function. Aerobic exercise capacity was particularly improved in patients with ALS following administration of TRH. , Mild to moderate improvement was found in 9 (56%) of 16 patients. , We thought such action of TRH to be useful to the therapy of ALS., With daily TRH, 10 patients noted subjective improvement without objective evidence, and 10 patients complained of worsening of the disease with objective decline after TRH was stopped. Statistical analysis, however, showed no beneficial effects from either acute or chronic TRH trials., A temporary increase in the strength of some muscles was detected following the administration of TRH, but no change in functional performance was noted. Neither the patients nor the investigators believed the effects were of any marked clinical significance., Nevertheless, statistically significant improvement was seen only in dynametric strength 1 hour after subcutaneous injection (p less than 0.05). Significant improvement occurred, in one patient only, on subjective speech testing during IV infusion of TRH. In none of six other ratings was there a significant difference between TRH and placebo. Subjective improvement was noted by 11 of 12 patients., Significant improvement, as shown by statistical analysis, was noted in muscle strength in the 9 patients by 5 infusions over a 4-week period and a sub-group of 5 patients treated by 8 infusions over 10 weeks., The progressive course of this disease, manifested by increasing atrophy, paralysis and disability score, was not altered. , Very high intravenous doses (2-19 mg/min) of thyrotropin-releasing hormone (TRH, L-pyroglutamyl-L-histidyl-L-prolinamide) given to 12 patients with amyotrophic lateral sclerosis (ALS) produced a moderate to marked improvement of functions caused by deficiency of lower motor neurons (weakness) and upper motor neurons (spasticity). The improvement was sustained throughout the infusion and for about 1 h thereafter; sometimes a slight improvement was evident 20 h after infusion., Aerobic exercise capacity was particularly improved in patients with ALS following administration of TRH[SEP]Relations: amyotrophic lateral sclerosis has relations: disease_protein with TRPM7, disease_protein with TRPM7, disease_protein with NEFH, disease_protein with NEFH, disease_disease with progressive muscular atrophy, disease_disease with progressive muscular atrophy, disease_protein with TARDBP, disease_protein with TARDBP, disease_protein with TREM2, disease_protein with TREM2.", "label": "yes"}
{"id": "converted_1450", "sentence1": "Does the 3D structure of  the genome remain stable during cell differentiation?", "sentence2": "We identify large, megabase-sized local chromatin interaction domains, which we term 'topological domains', as a pervasive structural feature of the genome organization., The domains are stable across different cell types and highly conserved across species, indicating that topological domains are an inherent property of mammalian genomes, Insulators are involved in 3D genome organization at multiple spatial scales and are important for dynamic reorganization of chromatin structure during reprogramming and differentiation., The relation between alterations in chromatin structure and changes in gene expression during cell differentiation has served as a paradigm to understand the link between genome organization and function., Architectural proteins orchestrate higher-order chromatin organization through the establishment of interactions between regulatory elements across multiple spatial scales. The regulation of these proteins, their interaction with DNA, and their co-occurrence in the genome, may be responsible for the plasticity of 3D chromatin architecture that dictates cell and time-specific blueprints of gene expression., The role of 3D genome organisation in the control and execution of lineage-specific transcription programmes during the development and differentiation of multipotent stem cells into specialised cell types remains poorly understood., Chromatin structural states and their remodelling, including higher-order chromatin folding and three-dimensional (3D) genome organisation, play an important role in the control of gene expression, Here, we show that substantial remodelling of the higher-order chromatin structure of the epidermal differentiation complex (EDC), a keratinocyte lineage-specific gene locus on mouse chromosome 3, occurs during epidermal morphogenesis., Many studies have suggested a link between the spatial organization of genomes and fundamental biological processes such as genome reprogramming, gene expression, and differentiation., Moreover, we reveal that formation of such highly condensed, transcriptionally repressed heterochromatin promotes transcriptional activation of differentiation genes and loss of pluripotency., The open chromatin of embryonic stem cells (ESCs) condenses into repressive heterochromatin as cells exit the pluripotent state., we find that localized heterochromatin condensation of ribosomal RNA genes initiates establishment of highly condensed chromatin structures outside of the nucleolus, We focus on the emerging relationship between genome organization and lineage-specific transcriptional regulation, which we argue are inextricably linked., Cells face the challenge of storing two meters of DNA in the three-dimensional (3D) space of the nucleus that spans only a few microns. The nuclear organization that is required to overcome this challenge must allow for the accessibility of the gene regulatory machinery to the DNA and, in the case of embryonic stem cells (ESCs), for the transcriptional and epigenetic changes that accompany differentiation, In this review we summarize some of the recent findings illuminating the 3D structure of the eukaryotic genome, as well as the relationship between genome topology and function from the level of whole chromosomes to enhancer-promoter loops with a focus on features affecting genome organization in ESCs and changes in nuclear organization during differentiation, We observe that although self-associating chromatin domains are stable during differentiation, chromatin interactions both within and between domains change in a striking manner, altering 36% of active and inactive chromosomal compartments throughout the genome[SEP]Relations: LORICRIN has relations: bioprocess_protein with keratinocyte differentiation, bioprocess_protein with keratinocyte differentiation, pathway_protein with Formation of the cornified envelope, pathway_protein with Formation of the cornified envelope, cellcomp_protein with cornified envelope, cellcomp_protein with cornified envelope, molfunc_protein with structural constituent of cytoskeleton, molfunc_protein with structural constituent of cytoskeleton. heterochromatin has relations: cellcomp_protein with BEND3, cellcomp_protein with BEND3.", "label": "no"}
{"id": "converted_2463", "sentence1": "Can Logic Alignment Free (LAF) be used for bacterial genomes classification?", "sentence2": "LAF: Logic Alignment Free and its application to bacterial genomes classification., In this paper, we present Logic Alignment Free (LAF), a method that combines alignment-free techniques and rule-based classification algorithms in order to assign biological samples to their taxa. This method searches for a minimal subset of k-mers whose relative frequencies are used to build classification models as disjunctive-normal-form logic formulas (if-then rules). We apply LAF successfully to the classification of bacterial genomes to their corresponding taxonomy. In particular, we succeed in obtaining reliable classification at different taxonomic levels by extracting a handful of rules, each one based on the frequency of just few k-mers. State of the art methods to adjust the frequency of k-mers to the character distribution of the underlying genomes have negligible impact on classification performance, suggesting that the signal of each class is strong and that LAF is effective in identifying it., In this paper, we present Logic Alignment Free (LAF), a method that combines alignment-free techniques and rule-based classification algorithms in order to assign biological samples to their taxa., LAF: Logic Alignment Free and its application to bacterial genomes classification.[SEP]Interleukin-1 binding has relations with NLRP7, TRIM16, A2M, HAX1, IL1R1 and A2R1. Molfunc_protein with NL RP7 has relations: molfunc-protein withNLRP7-TRIM16-A2M-HAX1-IL1 R1.", "label": "yes"}
{"id": "converted_3681", "sentence1": "Is Aptiganel effective for treatment of stroke?", "sentence2": "Trends for increased mortality with three NMDA antagonists were seen - selfotel (OR 1.19 [0.81-1.74]), aptiganel (OR 1.32 [0.91-1.93]) and gavestinel (OR 1.12 [0.95-1.32]) - but this did not achieve significance for the NMDA antagonists considered as a class (1.09 [0.96-1.23]). Aptiganel was also associated with a trend towards worse functional outcome (OR 1.20 [0.88-1.65]) although this was not the case for either of the other two compounds., No improvement in clinical outcome of stroke has been seen with competitive NMDA antagonists (selfotel) and non-competitive NMDA antagonists (dextrorphan, GV150526, aptiganel and eliprodil)., Glutamate N-methyl-D-aspartate (NMDA) receptor antagonists (competitive receptor antagonists, ion channel blockers, and glycine antagonists)--such as selfotel, aptiganel, eliprodil, licostinel and gavestinel--failed to show efficacy in clinical trials of stroke or traumatic brain injury. , There was no improvement in outcome for either aptiganel (low-dose or high-dose) group compared with the placebo group at 90 days (median Modified Rankin Scale score for all 3 treatment groups = 3; P =.31). At 7 days, placebo-treated patients exhibited slightly greater neurological improvement on the NIH Stroke Scale than high-dose aptiganel patients (mean improvement for placebo group, -0.8 points vs for high-dose aptiganel, 0.9 points; P =.04). The mortality rate at 120 days in patients treated with high-dose aptiganel was higher than that in patients who received placebo (26.3% vs 19.2%; P =.06)., CONCLUSIONS: Aptiganel was not efficacious in patients with acute ischemic stroke at either of the tested doses, and m ay be harmful. The larger proportion of patients with favorable outcomes and lower mortality rate in the placebo group suggest that glutamate blockade with aptiganel may have detrimental effects in an undifferentiated population of stroke patients., CONCLUSIONS\n\nAptiganel was not efficacious in patients with acute ischemic stroke at either of the tested doses, and m ay be harmful., The larger proportion of patients with favorable outcomes and lower mortality rate in the placebo group suggest that glutamate blockade with aptiganel may have detrimental effects in an undifferentiated population of stroke patients., There was no improvement in outcome for either aptiganel (low-dose or high-dose) group compared with the placebo group at 90 days (median Modified Rankin Scale score for all 3 treatment groups = 3; P =.31)., Glutamate N-methyl-D-aspartate (NMDA) receptor antagonists (competitive receptor antagonists, ion channel blockers, and glycine antagonists)--such as selfotel, aptiganel, eliprodil, licostinel and gavestinel--failed to show efficacy in clinical trials of stroke or traumatic brain injury., CONCLUSIONS Aptiganel was not efficacious in patients with acute ischemic stroke at either of the tested doses, and m ay be harmful., Glutamate N-methyl-D-aspartate ( NMDA ) receptor antagonists ( competitive receptor antagonists , ion channel blockers , and glycine antagonists)--such as selfotel , aptiganel , eliprodil , licostinel and gavestinel--failed to show efficacy in clinical trials of stroke or traumatic brain injury, No improvement in clinical outcome of stroke has been seen with competitive NMDA antagonists ( selfotel ) and non-competitive NMDA antagonists ( dextrorphan , GV150526 , aptiganel and eliprodil, There was no improvement in outcome for either aptiganel (low-dose or high-dose) group compared with the placebo group at 90 days (median Modified Rankin Scale score for all 3 treatment groups = 3; P =.31)., CONCLUSIONS: Aptiganel was not efficacious in patients with acute ischemic stroke at either of the tested doses, and m ay be harmful., The larger proportion of patients with favorable outcomes and lower mortality rate in the placebo group suggest that glutamate blockade with aptiganel may have detrimental effects in an undifferentiated population of stroke patients., There was no improvement in outcome for either aptiganel (low-dose or high-dose) group compared with the placebo group at 90 days (median Modified Rankin Scale score for all 3 treatment groups = 3; P =.31)., Aptiganel was not efficacious in patients with acute ischemic stroke at either of the tested doses, and m ay be harmful., The larger proportion of patients with favorable outcomes and lower mortality rate in the placebo group suggest that glutamate blockade with aptiganel may have detrimental effects in an undifferentiated population of stroke patients.[SEP]Relations: Ischemic stroke has relations: drug_effect with Paclitaxel, drug_effect with Paclitaxel, drug_effect with Ramipril, drug_effect with Ramipril, drug_effect with Aripiprazole, drug_effect with Aripiprazole, drug_effect with Sitaxentan, drug_effect with Sitaxentan, drug_effect with Pazopanib, drug_effect with Pazopanib.", "label": "no"}
{"id": "converted_1466", "sentence1": "Is the HRC Ser96Ala variant associated with sudden cardiac death in patients with dilated cardiomyopathy?", "sentence2": "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., The Ser96Ala (S96A) mutation within the histidine rich Ca(2+) binding protein (HRC) has recently been linked to cardiac arrhythmias in idiopathic dilated cardiomyopathy patients, potentially attributable to an increase in spontaneous Ca(2+) release events., 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., 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.,  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., 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, 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., 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, The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy., 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.[SEP]Relations: dilated cardiomyopathy has relations: disease_phenotype_positive with Sudden cardiac death, disease_phenotype_positive with Sudden cardiac death, disease_phenotype_positive with Sudden death, disease_phenotype_positive with Sudden death, disease_protein with SLC22A5, disease_protein with SLC22A5, disease_protein with ABCC9, disease_protein with ABCC9. Sudden death has relations: disease_phenotype_positive with dilated cardiomyopathy, disease_phenotype_positive with dilated cardiomyopathy.", "label": "yes"}
{"id": "converted_1570", "sentence1": "Does neuroglobin has neuroprotective properties in the setting of traumatic brain injury?", "sentence2": "Neuroglobin has shown rich neuroprotective effects against cerebral hypoxia, and therefore has the potential to impact outcomes after traumatic brain injury (TBI). , Neuroglobin (Ngb) is proposed to be a neuron-specific, hypoxia-responsive, neuroprotective protein. , CONCLUSION: The increased expression of neuroglobin in traumatic brain injury informed us that neuroglobin had anti-apoptosis action in post-injury neuron. It could protect the neuron from traumatic stress and secondary ischemia and hypoxia insults during ultra-early and acute stages., Neuroglobin-overexpression reduces traumatic brain lesion size in mice., BACKGROUND: Accumulating evidence has demonstrated that over-expression of Neuroglobin (Ngb) is neuroprotective against hypoxic/ischemic brain injuries. , CONCLUSION: Ngb over-expression reduced traumatic lesion volume, which might partially be achieved by decreasing oxidative stress., Neuroglobin upregulation offers neuroprotection in traumatic brain injury., OBJECTIVES: The aim of this study was to investigate rat neuroglobin (rNGB) expression level after traumatic brain injury (TBI) and further study its neuroprotective effects in TBI when it was overexpressed in adenoviral vector., CONCLUSIONS: NGB was upregulated in TBI and overexpressed rNGB had a significant neuroprotection in TBI. , This study suggested that rNGB overexpression may be a new strategy for treating of TBI., Neuroglobin has shown rich neuroprotective effects against cerebral hypoxia, and therefore has the potential to impact outcomes after traumatic brain injury (TBI)., The aim of this study was to investigate rat neuroglobin (rNGB) expression level after traumatic brain injury (TBI) and further study its neuroprotective effects in TBI when it was overexpressed in adenoviral vector., Accumulating evidence has demonstrated that over-expression of Neuroglobin (Ngb) is neuroprotective against hypoxic/ischemic brain injuries., Various studies seem to indicate that neuroglobin is a neuroprotective agent when overexpressed, acting as a potent inhibitor of oxidative and nitrosative stress. [SEP]Relations: brain injury has relations: contraindication with Phenobarbital, contraindication with Phenobarbital, contraindication with Isopropamide, contraindication with Isopropamide, contraindication with Homatropine, contraindication with Homatropine, contraindication with Difenoxin, contraindication with Difenoxin, contraindication with Cyclopentolate, contraindication with Cyclopentolate.", "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]UBE4B has relations: anatomy_protein_present with kidney, protein_protein with UBC. UBE2V1 has relations with UBE3V1 and UBE4V1. U BE4B also has relations with UBE2C, UBE1C, and U BE2C.", "label": "yes"}
{"id": "converted_4138", "sentence1": "Is methotrexate used for the treatment of Rheumatoid Arthritis (RA)?", "sentence2": "The use of methotrexate in rheumatoid arthritis., Historical perspective on the use of methotrexate for the treatment of rheumatoid arthritis., Aminopterin, a folic acid analogue was first reported in 1948 to produce temporary remission of acute leukemia of children, was also reported in 1951 to produce an important and rapid improvement in patients with rheumatoid arthritis (RA) and psoriasis, The safety and efficacy of the use of methotrexate in long-term therapy for rheumatoid arthritis., Methotrexate (MTX) is currently under study for use in juvenile rheumatoid arthritis. , The rational use of methotrexate in rheumatoid arthritis and other rheumatic diseases., Methotrexate-induced hepatic cirrhosis is less common in rheumatoid arthritis than previously thought, although its occurrence in psoriasis is probably higher than in rheumatoid arthritis. , Methotrexate is clearly effective in the treatment of rheumatoid arthritis and may be able to decrease the rate of formation of new bony erosions. , The use of methotrexate in rheumatoid arthritis., Review of the international literature on the clinical use of MTX in rheumatoid arthritis (RA) disease., MTX has emerged as a relatively safe and effective treatment for RA that compares favorably with other therapies, particularly because of its considerably longer median drug survival., The objective of this review is to update the recommendations of the 2010 Italian Consensus on the use of methotrexate (MTX) in rheumatoid arthritis (RA) and other rheumatic diseases, A new recommendation for patients with RA who are in MTX-induced clinical remission was also proposed and approved by the panel. Updated recommendations for the use of MTX in patients with RA or other rheumatologic disease are proposed., Methotrexate has been used in treatment of rheumatoid arthritis (RA) since the 1980s and to this day is often the first line medication for RA treatment., OBJECTIVE: Most recommendations for the use of methotrexate (MTX) in rheumatoid arthritis (RA) are issued by developed countries., Low dose pulse methotrexate (MTX) has become a widely used therapy for rheumatoid arthritis (RA) because of its good response rate profile. With, Treatment with methotrexate (MTX) in rheumatoid arthritis (RA) can lead to severe side-effects, especially pulmonary and haematological complications. The ai, Patients having rheumatoid arthritis (RA) treated with methotrexate (MTX) are at an increased risk of developing lymphoproliferative disorder (LPD). Epstei, Increasingly, methotrexate (MTX) and sulphasalazine (SASP) are used initially for second-line therapy of rheumatoid arthritis (RA). Althoug, OBJECTIVES: The folate antagonist methotrexate (MTX) has become established as the most commonly used disease-modifying anti-rheumatic drug (DMARD) in the treatment of rheumatoid arthritis (RA) but is commonly discontinued due to adverse effe, e suspected methotrexate (MTX)-associated lymphoproliferative disorder (LPD) induced by MTX treatment for rheumatoid arthritis (RA). About , BACKGROUND: Treatment with methotrexate (MTX) in patients with rheumatoid arthritis (RA) leads to decreased total immunoglobulin (Ig) levels and impairs vaccine-specific IgG antibody levels following pneumococcal vaccinat, In rheumatoid arthritis (RA) treatment, the concomitant use of methotrexate has been shown to reduce the incidence of antibodies to infliximab (ATI), on the other hand, it is unclear whether azathioprine can reduce ATI production. We enro, Methotrexate (MTX) is known as a first-line synthetic disease-modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA)., Biological treatments are expensive and using SC methotrexate can improve disease control in RA patients, thus potentially avoiding or delaying the requirement for future biological treatment., Most recommendations for the use of methotrexate (MTX) in rheumatoid arthritis (RA) are issued by developed countries., We reviewed existing recommendations on the use of MTX for the treatment of RA and summarized areas of agreement that could be relevant for least developed countries (LDCs).M, st covered some but not all of the following areas: baseline \"pre-MTX\" assessment (7/12;58%), prescription of MTX (10/12;83.3%), management of MTX side effects (6/12;50%), and special considerations (e.g., peri-operative management) (8/12; 66.7%). R, lectronic databases and registries were searched for recommendations on MTX use in RA, duplicates were eliminated, and the most updated version adopted when there were several versions on the same recommendation. , MTX must at the present time be used only in severe RA, refractory to more than one classical slow acting drug., MTX is as effective in treating RA as the other second line drugs and always more rapidly effective, perhaps because of anti-inflammatory properties., For the low doses used in RA (less than 15 mg/week), MTX is completely and rapidly absorbed with an active process membrane transport., Methotrexate, which is used for RA treatment, causes thrombocytopenia., Methorexate therapy in a patient with rheumatoid arthritis complicated by idiopathic thrombocytopenic purpura., This case shows that methotrexate may be used in patients diagnosed with RA that is associated with ITP under strict monitoring., Here, we report an RA case that also had ITP, which did not decrease in platelet count after methotrexate therapy., We started methotrexate therapy 10 mg per week for treatment of RA, and hydroxychloroquine therapy was stopped due to nonresponse., Methotrexate (MTX) is the anchor treatment for rheumatoid arthritis (RA) and has been very thoroughly studied in many different patient populations, as monotherapy and in combination with various other disease modifying antirheumatic drugs and biologic agents, as they became available., Although rheumatologists have been using methotrexate in the treatment of RA for some time, controlled studies have been needed to establish the safety and efficacy of this agent., Methotrexate is generally the first-line drug for the treatment of RA, psoriatic arthritis and other forms of inflammatory arthritis, and it enhances the effect of most biologic agents in RA., Despite the introduction of numerous biologic agents for the treatment of rheumatoid arthritis (RA) and other forms of inflammatory arthritis, low-dose methotrexate therapy remains the gold standard in RA therapy., A number of studies show the efficacy of methotrexate (MTX) for rheumatoid arthritis (RA) in general., Methotrexate (MTX) is currently the most frequently used drugs in the treatment of rheumatoid arthritis (RA)., Methotrexate (MTX) has been the anchor treatment in rheumatoid arthritis (RA) over the last 15 years, and is used in combination with biologic agents to enhance efficacy over the last decade or so.[SEP]Relations: Methotrexate has relations: drug_drug with Raltitrexed, drug_drug with Raltitrexed, drug_drug with Methohexital, drug_drug with Methohexital, drug_drug with Raltegravir, drug_drug with Raltegravir, drug_drug with Methadone, drug_drug with Methadone, drug_drug with Benzoic acid, drug_drug with Benzoic acid.", "label": "yes"}
{"id": "converted_967", "sentence1": "Are CTCF and BORIS involved in genome regulation and cancer?", "sentence2": "CTCF is ubiquitously expressed and plays diverse roles in gene regulation, imprinting, insulation, intra/interchromosomal interactions, nuclear compartmentalisation, and alternative splicing. CTCF has a single paralogue, the testes-specific CTCF-like gene (CTCFL)/BORIS. CTCF and BORIS can be deregulated in cancer. The tumour suppressor gene CTCF can be mutated or deleted in cancer, or CTCF DNA binding can be altered by epigenetic changes. BORIS is aberrantly expressed frequently in cancer, leading some to propose a pro-tumourigenic role for BORIS. However, BORIS can inhibit cell proliferation, and is mutated in cancer similarly to CTCF suggesting BORIS activation in cancer may be due to global genetic or epigenetic changes typical of malignant transformation,  The investigation of the molecular mechanisms engaged by CTCF to modulate tumor-related genes emphasizes the cell-type dependency of its tumor suppressor role. Indeed, the ability of CTCF to bind their promoters strictly depends by cell-type features as DNA methylation, BORIS-binding and post-translational modifications as PARYlation, Moreover, reduction of CTCF in normally BORIS-negative human fibroblasts resulted in derepression of BORIS promoters. These results provide a mechanistic basis for understanding cancer-related associations between haploinsufficiency of CTCF and BORIS derepression, and between the lack of functional p53 and aberrant activation of BORIS, CTCF and BORIS in genome regulation and cancer., The novel BORIS + CTCF gene family is uniquely involved in the epigenetics of normal biology and cancer., Collectively, these data indicate that reciprocal binding of CTCF and BORIS to the NY-ESO-1 promoter mediates epigenetic regulation of this CT gene in lung cancer cells, and suggest that induction of BORIS may be a novel strategy to augment immunogenicity of pulmonary carcinomas., BORIS is the only known paralog of CTCF, a gene intimately involved in genomic imprinting, chromatin insulation, and nuclear regulation., However, BORIS can inhibit cell proliferation, and is mutated in cancer similarly to CTCF suggesting BORIS activation in cancer may be due to global genetic or epigenetic changes typical of malignant transformation., We suggest that BORIS is likely tethering epigenetic machinery to a novel class of CTCF/BORIS 11ZF target sequences that mediate induction of cancer-testis genes., Unlike CTCF, BORIS expression has been reported only in the testis and certain malignancies, leading to its classification as a \"cancer-testis\" antigen.[SEP]Relations: testis has relations: anatomy_protein_present with CTCF, anatomy_protein_present with CTCF, anatomy_protein_present with CTCFL, anatomy_protein_present with CTCFL, anatomy_protein_present with BNC1, anatomy_protein_present with BNC1. Geneticin has relations: drug_drug with Cefsulodin, drug_drug with Cefsulodin. Protein S human has relations: drug_drug with Cefsulodin, drug_drug with Cefsulodin.", "label": "yes"}
{"id": "converted_2394", "sentence1": "Does erythromycin increase risk of hypertrophic pyloric stenosis?", "sentence2": "Post-natal erythromycin exposure and risk of infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis., PURPOSE: Macrolide antibiotics, erythromycin, in particular, have been linked to the development of infantile hypertrophic pyloric stenosis (IHPS).,  Overall, erythromycin exposure was significantly associated with development of IHPS [OR 2.45 (1.12-5.35), p = 0.02]. , Data on erythromycin exposure in the first 14 days of life was extracted from 4/9 studies and identified a strong association between erythromycin exposure and subsequent development IHPS [OR 12.89 (7.67-2167), p < 0.00001].CONCLUSION: This study demonstrates a significant association between post-natal erythromycin exposure and development of IHPS, which seems stronger when exposure occurs in the first 2 weeks of life., BACKGROUND AND OBJECTIVE: Use of oral erythromycin in infants is associated with infantile hypertrophic pyloric stenosis (IHPS)., CONCLUSIONS: Ingestion of oral azithromycin and erythromycin places young infants at increased risk of developing IHPS., An association between erythromycin and IHPS was also confirmed. Exposure to erythromycin in the first 14 days of life had an aOR of 13.3 (95% CI, 6.80-25.9), and 15 to 42 days of life, aOR 4.10 (95% CI, 1.69-9.91). , Early exposure to oral erythromycin in young infants, particularly in the first 2 weeks of life, has previously been associated with the development of hypertrophic pyloric stenosis. We report a case of an infant who received an abbreviated 4-day course of oral erythromycin for suspected Chlamydia conjunctivitis at 5 days of life then underwent pyloromyotomy for pyloric stenosis less than 2 weeks later., Maternal and infant use of erythromycin and other macrolide antibiotics as risk factors for infantile hypertrophic pyloric stenosis., A case report has suggested that exposure to erythromycin through breast milk might cause infantile hypertrophic pyloric stenosis., Macrolide antibiotics, erythromycin, in particular, have been linked to the development of infantile hypertrophic pyloric stenosis (IHPS)., Infants prescribed systemic erythromycin had increased risk of IHPS, with the highest risk in the first 2 weeks of age (relative risk = 10.51 for erythromycin in first 2 weeks, 95% CI 4.48, 24.66)., There was an association between maternal prescriptions for nonerythromycin macrolides and infantile hypertrophic pyloric stenosis (adjusted odds ratio 2.77, 95% confidence interval 1.22, 6.30, P =.01).<br><b>CONCLUSION</b>: The hypothesized association between erythromycin and infantile pyloric stenosis was not seen., Macrolide antibiotics, erythromycin, in particular, have been linked to the development of infantile hypertrophic pyloric stenosis (IHPS).[SEP]Relations: hypertrophic pyloric stenosis has relations: disease_disease with intestinal disease, disease_disease with intestinal disease, disease_disease with pyloric stenosis (disease), disease_disease with pyloric stenosis (disease), disease_disease with Mendelian disease, disease_disease with Mendelian disease, disease_disease with pyloric stenosis, infantile hypertrophic, disease_disease with pyloric stenosis, infantile hypertrophic. pyloric stenosis, infantile hypertrophic has relations: disease_phenotype_positive with Hypochloremic metabolic alkalosis, disease_phenotype_positive with Hypochloremic metabolic alkalosis.", "label": "yes"}
{"id": "converted_129", "sentence1": "Is amantadine effective for treatment of disorders conciousness?", "sentence2": "We here provide a systematic overview of the therapeutic effects of amantadine, apomorphine and zolpidem in patients recovering from coma. Evidence from clinical trials using these commonly prescribed pharmacological agents suggests positive changes in the neurological status in patients, leading sometimes to dramatic improvements., Pharmaceuticals that act in the oxygen based amino acid systems of the brain include the GABAergic medications zolpidem and baclofen, while those that act in the monoamine axes include the dopaminergic medications L Dopa, amantadine, bromocriptine, apomorphine and methylphenidate, and the noradrenergic and serotonergic medications desipramine, amitriptyline, protriptyline and fluoxetine. , Sporadic cases of recovery from a DOC have been reported after the administration of various pharmacological agents (baclofen, zolpidem, amantadine etc.)., Amantadine hydrochloride is one of the most commonly prescribed medications for patients with prolonged disorders of consciousness after traumatic brain injury. Preliminary studies have suggested that amantadine may promote functional recovery.,  During the 4-week treatment period, recovery was significantly faster in the amantadine group than in the placebo group, as measured by the DRS score (difference in slope, 0.24 points per week; P=0.007), indicating a benefit with respect to the primary outcome measure. , Amantadine accelerated the pace of functional recovery during active treatment in patients with post-traumatic disorders of consciousness., Sporadic cases of dramatic recovery from DOC after the administration of various pharmacological agents, such as baclofen, zolpidem and amantadine, have been recently supported by intriguing scientific observations. , According to the 16 eligible studies, medical management by dopaminergic agents (levodopa, amantadine), zolpidem and median nerve stimulation, or surgical management by deep brain stimulation, extradural cortical stimulation, spinal cord stimulation and intrathecal baclofen have shown to improve the level of consciousness in certain cases. , Higher exposure of amantadine (average concentration of amantadine during 6 mg/kg/day > 1.5 mg/L) may be associated with better recovery of consciousness. , Based on the preliminary data, higher dosing may be considered in the setting of brain injury., Patients treated with PK-Merz exhibited the more significant restoration of consciousness and better dynamics (regress) of neurological deficit with the most intensive restoration of neurological deficit in the first day that allows to recommend the use of amantadine sulfate in the first hours of ischemic stroke and for the prevention of reperfusion damage in recanalisation therapy of ischemic stroke., There was no significant difference in the slopes of recovery during either arm for the Coma/Near-Coma Scale (P = 0.24) or the Coma Recovery Scale-Revised (P = 0.28), although improvements in consciousness were noted by the physician during weeks when amantadine was given (P = 0.02). , This study suggests that amantadine facilitates recovery of consciousness in pediatric acquired brain injury and provides important information necessary to design future more definitive studies., The study has shown a positive effect of this drug at coma emergence, which manifested itself as clinical improvement and a better outcome of the disease., This article will review the evidence for the use of psychostimulants (methylphenidate), antidepressants (amitriptyline, selective serotonin reuptake inhibitors, and buproprion), Parkinson's medications (amantadine, bromocriptine, carbidopa/levodopa), anticonvulsants (valproic acid), modafinil (Provigil), lactate, hyperbaric oxygen chamber, electroconvulsive therapy, and transmagnetic stimulation, in patients following a head injury., Of the psychoactive medications, amantadine hydrochloride was associated with greater recovery and dantrolene sodium was associated with less recovery, in terms of the DRS score at 16 weeks but not the time until commands were followed.[SEP]Relations: Amantadine has relations: contraindication with mental disorder, contraindication with mental disorder, contraindication with mental disorder, contraindication with mental disorder, contraindication with substance-related disorder, contraindication with substance-related disorder, contraindication with substance-related disorder, contraindication with substance-related disorder, contraindication with psychotic disorder, contraindication with psychotic disorder.", "label": "yes"}
{"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]Ewing sarcoma has relations with EWSR1, EWSR2, EGR2 and FLI1. Ewing Sarcoma can also be identified by itsphenotype, which is positive or negative. The disease_phenotype_positive with Ewing sar coma can be found at the bottom of the page.", "label": "yes"}
{"id": "converted_3754", "sentence1": "Glucoraphanin from broccoli can help reduce obesity , yes or no?", "sentence2": "Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance., A recent study demonstrated that glucoraphanin, a precursor of the Nrf2 activator sulforaphane, ameliorates obesity by enhancing energy expenditure and browning of white adipose tissue, and attenuates obesity-related inflammation and insulin resistance by polarizing M2 macrophages and reducing metabolic endotoxemia., Thus, this review focuses on the efficiency and safety of glucoraphanin in alleviating obesity, insulin resistance, and NAFLD., Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance, tudy demonstrated that glucoraphanin, a precursor of the Nrf2 activator sulforaphane, ameliorates obesity by enhancing energy expenditure and browning of white adipose tissue, and attenuates obesity-related inflammation and insulin resistance by polarizing M2 macrophages and reducing metabolic endotoxemia. Thus, this , iew focuses on the efficiency and safety of glucoraphanin in alleviating obesity, insulin resistance, and NAFLD. Abbreviations: [SEP]NFE2L2 has relations: anatomy_protein_present with Brodmann (1909) area 9. It also has relations with bioprocess_protein with cellular response to glucose starvation. It has also relations with GSK3B, protein_ protein with GCLM, and protein_protein with GCLM.", "label": "yes"}
{"id": "converted_855", "sentence1": "Do carmustine wafers improve survival of glioblastoma patients?", "sentence2": "At recurrence, treatment options include repeat surgery (with or without Gliadel wafer placement), reirradiation or systemic therapy. , DISCUSSION: Carmustine wafers for primary HGG surgery in accordance with the NICE TA121 were associated with a median survival of 15.3 months; this is improved compared with previously reported randomised trials. Multimodal treatment with carmustine wafers, radical radiotherapy and concomitant temozolomide was associated with improved survival., Gliadel wafer is a new approach to the treatment of glioblastoma, which involves controlled release delivery of carmustine from biodegradable polymer wafers. It has shown promising results and provides a silver lining for glioblastoma patients., For patient with and without Gliadel, median and 1-year RFS were 12.9 months and 52% vs. 14 months and 42%, respectively (p = 0.89)., According to pathology, Gliadel did not influence OS of patients with Grade III or glioblastoma, CONCLUSION: In patients with high-grade gliomas, adding Gliadel before performing a Stupp protocol did not improve survival., Randomized phase III trials have shown significant improvement of survival 1, 2, and 3 years after implantation of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers for patients with newly diagnosed malignant glioma. , CONCLUSIONS: The combination of aggressive resection, Gliadel wafer implantation, and GKS in addition to standard fractionated RT in selected patients resulted in increased local control and increased survival compared with a historical control group treated with surgery and involved-field RT alone., OBJECT: Gliadel (BCNU) wafer and concomitant temozolomide (TMZ) therapy, when used individually as adjuvant therapies, extend survival from that achieved by resection and radiation therapy (XRT) for glioblastoma multiforme (GBM). , BACKGROUND: Gliadel (polifeprosan 20 with carmustine [BCNU] implant) is commonly used for local delivery of BCNU to high-grade gliomas after resection and is associated with increased survival., Temozolomide administered according to this protocol produced a median survival benefit of 2 months in glioblastomas, and carmustine a similar benefit in high-grade gliomas., Analysis of a large trial by Westphal and colleagues (n = 240) showed a 29% risk reduction (P = 0.03) in the BCNU wafer-treated group over the course of the 30-month trial., Median survival of patients treated with BCNU wafers was 13.8 months vs 11.6 months in placebo-treated patients (P = 0.017) with a hazard ratio of 0.73 (P = 0.018), representing a 27% significant risk reduction. This survival advantage was maintained at 1, 2, and 3 years and was statistically significant (P = 0.01) at 3 years., CONCLUSION: Malignant glioma patients treated with BCNU wafers at the time of initial surgery in combination with radiation therapy demonstrated a survival advantage at 2 and 3 years follow-up compared with placebo., OBJECTIVE: Recently a randomized placebo-controlled phase III trial of biodegradable polymers containing carmustine has demonstrated a significant survival benefit for patients treated with local chemotherapy. , CONCLUSION: In this subgroup analysis of a phase III trial population both the clinical progression and radiological progression were significantly delayed in patients treated with local chemotherapy, resulting in an increased survival time., A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers (Gliadel wafers) prolong survival in patients with recurrent glioblastoma multiforme. A previously completed phase 3 trial, also placebo controlled, in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers., Median survival in the intent-to-treat group was 13.9 months for the BCNU wafer-treated group and 11.6 months for the placebo-treated group (log-rank P -value stratified by country = 0.03), with a 29% reduction in the risk of death in the treatment group. When adjusted for factors affecting survival, the treatment effect remained positive with a risk reduction of 28% ( P = 0.03). , Controlled release delivery of carmustine from biodegradable polymer wafers was approved as an adjunct to surgical resection in the treatment of recurrent glioblastoma multiforme after it was shown in clinical trials to be well tolerated and effective. , Clinical trials have demonstrated significant improvements in survival and quality of life for patients after complete tumour resection and BCNU wafer implantation., BCNU wafers are an effective means of increasing survival and quality of life in patients diagnosed with malignant glioma, and are a valuable addition to the overall multimodal treatment strategy for these tumours., CONCLUSIONS: Carmustine wafer with concurrent TMZ and radiation followed by rotational chemotherapy is a well tolerated, effective therapy, and has a survival benefit compared with radiation alone., Median overall survival in 14 studies of newly-diagnosed patients suggested a modest improvement versus resection followed by Stupp protocol or resection with BCNU wafers, with an acceptable and manageable safety profile., The efficacy of carmustine wafers for older patients with glioblastoma multiforme: prolonging survival., DISCUSSION: Older patients with GBM may benefit from carmustine wafers. The survival for older patients who received carmustine wafers is significantly longer than matched patients who did not receive carmustine wafers., For glioblastoma patients who received ≥90% resection in the BCNU wafer study, median survival increased for BCNU wafer versus placebo (14.5 versus 12.4 months, respectively; P = 0.02), but no survival increase was found for <90% resection (11.7 versus 10.6 months, respectively; P = 0.98)., A wafer impregnated with carmustine, for use as an implant after surgical removal of recurrent GBM showed a prolongation in the median survival time of only 2 mo, from 20 to 28 wk in a study with a total of 222 patients. , No clear survival benefit associated with wafer implantation was identified., In three of the trials, patients with GBM who received carmustine wafers had significantly longer median survival than patients who did not receive wafers. , TMZ and carmustine (BCNU) biodegradable wafer (Gliadel) are the only adjuvant chemotherapies that have improved survival in randomised GB clinical trials . , The carmustine implant wafer was demonstrated to improve survival in blinded placebo-controlled trials in selected patients with newly diagnosed or recurrent malignant glioma, with little increased risk of adverse events. , For patients undergoing repeat resection for malignant glioma, a randomized, blinded, placebo-controlled trial demonstrated a median survival for 110 patients who received carmustine polymers of 31 weeks compared with 23 weeks for 122 patients who only received placebo polymers., Median survival was improved from 11.6 to 13.9 months (P = 0.03), with a 29% reduction in the risk of death. When patients with glioblastoma multiforme alone were analyzed, the median survival improved from 11.4 to 13.5 months, but this improvement was not statistically significant. , OBJECT: Locoregional chemotherapy with carmustine wafers, positioned at surgery and followed by radiation therapy, has been shown to prolong survival in patients with newly diagnosed glioblastoma, as has concomitant radiochemotherapy with temozolomide., Following the resection of newly diagnosed or recurrent glioblastomas, local implantation of carmustine-impregnated biodegradable wafers (Gliadel) in the resection cavity constitutes an adjuvant therapy that can improve the possibilities of survival., The carmustine implant wafer was demonstrated to improve survival in blinded placebo-controlled trials in selected patients with newly diagnosed or recurrent malignant glioma, with little increased risk of adverse events., However, patients with carmustine wafers demonstrated prolonged survival as compared to patients without wafers., The median survival for patients with carmustine wafers was 8.7 months, while median survival for patients without wafers was 5.5 months (P=0.007)., Likewise, in subgroup analysis, patients older than 70 years (P=0.0003) and 75 years (P=0.04) who had carmustine wafers had significantly longer survival than matched patients without wafers., Implantation of carmustine wafers did not significantly improve progression-free survival, In three of the trials, patients with GBM who received carmustine wafers had significantly longer median survival than patients who did not receive wafers, A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers (Gliadel wafers) prolong survival in patients with recurrent glioblastoma multiforme, A previously completed phase 3 trial, also placebo controlled, in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers, Following the resection of newly diagnosed or recurrent glioblastomas, local implantation of carmustine-impregnated biodegradable wafers (Gliadel) in the resection cavity constitutes an adjuvant therapy that can improve the possibilities of survival, Multimodal treatment with carmustine wafers, radical radiotherapy and concomitant temozolomide was associated with improved survival, The carmustine implant wafer was demonstrated to improve survival in blinded placebo-controlled trials in selected patients with newly diagnosed or recurrent malignant glioma, with little increased risk of adverse events, TMZ and carmustine (BCNU) biodegradable wafer (Gliadel) are the only adjuvant chemotherapies that have improved survival in randomised GB clinical trials [SEP]Relations: Carmustine has relations: drug_effect with Renal insufficiency, drug_effect with Renal insufficiency, contraindication with lung disease, contraindication with lung disease, drug_effect with Diplopia, drug_effect with Diplopia, drug_effect with Erythema, drug_effect with Erythema, drug_effect with Stomatitis, drug_effect with Stomatitis.", "label": "yes"}
{"id": "converted_983", "sentence1": "Have mutations in the ZEB2 gene been found in any human syndrome?", "sentence2": "Mowat-Wilson syndrome is a genetic disease caused by heterozygous mutations or deletions of the zinc finger E-box-binding homeobox 2 (ZEB2) gene, Mowat-Wilson syndrome (MWS; OMIM#235730) have characteristic facial features, a variety of congenital anomalies such as Hirschsprung disease, and intellectual disabilities caused by mutation or deletion of ZEB2 gene., owat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene, MWS is caused by de novo heterozygous mutations in the ZEB2 gene, The cause of MWS is a de novo mutation in the ZEB2 gene, owat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene, MWS have a heterozygous loss-of-function mutation in the zinc finger E-box protein 2 (ZEB2) gene, also called SIP1 (Smad-interacting protein 1) and ZFHX1B,,  human Mowat-Wilson syndrome, we suggest that deletion of ZEB2, is responsible for most of the effects of the mutation, Mutations at the hZeb2 locus cause Mowat-Wilson syndrome (MWS), Mowat-Wilson syndrome and a mutation in ZEB2, owat-Wilson syndrome (MWS) is caused by a heterozygous mutation or deletion of the ZEB2 gene, The syndrome is caused by mutations or deletions of the ZEB2 gene, owat-Wilson syndrome (MWS) is an autosomal dominant intellectual disability syndrome, single-copy ZEB2 gene deletion at 2q22.3 consistent with Mowat-Wilson syndrome, Mowat-Wilson syndrome, confirmed by molecular analysis as a heterozygous deletion of the ZEB2 gene., deletion encompassing ZEB2, the gene responsible for the Mowat-Wilson syndrome,  Six patients had deletions in the ZEB2 gene, ZEB2 gene analysis for Mowat-Wilson syndrome, Mowat-Wilson syndrome (MWS) like appearance was noted. The disease is caused by mutation or deletion of ZEB2 gene, owat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene, owat-Wilson syndrome (MWS) is an autosomal dominant developmental disorder with mental retardation and variable multiple congenital abnormalities due to mutations of the ZEB2 (ZFHX1B) , MWS is caused by heterozygous mutations or deletions in the Zinc finger E-box-binding homeobox 2 gene, ZEB2, previously called ZFHX1B (SIP1), owat-Wilson syndrome (MWS) is a multiple congenital anomaly-mental retardation complex caused by mutations in the Zinc Finger Homeobox 1 B gene (ZFHX1B), the ZFHX1B gene, which is known to be involved in the Mowat-Wilson syndrom, de novo heterozygous mutations or deletions of the ZFHX1B gene located at 2q22, owat-Wilson syndrome (MWS) is a recently delineated mental retardation (MR)-multiple congenital anomaly syndrome, FHX1B mutations in patients with Mowat-Wilson syndrome, Mutations leading to haploinsufficiency of the ZFHX1B gene, mutation in the ZFHX1B gene associated with an atypical Mowat-Wilson syndrome phenotype, ZFHX1B mutation associated with a mild Mowat-Wilson syndrome, Patients with zinc finger homeo box 1B (ZFHX1B) mutations or deletions develop multiple congenital anomalies including Hirschsprung disease, known as Mowat-Wilson syndrome (MWS), Heterozygous mutations or deletions involving the gene ZFHX1B (previously SIP1) [OMIM 605802] have recently been found to cause MWS,  ZFHX1B deletions, splice site or truncating mutations were detected in all 28 patients classified as typical MWS, Mowat-Wilson syndrome with deletion/mutation in the zinc finger homeo box 1B gene (ZFHX1B),  mutations in the zinc finger homeo box 1B gene, ZFHX1B (SIP1), ZFHX1B gene transcripts during mouse and human development supports the various clinical manifestations of the \"Mowat-Wilson\" syndrome,  ZFHX1B mutations cause a complex developmental phenotype characterized by severe mental retardation (MR) and multiple congenital defects, mutation of the zinc finger homeo box 1 B gene in syndromic corpus callosum agenesis (Mowat-Wilson syndrome, syndrome is the result of heterozygous deletions or truncating mutations of the ZFHX1B (SIP1) gene, humans with Zfhx1b mutations (Mowat-Wilson syndrome, syndrome occurs as a result of heterozygous mutations or deletions in the zinc finger E-box-binding homeobox 2 gene, ZEB2, previously called ZFHX1B (SIP1), owat-Wilson syndrome (MWS) is a recently delineated mental retardation;, Mowat-Wilson syndrome is a congenital syndrome caused by a defect of the transcriptional repressor ZFHX1B (SIP1), Mowat-Wilson syndrome patients, and all siblings had the same E87X nonsense mutation in ZFHX1B[SEP]Relations: ZEB2 has relations: disease_protein with Mowat-Wilson syndrome due to a ZEB2 point mutation, disease_protein with Mowat-Wilson syndrome due to a ZEB2 point mutation, protein_protein with SMAD2, protein_protein with SMAD2, anatomy_protein_present with blood, anatomy_protein_present with blood, anatomy_protein_present with brain, anatomy_protein_present with brain, anatomy_protein_present with embryo, anatomy_protein_present with embryo.", "label": "yes"}
{"id": "converted_1484", "sentence1": "Can clonidine be used to reduce agitation in children.", "sentence2": "Children receiving clonidine immediately after anesthesia induction had statistically significant improvement in postoperative agitation at the 15-minute mark (P = .096) and last score obtained (P = .095) using the Watcha scale., Clonidine has proven to be effective in reducing the incidence of post-operative agitation at a higher dose (3 and 2 μg kg⁻¹)., Post-anaesthetic agitation was observed in two patients (6.6%) in group 1, eight patients (26.6%) in group 2 as compared to 12 patients (40%) in group 3 after 15 min of post-operative observation., The mean scores in group 1 at 15 and 30 min were significantly lower than those in group 3 (P value <0.05), Caudal clonidine at a lower dose (1 μg kg⁻¹) could be effective in reducing the incidence of sevoflurane-induced emergence agitation in children undergoing urogenital and lower limb surgery without any significant adverse effects., Only the 4 microg kg-1 dose of clonidine was associated with a significant reduction in emergence agitation., Fewer children in the clonidine 4 microg kg-1 group displayed agitation (25%) than in the midazolam group (60%) (P=0.025)., In comparison with midazolam, clonidine 4 microg kg-1 reduced sevoflurane-induced emergence agitation without increasing postoperative side-effects., Prophylactic use of clonidine against sevoflurane-induced agitation may represent a new and promising application., One hundred and twenty children were included in this study: 59 of whom received clonidine, and 61 placebo; 41% of those in the placebo group exhibited moderate-severe EA compared with only 22% of those in the clonidine group (P < 0.03)., Findings demonstrate that i.v. clonidine administered after induction of anesthesia significantly reduces the incidence of EA in young children, but is associated with sleepiness postoperatively., Clonidine could not prevent agitation (incidence 54%, 13/24), Clonidine 1.5 microg/kg did not differ from placebo with respect to postoperative agitation., Clonidine is effective in treating sevoflurane-induced postanesthesia agitation in children., Pain and discomfort scores were significantly decreased in the clonidine group; the incidence of agitation was reduced by 57% (P = 0.029) and the incidence of severe agitation by 67% (P = 0.064). Relative risks for developing agitation and severe agitation were 0.43 (95% confidence interval, 0.24-0.78) and 0.32 (0.09-1.17), respectively., Clonidine produces a substantial reduction in the risk of postsevoflurane agitation in children., Agitation was observed in 12 midazolam-treated and five clonidine-treated patients (P=0.05)., Compared with midazolam, clonidine premedication reduced agitation during sevoflurane induction., Clonidine 3 micrograms kg-1 prevented agitation after sevoflurane anaesthesia, independently of the route of administration. The effect of clonidine appears to be dose-dependent, as an epidural dose of 1 microgram kg-1 failed to reduce it., Clonidine prevents sevoflurane-induced agitation in children., In 16 placebo and 2 clonidine-treated patients agitation was observed (P < 0.001), In 6 patients of the Placebo group, agitation was graded as severe, whereas none of the patients in the Clonidine group developed severe agitation (P = 0.02)., We conclude that clonidine effectively prevents agitation after sevoflurane anesthesia., Clonidine 2 microg/kg IV after anesthetic induction effectively reduces the incidence of agitation without resulting in clinically relevant bradycardia and hypotension., Children receiving clonidine prior to undergoing strabismus surgery have a small but noticeable reduction in postoperative agitation, stay slightly longer in the post-anesthesia care unit, and have higher rates of parent satisfaction., We report three cases of preoperative use of intranasal clonidine in pediatric patients, all for different indications. One patient was treated for preoperative agitation and hallucinations associated with oral midazolam. One patient was given clonidine as a premedicant. The third patient was treated for preoperative agitation and hypertension. All three patients had subjective resolution of indicated symptoms and none experienced adverse outcomes., Oral or intravenous clonidine has been successfully used for the prevention of sevoflurane-induced agitation during emergence from anaesthesia.[SEP]Relations: Agitation has relations: drug_effect with Clonidine, drug_effect with Clonidine. Clonidine has relations: drug_effect with Agitation, drug_effect with Agitation, drug_effect with Anxiety, drug_effect with Anxiety, contraindication with anxiety disorder, contraindication with anxiety disorder, drug_effect with Headache, drug_effect with Headache.", "label": "yes"}
{"id": "converted_790", "sentence1": "Is recommended the use of perioperative treatment with thyroid hormone therapy in patients undergoing coronary artery bypass grafting?", "sentence2": "Short duration postoperative iv T(3) therapy increases cardiac index and does not alter mortality., We conclude that although widespread interest has been shown on the use of thyroid hormones in the perioperative period, and the effect of cardiopulmonary bypass on thyroid hormone metabolism widely studied, there is no substantial evidence to justify routine use of thyroid hormones in patients undergoing coronary artery bypass grafting., There is no clear evidence at this point to support thyroid hormone replacement in the latter patients, and it may be potentially harmful. Rather, we hold that T3 treatment of various surgical and other patients with nonthyroidal illness should be deferred until proof of its therapeutic efficacy is demonstrated., Perioperative administration of triiodothyronine increased cardiac output slightly and decreased systemic vascular resistance, but it had no effect on operative outcome. Routine use after coronary surgery is thus not recommended., Although mild effects on myocardial performance may exist, we cannot recommend at this time the routine use of intravenous T(3) as an inotropic agent in patients undergoing coronary artery bypass graft surgery., Raising serum triiodothyronine concentrations in patients undergoing coronary-artery bypass surgery increases cardiac output and lowers systemic vascular resistance, but does not change outcome or alter the need for standard postoperative therapy., Thus, there seems to be no sound justification for a routine use of T3 in patients undergoing open-heart procedures.[SEP]Liothyronine has relations with coronary artery disease, contraindication with pituitary hormone defiency from vascular origin, thyroid crisis (disease) and genetic form. It is also a potential cause of thyroid cancer, thyroid cancer and thyroid cancer-like symptoms. It can also be used to treat some forms of cancer, such as cancer of the pancreas.", "label": "no"}
{"id": "converted_1287", "sentence1": "Can the apoptosis regulator BAX trigger the release of cytochrome c?", "sentence2": "6-Shogaol reduced the mitochondrial membrane potential (MMP) and released cytochrome c from mitochondria to cytosol via Bax activation. , Moreover, overexpression of ERβ prevented Bax activation, cytochrome c release, caspase-3 activation, and PARP cleavage during apoptosis., In this study, we demonstrated that EV71 infection altered Bax conformation and triggered its redistribution from the cytosol to mitochondria in RD cells. Subsequently, cytochrome c was released from mitochondria to cytosol., associated with translocation of Bax from the cytosol to the mitochondrial membrane, cytochrome c release, and caspase activation. , Once activated, BAK and BAX form proteolipid pores in the OMM leading to mitochondrial outer membrane permeabilization (MOMP), and the release of inner membrane space proteins, such as cytochrome c, which promotes caspase activation. ,  Our results showed that OC induced a caspase-dependent apoptosis by triggering a series of events in HeLa cells including Bax translocation, cytochrome c release, caspase-3 activation, chromosome fragmentation followed by caspase-8 activation, Bid cleavage and eventually cell death. , Bax plays a key role in intrinsic apoptotic signaling in neurons by allowing the release of mitochondrial cytochrome c. [SEP] mitochondrion has relations with BAX, GPX4, and cytochrome c metabolic process. HELLS has relations: bioprocess_protein with negative regulation of intrinsic apoptotic signaling pathway, biop rocess with cyto chrome metabolic process, and HELLS with intrinsic apoptotic signaling pathway. mitochondrions have relations with each other and with other proteins.", "label": "yes"}
{"id": "converted_181", "sentence1": "Is the abnormal dosage of ultraconserved elements disfavored in cancer cells?", "sentence2": "Abnormal dosage of ultraconserved elements is highly disfavored in healthy cells but not cancer cells., We begin by showing that depletion for UCEs characterizes the most recent large-scale human CNV datasets and then find that even newly formed de novo CNVs, which have passed through meiosis at most once, are significantly depleted for UCEs. In striking contrast, CNVs arising specifically in cancer cells are, as a rule, not depleted for UCEs and can even become significantly enriched. This observation raises the possibility that CNVs that arise somatically and are relatively newly formed are less likely to have established a CNV profile that is depleted for UCEs. Alternatively, lack of depletion for UCEs from cancer CNVs may reflect the diseased state. In support of this latter explanation, somatic CNVs that are not associated with disease are depleted for UCEs. Finally, we show that it is possible to observe the CNVs of induced pluripotent stem (iPS) cells become depleted of UCEs over time, suggesting that depletion may be established through selection against UCE-disrupting CNVs without the requirement for meiotic divisions., Alternatively, lack of depletion for UCEs from cancer CNVs may reflect the diseased state.[SEP]Disease_disease with cancer has relations with giant cell tumor. Malignant giant cell tumors of soft tissue have relations with soft tissue tumor of bone. Malignancy in giant cell tumour of bone is called a \"giant cell tumor\" or a \"tumor of bone\" or \"gigantic tumor\"", "label": "no"}
{"id": "converted_4546", "sentence1": "Is METTL1 overexpression associated with better patient survival?", "sentence2": " Here we find METTL1 is frequently amplified and overexpressed in cancers and is associated with poor patient survival. METTL1 depletion causes decreased abundance of m7G-modified tRNAs and altered cell cycle and inhibits oncogenicity. Conversely, METTL1 overexpression induces oncogenic cell transformation and cancer. [SEP]MetTL1 has relations: protein_protein with MAX, protein_ protein with MAX. Relations: anatomy_protein_present with heart, anatomy_ proteins present with colon, anatomy protein present with lung, anatomy  protein_ present with brain.", "label": "no"}
{"id": "converted_3813", "sentence1": "Is aggrephagy a variant of autophagy?", "sentence2": "The selective branch of autophagy that deals with identification, capture and degradation of protein aggregates is called aggrephagy., Mechanistic insights into aggrephagy, a selective basal autophagy process to clear misfolded protein aggregates, , , it is largely unknown how misfolded polypeptides form aggresomes and are eventually cleared by the aggresome-macroautophagy/autophagy pathway, so-called aggrephagy.[SEP]Protein C has relations with Nonacog beta pegol, Vatreptacog alfa, Anagrelide, Damoctocog and Sarpogrelate. Protein C has also relations with Sarpogsrelate, which is a form of Anagrelides.", "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] alpha-amylase activity has relations: molfunc_protein with AMY1A, molfuncula with AMY2A and AMY2B. Molfunc protein has relations with AMy1C, AMY 1C and AMy 1B. alpha amylases have relations with each other.", "label": "yes"}
{"id": "converted_4125", "sentence1": "Is vocimagene amiretrorepvec effective for glioblastoma?", "sentence2": "CONCLUSIONS: These results support an immune-related mechanism of action for Toca 511 and Toca FC, and suggest that molecular and immunologic signatures are related to clinical benefit from treatment., The median OS was 11.10 months for the Toca 511/FC group and 12.22 months for the control group (hazard ratio, 1.06; 95% CI 0.83, 1.35; P = .62). The secondary end points did not demonstrate statistically significant differences. The rates of adverse events were similar in the Toca 511/FC group and the SOC control group.Conclusions and Relevance: Among patients who underwent tumor resection for first or second recurrence of glioblastoma or anaplastic astrocytoma, administration of Toca 511 and Toca FC, compared with SOC, did not improve overall survival or other efficacy end points.[SEP]Adult glioblastoma has relations: disease_disease with gliOBlastoma (diseases), disease_Disease. with adult infiltrating astrocytic neoplasm. anaplasticastrocytoma has Relations: contraindication with Temsirolimus, contrain dication with Sirolimu, and contraindications with TemsIROlimus.", "label": "no"}
{"id": "converted_3777", "sentence1": "Does protein ALEX1 contain armadillo repeats?", "sentence2": "ALEX1 (Arm protein lost in epithelial cancers, on chromosome X), contains two armadillo repeats domains, is expressed different in normal and carcinomas tissues., Arm protein lost in epithelial cancers, on chromosome X 1 (ALEX1) is a novel member of the Armadillo family which has two Armadillo repeats as opposed to more than six repeats in the classical Armadillo family members.[SEP]Carcinoma has relations: disease_protein with S1PR1, disease_ protein with TSC22D1, and disease_ proteins with MPZL1 and BCL2L1. It also has relations with MC1R and MC2R, and with MC2D and MC3D.", "label": "yes"}
{"id": "converted_300", "sentence1": "Is alternative splicing of apoptotic genes playing a role in the response to DNA or mitochondrial damage?", "sentence2": "Apoptosis promoted by UV in cells lacking p53 is prevented when the change in AS of the apoptotic gene bcl-x is reverted, confirming the relevance of this mechanism., We demonstrate that E2F1 requires SC35 to switch the alternative splicing profile of various apoptotic genes such as c-flip, caspases-8 and -9 and Bcl-x, towards the expression of pro-apoptotic splice variants. Finally, we provide evidence that E2F1 upregulates SC35 in response to DNA-damaging agents and show that SC35 is required for apoptosis in response to these drugs., This analysis revealed that DNA damage resulted in changes in splicing activity that modified the splicing pattern of Fas, a key pro-apoptotic, p53-inducible death receptor., Bortezomib induces mitochondrial damage in native cells and also activates the UPR by splicing of Xbp-1 and induction of CHOP, which is significantly reduced by silencing of MUC4., The tumour-suppressor protein p53 is an important activator of apoptosis. Although p53-deficient cancer cells are less responsive to chemotherapy, their resistance is not complete, which suggests that other apoptotic pathways may exist. A p53-related gene, p73, which encodes several proteins as a result of alternative splicing, can also induce apoptosis., Induction of apoptosis was significantly reduced in P388/SPR cells, as indicated by minimal DNA fragmentation. Analysis of oncogenes regulating apoptotic cell death revealed a marked decrease of bcl-2 in combination with a moderate reduction of bax protein, but a striking overexpression of the long form of the bcl-X protein.[SEP] mitochondrial matrix has relations: cellcomp_protein with AASS, cellcomp protein with aASS. Relations: positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator, bioprocess_ protein with RPL26, biocess_ proteins with R PL26, and bioeprocess protein with RPL26.", "label": "yes"}
{"id": "converted_2286", "sentence1": "Does a tonsillectomy affect the patient's voice?", "sentence2": " Group B had a better awareness of tooth damage (78% vs 30% of patients, P ≤ .001), voice change (61 vs 19%, P = .005), and burns to lips and mouth (44% vs 8%, P = .005). Finally, 35% more patients from group B rated their understanding of tonsillectomy as good or very good (P = .017).,  Some patients complaint for dry throat, foreign body sensation or voice change after tonsillectomy., The percentage of patients who had temporary voice change was 62.7%, and 15.4% had a follow-up clinic visit., There is no dose-escalation response to dexamethasone (0.0625-1.0 mg/kg) in pediatric tonsillectomy or adenotonsillectomy patients for preventing vomiting, reducing pain, shortening time to first liquid intake, or the incidence of voice change., There were no differences in secondary outcomes (analgesic requirements, time to first liquid, and change in voice) across treatment groups., Voice change, reported by approximately 70% of all patients, was the most common complaint, but it resolved in all instances., The incidence rates of voice change, velopharyngeal insufficiency, bleeding, constipation, dehydration, and pain were measured. , Tonsillectomy affects voice performance negatively in adults in short term; however, it does not affect voice performance in long term after surgery., The surgical technique, whether it is cold knife or thermal welding system, does not appear to affect voice and speech in tonsillectomy patients., OBJECTIVE: To evaluate changes in acoustic features of voice after tonsillectomy., Surgical indications for tonsillectomy in the young voice patient are discussed., OBJECTIVE: Our goal was to assess patient perception and acoustic characteristics of voice before and after upper airway surgery., In this report, we examined the change in pharyngeal size and acoustic feature of voice after tonsillectomy., CONCLUSION Tonsillectomy affects voice performance negatively in adults in short term; however, it does not affect voice performance in long term after surgery., Some patients complaint for dry throat, foreign body sensation or voice change after tonsillectomy., Tonsillectomy affects voice performance negatively in adults in short term; however, it does not affect voice performance in long term after surgery.., The surgical technique, whether it is cold knife or thermal welding system, does not appear to affect voice and speech in tonsillectomy patients.., There is no dose-escalation response to dexamethasone (0.0625-1.0 mg/kg) in pediatric tonsillectomy or adenotonsillectomy patients for preventing vomiting, reducing pain, shortening time to first liquid intake, or the incidence of voice change.[SEP]Relations: Dexamethasone has relations: drug_effect with Vertebral compression fractures, drug_effect with Vertebral compression fractures, drug_effect with Reduced visual acuity, drug_effect with Reduced visual acuity, drug_effect with Increased intracranial pressure, drug_effect with Increased intracranial pressure. Velopharyngeal insufficiency has relations: disease_phenotype_positive with Dubowitz syndrome, disease_phenotype_positive with Dubowitz syndrome, disease_phenotype_positive with cleft palate, disease_phenotype_positive with cleft palate.", "label": "yes"}
{"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]Relations: Sotos syndrome has relations: disease_protein with SETD2, disease_protein with SETD2, disease_disease with Malan overgrowth syndrome, disease_disease with Malan overgrowth syndrome, disease_disease with chromosomal disease with overgrowth, disease_disease with chromosomal disease with overgrowth, disease_protein with NRK, disease_protein with NRK. Weaver syndrome has relations: disease_disease with overgrowth syndrome, disease_disease with overgrowth syndrome.", "label": "yes"}
{"id": "converted_4633", "sentence1": "Is PCAT6 a microRNA?", "sentence2": "In this work, we investigated the role and regulatory mechanism of lncRNA prostate cancer-associated transcript 6 (PCAT6) in breast cancer progression.[SEP]Long noncoding RNA binding has relations: molfunc_protein with MIR384. benign neoplasm of male breast has relations with disease_disease.", "label": "no"}
{"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]Relations: Glioma has relations: disease_phenotype_positive with glioblastoma (disease), disease_phenotype_positive with glioblastoma (disease), disease_phenotype_positive with retinoblastoma, disease_phenotype_positive with retinoblastoma, disease_phenotype_positive with neurofibromatosis, disease_phenotype_positive with neurofibromatosis, disease_phenotype_positive with glioma susceptibility, disease_phenotype_positive with glioma susceptibility, drug_effect with Aminolevulinic acid, drug_effect with Aminolevulinic acid.", "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]Relations: Tocilizumab has relations: drug_drug with Tetanus Immune Globulin, drug_drug with Tetanus Immune Globulin, drug_drug with Nemolizumab, drug_drug with Nemolizumab, drug_drug with Afelimomab, drug_drug with Afelimomab, drug_drug with Antipyrine, drug_drug with Antipyrine, drug_drug with Concizumab, drug_drug with Concizumab.", "label": "no"}
{"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]Relations: ulcerative colitis (disease) has relations: contraindication with Benzthiazide, contraindication with Benzthiazide, contraindication with Icosapent, contraindication with Icosapent, contraindication with Polythiazide, contraindication with Polythiazide, contraindication with Chlorothiazide, contraindication with Chlorothiazide, contraindication with Trolnitrate, contraindication with Trolnitrate.", "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]Relations: mRNA transcription has relations: bioprocess_protein with EREG, bioprocess_protein with EREG, bioprocess_protein with HIPK3, bioprocess_protein with HIPK3, bioprocess_bioprocess with mRNA transcription by RNA polymerase II, bioprocess_bioprocess with mRNA transcription by RNA polymerase II, bioprocess_protein with HSF1, bioprocess_protein with HSF1. RNA localization to chromatin has relations: bioprocess_protein with HNRNPU, bioprocess_protein with HNRNPU.", "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]Relations: transcription factor binding has relations: molfunc_protein with PARK7, molfunc_protein with PARK7, molfunc_protein with ARNT, molfunc_protein with ARNT, molfunc_protein with HOXA7, molfunc_protein with HOXA7, molfunc_protein with CEBPG, molfunc_protein with CEBPG. SLC12A3 has relations: anatomy_protein_absent with decidua, anatomy_protein_absent with decidua.", "label": "yes"}
{"id": "converted_1414", "sentence1": "Are genes symmetrically distributed between leading and lagging DNA strand in bacteria?", "sentence2": "Genomic DNA is used as the template for both replication and transcription, whose machineries may collide and result in mutagenesis, among other damages. Because head-on collisions are more deleterious than codirectional collisions, genes should be preferentially encoded on the leading strand to avoid head-on collisions, as is observed in most bacterial genomes examined., Most genes in bacteria are encoded on the leading strand of replication. This presumably avoids the potentially detrimental head-on collisions that occur between the replication and transcription machineries when genes are encoded on the lagging strand., The majority of bacterial genes are located on the leading strand, genes of some functional categories such as ribosome have higher preferences to be on the leading strands, genes of some functional categories such as transcription factor have higher preferences on the lagging strands, essential genes are more preferentially situated at the leading strand than at the lagging strand, remarkable strand-bias of the distribution of essential genes, Head-on encounters between the replication and transcription machineries on the lagging DNA strand can lead to replication fork arrest and genomic instability. To avoid head-on encounters, most genes, especially essential and highly transcribed genes, are encoded on the leading strand such that transcription and replication are co-directional., Replication-associated purine asymmetry may contribute to strand-biased gene distribution., strand-biased gene distribution (SGD), SGD correlates not only with polC, but also with purine asymmetry (PAS), In bacteria, most genes are on the leading strand of replication, a phenomenon attributed to collisions between the DNA and RNA polymerases., genes whose expression is important for fitness are selected to the leading strand because this reduces the duration of these interruptions, Among prokaryotic genomes, the distribution of genes on the leading and lagging strands of the replication fork is known to be biased. , We show that the evidence they provided is invalid and that the existence of lagging strand encoded genes is explainable by a balance between deleterious mutations that bring genes from the leading to the lagging strand and purifying selection purging such mutants., Based on those experimentally determined for 10 bacteria, we find that essential genes are more preferentially situated at the leading strand than at the lagging strand, for all the 10 genomes studied, confirming previous findings based on either smaller datasets or putatively assigned ones by homology search., The majority of bacterial genes are located on the leading strand, and the percentage of such genes has a large variation across different bacteria., Most genes in bacteria are encoded on the leading strand of replication., This paradox could be explained by assuming that the stronger mutation pressure and selection after inversion preferentially eliminate genes transferred from the leading to the lagging DNA strand., We have shown that the relative number of translocations which have switched positions of genes from the leading to the lagging DNA strand is lower than the number of translocations which have transferred genes from the lagging strand to the leading strand of prokaryotic genomes., Most genes in bacteria are encoded on the leading strand of replication, The majority of bacterial genes are located on the leading strand, and the percentage of such genes has a large variation across different bacteria, We have shown that the relative number of translocations which have switched positions of genes from the leading to the lagging DNA strand is lower than the number of translocations which have transferred genes from the lagging strand to the leading strand of prokaryotic genomes, Using Monte Carlo methods, we have simulated, under experimentally determined directional mutation pressure, the divergence rate and the elimination rate of genes depending on their location in respect to the leading/lagging DNA strands in the asymmetric prokaryotic genome[SEP]Relations: transcription factor binding has relations: molfunc_protein with CD34, molfunc_protein with CD34, molfunc_protein with TWIST1, molfunc_protein with TWIST1, molfunc_protein with SMARCA1, molfunc_protein with SMARCA1, molfunc_protein with MAFB, molfunc_protein with MAFB. Bacteremia has relations: disease_phenotype_positive with staphylococcal pneumonia, disease_phenotype_positive with staphylococcal pneumonia.", "label": "no"}
{"id": "converted_2669", "sentence1": "Is CXCL7 a chemokine?", "sentence2": "CXCL7, a chemokine highly expressed in platelets, , Chemokine CXCL7 Heterodimers[SEP] Chemokine receptors bind chemokines has relations with CXCL8, CXCl5, CxCL6, C xCL9, C XCL11 and CXXCL11. Chemokines bind receptors by binding to receptors that bind to their receptors.", "label": "yes"}
{"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]Relations: idiopathic pulmonary fibrosis has relations: disease_disease with pulmonary fibrosis, disease_disease with pulmonary fibrosis, disease_protein with WNT5A, disease_protein with WNT5A, disease_protein with MUC5B, disease_protein with MUC5B, disease_protein with RTEL1, disease_protein with RTEL1, disease_protein with HIF1A, disease_protein with HIF1A.", "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]Relations: cohesin complex has relations: cellcomp_protein with SMC3, cellcomp_protein with SMC3, cellcomp_protein with SMC1A, cellcomp_protein with SMC1A, cellcomp_protein with STAG1, cellcomp_protein with STAG1, cellcomp_protein with SMC1B, cellcomp_protein with SMC1B, cellcomp_protein with STAG3L4, cellcomp_protein with STAG3L4.", "label": "yes"}
{"id": "converted_2372", "sentence1": "Is there any linear-time and linear-space algorithm for the computation of avoided words in biological sequences?", "sentence2": "The systematic search for avoided words is particularly useful for biological sequence analysis. We present a linear-time and linear-space algorithm for the computation of avoided words of lengthkin a given sequencex. We suggest a modification to this algorithm so that it computes all avoided words ofx, irrespective of their length, within the same time complexity. We also present combinatorial results with regards to avoided words and absent words., We present a linear-time and linear-space algorithm for the computation of avoided words of length <br>, <b>BACKGROUND</b>: The deviation of the observed frequency of a word <br><b>RESULTS</b>: In this article, we propose an [Formula: see text]-time and [Formula: see text]-space algorithm to compute all [Formula: see text]-avoided words of length <br><b>CONCLUSIONS</b>: The systematic search for avoided words is particularly useful for biological sequence analysis., We present a linear-time and linear-space algorithm for the computation of avoided words of length, We present a linear-time and linear-space algorithm for the computation of avoided words of length k in a given sequence x., Hence, computing all such words naïvely can be a very time-consuming procedure, in particular for large k.   RESULTS In this article, we propose an [Formula: see text]-time and [Formula: see text]-space algorithm to compute all [Formula: see text]-avoided words of length k in a given sequence of length n over a fixed-sized alphabet., We also present a time-optimal [Formula: see text]-time algorithm to compute all [Formula: see text]-avoided words (of any length) in a sequence of length n over an integer alphabet of size [Formula: see text]., the deviation of the observed frequency of a word from its expected frequency in a given sequence is used to determine whether or not the word is this concept is particularly useful in dna linguistic analysis the value of the deviation of denoted by formula see text effectively characterises the extent of a word by its edge contrast in the context in which it occurs a word of length formula see text is a formula see text avoided word in if formula see text for a given threshold formula see text notice that such a word may be completely from hence computing all such words naïvely can be a very time consuming procedure in particular for large in this article we propose an formula see text time and formula see text space algorithm to compute all formula see text avoided words of length in a given sequence of length over a fixed sized alphabet we also present a time optimal formula see text time algorithm to compute all formula see text avoided words of any length in a sequence of length over an integer alphabet of size formula see text in addition we provide a tight asymptotic upper bound for the number of formula see text avoided words over an integer alphabet and the expected length of the longest one we make available an implementation of our algorithm experimental results using both real and synthetic data show the efficiency and applicability of our implementation in biological sequence analysis the systematic search for avoided words is particularly useful for biological sequence analysis we present a linear time and linear space algorithm for the computation of avoided words of length in a given sequence we suggest a modification to this algorithm so that it computes all avoided words of irrespective of their length within the same time complexity we also present combinatorial results with regards to avoided words and absent words.[SEP]Relations: response to nickel cation has relations: bioprocess_protein with CACNA1G, bioprocess_protein with CACNA1G, bioprocess_bioprocess with cellular response to nickel ion, bioprocess_bioprocess with cellular response to nickel ion, bioprocess_bioprocess with response to metal ion, bioprocess_bioprocess with response to metal ion.", "label": "yes"}
{"id": "converted_2559", "sentence1": "Are there ways of joint Bayesian inference of risk variants?", "sentence2": "Joint Bayesian inference of risk variants and tissue-specific epigenomic enrichments across multiple complex human diseases., Genome wide association studies (GWAS) provide a powerful approach for uncovering disease-associated variants in human, but fine-mapping the causal variants remains a challenge. This is partly remedied by prioritization of disease-associated variants that overlap GWAS-enriched epigenomic annotations. Here, we introduce a new Bayesian model RiVIERA (Risk Variant Inference using Epigenomic Reference Annotations) for inference of driver variants from summary statistics across multiple traits using hundreds of epigenomic annotations. In simulation, RiVIERA promising power in detecting causal variants and causal annotations, the multi-trait joint inference further improved the detection power. We applied RiVIERA to model the existing GWAS summary statistics of 9 autoimmune diseases and Schizophrenia by jointly harnessing the potential causal enrichments among 848 tissue-specific epigenomics annotations from ENCODE/Roadmap consortium covering 127 cell/tissue types and 8 major epigenomic marks. RiVIERA identified meaningful tissue-specific enrichments for enhancer regions defined by H3K4me1 and H3K27ac for Blood T-Cell specifically in the nine autoimmune diseases and Brain-specific enhancer activities exclusively in Schizophrenia. Moreover, the variants from the 95% credible sets exhibited high conservation and enrichments for GTEx whole-blood eQTLs located within transcription-factor-binding-sites and DNA-hypersensitive-sites., Here, we introduce a new Bayesian model RiVIERA (Risk Variant Inference using Epigenomic Reference Annotations) for inference of driver variants from summary statistics across multiple traits using hundreds of epigenomic annotations., Joint Bayesian inference of risk variants and tissue-specific epigenomic enrichments across multiple complex human diseases.[SEP] autoimmune disease has relations with euthyroid Graves orbitopathy, disease_disease with vitiligo-associated multiple autoimmune disease susceptibility 1. schizophreniform disorder has relations: contraindication with Betamethasone and Hydrocortisone. Bioprocess_protein with IKBKE. gene expression has relations. with I KBKE.", "label": "yes"}
{"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]Relations: malignant neoplasm of chest wall has relations: disease_disease with thoracic cancer, disease_disease with thoracic cancer, disease_disease with chest wall bone cancer, disease_disease with chest wall bone cancer. Multiple myeloma has relations: disease_phenotype_positive with capillary leak syndrome, disease_phenotype_positive with capillary leak syndrome, drug_effect with Lenalidomide, drug_effect with Lenalidomide. Neoplasm of the thyroid gland has relations: disease_phenotype_positive with familial colorectal cancer, disease_phenotype_positive with familial colorectal cancer.", "label": "yes"}
{"id": "converted_1883", "sentence1": "Is there any tool that facilitates the functional analysis of cis-regulatory regions in zebrafish?", "sentence2": "Zebrafish enhancer detection (ZED) vector: a new tool to facilitate transgenesis and the functional analysis of cis-regulatory regions in zebrafish., he cis-regulatory sequences control when, where, and how much genes are transcribed and can activate (enhancers) or repress (silencers) gene expression. Here, we describe a novel Tol2 transposon-based vector for assessing enhancer activity in the zebrafish (Danio rerio). This Zebrafish Enhancer Detector (ZED) vector harbors several key improvements, among them a sensitive and specific minimal promoter chosen for optimal enhancer activity detection, insulator sequences to shield the minimal promoter from position effects, and a positive control for transgenesis. Additionally, we demonstrate that highly conserved noncoding sequences homologous between humans and zebrafish largely with enhancer activity largely retain their tissue-specific enhancer activity during vertebrate evolution. More strikingly, insulator sequences from mouse and chicken, but not conserved in zebrafish, maintain their insulator capacity when tested in this model., Zebrafish enhancer detection (ZED) vector: a new tool to facilitate transgenesis and the functional analysis of cis-regulatory regions in zebrafish, Zebrafish enhancer detection (ZED) vector: a new tool to facilitate transgenesis and the functional analysis of cis-regulatory regions in zebrafish.[SEP]Regulation of antisense RNA transcription has relations with regulation of transcription, DNA-templated, bioprocess_biop rocess. promoter clearance from RNA polymerase I promoter for nuclear large rRNA transcript has relations. Bioprocession_biobrocess with promoter clearance during DNA-Templated transcription, bio-prolificase-I promoter for DNA- Templated Transcripts. Bio-Prolifica-I Promoter for Nuclear Large RRNA Transcripts (BPRR) has relations: BPRR-N, BPR-N-N.", "label": "yes"}
{"id": "converted_3880", "sentence1": "Does inactivation of CYLD help in colorectal cancer?", "sentence2": "Inactivation of CYLD in intestinal epithelial cells exacerbates colitis-associated colorectal carcinogenesis - a short report., CYLD is a tumor suppressor that has been linked to the development of various human malignancies, including colon cancer. The tumor-suppressing function of CYLD is associated with its deubiquitinating activity, which maps to the carboxyl-terminal region of the protein. In the present study we evaluated the role of intestinal epithelial CYLD in colitis-associated cancer using a conditional mouse CYLD inactivation model.METHODS: In order to evaluate the role of CYLD in intestinal epithelial carcinogenesis, mice (IEC-Cyld (Δ9) mice) that carry a mutation that eliminates the deubiquitinating domain of CYLD in intestinal epithelial cells (IEC) were generated by crossing Villin-Cre transgenic mice to previously generated mice carrying a loxP-flanked Cyld exon 9 (Cyld (flx9) mice).RESULTS: We found that IEC-Cyld (Δ9) mice did not present spontaneous intestinal abnormalities up to one year of age. However, upon challenge with a combination of genotoxic (AOM) and pro-inflammatory (DSS) agents we found that the number of adenomas in the IEC-Cyld (Δ9) mice was dramatically increased compared to the control mice. Inactivation of CYLD in intestinal epithelial cells did not affect the classical nuclear factor-kappaB (NF-κB) and c-Jun kinase (JNK) activation pathways under physiological conditions, suggesting that these pathways do not predispose CYLD-deficient intestinal epithelia to colorectal cancer development before the onset of genotoxic and/or pro-inflammatory stress.CONCLUSIONS: Our findings underscore a critical tumor-suppressing role for functional intestinal epithelial CYLD in colitis-associated carcinogenesis. CYLD expression and its associated pathways in intestinal tumors may be exploited for future prognostic and therapeutic purposes., Inactivation of CYLD in intestinal epithelial cells exacerbates colitis-associated colorectal carcinogenesis - a short report[SEP]Malignant colon neoplasm has relations: disease_disease with colorectal cancer, disease_protein with RECK. Contraindication with Indomethacin.", "label": "no"}
{"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]Relations: subarachnoid hemorrhage (disease) has relations: disease_protein with PPARG, disease_protein with PPARG, disease_protein with EDNRB, disease_protein with EDNRB, disease_protein with UNC5B, disease_protein with UNC5B, disease_protein with CASP3, disease_protein with CASP3, disease_protein with ADORA1, disease_protein with ADORA1.", "label": "yes"}
{"id": "converted_2459", "sentence1": "Is there any link between ERCC1-XPF and cohesin?", "sentence2": "ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes., Using an in vivo biotinylation tagging approach in mice, we show that the nucleotide excision repair (NER) structure-specific endonuclease ERCC1-XPF complex interacts with the insulator binding protein CTCF, the cohesin subunits SMC1A and SMC3 and with MBD2; the factors co-localize with ATRX at the promoters and control regions (ICRs) of imprinted genes during postnatal hepatic development. Loss of Ercc1 or exposure to MMC triggers the localization of CTCF to heterochromatin, the dissociation of the CTCF-cohesin complex and ATRX from promoters and ICRs, altered histone marks and the aberrant developmental expression of imprinted genes without altering DNA methylation. We propose that ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes and that persistent DNA damage triggers chromatin changes that affect gene expression programs associated with NER disorders., Using an in vivo biotinylation tagging approach in mice, we show that the nucleotide excision repair (NER) structure-specific endonuclease ERCC1-XPF complex interacts with the insulator binding protein CTCF, the cohesin subunits SMC1A and SMC3 and with MBD2; the factors co-localize with ATRX at the promoters and control regions (ICRs) of imprinted genes during postnatal hepatic development., We propose that ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes and that persistent DNA damage triggers chromatin changes that affect gene expression programs associated with NER disorders., We propose that ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes and that persistent DNA damage triggers chromatin changes that affect gene expression programs associated with NER disorders., We propose that ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes and that persistent DNA damage triggers chromatin changes that affect gene expression programs associated with NER disorders.<br>, ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes., We propose that ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes and that persistent DNA damage triggers chromatin changes that affect gene expression programs associated with NER disorders..[SEP]Relations: heterochromatin has relations: cellcomp_protein with HSF1, cellcomp_protein with HSF1, cellcomp_protein with FOXC1, cellcomp_protein with FOXC1, cellcomp_protein with MORC2, cellcomp_protein with MORC2, cellcomp_protein with ORC2, cellcomp_protein with ORC2, cellcomp_protein with CBX1, cellcomp_protein with CBX1.", "label": "yes"}
{"id": "converted_3475", "sentence1": "Is the protein ABCG2 (ATP-Binding Cassette, subfamily G, member 2, transporter) excreting uric acid?", "sentence2": "TP-binding cassette transporter, sub-family G, member 2 (ABCG2/BCRP) is a well-studied urate transporter expressed on apical membranes in several tissues, including the intestine, liver, and kidney., the discovery that ABCG2 plays a central role on extra-renal uric acid excretion,[SEP] intestine has relations with ABCA2, ABCC2, and ABCC6P2. intestine is present with ABCG1 and ABCG2, but not ABCA1 or ABCC1. intestine can also be seen with ABCP2 and ABCP3.", "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_501", "sentence1": "Is Kanzaki disease associated with deficiency in alpha-N-acetylgalactosaminidase?", "sentence2": "Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr. ,  Our findings suggest that the association of alpha-NAGA with its substrates is strongly affected by the amino acid substitution at R329 and that the association with GalNAcalpha1-O-Thr is more highly susceptible to structural changes. The residual mutant enzyme in R329W could not associate with GalNAcalpha1-O-Thr and GalNAcalpha1-O-Ser. However, the residual mutant enzyme in R329Q catalyzed GalNAcalpha1-O-Ser to some extent. Therefore, the urinary ratio of GalNAcalpha1-O-Ser:GalNAcalpha1-O-Thr was lower and the clinical phenotype was milder in the R329Q mutation. , Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr., Alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency (Schindler/Kanzaki disease) is a clinically and pathologically heterogeneous genetic disease with a wide spectrum including an early onset neuroaxonal dystrophy (Schindler disease) and late onset angiokeratoma corporis diffusum (Kanzaki disease)., Structural and immunocytochemical studies on alpha-N-acetylgalactosaminidase deficiency (Schindler/Kanzaki disease)., We describe the neurologic findings in a patient with alpha-N-acetylgalactosaminidase deficiency (Kanzaki disease)., Three dimensional structural studies of alpha-N-acetylgalactosaminidase (alpha-NAGA) in alpha-NAGA deficiency (Kanzaki disease): different gene mutations cause peculiar structural changes in alpha-NAGAs resulting in different substrate specificities and clinical phenotypes., alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency is a rare hereditary lysosomal storage disease, and only three alpha-NAGA-deficient patients with angiokeratoma corporis diffusum (Kanzaki) have been described., Schindler disease and Kanzaki disease are caused by a deficient lysosomal enzyme, alpha-N-acetylgalactosaminidase (E.C.3.2.1.49)., The 1.9 a structure of human alpha-N-acetylgalactosaminidase: The molecular basis of Schindler and Kanzaki diseases., These data suggest that a prototype of alpha-NAGA deficiency in Kanzaki disease and factors other than the defect of alpha-NAGA may contribute to severe neurological disorders, and Kanzaki disease is thought to be caused by a single enzyme deficiency., Alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency (Schindler/Kanzaki disease) is a clinically and pathologically heterogeneous genetic disease with a wide spectrum including an early onset neuroaxonal dystrophy (Schindler disease) and late onset angiokeratoma corporis diffusum (Kanzaki disease). , alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency is a rare hereditary lysosomal storage disease, and only three alpha-NAGA-deficient patients with angiokeratoma corporis diffusum (Kanzaki) have been described. , Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr. Missense mutations, R329W or R329Q were identified in two Japanese Kanzaki patients., Alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency (Schindler/Kanzaki disease) is a clinically and pathologically heterogeneous genetic disease with a wide spectrum including an early onset neuroaxonal dystrophy (Schindler disease) and late onset angiokeratoma corporis diffusum (Kanzaki disease)., Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49),, Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr., alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency is a rare hereditary lysosomal storage disease, and only three alpha-NAGA-deficient patients with angiokeratoma corporis diffusum (Kanzaki) have been described.[SEP]Relations: NAGA has relations: disease_protein with alpha-N-acetylgalactosaminidase deficiency, disease_protein with alpha-N-acetylgalactosaminidase deficiency, molfunc_protein with alpha-N-acetylgalactosaminidase activity, molfunc_protein with alpha-N-acetylgalactosaminidase activity, disease_protein with neurodegeneration with brain iron accumulation, disease_protein with neurodegeneration with brain iron accumulation. alpha-N-acetylgalactosaminidase activity has relations: molfunc_protein with NAGA, molfunc_protein with NAGA. nervous system disorder has relations: disease_disease with drug-induced akathisia, disease_disease with drug-induced akathisia.", "label": "yes"}
{"id": "converted_367", "sentence1": "Is bapineuzumab effective for treatment of patients with Alzheimer's disease?", "sentence2": " Thus far, results from two large phase 3 trial programs with bapineuzumab and solaneuzumab, respectively, have brought rather disappointing results., More recently, in phase III studies, bapineuzumab has been discontinued because it did not prove clinically effective (despite its significant effect on biomarkers), while solaneuzumab has been found effective in slowing AD progression. , Passive immunotherapy with monoclonal antibodies (mAbs) against Aβ is in late clinical development but recently the two most advanced mAbs, Bapineuzumab and Solanezumab, targeting an N-terminal or central epitope, respectively, failed to meet their target of improving or stabilizing cognition and function., The marginal effects observed in recent clinical studies of solanezumab, targeting monomeric Aβ, and bapineuzumab, targeting amyloid plaques, prompted expert comments that drug discovery efforts in Alzheimer's disease should focus on soluble forms of Aβ rather than fibrillar Aβ deposits found in amyloid plaques., Phase III trials showed that bapineuzumab failed to improve cognitive and functional performances in AD patients, and was associated with a high incidence of amyloid-related imaging abnormalities (ARIA)., Clinical trials on various drugs, including AN1792, bapineuzumab, and solanezumab, have been carried out; however, all trials have failed to demonstrate apparent clinical benefits. , Despite the alteration in biochemical composition, all 3 immunized subjects exhibited continued cognitive decline., Despite negative topline phase 3 clinical trial results for bapineuzumab and solanezumab in mild to moderate AD, findings from these trials and recent advances suggest renewed optimism for anti-amyloid therapies. , The lack of progress in the development of disease-modifying therapy in Alzheimer's disease (AD) was highlighted recently by the cessation of a phase 3 clinical trial studying the effects of bapineuzumab on mild to moderate disease. No treatment benefit was apparent, whereas several serious side effects occurred more commonly in the treatment group compared to placebo. , Clinical studies using the N-terminal-directed anti-Aβ antibody bapineuzumab have demonstrated reduced brain PET-Pittsburg-B signals, suggesting the reduction of Aβ plaques, and reduced levels of total and phosphorylated tau protein in the CSF of treated AD patients. Preclinical studies using 3D6 (the murine form of bapineuzumab) have demonstrated resolution of Aβ plaque and vascular burdens, neuritic dystrophy, and preservation of synaptic density in the transgenic APP mouse models., The clinical results of the initial studies with bapineuzumab were equivocal in terms of cognitive benefit. The occurrence of vasogenic edema after bapineuzumab, and more rarely brain microhemorrhages (especially in Apo E ε4 carriers), has raised concerns on the safety of these antibodies directed against the N-terminus of the Aβ peptide. ,  The most advanced of these immunological approaches is bapineuzumab, composed of humanized anti-Aβ monoclonal antibodies, that has been tested in two Phase II trials, demonstrating to reduce Aβ burden in the brain of AD patients. However, the preliminary cognitive efficacy of bapineuzumab appears uncertain. The occurrence of vasogenic edema, especially in apolipoprotein E 4 carriers, may limit its clinical use and have led to abandon the highest dose of the drug (2 mg/kg)., However, the preliminary cognitive efficacy of bapineuzumab, a humanized anti-Aβ monoclonal antibody, appears uncertain. Moreover, the occurrence of vasogenic edema and, more rarely, brain microhemorrhages, especially in apolipoprotein E ϵ4 carriers, have led to abandoning of the highest dose of the drug. , However, the preliminary equivocal cognitive results obtained with bapineuzumab as well as the detrimental cognitive effects observed with semagacestat, a potent γ-secretase inhibitor, raise the possibility that targeting Aβ may not be clinically efficacious in AD. , The patient received four bapineuzumab infusions over a 39 week period. During the course of this treatment, there was no remarkable change in cognitive impairment as determined by MMSE scores. Forty-eight days after the fourth bapineuzumab infusion was given, MRI revealed that the patient had developed lacunar infarcts and possible vasogenic edema, probably related to immunotherapy, but a subsequent MRI scan 38 days later demonstrated resolution of vasogenic edema. The patient expired due to acute congestive heart failure complicated by progressive AD and cerebrovascular accident 378 days after the first bapineuzumab infusion and 107 days after the end of therapy. Neuropathological and biochemical analysis did not produce evidence of lasting plaque regression or clearance of Aβ due to immunotherapy., These results suggest that, in this particular case, bapineuzumab immunotherapy neither resulted in detectable clearance of amyloid plaques nor prevented further cognitive impairment., Bapineuzumab has been shown to reduce Aβ burden in the brain of AD patients. However, its preliminary cognitive efficacy appears uncertain, particularly in ApoE ε4 carriers, and vasogenic edema may limit its clinical use. , Bapineuzumab appears capable of reducing the cerebral beta-amyloid peptide burden in patients with Alzheimer's disease. However, particularly in APOE 4 carriers, its ability to slow disease progression remains uncertain, and vasogenic edema - a dose-limiting and potentially severe adverse reaction - may limit its clinical applicability., The first is a phase 2 study of passive immunotherapy with bapineuzumab, a humanized anti-Abeta monoclonal antibody directed against the N-terminus of Abeta. This trial showed no differences within dose cohorts on the primary efficacy analysis. Exploratory analyses showed potential treatment differences on cognitive and functional endpoints in study completers and apolipoprotein E epsilon4 noncarriers. A safety concern was the occurrence of reversible vasogenic edema. , The first passive immunotherapy trial with bapineuzumab, a humanized monoclonal antibody against the end terminus of Abeta, also encountered some dose dependent adverse events during the Phase II portion of the study, vasogenic edema in 12 cases, which were significantly over represented in ApoE4 carriers.[SEP]Relations: Bapineuzumab has relations: drug_drug with Abituzumab, drug_drug with Abituzumab, drug_drug with Alemtuzumab, drug_drug with Alemtuzumab, drug_drug with Olaratumab, drug_drug with Olaratumab, drug_drug with Fasinumab, drug_drug with Fasinumab, drug_drug with Adalimumab, drug_drug with Adalimumab.", "label": "no"}
{"id": "converted_2577", "sentence1": "Is Citrobacter rodentium pathogenic?", "sentence2": "One day after colonization, mice were infected with the colonic pathogen, Citrobacter rodentium., The human pathogen enteropathogenic Escherichia coli (EPEC), as well as the mouse pathogen Citrobacter rodentium, colonize the gut mucosa via attaching and effacing lesion formation and cause diarrheal diseases., EPEC-like mouse pathogen Citrobacter rodentium, Here, we develop a model that provides that link for the investigation of Citrobacter rodentium infection, a mouse model for enteropathogenic Escherichia coli (EPEC). [SEP]Disease_phenotype_positive with Recurrent gram-negative bacterial infections. Disease_disease with infectious disease has relations with disease_phenotype_negative. Disease-phenotype-negative infection is more common than disease-positive infection.", "label": "yes"}
{"id": "converted_1874", "sentence1": "Is there an association between Muenke Syndrome and FGFR3 gene mutation?", "sentence2": "RESULTS: Forty-four with a positive FGFR3 mutation, median age 9 years, range 7 months to 52 years were enrolled. In addition, 10 unaffected siblings served as controls (5 males, 5 females; median age, 13 years; range, 3-18 years)., Muenke is a fibroblast growth factor receptor 3 (FGFR-3)-associated syndrome, which was first described in late 1990 s. , The syndrome is defined molecularly by a unique point mutation c.749C>G in exon 7 of the FGFR3 gene which results to an amino acid substitution p.Pro250Arg of the protein product. , Muenke syndrome caused by point mutation (C749G) in the FGFR3 gene affects 1 in 30,000 newborns and accounts for 25% to 30% of genetic causes of craniosynostosis., Phenotypic variability in two families of Muenke syndrome with FGFR3 mutation., PURPOSE: There are a number of craniosynostosis syndromes with hearing loss-including Muenke, Apert, Pfeiffer, Crouzon, Beare-Stevenson, Crouzon with acanthosis nigricans, and Jackson-Weiss syndromes-that result from mutations in the fibroblast growth factor receptor (FGFR) genes. , Muenke syndrome is an autosomal dominant craniosynostosis syndrome resulting from a defining point mutation in the Fibroblast Growth Factor Receptor3 (FGFR3) gene., Talocalcaneal coalition in Muenke syndrome: report of a patient, review of the literature in FGFR-related craniosynostoses, and consideration of mechanism., To better understand the pathophysiology of the Muenke syndrome, we present collective findings from several recent studies that have characterized a genetically equivalent mouse model for Muenke syndrome (FgfR3 (P244R)) and compare them with human phenotypes., We show in this study that knock-in mice harboring the mutation responsible for the Muenke syndrome (FgfR3(P244R)) display postnatal shortening of the cranial base along with synchondrosis growth plate dysfunction characterized by loss of resting, proliferating and hypertrophic chondrocyte zones and decreased Ihh expression., Muenke syndrome is caused by a single defining point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene., The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes., Epilepsy in Muenke syndrome: FGFR3-related craniosynostosis., Muenke syndrome (FGFR3-related craniosynostosis): expansion of the phenotype and review of the literature., The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes., PURPOSE: The Muenke syndrome mutation (FGFR3 (P250R)), which was discovered 15 years ago, represents the single most common craniosynostosis mutation., The heterozygous Pro250Arg substitution mutation in fibroblast growth factor receptor 3 (FGFR3), which increases ligand-dependent signalling, is the most common genetic cause of craniosynostosis in humans and defines Muenke syndrome., P250R mutation in the FGFR3 gene also known as Muenke syndrome is associated with coronal craniosynostosis, sensorineural deafness, craniofacial, and digital abnormalities., Muenke syndrome caused by the FGFR3 Pro250Arg mutation is associated with craniosynostosis, hearing loss, and various bony anomalies., Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene., Muenke syndrome, defined by heterozygosity for a Pro250Arg substitution in fibroblast growth factor receptor 3 (FGFR3), is the most common genetic cause of craniosynostosis in humans., In addition, sensorineural hearing loss is detected in all FgfR3 (P244R) mutant mice as in the majority of Muenke syndrome patients., Genetic testing identifies a pathogenic mutation or chromosomal abnormality in ∼ 21% of cases, but it is likely that further causative mutations remain to be discovered.To identify a shared signature of genetically determined craniosynostosis by comparing the expression patterns in three monogenic syndromes with a control group of patients with non-syndromic sagittal synostosis.Fibroblasts from 10 individuals each with Apert syndrome (FGFR2 substitution S252W), Muenke syndrome (FGFR3 substitution P250R), Saethre-Chotzen syndrome (various mutations in TWIST1) and non-syndromic sagittal synostosis (no mutation detected) were cultured, The craniosynostosis syndromes: Apert syndrome, Beare-Stevenson syndrome, Crouzon syndrome, Jackson-Weiss syndrome, Muenke syndrome, Pfeiffer syndrome and Saethre-Chotzen syndrome can be caused by mutation in either FGFR1, FGFR2, or FGFR3, Identical proline-->arginine gain-of-function mutations in fibroblast growth factor receptor (FGFR) 1 (Pro252Arg), FGFR2 (Pro253Arg) and FGFR3 (Pro250Arg), result in type I Pfeiffer, Apert and Muenke craniosynostosis syndromes, respectively, The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes, Mutation analysis of FGFR-3 revealed a missense mutation in exon 6, c.749 C>G, with a resultant amino acid change from proline to arginine at codon 250 (P250R), in keeping with Muenke syndrome (Am J Hum Genet 1997;60:555-564), In an attempt to delineate functional features separating SCS from Muenkes syndrome, we screened patients presenting with coronal suture synostosis for mutations in the TWIST 1 gene, and for the Pro250Arg mutation in FGFR3, Since the Gly380Arg achondroplasia mutation was recognized, similar observations regarding the conserved nature of FGFR mutations and resulting phenotype have been made regarding other skeletal phenotypes, including hypochondroplasia, thanatophoric dysplasia, and Muenke coronal craniosynostosis, Mutations in the gene that encodes Fibroblast Growth Factor Receptor 3 (FGFR3) are associated with Achondroplasia (MIM 100800), Hypochondroplasia (MIM 146000), Muenke Syndrome (MIM 602849), Thanatophoric Dysplasia (MIM 187600, MIM 187601) and Lacrimo-Auriculo-Dento-Digital Syndrome (MIM 149730).Here we report a clinical and molecular study in a large cohort of 125 Portuguese patients with these skeletal disorders. , The Muenke syndrome (MS) is characterized by unicoronal or bicoronal craniosynostosis, midfacial hypoplasia, ocular hypertelorism, and a variety of minor abnormalities associated with a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. , P250R mutation in the FGFR3 gene also known as Muenke syndrome is associated with coronal craniosynostosis, sensorineural deafness, craniofacial, and digital abnormalities. , METHODS: Fibroblasts from 10 individuals each with Apert syndrome (FGFR2 substitution S252W), Muenke syndrome (FGFR3 substitution P250R), Saethre-Chotzen syndrome (various mutations in TWIST1) and non-syndromic sagittal synostosis (no mutation detected) were cultured. , Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene. , Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3). , In spite of a variable phenotype, Muenke syndrome has been related to a unique mutation on the FGFR3 gene, Pro 250 to Arg, which is characteristic of this disease. , Skeletal analysis of the Fgfr3(P244R) mouse, a genetic model for the Muenke craniosynostosis syndrome., Muenke syndrome is caused by a single defining point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene., Epilepsy in Muenke syndrome: FGFR3-related craniosynostosis., Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3)., The Muenke syndrome mutation (FGFR3 (P250R)), which was discovered 15 years ago, represents the single most common craniosynostosis mutation.[SEP]Relations: Muenke syndrome has relations: disease_protein with FGFR3, disease_protein with FGFR3. FGFR3 has relations: disease_protein with Muenke syndrome, disease_protein with Muenke syndrome, disease_protein with apert syndrome, disease_protein with apert syndrome, disease_protein with LADD syndrome, disease_protein with LADD syndrome. apert syndrome has relations: disease_protein with FGFR3, disease_protein with FGFR3.", "label": "yes"}
{"id": "converted_1619", "sentence1": "Does triiodothyronine play a regulatory role in insulin secretion from pancreas?", "sentence2": "Our findings establish that p43 is an important regulator of glucose homeostasis and pancreatic β-cell function and provide evidence for the first time of a physiological role for a mitochondrial endocrine receptor., The p43(-/-) mice had a major defect in insulin secretion both in vivo and in isolated pancreatic islets and a loss of glucose-stimulated insulin secretion., We demonstrated that treatment of primary cultures of rat pancreatic islets with T3 results in augmented β-cell vitality with an increase of their functional properties., Nonetheless, the insulin secretion is sensibly augmented after T3 stimulation., Plasma glucose concentration of the fetal hypothyroid group during intravenous glucose tolerance test was significantly higher (p=0.003) at 5-20 min as compared to the control group, whereas plasma insulin concentration was significantly lower (p=0.012) at 5-20 min, Although adult offspring born from hypothyroid mothers were euthyroid, their glucose tolerance and glucose stimulated insulin secretion of islets were altered, hyroid hormones modulate the immune system and metabolism, influence insulin secretion, Only T(3) concentrations higher than 250 microM were able to decrease cell viability and proliferation rate, to increase the rate of apoptosis and to reduce glucose-induced insulin secretion., Islets preincubated with glucose (3.3 mmol/l) and glucagon (1.4 mumol/l) plus theophylline (10 mmol/l), ACTH (0.11 nmol/l), bovine GH (0.46 mumol/l), prolactin (0.2 mumol/l) or tri-iodothyronine (1.0 nmol/l) have significantly lower Ca(2+)-ATPase activity than those preincubated with only 3.3 mmol glucose/l. All these hormones increased the release of insulin significantly., T3 (0.2 nM) did not affect insulin secretion in the absence or presence of glucose or in the presence of secretagogues (potassium and glyceraldehyde)., In the perfused rat pancreas, the addition of thyroxine (10 micrograms/dL) or 3,5,3'-triiodothyronine (150 ng/dL) to the perfusing medium did not affect insulin secretion., The administration of thyroxine (40 micrograms/kg, s.c.) in vivo increased the plasma insulin level from 11 +/- 2 microUnits/mL (mean +/- SD) to 30 +/- 7 microUnits/mL, Addition of T3 to the incubation medium, significantly modified the insulin release, but its effect varied according to the glucose concentration in the medium, i.e. it enhanced the insulin release at a glucose concentration between 2 to 8 mmol/l; it has no effect at 12 mmol/glucose, and significantly inhibited the secretion of insulin in the presence of 16.6 mmol/l glucose., Both T3 and T4 inhibited insulin secretion[SEP]Relations: Levothyroxine has relations: drug_drug with Insulin tregopil, drug_drug with Insulin tregopil, drug_drug with Insulin peglispro, drug_drug with Insulin peglispro, drug_drug with Insulin glargine, drug_drug with Insulin glargine, drug_drug with Insulin human, drug_drug with Insulin human. Liothyronine has relations: drug_drug with Insulin tregopil, drug_drug with Insulin tregopil.", "label": "yes"}
{"id": "converted_74", "sentence1": "Do patients with Pendred syndrome present congenital deafness?", "sentence2": "Pendred Syndrome can be characterized by the triad composed of familial goitre, abnormal perchlorate discharge and congenital deafness., Pendred syndrome is an autosomal recessive disorder characterized by congenital deafness and goiter. , Pendred syndrome comprises congenital sensorineural hearing loss, thyroid goiter, and positive perchlorate discharge test. , The cause of the congenital deafness in Pendred syndrome is obscure, although a Mondini type malformation of the cochlea exists in some patients., Pendred syndrome is an autosomal recessive disorder characterized by congenital deafness and goiter., Pendred syndrome is the autosomal recessively transmitted association of familial goiter and congenital deafness., Pendred syndrome (PDS) is an autosomal recessive disorder characterized by congenital deafness, goiter and iodide organification defect., Pendred syndrome is a recessively inherited disorder with the hallmark features of congenital deafness and thyroid goitre., Pendred syndrome, a common autosomal-recessive disorder characterized by congenital deafness and goiter, is caused by mutations of SLC26A4, which codes for pendrin., These studies provide compelling evidence that defects in pendrin cause Pendred syndrome thereby launching a new area of investigation into thyroid physiology, the pathogenesis of congenital deafness and the role of altered sulphate transport in human disease., Mutations in the Pendred syndrome gene have been observed in patients with deafness and vestibular aqueduct dilatation, in the absence of other Pendred syndrome features., The occurrence of congenital deafness, mutism and goitre unassociated with cretinism or mental retardation in euthyroid patients is known as Pendred's Syndrome., The autosomal recessive Pendred's syndrome is defined by congenital sensorineural deafness, goiter, and impaired iodide organification., Pendred's syndrome is an autosomal recessive disease characterized by goiter, impaired iodide organification, and congenital sensorineural deafness., Pendred syndrome is an autosomal recessive disorder characterized by congenital sensorineural deafness, goiter, and impaired iodide organification., Pendred's syndrome is manifested by congenital sensorineural deafness in association with familial goiter due to defective organic binding of iodine in the thyroid gland., Although the textbook view of the Pendred syndrome is that of an autosomal recessive condition characterised by deafness and goitre, it is increasingly clear that not all patients present this classical clinical description., Pendred's syndrome may account for up to 10% of the cases with hereditary hearing loss, and pendrin mutations have also been found in a kindred with non-syndromic deafness., Pendred syndrome comprises the association of severe congenital sensorineural deafness with thyroid pathology., The first one is named Pendred Syndrome (PS) when deafness is associated with thyroid goiter; the second is called DFNB4, when no other symptoms are present., Pendred syndrome is an autosomal recessive disorder characterized by sensorineural deafness, a partial defect in iodide organification, and dyshormonogenetic goiter., Pendred syndrome and non-syndromic recessive deafness associated with enlarged vestibular aqueduct (NSRD with EVA) are caused by mutations in the SLC26A4 (PDS) gene., Although the textbook view of Pendred syndrome is that of an autosomal recessive condition characterized by deafness and goitre, it is increasingly clear that not all such patients present this classical clinical picture. , The occurrence of congenital deafness, mutism and goitre unassociated with cretinism or mental retardation in euthyroid patients is known as Pendred's Syndrome. , The cause of the congenital deafness in Pendred syndrome is obscure, although a Mondini type malformation of the cochlea exists in some patients. , The discovery of mutations in the SLC26A4 gene in patients with Pendred syndrome (congenital deafness, goiter, and defective iodide organification) suggested a possible role for the encoded protein, pendrin, as an apical iodide transporter. , Pendred syndrome is a recessively inherited disorder with the hallmark features of congenital deafness and thyroid goitre. , Pendred&apos;s syndrome is manifested by congenital sensorineural deafness in association with familial goiter due to defective organic binding of iodine in the thyroid gland. The majority of patients with Pendred&apos;s syndrome are euthyroid. We report on an unusual case of a patient with Pendred&apos;s syndrome presenting with amenorrhea and late-onset hypothyroidism.,  Although the textbook view of Pendred syndrome is that of an autosomal recessive condition characterized by deafness and goitre, it is increasingly clear that not all such patients present this classical clinical picture. Malformations of the inner ear, specifically enlargement of the vestibular aqueduct, are common in Pendred syndrome and mutations in the PDS (Pendred Syndrome) gene have been recorded in patients presenting with deafness and vestibular aqueduct dilatation only, without other features of Pendred syndrome., The occurrence of congenital deafness, mutism and goitre unassociated with cretinism or mental retardation in euthyroid patients is known as Pendred&apos;s Syndrome. It has been estimated that 4-10 % of children with congenital deafness suffer from this condition., Malformations of the inner ear, specifically enlargement of the vestibular aqueduct, are common in Pendred syndrome and mutations in the PDS (Pendred Syndrome) gene have been recorded in patients presenting with deafness and vestibular aqueduct dilatation only, without other features of Pendred syndrome. Since this is the most common radiological malformation of the cochlea in deaf patients, we investigated what proportion of such cases were due to mutation of the PDS gene., Although the textbook view of Pendred syndrome is that of an autosomal recessive condition characterized by deafness and goitre, it is increasingly clear that not all such patients present this classical clinical picture. Malformations of the inner ear, specifically enlargement of the vestibular aqueduct, are common in Pendred syndrome and mutations in the PDS (Pendred Syndrome) gene have been recorded in patients presenting with deafness and vestibular aqueduct dilatation only, without other features of Pendred syndrome.[SEP]Relations: Pendred syndrome has relations: disease_disease with syndromic genetic deafness, disease_disease with syndromic genetic deafness, disease_phenotype_positive with Congenital sensorineural hearing impairment, disease_phenotype_positive with Congenital sensorineural hearing impairment, disease_phenotype_positive with Neurological speech impairment, disease_phenotype_positive with Neurological speech impairment, disease_disease with syndromic hypothyroidism, disease_disease with syndromic hypothyroidism. Congenital sensorineural hearing impairment has relations: disease_phenotype_positive with Pendred syndrome, disease_phenotype_positive with Pendred syndrome.", "label": "yes"}
{"id": "converted_3835", "sentence1": "Do exon 38 or 39 KMT2D missense variants cause Kabuki syndrome type 1 (KS1)?", "sentence2": "A restricted spectrum of missense KMT2D variants cause a multiple malformations disorder distinct from Kabuki syndrome., To investigate if specific exon 38 or 39 KMT2D missense variants (MVs) cause a condition distinct from Kabuki syndrome type 1 (KS1).METHODS: Multiple individuals, with MVs in exons 38 or 39 of KMT2D that encode a highly conserved region of 54 amino acids flanked by Val3527 and Lys3583, were identified and phenotyped. Functional tests were performed to study their pathogenicity and understand the disease mechanism.RESULTS: The consistent clinical features of the affected individuals, from seven unrelated families, included choanal atresia, athelia or hypoplastic nipples, branchial sinus abnormalities, neck pits, lacrimal duct anomalies, hearing loss, external ear malformations, and thyroid abnormalities. None of the individuals had intellectual disability. The frequency of clinical features, objective software-based facial analysis metrics, and genome-wide peripheral blood DNA methylation patterns in these patients were significantly different from that of KS1. Circular dichroism spectroscopy indicated that these MVs perturb KMT2D secondary structure through an increased disordered to ɑ-helical transition.CONCLUSION: KMT2D MVs located in a specific region spanning exons 38 and 39 and affecting highly conserved residues cause a novel multiple malformations syndrome distinct from KS1. Unlike KMT2D haploinsufficiency in KS1, these MVs likely result in disease through a dominant negative mechanism.[SEP]Kabuki syndrome has relations with KDM6A, RAP1B, KDM2D and KDM3D. Kabuki syndrome is a rare genetic disorder. It is thought to be caused by a genetic defect in one of the chromosomes of the Japanese people.", "label": "no"}
{"id": "converted_4469", "sentence1": "Is sacituzumab govitecan effective for breast cancer?", "sentence2": "Sacituzumab Govitecan (also known by the brand name TRODELVY®) is a new and available treatment for metastatic triple-negative breast cancer, or mTNBC for short. , Sacituzumab govitecan (sacituzumab govitecan-hziy; Trodelvy™) is a Trop-2-directed antibody conjugated to a topoisomerase I inhibitor (SN-38) that is being developed by Immunomedics for the treatment of solid tumours, including breast cancer., Results from a phase I/II trial suggest that an antibody-drug conjugate, sacituzumab govitecan, is active against refractory, metastatic triple-negative breast cancer. A, INTRODUCTION: Sacituzumab govitecan-hziy, approved in 2020 for treatment of metastatic triple-negative breast cancer, provides a new option for a population with a historically poor prognosis with standard , Sacituzumab govitecan (SG), the first antibody-drug conjugate (ADC) approved for triple-negative breast cancer, incorporates the anti-TROP2 antibody hRS7 conjugated to a topoisomerase-1 (TOP1) inhibitor payload. We so, Sacituzumab govitecan was initially approved in April 2020 under accelerated approval for the treatment of patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease, The ASCENT trial reports impressive results with a median overall survival (OS) increased from 6.7 months to 12.1 months with sacituzumab govitecan over single-agent chemotherapy, in metastatic triple negative breast cancer (TNBC) patients in second and subsequent line of therapy. We , A phase II study indicates that sacituzumab govitecan (IMMU-132), a Trop-2-specific antibody linked to the irinotecan metabolite SN-38, prolongs the progression-free survival of patients with advanced triple-negative breast cancer. I, agents, sacituzumab govitecan, has been recently granted an accelerated approval for therapy of metastatic triple-negative breast cancer. In this artic, l 2020, sacituzumab govitecan received accelerated approval in the USA for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease. Sacituzu, Sacituzumab Govitecan for Metastatic Triple-Negative Breast Cancer: Clinical Overview and Management of Potential Toxicities., ood and Drug Administration) recently approved the use of a Trop2-targeting ADC (antibody-drug conjugate), Sacituzumab Govitecan (IMMU-132), for metastatic, triple-negative breast cancer with at least two prior therapies. Here, we review, sive disease. Sacituzumab govitecan represents an important advance in the treatment of mTNBC because of its efficacy an, Sacituzumab govitecan (SG) is a novel antibody-drug conjugate (ADC) that has shown promising efficacy in mTNBC, The activity of sacituzumab govitecan likely extends beyond TNBC with promising early efficacy data in many other epithelial cancers, including hormone receptor-positive breast cancer., In a basket design phase I/II study, sacituzumab govitecan demonstrated promising single-agent therapeutic activity in multiple cancer cohorts, leading to accelerated approval by the U.S. Food and Drug Administration of sacituzumab govitecan-hziy (TRODELVY) for the treatment of patients with metastatic triple-negative breast cancer who had received at least two prior therapies in the metastatic setting., Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer., Expert opinion: Sacituzumab govitecan has promising anti-cancer activity in patients with metastatic TNBC previously treated with at least two prior lines of systemic therapy based on a single arm Phase I/II clinical trial., Sacituzumab govitecan has shown promise in cancers outside of TNBC, such as urothelial and lung and is being evaluated in HR-positive breast cancers.,  prognosis. Sacituzumab govitecan is an antibody-drug conjugate composed of an antibody targeting the human trophoblast cell-surface antigen 2 (Trop-2), which is expressed in the majority of breast cancers, coupled to SN-38 (topoisomerase I inhibitor) through a proprietary hydrolyzable linker.METHODS: In this randomized, phase 3 trial, we evaluated sacituzumab govitecan as compared with single-agent chemotherapy of the physician's choice (eribulin, vinorelbine, capecitabine, or gemcitabine) in patients with relapsed or refractory metastatic triple-ne, Expert opinion Sacituzumab govitecan has promising survival benefits in patients with previously treated mTNBC based on data from the ASCENT trial., Conclusion Sacituzumab govitecan was well tolerated and induced early and durable responses in heavily pretreated patients with metastatic TNBC., Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer., Sacituzumab Govitecan (also known by the brand name TRODELVY®) is a new and available treatment for metastatic triple-negative breast cancer, or mTNBC for short.[SEP]Relations: Sacituzumab govitecan has relations: drug_drug with Cemiplimab, drug_drug with Cemiplimab, drug_drug with Cetuximab, drug_drug with Cetuximab, drug_drug with Sonepcizumab, drug_drug with Sonepcizumab, drug_drug with Caplacizumab, drug_drug with Caplacizumab, drug_drug with Necitumumab, drug_drug with Necitumumab.", "label": "yes"}
{"id": "converted_3466", "sentence1": "Is Hemochromatosis type 4 is caused by a mutation in a recessive gene?", "sentence2": " severely affect iron homeostasis causing type 4 hereditary hemochromatosis, an autosomal dominant iron overload condition with variable phenotypic manifestations, Hemochromatosis type 4, also known as ferroportin disease, is an autosomal dominant genetic disorder caused by pathogenic mutations in the SLC40A1 gene, which encodes ferroportin 1 (FPN1)., Hemochromatosis type 4 is a rare form of primary iron overload transmitted as an autosomal dominant trait caused by mutations in the gene encoding the iron transport protein ferroportin 1 (SLC40A1)., Type 4 hemochromatosis follows an autosomal dominant trait; the corresponding mutation affects the basolateral iron carrier ferroportin 1., Type 4 hemochromatosis follows an autosomal dominant trait; the corresponding mutation affects the basolateral iron carrier ferroportin 1, Type 4 hemochromatosis follows an autosomal dominant trait; the corresponding mutation affects the basolateral iron carrier ferroportin 1.[SEP]Hemochromatosis has relations: disease_phenotype_positive with Autosomal recessive inheritance. SLC40A1 has relations with hemochrom atosis 4 (HFE4) (duodenum) SLC 40A1 causes hemochchromatosis 4, HFE4, and HFE5 (duotenum) HFE6 has relations to HFE7, Hfe8, HFe9, H FE10, HF11. HFE12 has relations.", "label": "no"}
{"id": "converted_2136", "sentence1": "Is Cri Du Chat associated with an expansion of a repeat with in the gene found on chromosome 5?", "sentence2": "Cri-du-chat syndrome is a chromosomal disorder caused by a deletion of the short arm of chromosome 5, The typical cri du chat syndrome, due to 5p15.2 deletion, includes severe intellectual disability, facial dysmorphisms, neonatal hypotonia and pre- and post-natal growth retardation, whereas more distal deletions in 5p15.3 lead to cat-like cry and speech delay and produce the clinical picture of the atypical cri du chat syndrome, with minimal or absent intellectual impairment., Cri-du-chat is a human contiguous gene deletion syndrome resulting from hemizygous deletions of chromosome 5p., Cri-du-chat is a chromosomal deletion syndrome characterized by partial deletion of the short arm of chromosome 5., The karyotype showed a terminal deletion of the short arm of chromosome 5 including the critical region 5p15 for cri du chat syndrome., Fewer than 1 in 200 of cri du chat syndrome cases are due to recombination aneusomy arising from a parental inversion of chromosome 5., Molecular approach to analyzing the human 5p deletion syndrome, cri du chat., Cri-du-chat is a human contiguous gene deletion syndrome resulting from hemizygous deletions of chromosome 5p, The cri du chat syndrome (CdCS) is a chromosomal deletion syndrome associated with a partial deletion of the short (p) arm of chromosome 5, The cri-du-chat syndrome is a contiguous gene syndrome that results from a deletion of the short arm of chromosome 5 (5p)., Cri-du-chat syndrome is associated with a deletion of the short arm of chromosome 5., The deletion of the short arm of chromosome 5 is associated with the cri-du-chat syndrome., The Cri du Chat syndrome (CdCS) is a genetic disease resulting from a deletion of variable size occurring on the short arm of chromosome 5 (5p-)., Cri-du-chat is a well described partial aneusomy resulting from deletion of the short arm of chromosome 5., Cri-du-chat syndrome is caused by haploinsufficiency of the genes on the distal part of the short arm of chromosome 5, and characteristic features include microcephaly, developmental delays, and a distinctive high-pitched mewing cry., The pathological condition of cri du chat syndrome is due to the cytogenetic deletion of band p15.2 of chromosome 5. ,  Karyotype analysis indicated that the patient has carried a terminal deletion in 5p. FISH with Cri du Chat syndrome region probe confirmed that D5S23 and D5S721 loci are deleted. [SEP]Relations: Cri-du-chat syndrome has relations: disease_disease with partial deletion of the short arm of chromosome 5, disease_disease with partial deletion of the short arm of chromosome 5, disease_protein with CTNND2, disease_protein with CTNND2, disease_protein with SEMA5A, disease_protein with SEMA5A, disease_phenotype_positive with Growth delay, disease_phenotype_positive with Growth delay, disease_protein with TERT, disease_protein with TERT.", "label": "no"}
{"id": "converted_4558", "sentence1": "Do mutations in KCNT2 only cause phenotypes with epilepsy?", "sentence2": "KCNT2 variants resulting in substitutions affecting the Arg190 residue have been shown to cause epileptic encephalopathy and a recognizable facial gestalt. We report two additional individuals with intellectual disability, dysmorphic features, hypertrichosis, macrocephaly and the same de novo KCNT2 missense variants affecting the Arg190 residue as previously described. Notably, neither patient has epilepsy. Homology modeling of these missense variants revealed that they are likely to disrupt the stabilization of a closed channel conformation of KCNT2 resulting in a constitutively open state. This is the first report of pathogenic variants in KCNT2 causing a developmental phenotype without epilepsy.[SEP] epilepsy has relations with KCNT2, KCND2, and KCNAB2. It also has relationships with KCNQ2 and KCQ2. The disease_protein is a type of protein used to test for epilepsy. It can also be used to diagnose epilepsy.", "label": "no"}
{"id": "converted_996", "sentence1": "Has Revlimid been approved by the US Food and Drug Administration?", "sentence2": "In the past decade, immunomodulatory drugs have been approved by the US Food and Drug Administration for the treatment of multiple myeloma (MM)-and a number of emerging agents that target the cellular pathways or proteins involved in the pathophysiology of MM are currently in development. Lenalidomide (Revlimid) and pomalidomide induce apoptosis and sensitize MM cells while demonstrating superior efficacy and better tolerability than thalidomide (Thalomid)., In the past decade we have seen four new agents approved by the US Food and Drug Administration for treatment of multiple myeloma: the proteasome inhibitor (PI) bortezomib (Velcade), the immunomodulatory agents lenalidomide (Revlimid) and thalidomide (Thalomid), and liposomal doxorubicin. , In the past decade we have seen four new agents approved by the US Food and Drug Administration for treatment of multiple myeloma: the proteasome inhibitor (PI) bortezomib (Velcade), the immunomodulatory agents lenalidomide (Revlimid) and thalidomide (Thalomid), and liposomal doxorubicin., Thalidomide, lenalidomide (Revlimid), and bortezomib (Velcade) are directed not only at MM cells but also at the BM milieu and have moved rapidly from the bench to the bedside and United States Food and Drug Administration approval to treat MM., Lenalidomide (CC-5013, Revlimid; Celgene Corporation, Summit, NJ), a thalidomide analogue, was granted approval by the U.S. Food and Drug Administration (FDA) on June 29, 2006, for use in combination with dexamethasone in patients with multiple myeloma (MM) who have received at least one prior therapy., Lenalidomide, an IMiD drug (a novel type of immunomodulating drug) was recently approved by the US Food and Drug Administration for the treatment of transfusion-dependent anemia in patients with myelodysplastic syndromes (MDS) and interstitial deletions of chromosome 5q [del(5q)], Lenalidomide, a second-generation immunomodulatory drug (IMiD), is approved by the US Food and Drug Administration for treatment of transfusion-dependent anemia in lower-risk MDS patients with deletion 5q chromosomal abnormality, In the past decade we have seen four new agents approved by the US Food and Drug Administration for treatment of multiple myeloma: the proteasome inhibitor (PI) bortezomib (Velcade), the immunomodulatory agents lenalidomide (Revlimid) and thalidomide (Thalomid), and liposomal doxorubicin., lenalidomide (CC5103 or revlimid) are recently approved for the treatment of multiple myeloma.,  In the past decade, immunomodulatory drugs have been approved by the US Food and Drug Administration for the treatment of multiple myeloma (MM)-and a number of emerging agents that target the cellular pathways or proteins involved in the pathophysiology of MM are currently in development. Lenalidomide (Revlimid) and pomalidomide induce apoptosis and sensitize MM cells while demonstrating superior efficacy and better tolerability than thalidomide (Thalomid).[SEP]Relations: Lenalidomide has relations: drug_drug with Reviparin, drug_drug with Reviparin. Pomalidomide has relations: drug_drug with Reviparin, drug_drug with Reviparin, drug_drug with Revefenacin, drug_drug with Revefenacin. Bortezomib has relations: drug_drug with Reviparin, drug_drug with Reviparin. Thalidomide has relations: drug_drug with Reviparin, drug_drug with Reviparin.", "label": "yes"}
{"id": "converted_3773", "sentence1": "Do circular exons increase gene expression?", "sentence2": "Each of these species was present at very low copy numbers in primary and cultured cells; however, only the expression of ANRIL isoforms containing exons proximal to the INK4/ARF locus correlated with the ASVD risk alleles., These results identify novel circular RNA products emanating from the ANRIL locus and suggest causal variants at 9p21.3 regulate INK4/ARF expression and ASVD risk by modulating ANRIL expression and/or structure., To explore the potential for using this methodology to express circular RNA in vivo, circular forms of the HDV ribozyme and RNaseP RNA were produced in E. coli. , The activity of in vivo expressed circular ribozymes could be demonstrated indicating that they fold into active conformation, We found that: i) the circRNA expression profile revealed 1,285 significant differences in circRNA expression, with circRNA expression downregulated in 594 samples and upregulated in 691 samples via interactions with miRNAs., These circRNAs regulated the expression of target genes through interactions with miRNAs and might become new molecular biomarkers for GC in the future, 69 differentially expressed circRNAs were found that might adsorb specific miRNAs to regulate the expression of their target gene mRNAs., Novel coding, translation, and gene expression of a replicating covalently closed circular RNA of 220 nt., The highly structured (64% GC) covalently closed circular (CCC) RNA (220 nt) of the virusoid associated with rice yellow mottle virus codes for a 16-kDa highly basic protein using novel modalities for coding, translation, and gene expression, Recent evidence has demonstrated that circular RNAs (circRNAs) played crucial roles in fine-tuning the levels of gene expression by sequestering the corresponding microRNA (miRNAs). , It has been proposed that circRNA regulate gene expression at the transcriptional or post-transcriptional level by interacting with miRNAs and that circRNAs may have a role in regulating miRNA function in cancer initiation and progression.[SEP]Protein C has relations: drug_drug with Interferon gamma-1b, drug_ drug with interferon beta-1a, drug-drug with interfereon alfa-2a, Recombinant. Protein C also has relations with Interferon alFA-2b, Interfers gamma and alfa n1.", "label": "no"}
{"id": "converted_949", "sentence1": "Do R-loops tend to form at sites of DNA replication?", "sentence2": "Escherichia coli rnhA mutants devoid of RNase HI exhibit constitutive stable DNA replication, cSDR, which is thought to be initiated from R-loops stabilized in the absence of RNase HI., We propose that the organized structure of the R-loop is critical for primer RNA function in vivo with important implications for the RNA processing and DNA replication machinery., The precursor primer RNA exists as a persistent RNA-DNA hybrid, known as an R-loop, formed during transcription through the replication origin (Xu, B., and Clayton, D. A. (1996) EMBO J. 15, 3135-3143)., We found that overproduction of RecG protein drastically decreased copy numbers of ColE1-type plasmids, which require R-loop formation between the template DNA and a primer RNA transcript (RNA II) for the initiation of replication., These results suggest that overproduced RecG inhibits the initiation of replication by prematurely resolving the R-loops formed at the replication origin region of these plasmids with its unique helicase activity. The possibility that RecG regulates the initiation of a unique mode of DNA replication, oriC-independent constitutive stable DNA replication, by its activity in resolving R-loops is discussed., We propose that downstream of a replication block, RNA at R-loops is extended by DNA polymerase I, opening up the DNA duplex and leading to the recruitment of the replisome. This would allow replication to proceed while the original block is repaired or bypassed, Furthermore, increased RNaseH expression significantly alleviated genomic instability in deficient fibroblasts suggesting that cotranscriptional R-loops formation contributes to the genesis of replication-dependent DSBs in these cells., Transcription is an important source of replicative stress and consequently, maintenance of genome integrity requires the protection of chromosomes from the deleterious effects arising from the interaction between nascent RNAs and template DNA, leading to stable DNA-RNA hybrids (R-loop) formation., Strikingly, we found that attenuation of replication strongly suppresses R-loop-mediated DNA rearrangements in both E. coli and HeLa cells., More importantly, we then show that R-loop formation causes DNA replication fork stalling, and that this in fact underlies the effects of R loops on genomic stabilit, R-loop-mediated genomic instability is caused by impairment of replication fork progression, When any of these processes are not properly coordinated, aberrant outcomes such as fork reversal and R-loop formation arise and trigger unscheduled recombinogenic events and genome rearrangements. , Many studies show that cells can manage R loop formation with efficiency, and can also process the R-loops already formed in the cell, and by which, the bad effects of R-loops on DNA replication, gene mutation and homologous recombination can be regulated., Here we propose that physiological R-loop formation at CpG island promoters can contribute to DNA replication origin specification at these regions, the most efficient replication initiation sites in mammalian cells. , In agreement with this, we found that R-loops co-localize with the ORC within the same CpG island region in a significant fraction of these efficient replication origins, precisely at the position displaying the highest density of G4 motifs. , connection between transcription and replication in human cells and suggests that R-loop dysregulation at CpG island promoter-origins might contribute to the phenotype of DNA replication abnormalities and loss of genome integrity detected in cancer cells., We show that RNA:DNA hybrids (R-loops) form at sites of transcription/replication collisions and that RNase H1 functions to suppress CFS instability., R-loops and initiation of DNA replication in human cells: a missing link?, Stable RNA-DNA hybrids (R-loops) prime the initiation of replication in Escherichia coli cells., We propose that downstream of a replication block, RNA at R-loops is extended by DNA polymerase I, opening up the DNA duplex and leading to the recruitment of the replisome., Immediately after infection, RNA-DNA hybrids (R-loops) occur on (at least some) replication origins, with the annealed RNA serving as a primer for leading-strand synthesis in one direction., Here we propose that physiological R-loop formation at CpG island promoters can contribute to DNA replication origin specification at these regions, the most efficient replication initiation sites in mammalian cells., ColE1 plasmid origins of replication and oriK sites initiate primosome assembly by an RNA-DNA hybrid structure known as R-loop., This scenario builds on the connection between transcription and replication in human cells and suggests that R-loop dysregulation at CpG island promoter-origins might contribute to the phenotype of DNA replication abnormalities and loss of genome integrity detected in cancer cells., The multiple cleavage sites on the R-loop substrate match the priming sites observed in vivo, suggesting that RNase MRP alone is capable of generating virtually all of the leading-strand replication primers., Mechanisms of primer RNA synthesis and D-loop/R-loop-dependent DNA replication in Escherichia coli., Alternative oriC-independent modes of replication initiation are possible, one of which is constitutive stable DNA replication (cSDR) from transcription-associated RNA-DNA hybrids or R-loops., Our results suggest that Top1 execute this function by suppressing the formation of DNA-RNA hybrids during transcription, these so-called R-loops interfering with the progression of replication forks., Critical role of R-loops in processing replication blocks., The possibility that RecG regulates the initiation of a unique mode of DNA replication, oriC-independent constitutive stable DNA replication, by its activity in resolving R-loops is discussed., Competition between the RNA transcript and the nontemplate DNA strand during R-loop formation in vitro: a nick can serve as a strong R-loop initiation site., More importantly, we then show that R-loop formation causes DNA replication fork stalling, and that this in fact underlies the effects of R loops on genomic stability. , Consistent with this hypothesis, the 3' ends of the mitochondrial R-loop formed by in vitro transcription are located close to the initiation sites of the mitochondrial DNA replication. , A hybrid G-quadruplex structure formed between RNA and DNA explains the extraordinary stability of the mitochondrial R-loop., Previous studies have shown that the newly synthesized primers form a stable and persistent RNA-DNA hybrid, a R-loop, near the leading-strand origin of DNA replication. , Escherichia coli rnhA mutants devoid of RNase HI exhibit constitutive stable DNA replication, cSDR, which is thought to be initiated from R-loops stabilized in the absence of RNase HI. [SEP]Relations: HELLS has relations: bioprocess_protein with DNA methylation-dependent heterochromatin assembly, bioprocess_protein with DNA methylation-dependent heterochromatin assembly, anatomy_protein_present with lymph node, anatomy_protein_present with lymph node, bioprocess_protein with maintenance of DNA methylation, bioprocess_protein with maintenance of DNA methylation. snRNA transcription by RNA polymerase III has relations: bioprocess_protein with ZC3H8, bioprocess_protein with ZC3H8, bioprocess_protein with ELL, bioprocess_protein with ELL.", "label": "yes"}
{"id": "converted_3010", "sentence1": "In clinical trials, the H3 R antagonist CEP-26401 has a positive effect on cognition, yes or no?", "sentence2": "CEP-26401 is a novel orally active, brain-penetrant, high-affinity histamine H3 receptor (H3R) antagonist, with potential therapeutic utility in cognition enhancement, hese results demonstrate potent behavioral effects of CEP-26401 in rodent models and suggest that this novel H₃R antagonist may have therapeutic utility in the treatment of cognitive and attentional disorders, CEP-26401 is a novel orally active, brain-penetrant, high-affinity histamine H3 receptor (H3R) antagonist, with potential therapeutic utility in cognition enhancement., CEP-26401 (irdabisant), a potent and selective histamine H₃ receptor antagonist/inverse agonist with cognition-enhancing and wake-promoting activities., However, although a number of clinical studies examining the efficacy of H3 receptor antagonists for a variety of cognitive disorders are currently underway, no clinical proof of concept for an H3 receptor antagonist has been reported to date., Further clinical studies are required to establish the potential of low-dose CEP-26401 in cognition enhancement.<br>[SEP]Histamine receptors has relations: pathway_protein with HRH3, pathway_ protein with HR h1, and pathway_ proteins with HRh4. cognitive disorder has relations with Lithium citrate, Lithium carbonate, and Lithium Citrate.", "label": "yes"}
{"id": "converted_2779", "sentence1": "Are there microbes in human breast milk?", "sentence2": "Contrary to long-held dogma, human milk is not sterile. Instead, it provides infants a rich source of diverse bacteria, particularly microbes belonging to the Staphylococcus, Streptococcus, and Pseudomonas genera., The origins of the bacteria in milk are thought to include the maternal gastrointestinal tract (via an entero-mammary pathway) and through bacterial exposure of the breast during nursing.[SEP]The breast has relations with VIM, RIMKLB, GCSAM, and anatomy. Peptostreptococcus infectious disease has relations: disease_disease with anaerobic bacteria infectious disease. The breast is a part of the human body. It is not a separate organ.", "label": "yes"}
{"id": "converted_1662", "sentence1": "Are Notch mutations related to T-cell Acute Lymphoblastic Leukemia (T-ALL)?", "sentence2": "Notch receptors participate in a highly conserved signalling pathway that regulates normal development and tissue homeostasis in a context- and dose-dependent manner. Deregulated Notch signalling has been implicated in many diseases, but the clearest example of a pathogenic role is found in T-cell lymphoblastic leukaemia/lymphoma (T-LL), in which the majority of human and murine tumours have acquired mutations that lead to aberrant increases in Notch1 signalling., NOTCH proteins (NOTCH1, NOTCH2, NOTCH3 and NOTCH4) play crucial roles in embryonic development. Also, mounting evidence indicates that NOTCH contributes to the pathogenesis of hematopoietic and solid malignancies. Recent studies reported a high incidence of gain-of-function mutations of the NOTCH1 gene in T-cell acute lymphoblastic leukemias (ALL). , Our data indicate that NOTCH1 is mutated in T-ALL, but not in other common human cancers, and that NOTCH2, NOTCH3 and NOTH4 genes are rarely mutated in common human cancers. , The Notch signaling pathway plays a critical role in maintaining the balance between cell proliferation, differentiation and apoptosis, and is a highly conserved signaling pathway that regulates normal development in a context- and dose-dependent manner. Dysregulation of Notch signaling has been suggested to be key events in a variety of hematological malignancies. Notch1 signaling appears to be the central oncogenic trigger in T cell acute lymphoblastic leukemia (T-ALL), in which the majority of human malignancies have acquired mutations that lead to constitutive activation of Notch1 signaling., T-cell acute lymphoblastic leukemia (T-ALL) is characterized as a high-risk stratified disease associated with frequent relapse, chemotherapy resistance, and a poorer prognostic outlook than B-precursor ALL. Many of the challenges in treating T-ALL reflect the lack of prognostic cytogenetic or molecular abnormalities on which to base therapy, including targeted therapy. Notch1 activating mutations were identified in more than 50% of T-ALL cases and can be therapeutically targeted with γ-secretase inhibitors (GSIs). , Notch1 is a transmembrane receptor that is frequently mutated in human T-cell acute lymphoblastic leukemia (T-ALL). , T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) is characterized by aberrant activation of NOTCH1 in over 60% of T-ALL cases. The high prevalence of activating NOTCH1 mutations highlights the critical role of NOTCH signaling in the pathogenesis of this disease and has prompted the development of therapeutic approaches targeting the NOTCH signaling pathway. , Activating mutations in NOTCH1, an essential regulator of T cell development, are frequently found in human T cell acute lymphoblastic leukemia (T-ALL). , NOTCH signaling pathway is essential in T-cell development and NOTCH1 mutations are frequently present in T-cell acute lymphoblastic leukemia (T-ALL)., Activating Notch-1 mutations are frequent in T-cell acute lymphoblastic leukemia (T-ALL), occurring in >50% of patients., Mutations in NOTCH1/FBXW7 activate NOTCH signaling and are of prognostic significance in patients with T-cell acute lymphoblastic leukemia (T-ALL)., Gain-of-function mutations in Notch-1 have been reported in more than 50% of human T-cell acute lymphoblastic leukemia (T-ALL)., Notch signaling is of crucial importance in normal T-cell development and Notch 1 is frequently mutated in T-cell acute lymphoblastic leukemias (T-ALL), leading to aberrantly high Notch signaling., Activation of the Notch pathway occurs commonly in T acute lymphoblastic leukemia (T-ALL) because of mutations in Notch1 or Fbw7 and is involved in the regulation of cell proliferation and survival., T-cell acute lymphoblastic leukemia (T-ALL) patients frequently display NOTCH1 activating mutations and Notch can transcriptionally down-regulate the tumor suppressor PTEN., The identification of activating mutations in NOTCH1 in over 50% of T-cell acute lymphoblastic leukemias (T-ALL) has generated major interest in the elucidation of the mechanisms of transformation downstream of oncogenic NOTCH and in the targeting of the NOTCH signaling pathway in this disease., BACKGROUND: In T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL), activating mutations of NOTCH1 are observed in more than 50% of cases, whereas the t(7;9)(q34;q34) involving NOTCH1 at 9q34 and TRB@ at 7q34 is an extremely rare but recurrent translocation., Activating mutations in NOTCH1 consitute the most prominent genetic abnormality in T-cell acute lymphoblastic leukemia (T-ALL)., T cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer that is frequently associated with activating mutations in NOTCH1 and dysregulation of MYC, The Notch signaling pathway has been recognized as a key factor for the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL), because of the high incidence of activating mutations of Notch1, Notch signaling is of crucial importance in normal T-cell development and Notch 1 is frequently mutated in T-cell acute lymphoblastic leukemias (T-ALL), leading to aberrantly high Notch signaling, NOTCH signaling pathway is essential in T-cell development and NOTCH1 mutations are frequently present in T-cell acute lymphoblastic leukemia (T-ALL), Activating Notch-1 mutations are frequent in T-cell acute lymphoblastic leukemia (T-ALL), occurring in >50% of patients, Gain-of-function mutations in Notch-1 have been reported in more than 50% of human T-cell acute lymphoblastic leukemia (T-ALL)[SEP]Relations: NOTCH1 has relations: disease_protein with precursor T-cell acute lymphoblastic leukemia, disease_protein with precursor T-cell acute lymphoblastic leukemia, disease_protein with acute lymphoblastic leukemia, disease_protein with acute lymphoblastic leukemia, disease_protein with acute lymphoblastic/lymphocytic leukemia, disease_protein with acute lymphoblastic/lymphocytic leukemia, disease_protein with acute lymphoblastic leukemia (disease), disease_protein with acute lymphoblastic leukemia (disease). NOTCH2 has relations: disease_protein with acute lymphoblastic leukemia (disease), disease_protein with acute lymphoblastic leukemia (disease).", "label": "yes"}
{"id": "converted_1848", "sentence1": "Is rucaparib used for ovarian cancer treatment?", "sentence2": "While olaparib is the first PARP inhibitor to receive approval for ovarian cancer treatment, others including rucaparib and niraparib are clearly effective in this disease and, within the next year or two, the results of ongoing randomised trials will clarify their respective roles. , Similar trials with other PARP inhibitors (rucaparib, niraparib and veliparib) are in progress and include non-BRCA-mutated ovarian cancer. , IMPLICATIONS FOR PRACTICE: The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib has recently received approval from the Food and Drug Administration (FDA) and European Medicines Agency (EMA), with a second agent (rucaparib) likely to be approved in the near future., Ovarian Cancers Harbour Defects in Non-Homologous End Joining Resulting in Resistance to Rucaparib., There are a number of other PARP inhibitors in late phase clinical development in ovarian cancer including rucaparib, niraparib, veliparib, and talazoparib. , Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial., INTERPRETATION: In patients with BRCA mutant or BRCA wild-type and LOH high platinum-sensitive ovarian carcinomas treated with rucaparib, progression-free survival was longer than in patients with BRCA wild-type LOH low carcinomas. Our results suggest that assessment of tumour LOH can be used to identify patients with BRCA wild-type platinum-sensitive ovarian cancers who might benefit from rucaparib. , Genomic LOH May Predict Rucaparib Response in Ovarian Cancer., High LOH is associated with response to the PARP inhibitor rucaparib in BRCA wild-type ovarian cancer., Therapeutic potential of the poly(ADP-ribose) polymerase inhibitor rucaparib for the treatment of sporadic human ovarian cancer., While olaparib is the first PARP inhibitor to receive approval for ovarian cancer treatment, others including rucaparib and niraparib are clearly effective in this disease and, within the next year or two, the results of ongoing randomised trials will clarify their respective roles., These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer., Here, we investigate the potential role of the PARP inhibitor rucaparib (CO-338, formerly known as AG014699 and PF-01367338) for the treatment of sporadic ovarian cancer., Rucaparib received US FDA Breakthrough Therapy designation for treatment of platinum-sensitive BRCA-mutated advanced ovarian cancer patients who received greater than two lines of platinum-based therapy., These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer., Ongoing clinical trials are assessing the efficacy of rucaparib alone or in combination with other cytotoxic drugs, mainly in breast and ovarian cancer patients with mutations in the breast cancer associated (BRCA) genes.PURPOSE: We aimed to establish whether the multidrug efflux transporters ABCG2 (BCRP) and ABCB1 (P-gp, MDR1) affect the oral availability and brain penetration of rucaparib in mice.RESULTS: In vitro, rucaparib was efficiently transported by both human ABCB1 and ABCG2, and very efficiently by mouse Abcg2., Therapeutic potential of the poly(ADP-ribose) polymerase inhibitor rucaparib for the treatment of sporadic human ovarian cancer, Here, we investigate the potential role of the PARP inhibitor rucaparib (CO-338, formerly known as AG014699 and PF-01367338) for the treatment of sporadic ovarian cancer, These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer.<CopyrightInformation>©2013 AACR</, Ongoing clinical trials are assessing the efficacy of rucaparib alone or in combination with other cytotoxic drugs, mainly in breast and ovarian cancer patients with mutations in the breast cancer associated (BRCA) genes.We aimed to establish whether the multidrug efflux transporters ABCG2 (BCRP) and ABCB1 (P-gp, MDR1) affect the oral availability and brain penetration of rucaparib in mice.In vitro, rucaparib was efficiently transported by both human ABCB1 and ABCG2, and very efficiently by mouse Abcg2, Here, we investigate the potential role of the PARP inhibitor rucaparib (CO-338, formerly known as AG014699 and PF-01367338) for the treatment of sporadic ovarian cancer. , While olaparib is the first PARP inhibitor to receive approval for ovarian cancer treatment, others including rucaparib and niraparib are clearly effective in this disease and, within the next year or two, the results of ongoing randomised trials will clarify their respective roles., We investigated the efficacy and safety of single-agent rucaparib in germline (g) BRCA mutation carriers with advanced breast and ovarian cancers.Phase II, open-label, multicentre trial of rucaparib in proven BRCA-1/2 mutation carriers with advanced breast and or ovarian cancer, WHO PS 0-1 and normal organ function., These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer.<CopyrightInformation>©2013 AACR</C, Similar trials with other PARP inhibitors (rucaparib, niraparib and veliparib) are in progress and include non-BRCA-mutated ovarian cancer., Rucaparib received US FDA Breakthrough Therapy designation for treatment of platinum-sensitive BRCA-mutated advanced ovarian cancer patients who received greater than two lines of platinum-based therapy., Therapeutic potential of the poly(ADP-ribose) polymerase inhibitor rucaparib for the treatment of sporadic human ovarian cancer., These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer..[SEP]Relations: Rucaparib has relations: drug_drug with Lobucavir, drug_drug with Lobucavir, drug_drug with Estradiol, drug_drug with Estradiol, drug_drug with Antipyrine, drug_drug with Antipyrine, drug_drug with Olaparib, drug_drug with Olaparib, drug_drug with Capsaicin, drug_drug with Capsaicin.", "label": "yes"}
{"id": "converted_3157", "sentence1": "Is Apelin usually decreased in diabetes?", "sentence2": "Apelin has been shown to act on glucose and lipid metabolism but also to modulate insulin secretion. Moreover, different studies in both animals and humans have shown that plasma apelin concentrations are usually increased during obesity and type 2 diabetes., Upregulated expression of resistin, vaspin, apelin and TNF-α plays a significant role in induction of insulin resistance linked with obesity and type 2 diabetes., Moreover, different studies in both animals and humans have shown that plasma apelin concentrations are usually increased during obesity and type 2 diabetes., Apelin levels are increased in morbidly obese subjects with type 2 diabetes mellitus., In men at risk for diabetes (HbA1c 5.7-6.4%, FPG 100-125mg/dl, or OGTT-2h-PG 140-199mg/dl), the risk for developing diabetes was higher in those with higher plasma apelin concentration than in those with lower plasma apelin concentrations (10.6%/year vs. 5.1%/year, p<0.001).<br><b>CONCLUSIONS</b>: Plasma apelin is a novel biomarker for predicting type 2 diabetes in men.<br>[SEP]Noninsulin-dependent has relations: disease_disease with type 2 diabetes mellitus. Type I has relations with vasculitis due to ADA2 deficiency, disease_phenotype_positive with late-onset isolated ACTH deficiency, and Wolcott-Rallison syndrome. Diabetes mellitus is a type of type I diabetes. It is the most common form of the disease.", "label": "no"}
{"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] phosphoglycoprotein 1 has relations with Mendelian disease. neuronal tumor has relations: disease_disease with neuroepithelial neoplasm, disease_Disease. with extraventricular neurocytoma, disease-diseases with central neurocyToma and cerebellar liponeurocytomas. neuronal tumors have relations with other types of cancer.", "label": "yes"}
{"id": "converted_1745", "sentence1": "Are microtubules marked by glutamylation?", "sentence2": "Together with detyrosination, glutamylation and other modifications, tubulin acetylation may form a unique 'language' to regulate microtubule structure and function., Glutamylation, the most prevalent tubulin posttranslational modification, marks stable microtubules and regulates recruitment and activity of microtubule- interacting proteins., Enzymes of the tubulin tyrosine ligase-like (TTLL) family posttranslationally modify and thereby mark microtubules by glutamylation, generating specific recognition sites for microtubule-interacting proteins.,  PTMs of the cytoskeleton, including phosphorylation, glycosylation, ubiquitination, detyrosination/tyrosination, (poly)glutamylation and (poly)glycylation, acetylation, sumoylation, and palmitoylation, will be addressed in this chapter., The tubulin posttranslational modifications: acetylation, detyrosination, polyglutamylation, and polyglycylation play important roles in microtubule functions, In most eukaryotic cells, tubulin is subjected to posttranslational glutamylation, a conserved modification of unclear function.[SEP]Microtubule has relations with KIFC1, KLC1, INCENP and KLC3. Cellcomp_protein with K LC1 is related to cellcomp_ proteins with KLC2 and K LC3. microtubule is related with KL1 by having a relationship with the protein KL.", "label": "yes"}
{"id": "converted_3788", "sentence1": "Is Semagacestat effective for 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)., CONCLUSION: 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. , INTRODUCTION: The negative efficacy study examining the γ-secretase inhibitor semagacestat in mild to moderate Alzheimer's disease (AD) included a number of biomarkers of the disease as well as safety outcomes., A clinical trial with the wide-spectrum γ-secretase inhibitor semagacestat has, however, demonstrated that global inhibition of all γ-secretases causes serious toxicity. , ESULTS: Semagacestat treatment was associated with increased reporting of suspected Notch-related adverse events (gastrointestinal, infection, and skin cancer related). 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. , CONCLUSIONS: As compared with placebo, semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability., RESULTS: The trial was terminated before completion on the basis of a recommendation by the data and safety monitoring board., The ADAS-cog scores worsened in all three groups (mean change, 6.4 points in the placebo group, 7.5 points in the group receiving 100 mg of the study drug, and 7.8 points in the group receiving 140 mg; P=0.15 and P=0.07, respectively, for the comparison with placebo). The ADCS-ADL scores also worsened in all groups (mean change at week 76, -9.0 points in the placebo group, -10.5 points in the 100-mg group, and -12.6 points in the 140-mg group; P=0.14 and P<0.001, respectively, for the comparison with placebo). 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). , 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., ntly 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. Since, ts 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. Furthermore, sem, rge Phase III clinical trials of semagacestat in mild-to-moderate AD patients were prematurely interrupted because of the observation of a detrimental cognitive and functional effect of the drug. These detrimental ef, BACKGROUND: In a recent report, 76 weeks' treatment with a gamma-secretase inhibitor (semagacestat) was associated with poorer cognitive outcomes in Alzheimer's d, 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., However, the preliminary equivocal cognitive results obtained with bapineuzumab as well as the detrimental cognitive effects observed with semagacestat, a potent γ-secretase inhibitor, raise the possibility that targeting Aβ may not be clinically efficacious in AD.[SEP]Relations: familial Alzheimer disease has relations: disease_disease with Alzheimer disease, disease_disease with Alzheimer disease, disease_phenotype_positive with Perseveration, disease_phenotype_positive with Perseveration, disease_protein with PRNP, disease_protein with PRNP, disease_disease with inherited prion disease, disease_disease with inherited prion disease. cognitive disorder has relations: disease_disease with dementia (disease), disease_disease with dementia (disease).", "label": "no"}
{"id": "converted_3556", "sentence1": "Is GRG5 involved only in late embryonic mouse development?", "sentence2": "Groucho related gene 5 (GRG5) is a multifunctional protein that has been implicated in late embryonic and postnatal mouse development. Here, we describe a previously unknown role of GRG5 in early developmental stages by analyzing its function in stem cell fate decisions. By both loss and gain of function approaches we demonstrate that ablation of GRG5 deregulates the Embryonic Stem Cell (ESC) pluripotent state whereas its overexpression leads to enhanced self-renewal and acquisition of cancer cell-like properties. The malignant characteristics of teratomas generated by ESCs that overexpress GRG5 reveal its pro-oncogenic potential. [SEP]HSD17B4 has relations: anatomy_protein_present with embryo, bioprocess_protein with Sertoli cell development. TLE5 has relations with GRN, protein_ protein with GRB2, and protein_ proteins with GRb2.", "label": "no"}
{"id": "converted_2486", "sentence1": "Is vorinostat effective for glioblastoma?", "sentence2": "Conclusions: Vorinostat combined with standard chemoradiation had acceptable tolerability in newly diagnosed glioblastoma. Although the primary efficacy endpoint was not met, vorinostat sensitivity and resistance signatures could facilitate patient selection in future trials., LESSONS LEARNED: Combination regimen with bevacizumab (BEV) and vorinostat is well tolerated in patients with recurrent glioblastoma., CONCLUSION: Combination treatment of BEV and VOR was well tolerated. This combination therapy for this study population did not improve PFS6 or median OS when compared with BEV monotherapy., We present two patients with glioblastoma multiforme who developed severe hemolytic anemia shortly after initiating therapy with vorinostat, a pan-active histone deacetylase inhibitor, while on prophylactic dapsone., Vorinostat is the most advanced HDAC inhibitor that entered clinical trials in glioblastoma, showing activity in recurrent disease. Multiple phase II trials with vorinostat in combination with targeted agents, temozolomide and radiotherapy are currently recruiting. , . On the basis of the results of this phase II study, further evaluation of the vorinostat-bortezomib combination in GBM patients in this dose and schedule is not recommended., ith the increased toxicities associated with CPT-11 coupled with its unclear clinical significance, investigating the efficacy of vorinostat combined with bevacizumab alone may represent a more promising strategy to evaluate in the context of a phase II clinical trial., CONCLUSION: Vorinostat in combination with temozolomide is well tolerated in patients with HGG. A phase I/II trial of vorinostat with radiotherapy and concomitant TMZ in newly diagnosed glioblastoma is underway.[SEP]Vorinostat has relations with Cholecystitis, Erythroderma, T-cell lymphoma, and Xerostomia. It also has a drug_effect with Ery Throderma and drug_drug with Entinostats.", "label": "no"}
{"id": "converted_897", "sentence1": "Does magnesium sulfate improve outcomes of subarachnoid hemorrhage patients?", "sentence2": "CONCLUSION: Patients assigned a higher serum magnesium concentration had a reduced incidence of vasospasm as seen by angiography, but the difference was not statistically significant. Clinically significant outcomes were not different between groups., 158 patients (26·2%) had poor outcome in the magnesium group compared with 151 (25·3%) in the placebo group (risk ratio [RR] 1·03, 95% CI 0·85-1·25). Our updated meta-analysis of seven randomised trials involving 2047 patients shows that magnesium is not superior to placebo for reduction of poor outcome after aneurysmal subarachnoid haemorrhage (RR 0·96, 95% CI 0·86-1·08). INTERPRETATION: Intravenous magnesium sulphate does not improve clinical outcome after aneurysmal subarachnoid haemorrhage, therefore routine administration of magnesium cannot be recommended. , There is a tendency in the magnesium group to have better outcomes. , Due to inconsistently reported benefits and the occurrence of side effects, phase II data suggested that intravenous magnesium for SAH provided either no overall net benefit or uncertain trade-offs. Benefit was likewise not supported in the single phase III clinical trial., tatistically significant clinical benefits could not be demonstrated for the other drugs (clazosentan, statins, and magnesium). CONCLUSIONS: Insufficient evidence is available to support the use of the triple-H therapy, clazosentan, statins, or magnesium sulfate for the prevention of cerebral vasospasm following subarachnoid hemorrhage. , Magnesium sulfate decreased the rate of cerebral infarction, but not of DCI or poor functional outcome. Regarding outcome, a beneficial effect of magnesium sulfate on outcome can not be ruled out because of sample size limitations., CONCLUSIONS: The present findings do not lend support to a beneficial effect of magnesium sulphate infusion on delayed cerebral infarction. The reduction in DCI and improvement in the clinical outcomes of aneurysmal SAH patients following magnesium sulphate infusion observed in previous pilot studies are not confirmed, although a beneficial effect cannot be ruled out because of sample size limitation., Favorable outcome (Good recovery and moderate disability, as defined by Glasgow Outcome Scale) was achieved in 20 of 30 (67%) patients receiving magnesium sulfate infusion and 16 of 30 (53%) patients receiving placebo treatment, p = 0.292, odds ratio 1.750, 95% CI 0.616-4.974., Similarly, the pooled odds ratio for favorable outcome is 1.598, 95% CI 1.074-2.377, statistically significant. , RESULTS: The worst clinical outcomes at 6 months were seen in MgSO(4) group patients, with mean plasma magnesium concentrations in the fourth quartile, and in placebo group patients, with mean such concentrations in the third and fourth quartiles. CONCLUSIONS: No evidence was found to suggest that a higher mean plasma magnesium concentration improves clinical outcomes. On the contrary, we found an association between high plasma magnesium concentration and worse clinical outcomes., The proportions of patients with a favorable outcome at 6 months (Extended Glasgow Outcome Scale 5 to 8) were similar, 64% in the magnesium sulfate group and 63% in the saline group (OR, 1.0; 95% CI, 0.7 to 1.6). Secondary outcome analyses (modified Rankin Scale, Barthel Index, Short Form 36, and clinical vasospasm) also showed no significant differences between the 2 groups. , CONCLUSIONS: The results do not support a clinical benefit of intravenous magnesium sulfate infusion over placebo infusion in patients with acute aneurysmal subarachnoid hemorrhage., Magnesium infusion reduced the risk of poor outcome and delayed cerebral ischemia (DCI): the relative risk was 0.62 (95% confidence interval (CI) 0.46-0.83) and 0.73 (95% CI 0.53-1.00), respectively. , CONCLUSION: The meta-analysis suggests that intravenous magnesium therapy reduces the risk of DCI and poor outcome after aneurysmal SAH. , The incidence of delayed ischemic infarction was significantly lower in magnesium-treated patients (22% vs. 51%; p = .002); 34 of 54 magnesium patients and 27 of 53 control patients reached good outcome (p = .209)., BACKGROUND: A meta-analysis of current data suggests that magnesium sulfate infusion improves the outcome after aneurysmal subarachnoid hemorrhage through a reduction in delayed ischemic neurological deficit. , These data imply that intravenous magnesium therapy, besides a supposed beneficial effect on outcome, also provides pain relief for SAH patients, for whom it might also improve functional outcome., Preliminary evidence has suggested that magnesium sulfate infusion reduces delayed ischemic neurological deficit and improves clinical outcome after aneurysmal subarachnoid hemorrhage. , In a phase II randomized clinical trial of 283 patients, magnesium treatment reduced the risk of DCI by 34% and of poor outcome by 23%., BACKGROUND: Recent studies suggest that high-dose MgSO4 therapy is safe and reduces the incidence of DIND and subsequent poor outcome after SAH. , On-treatment analysis showed a significantly better outcome after 3 months (P = .017) and a trend toward better outcome after 1 year (P = .083). ,  CONCLUSIONS: High-dose MgSO4 therapy might be efficient as a prophylactic adjacent therapy after SAH to reduce the risk for poor outcome. , There was no significant difference in mortality rate at discharge (p = 0.328). A trend toward improved outcome as measured by the modifed Rankin Scale (p = 0.084), but not the Glasgow Outcome Scale (p = 1.0), was seen in the MgSO4 treated group. CONCLUSIONS: Analysis of the results suggests that MgSO4 infusion may have a role in cerebral vasospasm prophylaxis if therapy is initiated within 48 hours of aneurysm rupture., There was, however, no difference between groups in functional recovery or Glasgow Outcome Scale score. , Patients receiving MgSO4 tended to have fewer neurological deficits, better functional recovery and an improved score in GOS. , CONCLUSIONS: MgSO4 infusion after aneurysmal SAH is well tolerated and may be useful in producing better outcome., CONCLUSION: Magnesium did not seem to interfere in vasospasm frequency but apparently acted favorably in decreasing morbidity and length of hospital stay., None of the patients died; no CT evidence of ischemic infarction was present; and most had good outcomes (GOS 5 in 10 patients; GOS 4 in 8 patients)., At that time, 18 patients in the treatment group and 6 in the placebo group had an excellent outcome (risk ratio, 3.4; 95% CI, 1.3 to 8.9). CONCLUSIONS: This study suggests that magnesium reduces DCI and subsequent poor outcome, but the results are not yet definitive. , We observed a trend in which a higher percentage of patients obtained GOS scores of 4 or 5 in the group treated with MgSO4, but the trend did not reach a statistically significant level. , Magnesium sulfate treatment improves outcome in patients with subarachnoid hemorrhage: a meta-analysis study., BACKGROUND AND PURPOSE: Pilot clinical trials using magnesium sulfate in patients with acute aneurysmal subarachnoid hemorrhage have reported trends toward improvement in clinical outcomes., Preliminary evidence has suggested that magnesium sulfate infusion reduces delayed ischemic neurological deficit and improves clinical outcome after aneurysmal subarachnoid hemorrhage., Our results indicate that although there was reduced likelihood of a poor outcome for patients treated with magnesium sulfate after SAH, patient mortality was not improved., CONCLUSION: Administration of intra-arterial magnesium sulfate in combination with nicardipine was well tolerated in patients with subarachnoid hemorrhage and cerebral vasospasm without a significant change in MAP and ICP., Current evidence does not support the prophylactic use of magnesium sulfate in aneurysmal subarachnoid hemorrhage, Preliminary evidence has suggested that magnesium sulfate infusion reduces delayed ischemic neurological deficit and improves clinical outcome after aneurysmal subarachnoid hemorrhage, A meta-analysis of current data suggests that magnesium sulfate infusion improves the outcome after aneurysmal subarachnoid hemorrhage through a reduction in delayed ischemic neurological deficit, Despite the publication of several randomized controlled studies, there is still much debate on whether magnesium sulfate improves outcome in patients with aneurysmal subarachnoid hemorrhage, Magnesium sulphate is a neuroprotective agent that might improve outcome after aneurysmal subarachnoid haemorrhage by reducing the occurrence or improving the outcome of delayed cerebral ischaemia[SEP]Relations: Magnesium sulfate has relations: contraindication with hypercalcemia disease, contraindication with hypercalcemia disease, contraindication with chronic diarrheal disease, contraindication with chronic diarrheal disease, contraindication with kidney disease, contraindication with kidney disease, drug_drug with Tubocurarine, drug_drug with Tubocurarine, drug_drug with Thioridazine, drug_drug with Thioridazine.", "label": "no"}
{"id": "converted_3916", "sentence1": "Is HbA1c an ideal biomarker of well-controlled diabetes?", "sentence2": "HbA1c is a biomarker with a central role in the diagnosis and follow-up of patients with diabetes, although not a perfect one. Common comorbidities encountered in patients with diabetes mellitus, such as renal insufficiency, high output states (iron deficiency anaemia, haemolytic anaemia, haemoglobinopathies and pregnancy) and intake of specific drugs could compromise the sensitivity and specificity of the biomarker. COVID-19 pandemic poses a pressing challenge for the diabetic population, since maintaining optimal blood glucose control is key to reduce morbidity and mortality rates.[SEP]Elevated hemoglobin A1c has relations with neonatal diabetes mellitus, maturity-onset diabetes of the young, and abnormal hemoglobin. hemoglobinopathy has relations: disease_protein with HBA1, disease_ protein with H BA2, and disease_ proteins with HAA1 and HAA2.", "label": "no"}
{"id": "converted_1405", "sentence1": "Can tetracycline affect tooth formation?", "sentence2": "he results of that study, reported earlier (Rebich et al., 1983), indicated that over one-fifth of the American Indian children had discoloration of the dentition due to ingestion of tetracycline during the years of tooth formatio, ale Wistar rats prelabeled with tetracycline to mark surfaces of bone and tooth formation-mineralization were placed into orbit for 18.5 days aboard the Soviet COSMOS-1129 Biosatellit, It was concluded that the increased tetracycline incorporation reflected a higher rate of mineralization associated with faster tooth formation in the unimpeded toot, n this investigation an attempt has been made to determine the relationship between the staining of permanent teeth by tetracycline administered during the period of tooth formation with the dosage of the drug and the duration of therap,  definite relationship between total dosage and staining and duration of administration and staining was established; the condition occurred with greater frequency (in more than one-third of the children) when the total dosage exceeded 3 g. or the duration of treatment was longer than 10 days, This case report suggests the possibility that discoloration from tetracycline may not be limited to tooth development in the child, but may also affect the adult dentition[SEP]Tetracycline has relations with Nausea, Glossitis, Vomiting and Arthralgia. It can also cause Hypoplasia of teeth and Glossitis. Tetracy Cline is a powerful anti-vomiting drug.", "label": "yes"}
{"id": "converted_3090", "sentence1": "Is eculizumab used for treatment of myasthenia gravis?", "sentence2": "Eculizumab treatment improved symptoms compared with placebo in a phase II study in patients with refractory gMG. D, Eculizumab (Soliris) has been approved in several countries for refractory forms of generalized seropositive severe myasthenia gravis. , The humanized monoclonal antibody eculizumab (Soliris®) is a complement inhibitor indicated for use in anti-acetylcholine receptor (AChR) antibody-positive adults with generalized myasthenia gravis (gMG) in the USA, refractory gMG in the EU, or gMG with symptoms that are difficult to control with high-dose IVIg therapy or PLEX in Japan. , Although several questions remain, such as duration of treatment, cost effectiveness and long-term efficacy and tolerability, current evidence indicates that eculizumab is a valuable emerging therapy for patients with refractory gMG., The 2 exceptions are acetylcholinesterase inhibitors and complement inhibition with eculizumab, which was recently approved by the US Food and Drug Administration for myasthenia gravis., INTRODUCTION\nA phase 2 study of eculizumab for treating myasthenia gravis (MG) used the quantitative myasthenia gravis score (QMG) and myasthenia gravis activities of daily living profile (MG-ADL) to evaluate baseline disease severity and treatment response., QMG and MG-ADL correlations: Study of eculizumab treatment of myasthenia gravis., Rituximab seems to be particularly effective in MuSK myasthenia gravis, and eculizumab arises as an option in refractory AChR myasthenia gravis., Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis., Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study., The humanized monoclonal antibody eculizumab (Soliris®) is a complement inhibitor indicated for use in anti-acetylcholine receptor (AChR) antibody-positive adults with generalized myasthenia gravis (gMG) in the USA, refractory gMG in the EU, or gMG with symptoms that are difficult to control with high-dose IVIg therapy or PLEX in Japan., Eculizumab (Soliris) has been approved in several countries for refractory forms of generalized seropositive severe myasthenia gravis., Eculizumab: A Review in Generalized Myasthenia Gravis., A randomized, double-blind, placebo-controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis., Eculizumab: A Review in Generalized Myasthenia Gravis.) , <b>INTRODUCTION</b>: A phase 2 study of eculizumab for treating myasthenia gravis (MG) used the quantitative myasthenia gravis score (QMG) and myasthenia gravis activities of daily living profile (MG-ADL) to evaluate baseline disease severity and treatment response., Correlations were then analyzed between these assessments.<br><b>METHODS</b>: Patients were given eculizumab or placebo during the first 16-week treatment period of the crossover study, with treatment assignments reversed for the second treatment period following a 5-week washout., A phase 2 study of eculizumab for treating myasthenia gravis (MG) used the quantitative myasthenia gravis score (QMG) and myasthenia gravis activities of daily living profile (MG-ADL) to evaluate baseline disease severity and treatment response., The 2 exceptions are acetylcholinesterase inhibitors and complement inhibition with eculizumab, which was recently approved by the US Food and Drug Administration for myasthenia gravis.[SEP]Relations: Eculizumab has relations: drug_drug with Trastuzumab, drug_drug with Trastuzumab, drug_drug with Briakinumab, drug_drug with Briakinumab, drug_drug with Inebilizumab, drug_drug with Inebilizumab, drug_drug with Parsatuzumab, drug_drug with Parsatuzumab. myasthenia gravis has relations: contraindication with Sulfisoxazole, contraindication with Sulfisoxazole.", "label": "yes"}
{"id": "converted_3237", "sentence1": "Is the crystal structure of Pim-1 available?", "sentence2": "Recent crystallographic studies of Pim-1 have identified unique structural features but have not provided insight into how the kinase recognizes its target substrates. , a co-crystal structure of lead molecule (HS38) in complex with DAPK3, a dual Pim/DAPK3 inhibitor (HS56), The crystal structure of this compound with PIM1 confirmed the predicted binding mode and protein-ligand interactions except those in the acidic ribose pocket. , Using the determined X-ray crystal structure of PIM1 complexed to the compound 1-R as a control, we discuss the importance of including the protein flexibility inherent in the ensemble docking protocol, for the accuracy of the structure prediction of the bound state. , Here, we describe the crystal structure of Pim1 in complex with a newly developed pyrido[4,3-d]pyrimidine-derivative inhibitor (SKI-O-068)., Crystallographic and docking data analyses have been undertaken using inhibitor complexes , The crystal structures of Pim1 in apo form and bound with AMPPNP have been solved[SEP]Protein C has relations with Pivhydrazine, Piroxicam, Pirlindole, and Peginterferon alfa-2b. Protein C is also involved in the development of the anti-fungal drug thiamine (THC)", "label": "yes"}
{"id": "converted_4131", "sentence1": "Can Panitumumab cause trichomegaly?", "sentence2": "Xerosis was present in two cases, and paronychia, pyogenic granuloma, trichomegaly, and madarosis were observed in one patient each. , Eyelash trichomegaly is an uncommon drug-associated sequelae experienced during treatment with epidermal growth factor receptor (EGFR) inhibitors. Elongation of the eyelashes induced by these agents has predominantly been observed in oncology patients with either colorectal or lung cancer. It is most frequently associated with cetuximab and erlotinib; however, it has also been described in individuals treated with gefitinib or panitumumab. , Trichomegaly of the eyelashes during therapy with epidermal growth factor receptor inhibitors:  report of 3 cases., Trichomegaly of the eyelashes is a rare adverse effect of EGFR inhibitor therapy and is characterized by a paradoxical overgrowth of eyelashes.[SEP]Panitumumab has relations with Tregalizumab, Pertuzumab and Sonepczumab. Panitumomab is also linked to Eculizumsab. It is not known if it has any relations with Concizums.", "label": "yes"}